Propensity-weighted long-term risk of urinary adverse events after prostate cancer surgery, radiation, or both.

PubMed

Jarosek, Stephanie L; Virnig, Beth A; Chu, Haitao; Elliott, Sean P

2015-02-01

Prostate cancer is the second most common cancer in men and has high survivorship, yet little is known about the long-term risk of urinary adverse events (UAEs) after treatment. To compare the long-term UAE incidence across treatment and control groups. Using a matched-cohort design, we identified elderly men treated with external-beam radiotherapy (EBRT; n=44 318), brachytherapy (BT; n=14 259), EBRT+BT (n=11 835), radical prostatectomy (RP; n=26 970), RP+EBRT (n=1557), or cryotherapy (n=2115) for non-metastatic prostate cancer and 144 816 non-cancer control individuals from the population-based Surveillance, Epidemiology, and End Results-Medicare linked data from 1992-2007 with follow-up through 2009. The incidence of treated UAEs and time from cancer treatment to first UAE were analyzed in terms of propensity-weighted survival. Median follow-up was 4.14 yr. At 10 yr, all treatment groups experienced higher propensity-weighted cumulative UAE incidence than the control group (16.1%; hazard risk [HR] 1.0), with the highest incidence for RP+EBRT (37.8%; HR 3.19, 95% confidence interval [CI] 2.79-3.66), followed by BT+EBRT (28.4%; HR 1.97, CI 1.85-2.10), RP (26.6%; HR 2.44, CI 2.34-2.55), cryotherapy (23.4%; HR 1.56, CI 1.30-1.87), BT (19.8%; HR 1.43, CI 1.33-1.53), and EBRT (19.7%; HR 1.11, CI 1.07-1.16). Bladder outlet obstruction was the most common event. Men undergoing RP, RP+EBRT, and BT+EBRT experienced the highest UAE risk at 10 yr, although UAEs accrued differently over extended follow-up. The significant background UAE rate among non-cancer control individuals yields a risk attributable to prostate cancer treatment that is 17% lower than prior estimates. We show that treatment for prostate cancer, especially combinations of two treatments such as radiation and surgery, carries a significant risk of urinary adverse events such as urethral stricture. This risk increases with time since treatment, emphasizing that treatments have long-term effects. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Australian patterns of prostate cancer care: Are they evolving?

PubMed Central

Lo, Jonathon; Papa, Nathan; Bolton, Damien M.; Murphy, Declan; Lawrentschuk, Nathan

2015-01-01

Background Approaches to prostate cancer (PCa) care have changed in recent years out of concern for overdiagnosis and overtreatment. Despite these changes, many patients continue to undergo some form of curative treatment and with a growing perception among multidisciplinary clinicians that more aggressive treatments are being favored. This study examines patterns of PCa care in Australia, focusing on current rates of screening and aggressive interventions that consist of high-dose-rate (HDR) brachytherapy and pelvic lymph node dissection (PLND). Methods Health services data were used to assess Australian men undergoing PCa screening and treatment from 2001 to 2014. Age-specific rates of prostate-specific antigen (PSA) screening were calculated. Ratios of radical prostatectomy (RP) with PLND to RP without PLND, and HDR brachytherapy to low-dose-rate (LDR) brachytherapy were determined by state jurisdictions. Results From 2008, the rate of PSA screening trended downward significantly with year for all age ranges (P < 0.02) except men aged ≥ 85 (P = 0.56). PLND rates for 2008–2014 were lower than rates for 2001–2007 across all states and territories. From 2008 to 2014, PLND was performed ≥ 2.7 times more frequently in New South Wales and the Australian Capital Territory than in other jurisdictions. Since 2007, brachytherapy practice across Australia has evolved towards a relatively low use of HDR brachytherapy (ratio of HDR to LDR brachytherapy < 0.5 for all jurisdictions except the Australian Capital Territory). Conclusion Rates of PLND and HDR brachytherapy for PCa have declined in Australia, providing evidence for the effect of stage migration due to widespread PSA screening. Currently, PSA screening rates remain high among older men, which may expose them to unnecessary investigations and treatment-related morbidity. PMID:27014660

Risk of radiation pneumonitis in patients receiving taxane-based trimodality therapy for locally advanced esophageal cancer.

PubMed

Shaikh, Talha; Churilla, Thomas M; Monpara, Pooja; Scott, Walter J; Cohen, Steven J; Meyer, Joshua E

There are limited data regarding clinical and treatment factors associated with radiation pneumonitis (RP) in patients receiving taxane-based trimodality therapy for esophageal cancer. The purpose of this study was to identify predictors of RP in patients undergoing trimodality therapy. We retrospectively reviewed patients undergoing chemoradiation followed by esophagectomy between 2006 and 2011. The association between clinical and dosimetric factors with RP was assessed using χ 2 test and Mann-Whitney U test. Multivariable regression was used to assess the relationship between grade 2+ RP and clinical/dosimetric factors. Receiver operator curves were generated to identify threshold doses for RP. A total of 139 patients were included; 19 (13.7%) patients experienced grade 2+ RP. Patients with upper/middle thoracic tumors (P = .038) and receiving higher radiation doses (P = .038) were more likely to develop grade 2+ RP. There was no association between taxane-based therapy and grade 2+ RP (P = .728). The percent volume of lung receiving 5 Gy (V5; P < .001), 10 Gy (P < .001), 20 Gy (V20; P < .001), and 30 Gy (P < .001) was associated with an increased risk of grade 2+ RP. On multivariable regression, the lung V5 (odds ratio, 1.101; 95% confidence interval, 1.1014-1.195) and V20 (odds ratio, 1.149; 95% confidence interval, 1.1015-1.301) remained associated with grade 2+ RP. A V5 ≤65% and V20 ≤25% were identified as optimal thresholds for increased grade 2+ RP. Dosimetric parameters are strong predictors of symptomatic RP in patients undergoing trimodality therapy for esophageal cancer. Mitigating the risk of RP in these patients should be an important consideration during treatment planning. Copyright © 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Influence of radical prostatectomy for prostate cancer on work status and working life 3 years after surgery.

PubMed

Dahl, Sigrun; Loge, Jon Håvard; Berge, Viktor; Dahl, Alv Andreas; Cvancarova, Milada; Fosså, Sophie Dorothea

2015-06-01

The purpose of this study is to study the influence of radical prostatectomy (RP) for prostate cancer on work status and working life in men 3 years after surgery. In a prospective, questionnaire-based study on adverse effects after RP, 330 prostate cancer (PCa) patients who had been active in the workforce before RP described their work status 3 years after having surgery. We dichotomized their postoperative work status into "unchanged or increased" versus "reduced." The participants also reported whether their working life was influenced by the PCa trajectory to no, some, or a great extent. Univariate and multiple logistic regression models were established with sociodemographic and clinical characteristics as independent variables and "work status" or "influence of PCa trajectory on working life" as dependent variables. Twenty-five percent of the participants had retired. Of the remaining participants, approximately 20 % had a reduced work status, which in the multivariate analyses was significantly associated with increasing age. One third of the men still active in the workforce considered the PCa to negatively influence their working life. This was independently associated with bother related to urinary leakage, fatigue, and having undergone additional oncological therapy (pelvic radiotherapy and/or hormone treatment). Though RP does not affect work status in most men, approximately one third of them experience problems in their working life due to adverse effects related to RP and/or additional post-RP anti-cancer therapy. Most PCa survivors can expect to remain in the workforce for at least 3 years after RP, but for some, persistent adverse effects after RP and /or additional anti-cancer treatment negatively affect their working life. Pre-RP counseling of men within the workforce should cover possible post-RP changes concerning work status and working life.

[Outcome of cataract surgery in patients with pigmentary retinal degeneration].

PubMed

Grześk, Magdalena; Kałuzny, Józef; Malukiewicz-Wiśniewska, Grazyna

2007-01-01

To evaluate the results of cataract surgery in patients with RP because retinitis pigmentosa is one of the disease entities that belongs to tapeto-retinal degenerations. The occurrence of RP appearance is 1:4000 to 1:3000. Twenty patients with RP (7 women and 13 men, 33 eyes), who underwent cataract surgery were examined retrospectively. Average age in our group was 46.6 years. Visual acuity, intraocular pressure, slip lamp examination, fundus examination, cataract morphology, visual field were taken before surgery and on discharge, on the basis of medical documentation. Control examination was taken, on average, eighty one months after cataract surgery. Nine eyes were operated by phacoemulsification, 24 eyes by means of extracapsular cataract extraction. In the same way control group of 18 patients who underwent cataract surgery without RP (33 eyes) was examined. In RP group in 63.6% patients on discharge from the hospital and in 60.6% patients during the control examination, improvement of visual acuity was revealed. Deterioration was noted in 18.2% of patients on discharge from hospital and in 24.2% of patients during the control examination. In the control group improvement of visual acuity was revealed in 90.9% of patients on discharge and in 97% patients during the control examination, whereas deterioration of visual acuity occurred in 6.1% patients on discharge and in 3% patients during the check examination. In patients with retinitis pigmentosa cataract occurs earlier then in the control group. Cataract surgery for relatively minor opacities is beneficial in patients with RP, and causes improvement of visual acuity in most of eyes undergoing surgery.

Hormonal changes after localized prostate cancer treatment. Comparison between external beam radiation therapy and radical prostatectomy.

PubMed

Planas, J; Celma, A; Placer, J; Maldonado, X; Trilla, E; Salvador, C; Lorente, D; Regis, L; Cuadras, M; Carles, J; Morote, J

2016-11-01

To determine the influence of radical prostatectomy (RP) and external beam radiation therapy (EBRT) on the hypothalamic pituitary axis of 120 men with clinically localized prostate cancer treated with RP or EBRT exclusively. 120 patients with localized prostate cancer were enrolled. Ninety two patients underwent RP and 28 patients EBRT exclusively. We measured serum levels of luteinizing hormone, follicle stimulating hormone (FSH), total testosterone (T), free testosterone, and estradiol at baseline and at 3 and 12 months after treatment completion. Patients undergoing RP were younger and presented a higher prostate volume (64.3 vs. 71.1 years, p<0.0001 and 55.1 vs. 36.5 g, p<0.0001; respectively). No differences regarding serum hormonal levels were found at baseline. Luteinizing hormone and FSH levels were significantly higher in those patients treated with EBRT at three months (luteinizing hormone 8,54 vs. 4,76 U/l, FSH 22,96 vs. 8,18 U/l, p<0,0001) while T and free testosterone levels were significantly lower (T 360,3 vs. 414,83ng/dl, p 0,039; free testosterone 5,94 vs. 7,5pg/ml, p 0,018). At 12 months FSH levels remained significantly higher in patients treated with EBRT compared to patients treated with RP (21,01 vs. 8,51 U/l, p<0,001) while T levels remained significantly lower (339,89 vs. 402,39ng/dl, p 0,03). Prostate cancer treatment influences the hypothalamic pituitary axis. This influence seems to be more important when patients with prostate cancer are treated with EBRT rather than RP. More studies are needed to elucidate the role that prostate may play as an endocrine organ. Copyright © 2016 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Regulation of plasma agouti-related protein and its relationship with hunger in lean and obese men.

PubMed

Hazell, Tom J; Sawula, Laura; Edgett, Brittany A; Walsh, Jeremy J; Gurd, Brendon J

2016-12-01

Agouti-related protein (AgRP) is an orexigenic (appetite stimulating) neuropeptide suggested to exert tonic control over long-term energy balance. While some have speculated AgRP is not involved in the episodic (i.e. meal to meal energy intake) control, acute decreases in plasma agouti-related protein (AgRP) following a meal have been observed in humans in a role consistent with episodic control for AgRP. Whether changes in plasma AgRP are associated with episodic, and/or tonic changes in appetite has yet to be directly examined. The present study examined the relationship between agouti-related protein (AgRP), leptin and the regulation of appetite following a 48-h fast and an acute meal challenge. Blood samples were obtained from young lean and obese men before and after a 48 h fast (lean n = 10; obese n = 7). Fasting resulted in an increase in AgRP and a decrease in leptin with these changes being greater in lean than obese. In addition, blood samples were obtained from lean men before and 1, 2, 3 and 4 h after a meal (n = 8). Following a meal, AgRP was reduced from 2 to 4 h, a change that was dissociated from both leptin and subjective measures of hunger and satiety. These results demonstrate that AgRP is not associated with changes in hunger or satiety, and can change without corresponding changes in leptin. This suggests that AgRP may not be involved in the episodic control of appetite and the release of AgRP may involve signals other than leptin. Copyright © 2016 Elsevier Ltd. All rights reserved.

Prevalence of the HOXB13 G84E mutation in Danish men undergoing radical prostatectomy and its correlations with prostate cancer risk and aggressiveness.

PubMed

Storebjerg, Tine M; Høyer, Søren; Kirkegaard, Pia; Bro, Flemming; Ørntoft, Torben F; Borre, Michael; Sørensen, Karina D

2016-10-01

To determine the prevalence of the HOXB13 G84E mutation (rs138213197) in Danish men with or without prostate cancer (PCa) and to investigate possible correlations between HOXB13 mutation status and clinicopathological characteristics associated with tumour aggressiveness. We conducted a case-control study including 995 men with PCa (cases) who underwent radical prostatectomy (RP) between 1997 and 2011 at the Department of Urology, Aarhus University Hospital, Denmark. As controls, we used 1622 healthy men with a normal prostate specific antigen (PSA) level. The HOXB13 G84E mutation was identified in 0.49% of controls and in 2.51% of PCa cases. The mutation was associated with a 5.12-fold increased relative risk (RR) of PCa (95% confidence interval [CI] 2.26-13.38; P = 13 × 10(-6) ). Furthermore, carriers of the risk allele were significantly more likely to have a higher PSA level at diagnosis (mean PSA 19.9 vs 13.6 ng/mL; P = 0.032), a pathological Gleason score ≥7 (83.3 vs 60.9%; P = 0.032), and positive surgical margins (56.0 vs 28.5%; P = 0.006) than non-carriers. Risk allele carriers were also more likely to have aggressive disease (54.2 vs 28.6%; P = 0.011), as defined by a preoperative PSA ≥20 ng/mL, pathological Gleason score ≥ (4+3) and/or presence of regional/distant disease. At a mean follow-up of 7 months, we found no significant association between HOXB13 mutation status and biochemical recurrence in this cohort of men who underwent RP. This is the first study to investigate the HOXB13 G84E mutation in Danish men. The mutation was detected in 0.49% of controls and in 2.51% of cases, and was associated with 5.12-fold increased RR of being diagnosed with PCa. In our RP cohort, HOXB13 mutation carriers were more likely to develop aggressive PCa. Further studies are needed to assess the potential of HOXB13 for future targeted screening approaches. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

Practice patterns of post-radical prostatectomy incontinence surgery in Ontario

PubMed Central

Wallis, Christopher J.D.; Herschorn, Sender; Liu, Ying; Carr, Lesley K.; Kodama, Ronald T.; Klotz, Laurence H.; Saskin, Refik; Nam, Robert K.

2014-01-01

Introduction: We assess the practice patterns of artificial urinary sphincter (AUS) and urethral sling insertion after radical prostatectomy (RP) from a large population-based cohort. Methods: We examined 25 346 men in Ontario, Canada who underwent RP between 1993 and 2006. Using hospital and cancer registry data, we identified patients who subsequently underwent an incontinence procedure. We characterized the practice patterns of post-prostatectomy incontinence procedures across Ontario during the study interval. Results: A total of 703 (2.8%) men underwent subsequent insertion of an AUS and 282 (1.1%) underwent a urethral sling procedure (985 total incontinence procedures, 3.9%) over the study period. During the study period, 121 hospitals performed RP. Among them, 32 (26%) hospitals performed both RP and AUS/sling procedures, and 89 (74%) performed RP only. Four hospitals performed AUS/sling procedures but not RP. Of the 36 institutions that performed AUS/sling procedures, the median annual case volume was 0.29 (interquartile range: 0.083-0.75). Of all incontinence procedures, 56% were performed at 3 academic institutions. When examining observed rates of AUS/sling procedures compared with expected rates from the overall cohort, 15 of 32 hospitals (47%) performed significantly fewer incontinence procedures than expected given their RP case volume (p range: <0.0001–0.0390) and 5 (16%) performed significantly more (p range: <0.0001–0.038). Conclusions: A small number of academic institutions provide most of the surgical care for men with incontinence following RP in Ontario. Many centres that perform RP refer out to other centres to surgically manage their patients’ incontinence. PMID:25408805

Lack of an Association between Neutrophil-to-Lymphocyte Ratio and PSA Failure of Prostate Cancer Patients Who Underwent Radical Prostatectomy.

PubMed

Maeda, Yoko; Kawahara, Takashi; Koizumi, Mitsuyuki; Ito, Hiroki; Kumano, Yohei; Ohtaka, Mari; Kondo, Takuya; Mochizuki, Taku; Hattori, Yusuke; Teranishi, Jun-Ichi; Yumura, Yasushi; Miyoshi, Yasuhide; Yao, Masahiro; Miyamoto, Hiroshi; Uemura, Hiroji

2016-01-01

Introduction. The neutrophil-to-lymphocyte ratio (NLR), which can be easily calculated from routine complete blood counts of the peripheral blood, has been suggested to serve as a prognostic factor for some solid malignancies. In the present study, we aimed to determine the relationship between NLR in prostate cancer patients undergoing radical prostatectomy (RP) and their prognosis. Materials and Methods. We assessed NLR in 73 men (patients) who received RP for their prostate cancer. We also performed immunohistochemistry for CD8 and CD66b in a separate set of RP specimens. Results. The median NLR in the 73 patients was 1.85. There were no significant correlations of NLR with tumor grade (p = 0.834), pathological T stage (p = 0.082), lymph node metastasis (p = 0.062), or resection margin status (p = 0.772). Based on the area under the receiver operator characteristic curve (AUROC) to predict biochemical recurrence after RP, potential NLR cut-off point was determined to be 2.88 or 3.88. However, both of these cut-off points did not precisely predict the prognosis. There were no statistically significant differences in the number of CD66b-positive neutrophils or CD8-positive lymphocytes between stromal tissues adjacent to cancer glands and stromal tissues away from cancer glands and between different grades or stages of tumors. Conclusions. There was no association between NLR and biochemical failure after prostatectomy.

Racial Differences in the Surgical Care of Medicare Beneficiaries With Localized Prostate Cancer.

PubMed

Schmid, Marianne; Meyer, Christian P; Reznor, Gally; Choueiri, Toni K; Hanske, Julian; Sammon, Jesse D; Abdollah, Firas; Chun, Felix K H; Kibel, Adam S; Tucker-Seeley, Reginald D; Kantoff, Philip W; Lipsitz, Stuart R; Menon, Mani; Nguyen, Paul L; Trinh, Quoc-Dien

2016-01-01

There is extensive evidence suggesting that black men with localized prostate cancer (PCa) have worse cancer-specific mortality compared with their non-Hispanic white counterparts. To evaluate racial disparities in the use, quality of care, and outcomes of radical prostatectomy (RP) in elderly men (≥ 65 years) with nonmetastatic PCa. This retrospective analysis of outcomes stratified according to race (black vs non-Hispanic white) included 2020 elderly black patients (7.6%) and 24,462 elderly non-Hispanic white patients (92.4%) with localized PCa who underwent RP within the first year of PCa diagnosis in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database between 1992 and 2009. The study was performed in 2014. Process of care (ie, time to treatment, lymph node dissection), as well as outcome measures (ie, complications, emergency department visits, readmissions, PCa-specific and all-cause mortality, costs) were evaluated using Cox proportional hazards regression. Multivariable conditional logistic regression and quantile regression were used to study the association of racial disparities with process of care and outcome measures. The proportion of black patients with localized prostate cancer who underwent RP within 90 days was 59.4% vs 69.5% of non-Hispanic white patients (P <  001). In quantile regression of the top 50% of patients, blacks had a 7-day treatment delay compared with non-Hispanic whites. (P <  001). Black patients were less likely to undergo lymph node dissection (odds ratio [OR], 0.76 [95% CI, 0.66-0.80]; P < .001) but had higher odds of postoperative visits to the emergency department (within 30 days: OR, 1.48 [95% CI, 1.18-1.86]); after 30 days or more (OR, 1.45 [95% CI, 1.19-1.76]) and readmissions (within 30 days: OR, 1.28 [95% CI, 1.02-1.61]); ≥ 30 days (OR, 1.27 [95% CI, 1.07-1.51]) compared with non-Hispanic whites. The surgical treatment of black patients was associated with a higher incremental annual cost (the top 50% of blacks spent $1185.50 (95% CI , $804.85-1 $1566.10; P < .001) more than the top 50% of non-Hispanic whites). There was no difference in PCa-specific mortality (P = .16) or all-cause mortality (P = .64) between black and non-Hispanic white men. Blacks treated with RP for localized PCa are more likely to experience adverse events and incur higher costs compared with non-Hispanic white men; however, this does not translate into a difference in PCa-specific or all-cause mortality.

Sexual function and bother after radical prostatectomy or radiation for prostate cancer: multivariate quality-of-life analysis from CaPSURE. Cancer of the Prostate Strategic Urologic Research Endeavor.

PubMed

Litwin, M S; Flanders, S C; Pasta, D J; Stoddard, M L; Lubeck, D P; Henning, J M

1999-09-01

To measure the effect of treatment choice (pelvic irradiation [XRT] versus radical prostatectomy [RP] with or without nerve sparing) on sexual function and sexual bother during the first 2 years after treatment. We studied sexual function and sexual bother in 438 men recently diagnosed with early-stage prostate cancer and treated with XRT or RP with or without nerve sparing. Outcomes were assessed with the University of California, Los Angeles Prostate Cancer Index, a validated health-related quality-of-life instrument that includes these two domains. To minimize the influence of other factors, we adjusted for age, comorbidity, general health, and previous treatment for erectile dysfunction. All subjects were drawn from CaPSURE, a national, longitudinal data base. Sexual function improved over time during the first year in all treatment groups; however, during the second year, sexual function began to decline in the XRT group. Older patients who received XRT showed substantial declines in sexual function throughout the 2 years, and older patients who underwent RP experienced a return of very low baseline sexual function. Sexual function was improved by the use of nerve-sparing procedures or erectile aids. Alterations in sexual bother were ameliorated by many factors, including age, general health perceptions, and sexual function. Patients undergoing XRT or RP with or without nerve sparing all showed comparable rates of improvement in sexual function during the first year after treatment for early-stage prostate cancer. However, in the second year after treatment, patients treated with XRT began to show declining sexual function; patients treated with RP did not.

Ejaculation profiles of men following radiation therapy for prostate cancer.

PubMed

Sullivan, John F; Stember, Doron S; Deveci, Serkan; Akin-Olugbade, Yemi; Mulhall, John P

2013-05-01

Radical prostatectomy (RP) is associated with anejaculation, which for some men is a source of bother and sexual dissatisfaction. Clinical experience has shown us some men after pelvic radiation therapy (RT) also experience anejaculation. This analysis was conducted to define the ejaculation profiles of men after RT for prostate cancer (PCa). As a routine part of the sexual health evaluation for post-RT patients, men provided information regarding their ejaculatory function and orgasm. Analysis was conducted of a sexual medicine database reviewing demographic data, PCa factors, erectile, ejaculatory, and orgasmic function. Men with prior history of RP, cryotherapy, focal therapies, and androgen deprivation therapy (ADT) were excluded. Patients completed the International Index of Erectile Function (IIEF) questionnaire at follow-up visits commencing with the first posttreatment visit and specific attention was paid to the IIEF orgasm domain. Three hundred and sixty-four consecutive patients were included. Two hundred and fifty-two patients had external beam, and 112 patients had brachytherapy (BT). Mean age was 64 ± 11 (42-78) years and mean follow-up after RT was 6 ± 4.5 years. Mean prostate size at time of RT was 42 ± 21 g. Of the entire population, 72% lost the ability to ejaculate in an antegrade fashion after prostate RT by their last visit. The proportion experiencing anejaculation at 1, 3, and 5 years after RT was 16%, 69%, and 89%, respectively. For men with at least two IIEF questionnaires completed, the orgasm domain scores decreased dramatically over the follow-up period; orgasm domain scores (0-10): <12 months post-RT 7.4, 13-24 months 5.4, 25-36 months 3.2, >36 months 2.8 (P < 0.01). Multivariable analysis identified several factors predictive of failure to ejaculate: older age, ADT, RT dose > 100 Gy, and smaller prostates at the time of RT. The vast majority of men after prostate RT will experience anejaculation and should be counseled accordingly prior to undergoing therapy. We have identified predictive factors. © 2013 International Society for Sexual Medicine.

Impact of a robotic surgical system on treatment choice for men with clinically organ-confined prostate cancer.

PubMed

Kobayashi, Takashi; Kanao, Kent; Araki, Motoo; Terada, Naoki; Kobayashi, Yasuyuki; Sawada, Atsuro; Inoue, Takahiro; Ebara, Shin; Watanabe, Toyohiko; Kamba, Tomomi; Sumitomo, Makoto; Nasu, Yasutomo; Ogawa, Osamu

2018-04-01

Introducing a new surgical technology may affect behaviors and attitudes of patients and surgeons about clinical practice. Robot-assisted laparoscopic radical prostatectomy (RALP) was approved in 2012 in Japan. We investigated whether the introduction of this system affected the treatment of organ-confined prostate cancer (PCa) and the use of radical prostatectomy (RP). We conducted a retrospective multicenter study on 718 patients with clinically determined organ-confined PCa treated at one of three Japanese academic institutions in 2011 (n = 338) or 2013 (n = 380). Two patient groups formed according to the treatment year were compared regarding the clinical characteristics of PCa, whether referred or screened at our hospital, comorbidities and surgical risk, and choice of primary treatment. Distribution of PCa risk was not changed by the introduction of RALP. Use of RP increased by 70% (from 127 to 221 cases, p < 0.0001), whereas the number of those undergoing radiotherapy or androgen deprivation therapy decreased irrespective of the disease risk of PCa. Increased use of RP (from 34 to 100 cases) for intermediate- or high-risk PCa patients with mild perioperative risk (American Society of Anesthesiologists score 2) accounted for 70% of the total RP increase, whereas the number of low- or very low-risk PCa patients with high comorbidity scores (Charlson Index ≥ 4) increased from 8 to 25 cases, accounting for 18%. Use of expectant management (active surveillance, watchful waiting) in very low-risk PCa patients was 15% in 2011 and 12% in 2013 (p = 0.791). Introduction of a robotic surgical system had little effect on the risk distribution of PCa. Use of RP increased, apparently due to increased indications in patients who are candidates for RP but have mild perioperative risk. Although small, there was an increase in the number of RPs performed on patients with severe comorbidities but with low-risk or very low-risk PCa.

Impact of robotic technique and surgical volume on the cost of radical prostatectomy.

PubMed

Hyams, Elias S; Mullins, Jeffrey K; Pierorazio, Phillip M; Partin, Alan W; Allaf, Mohamad E; Matlaga, Brian R

2013-03-01

Our present understanding of the effect of robotic surgery and surgical volume on the cost of radical prostatectomy (RP) is limited. Given the increasing pressures placed on healthcare resource utilization, such determinations of healthcare value are becoming increasingly important. Therefore, we performed a study to define the effect of robotic technology and surgical volume on the cost of RP. The state of Maryland mandates that all acute-care hospitals report encounter-level and hospital discharge data to the Health Service Cost Review Commission (HSCRC). The HSCRC was queried for men undergoing RP between 2008 and 2011 (the period during which robot-assisted laparoscopic radical prostatectomy [RALRP] was coded separately). High-volume hospitals were defined as >60 cases per year, and high-volume surgeons were defined as >40 cases per year. Multivariate regression analysis was performed to evaluate whether robotic technique and high surgical volume impacted the cost of RP. There were 1499 patients who underwent RALRP and 2565 who underwent radical retropubic prostatectomy (RRP) during the study period. The total cost for RALRP was higher than for RRP ($14,000 vs 10,100; P<0.001) based primarily on operating room charges and supply charges. Multivariate regression demonstrated that RALRP was associated with a significantly higher cost (β coeff 4.1; P<0.001), even within high-volume hospitals (β coeff 3.3; P<0.001). High-volume surgeons and high-volume hospitals, however, were associated with a significantly lower cost for RP overall. High surgeon volume was associated with lower cost for RALRP and RRP, while high institutional volume was associated with lower cost for RALRP only. High surgical volume was associated with lower cost of RP. Even at high surgical volume, however, the cost of RALRP still exceeded that of RRP. As robotic surgery has come to dominate the healthcare marketplace, strategies to increase the role of high-volume providers may be needed to improve the cost-effectiveness of prostate cancer surgical therapy.

African American men with low-grade prostate cancer have increased disease recurrence after prostatectomy compared with Caucasian men.

PubMed

Yamoah, Kosj; Deville, Curtiland; Vapiwala, Neha; Spangler, Elaine; Zeigler-Johnson, Charnita M; Malkowicz, Bruce; Lee, David I; Kattan, Michael; Dicker, Adam P; Rebbeck, Timothy R

2015-02-01

To explore whether disparities in outcomes exist between African American (AA) and Caucasian (CS) men with low-grade prostate cancer and similar cancer of the prostate risk assessment-postsurgery (CAPRA-S) features following prostatectomy (RP). The overall cohort consisted of 1,265 men (234 AA and 1,031 CS) who met the National comprehensive cancer network criteria for low- to intermediate-risk prostate cancer and underwent RP between 1990 and 2012. We first evaluated whether clinical factors were associated with adverse pathologic outcomes and freedom from biochemical failure (FFbF) using the entire cohort. Next, we studied a subset of 705 men (112 AA and 593 CS) who had pathologic Gleason score≤6 (low-grade disease). Using this cohort, we determined whether race affected FFbF in men with RP-proven low-grade disease and similar CAPRA-S scores. With a median follow-up time of 27 months, the overall 7-year FFbF rate was 86% vs. 79% in CS and AA men, respectively (P = 0.035). There was no significant difference in one or more adverse pathologic features between CS vs. AA men (27% vs. 31%; P = 0.35) or CAPRA-S score (P = 0.28). In the subset analysis of patients with low-grade disease, AA race was associated with worse FFbF outcomes (P = 0.002). Furthermore, AA race was a significant predictor of FFbF in men with low-grade disease (hazard ratio = 2.01, 95% CI: 1.08-3.72; P = 0.029). AA race is a predictor of worse FFbF outcomes in men with low-grade disease after RP. These results suggest that a subset of AA men with low-grade disease may benefit from more aggressive treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

Prostate cancer-specific mortality after radical prostatectomy or external beam radiation therapy in men with 1 or more high-risk factors.

PubMed

D'Amico, Anthony V; Chen, Ming-Hui; Catalona, William J; Sun, Leon; Roehl, Kimberly A; Moul, Judd W

2007-07-01

Estimates of prostate cancer-specific mortality (PCSM) were determined after radical prostatectomy (RP) or radiation therapy (RT) in men with >or=1 high-risk factors. The study cohort comprised 948 men who underwent RP (N = 660) or RT (N = 288) for localized prostate cancer between 1988 and 2004 and had at least 1 of the following high-risk factors: a prostate-specific antigen (PSA) velocity >2 ng/mL/year during the year before diagnosis, a biopsy Gleason score of >or=7, a PSA level of >or=10 ng/mL, or clinical category T2b or high disease. Grays regression was used to evaluate whether the number and type of high-risk factors were associated with time to PCSM. Multiple determinants of high risk were found to be significantly associated with a shorter time to PCSM after RP (P < .001) or RT (P 2 ng/mL/year was associated with an increased risk of PCSM after RP (hazards ratio [HR] of 7.3; 95% confidence interval [95% CI], 1.0-59 [P = .05]) or RT (HR of 12.1; 95% CI, 1.4-105 [P = .02]) when compared with men with any other single high-risk factor. Men with a PSA velocity >2 ng/mL/year had a significantly higher risk of PCSM compared with men who had any other single high-risk factor. These men should be considered for randomized trials evaluating the impact on PCSM from adding systemic agents to standards of care for men with high-risk PC. Copyright (c) 2007 American Cancer Society.

Association of Situational and Environmental Factors With Last Episode of Unprotected Anal Intercourse Among MSM in Hong Kong: A Case-Crossover Analysis.

PubMed

Lau, Joseph T F; Mo, Phoenix K H; Gu, Jing; Hao, Chun; Lai, CoCo H Y

2016-02-01

This study investigates event-specific factors that differentiate the last episodes of unprotected anal intercourse (UAI) from protected anal intercourse (PAI) with regular partner (RP) among 213 men who have sex with men (MSM) who did not use condoms consistently using case-crossover analysis. Factors positively associated with the last episode of UAI with RP included: two situational factors (i.e., participant's suggestion to have UAI, alcohol use) and three environmental/setting factors (i.e., sex took place overseas, during a weekday and not at home). Negative associations with an episode of UAI with RP included: five situational factors (i.e., discussion about condom use prior to sex, RP's suggestion to have PAI, participant's suggestion to have PAI, perception that RP would like to use a condom, participant's planning to use a condom) and two environmental/setting factors (i.e., condoms placed at the venue where sex took place, partner possessed a condom). Thus, these significant event-specific factors explained under which circumstances some MSM would use and would not use condoms during anal sex with RP.

LaRC-RP41: A Tough, High-Performance Composite Matrix

NASA Technical Reports Server (NTRS)

Pater, Ruth H.; Johnston, Norman J.; Smith, Ricky E.; Snoha, John J.; Gautreaux, Carol R.; Reddy, Rakasi M.

1991-01-01

New polymer exhibits increased toughness and resistance to microcracking. Cross-linking PMR-15 and linear LaRC-TPI combined to provide sequential semi-2-IPN designated as LaRC-RP41. Synthesized from PMR-15 imide prepolymer undergoing cross-linking in immediate presence of LaRC-TPI polyamic acid, also undergoing simultaneous imidization and linear chain extension. Potentially high-temperature matrix resin, adhesive, and molding resin. Applications include automobiles, electronics, aircraft, and aerospace structures.

The prognostic significance of the 2014 International Society of Urological Pathology (ISUP) grading system for prostate cancer.

PubMed

Samaratunga, Hemamali; Delahunt, Brett; Gianduzzo, Troy; Coughlin, Geoff; Duffy, David; LeFevre, Ian; Johannsen, Shulammite; Egevad, Lars; Yaxley, John

2015-10-01

The 2005 International Society of Urological Pathology (ISUP) modified Gleason grading system was further amended in 2014 with the establishment of grade groupings (ISUP grading). This study examined the predictive value of ISUP grading, comparing results with recognised prognostic parameters.Of 3700 men undergoing radical prostatectomy (RP) reported at Aquesta Pathology between 2008 and 2013, 2079 also had a positive needle biopsy available for review. We examined the association between needle biopsy 2014 ISUP grade and 2005 modified Gleason score, tumour volume, pathological stage of the subsequent RP tumour, as well as biochemical recurrence-free survival (BRFS). The median age was 62 (range 32-79 years). Median serum prostate specific antigen was 5.9 (range 0.4-69 ng/mL). For needle biopsies, 280 (13.5%), 1031 (49.6%), 366 (17.6%), 77 (3.7%) and 325 (15.6%) were 2014 ISUP grades 1-5, respectively. Needle biopsy 2014 ISUP grade showed a significant association with RP tumour volume (p < 0.001), TNM pT and N stage (p < 0.001) and BRFS (p < 0.001). Multivariate analysis using Cox proportional hazards regression model showed serum prostate specific antigen (PSA) at the time of diagnosis and ISUP grade >2 to be significantly associated with BRFS.This study provides evidence of the prognostic significance of ISUP grading for thin core needle biopsy of prostate.

Increased prostate cancer specific mortality following radical prostatectomy in men presenting with voiding symptoms-A whole of population study.

PubMed

Ta, Anthony D; Papa, Nathan P; Lawrentschuk, Nathan; Millar, Jeremy L; Syme, Rodney; Giles, Graham G; Bolton, Damien M

2015-09-01

Whole of population studies reporting long-term outcomes following radical prostatectomy (RP) are scarce. We aimed to evaluate the long-term outcomes in men with prostate cancer (PC) treated with RP in a whole of population cohort. A secondary objective was to evaluate the influence of mode of presentation on PC specific mortality (PCSM). A prospective database of all cases of RP performed in Victoria, Australia between 1995 and 2000 was established within the Victorian Cancer Registry. Specimen histopathology reports and prostate-specific antigen (PSA) values were obtained by record linkage to pathology laboratories. Mode of presentation was recorded as either PSA screened (PSA testing offered in absence of voiding symptoms) or symptomatic (diagnosis of PC following presentation with voiding symptoms). Multivariate Cox and competing risk regression models were fitted to analyze all-cause mortality, biochemical recurrence, and PCSM. Between 1995 and 2000, 2,154 men underwent RP in Victoria. During median follow up of 10.2 years (range 0.26-13.5 years), 74 men died from PC. In addition to Gleason score and pathological stage, symptomatic presentation was associated with PCSM. After adjusting for stage and PSA, no difference in PCSM was found between men with Gleason score ≤ 6 and Gleason score 3 + 4 = 7. Men with Gleason score 4 + 3 had significantly greater cumulative incidence of PCSM compared with men with Gleason score 3 + 4. Primary Gleason pattern in Gleason 7 PC is an important prognosticator of survival. Our findings suggest that concomitant voiding symptoms should be considered in the work-up and treatment of PC.

The Patient-Reported Information Multidimensional Exploration (PRIME) Framework for Investigating Emotions and Other Factors of Prostate Cancer Patients with Low Intermediate Risk Based on Online Cancer Support Group Discussions.

PubMed

Bandaragoda, Tharindu; Ranasinghe, Weranja; Adikari, Achini; de Silva, Daswin; Lawrentschuk, Nathan; Alahakoon, Damminda; Persad, Raj; Bolton, Damien

2018-06-01

This study aimed to use the Patient Reported Information Multidimensional Exploration (PRIME) framework, a novel ensemble of machine-learning and deep-learning algorithms, to extract, analyze, and correlate self-reported information from Online Cancer Support Groups (OCSG) by patients (and partners of patients) with low intermediate-risk prostate cancer (PCa) undergoing radical prostatectomy (RP), external beam radiotherapy (EBRT), and active surveillance (AS), and to investigate its efficacy in quality-of-life (QoL) and emotion measures. From patient-reported information on 10 OCSG, the PRIME framework automatically filtered and extracted conversations on low intermediate-risk PCa with active user participation. Side effects as well as emotional and QoL outcomes for 6084 patients were analyzed. Side-effect profiles differed between the methods analyzed, with men after RP having more urinary and sexual side effects and men after EBRT having more bowel symptoms. Key findings from the analysis of emotional expressions showed that PCa patients younger than 40 years expressed significantly high positive and negative emotions compared with other age groups, that partners of patients expressed more negative emotions than the patients, and that selected cohorts (< 40 years, > 70 years, partners of patients) have frequently used the same terms to express their emotions, which is indicative of QoL issues specific to those cohorts. Despite recent advances in patient-centerd care, patient emotions are largely overlooked, especially in younger men with a diagnosis of PCa and their partners. The authors present a novel approach, the PRIME framework, to extract, analyze, and correlate key patient factors. This framework improves understanding of QoL and identifies low intermediate-risk PCa patients who require additional support.

Prognostic Value of the New Prostate Cancer International Society of Urological Pathology Grade Groups.

PubMed

Offermann, Anne; Hohensteiner, Silke; Kuempers, Christiane; Ribbat-Idel, Julika; Schneider, Felix; Becker, Finn; Hupe, Marie Christine; Duensing, Stefan; Merseburger, Axel S; Kirfel, Jutta; Reischl, Markus; Lubczyk, Verena; Kuefer, Rainer; Perner, Sven

2017-01-01

Gleason grading is the best independent predictor for prostate cancer (PCa) progression. Recently, a new PCa grading system has been introduced by the International Society of Urological Pathology (ISUP) and is recommended by the World Health Organization (WHO). Following studies observed more accurate and simplified grade stratification of the new system. Aim of this study was to compare the prognostic value of the new grade groups compared to the former Gleason Grading and to determine whether re-definition of Gleason Pattern 4 might reduce upgrading from prostate biopsy to radical prostatectomy (RP) specimen. A cohort of men undergoing RP from 2002 to 2015 at the Hospital of Goeppingen (Goeppingen, Germany) was used for this study. In total, 339 pre-operative prostatic biopsies and corresponding RP specimens, as well as additional 203 RP specimens were re-reviewed for Grade Groups according to the ISUP. Biochemical recurrence-free survival (BFS) after surgery was used as endpoint to analyze prognostic significance. Other clinicopathological data included TNM-stage and pre-operative PSA level. Kaplan-Meier analysis revealed risk stratification of patients based on both former Gleason Grading and ISUP Grade Groups, and was statistically significant using the log-rank test ( p  < 0.001). Both grading systems significantly correlated with TNM-stage and pre-operative PSA level ( p  < 0.001). Higher tumor grade in RP specimen compared to corresponding pre-operative biopsy was observed in 44 and 34.5% of cases considering former Gleason Grading and ISUP Grade Groups, respectively. Both, former Gleason Grading and ISUP Grade Groups predict survival when applied on tumors in prostatic biopsies as well as RP specimens. This is the first validation study on a large representative German community-based cohort to compare the former Gleason Grading with the recently introduced ISUP Grade Groups. Our data indicate that the ISUP Grade Groups do not improve predictive value of PCa grading and might be less sensitive in deciphering tumors with 3 + 4 and 4 + 3 pattern on RP specimen. However, the Grade Group system results less frequently in an upgrading from biopsy to the corresponding RP specimens, indicating a lower risk to miss potentially aggressive tumors not represented on biopsies.

The effect of marital status on stage and survival of prostate cancer patients treated with radical prostatectomy: a population-based study.

PubMed

Abdollah, Firas; Sun, Maxine; Thuret, Rodolphe; Abdo, Al'a; Morgan, Monica; Jeldres, Claudio; Shariat, Shahrokh F; Perrotte, Paul; Montorsi, Francesco; Karakiewicz, Pierre I

2011-08-01

The detrimental effect of unmarried marital status on stage and survival has been confirmed in several malignancies. We set to test whether this applied to patients diagnosed with prostate cancer (PCa) treated with radical prostatectomy (RP). We identified 163,697 non-metastatic PCa patients treated with RP, within 17 Surveillance, Epidemiology, and End Results registries. Logistic regression analyses focused on the rate of locally advanced stage (pT3-4/pN1) at RP. Cox regression analyses tested the relationship between marital status and cancer-specific (CSM), as well as all-cause mortality (ACM). Respectively, 9.1 and 7.8% of individuals were separated/divorced/widowed (SDW) and never married. SDW men had more advanced stage at surgery (odds ratio: 1.1; p < 0.001), higher CSM and ACM (both hazard ratio [HR]: 1.3; p < 0.001) than married men. Similarly, never married marital status portended to a higher ACM rate (HR:1.2, p = 0.001). These findings were consistent when analyses were stratified according to organ confined vs. locally advanced stages. Being SDW significantly increased the risk of more advanced stage at RP. Following surgery, SDW men portended to a higher CSM and ACM rate than married men. Consequently, these individuals may benefit from a more focused health care throughout the natural history of their disease.

Sociodemographic Disparities in Cure-Intended Treatment in Localized Prostate Cancer.

PubMed

des Bordes, Jude K A; Lopez, David S; Swartz, Michael D; Volk, Robert J

2018-02-01

Disparities in prostate cancer (PCa) morbidity and mortality occur across various populations. We investigated the sociodemographic correlates of treatment and disparities in the application of cure-intended (i.e., radical prostatectomy [RP], radiation therapy [RT]) treatment strategies in localized PCa among Texas residents diagnosed with PCa. We analyzed data from the Texas Cancer Registry on men diagnosed with stage T1 or T2 PCa between 2004 and 2009. Multinomial logistic regression analysis was used to explore independent associations between cure-intended treatment modalities and sociodemographic characteristics (age, race/ethnicity, socioeconomic status [SES], and geographic location (rural versus urban)) using patients who did not receive definitive treatment as comparison group. Of 46,971 patients with available treatment data, age-adjusted treatment rates were 39.1% RP, 30.7% RT, and 30.2% for all other non-curative modalities. Compared to patients under 60 years, those ≥60 were less likely to receive RP, patients between 60 and 80 years were more likely to undergo RT, while those 80 years or older were less likely. Non-Hispanic blacks (OR =0.55, 95% CI, 0.50-0.59) and Hispanics (OR = 0.68, 95%CI, 0.62-0.74) were less likely to receive RP compared with whites. Hispanics were significantly less likely to receive RT (OR = 0.78, 95%CI, 0.72-0.85) than blacks and whites. People of low SES were 35% (OR = 0.65, 95%CI, 0.60-0.69) and 15% (OR = 0.85, 95%CI, 0.79-0.90) less likely to receive RP and RT, respectively, compared with those of high SES. Rural-urban status was not associated with cure-intended treatment. Potential sociodemographic disparities exist in the application of cure-intended treatment in localized prostate cancer in Texas particularly in race/ethnicity and SES.

Orgasm-associated incontinence (climacturia) after bladder neck-sparing radical prostatectomy: clinical and video-urodynamic evaluation.

PubMed

Manassero, Francesca; Di Paola, Giuseppe; Paperini, Davide; Mogorovich, Andrea; Pistolesi, Donatella; Valent, Francesca; Selli, Cesare

2012-08-01

Orgasm-Associated Incontinence (OAI) or climacturia has been observed in male patients maintaining sexual potency after radical prostatectomy and cystectomy. We investigated the incidence and video-urodynamic aspects of this event in continent and potent patients after bladder neck-sparing (BNS) radical prostatectomy (RP). Comparing functional and morphological aspects between climacturic and non-climacturic patients to identify a possible explanation of this unusual kind of leakage that could seriously impact the sexual life after surgery. In a pool of 84 men, potent and continent at least 1 year after BNS RP, 24 (28.6%) reported climacturia and 7 agreed to undergo video-urodynamic evaluation (group 1), which was performed also in 5 controls (group 2). Those 12 men were also evaluated with 24-hour pad test, 5-item International Index of Erectile Function and International Prostate Symptom Score questionnaires. Functional urethral length (FUL) was significantly lower in the climacturia group (P=0.02) and time to continence recovery was significantly longer (P=0.05). No other significant differences were found between the two groups. The radiological appearance of the vesicourethral junction at voiding cystourethrography was similar. To the best of our knowledge, this is the first functional and morphological evaluation of climacturia after RP. In our experience, this event is indirectly associated with a reduced FUL in the sphincter area, although both patients and controls were continent during daily activities. BNS technique seems to reduce time to continence recovery, although climacturic patients need longer time than control patients. Since in our series no rigidity of the vesicourethral anastomosis was radiographically evident, we believe that differences in FUL could explain OAI. Anatomical difference in membranous urethra length could explain the occurrence of this symptom in patients treated with the same surgical technique. © 2012 International Society for Sexual Medicine.

Trends in Radical Prostatectomy Risk Group Distribution in a European Multicenter Analysis of 28 572 Patients: Towards Tailored Treatment.

PubMed

van den Bergh, Roderick; Gandaglia, Giorgio; Tilki, Derya; Borgmann, Hendrik; Ost, Piet; Surcel, Christian; Valerio, Massimo; Sooriakumaran, Prasanna; Salomon, Laurent; Briganti, Alberto; Graefen, Markus; van der Poel, Henk; de la Taille, Alexandre; Montorsi, Francesco; Ploussard, Guillaume

2017-08-08

Active surveillance (AS) has been increasingly proposed as the preferential initial management strategy for low-risk prostate cancer (PC), while in high-risk PC the indication for surgery has widened. To evaluate the development of risk group distribution of patients undergoing radical prostatectomy (RP). Retrospective database review of combined RP databases (2000-2015) of four large European centers (Créteil, Paris; San Rafaele, Milan; Martini Klinik, Hamburg; NKI, AvL, Amsterdam). Clinical and pathological characteristics per year of surgery. Eligibility for AS was defined according to Prostate Cancer Research International Active Surveillance criteria: cT≤2c, cN0/X, cM0/X, PSA ≤10ng/ml, prostate-specific antigen density <0.2ng/ml/ml, one to two positive biopsies, and Gleason score ≤6, high-risk disease as: cT≥3, c N1, cM1, PSA >20ng/ml, and/or Gleason ≥8. In total, 28572 patients had complete clinical and 24790 complete pathological data available. The absolute number of RPs increased: 401, 975, 2344, and 2504 in 2000, 2005, 2010, and 2015, respectively. The proportion of cases considered suitable for AS decreased: 31%, 32%, 18%, and 5%, while the cases considered high risk increased: 10%, 8%, 16%, and 30%. The percentage of patients having only localized Gleason 6 disease after RP decreased: 46%, 34%, 14%, and 8% for all patients (p<0.01), as well as for AS-suitable patients: 70%, 54%, 41%, and 38% (p<0.01). Comparisons between centers were outside the scope of this article. Developments in diagnostics may have impacted on results. This European analysis confirmed the risk profile of patients undergoing RP shifting away of the most favorable disease spectrum. Patients with PC clinically considered suitable for AS and men having only localized Gleason 6 disease pathologically comprised a decreasing share of all RP performed. High-risk disease comprised an increasing share of all RPs. The databases of four large European centers of prostate cancer surgery were analyzed. In recent years, the risk profile of patients shifted away of low-risk cancer, while high-risk cancer comprised a larger part of cases. This confirms the introduction of active surveillance for low-risk prostate cancer and increase in potentially curative options for high-risk disease. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Parameters of two-dimensional perineal ultrasonography for evaluation of urinary incontinence after Radical Prostatectomy.

PubMed

Costa Cruz, Danilo Souza Lima da; D'Ancona, Carlos Arturo Levi; Baracat, Jamal; Alves, Marco Antonio Dionisio; Cartapatti, Marcelo; Damião, Ronaldo

2014-01-01

Urinary incontinence remains a major concern for patients undergoing radical prostatectomy. Its prevalence can reach 20% in the late postoperative period. This clinical study investigated the differences of a dynamic evaluation of the urethra and pelvic floor contraction using perineal ultrasound in men without prostate surgery and in men submitted to radical prostatectomy with and without stress urinary incontinence. Ninety two male patients were included, which 70% of them underwent radical prostatectomy (RP) for more than one year. Thirty one men with clinically post prostatectomy incontinence were compared by two-dimensional (2D) perineal ultrasound to 34 patients without post prostatectomy incontinence and to 27 men without surgery in two centers in Brazil. Our results showed that the continent group presented the urethral angle at rest significantly lower than the prostate group (p = 0.0002). We also observed that the incontinent group showed the displacement of the anterior bladder neck during contraction significantly lower than the continent group (p = 0.008). We found that the continent group presented the urethral angle at rest significantly lower than the prostate group. The incontinent group also showed the anterior bladder neck displacement during contraction significantly lower than the continent group. It was more evident when the severe incontinent group and the continent group were compared.

Use of Laser Speckle Contrast Imaging to Assess Digital Microvascular Function in Primary Raynaud Phenomenon and Systemic Sclerosis: A Comparison Using the Raynaud Condition Score Diary.

PubMed

Pauling, John D; Shipley, Jacqueline A; Hart, Darren J; McGrogan, Anita; McHugh, Neil J

2015-07-01

Evaluate objective assessment of digital microvascular function using laser speckle contrast imaging (LSCI) in a cross-sectional study of patients with primary Raynaud phenomenon (RP) and systemic sclerosis (SSc), comparing LSCI with both infrared thermography (IRT) and subjective assessment using the Raynaud Condition Score (RCS) diary. Patients with SSc (n = 25) and primary RP (n = 18) underwent simultaneous assessment of digital perfusion using LSCI and IRT with a cold challenge on 2 occasions, 2 weeks apart. The RCS diary was completed between assessments. The relationship between objective and subjective assessments of RP was evaluated. Reproducibility of LSCI/IRT was assessed, along with differences between primary RP and SSc, and the effect of sex. There was moderate-to-good correlation between LSCI and IRT (Spearman rho 0.58-0.84, p < 0.01), but poor correlation between objective assessments and the RCS diary (p > 0.05 for all analyses). Reproducibility of IRT and LSCI was moderate at baseline (ICC 0.51-0.63) and immediately following cold challenge (ICC 0.56-0.86), but lower during reperfusion (ICC 0.3-0.7). Neither subjective nor objective assessments differentiated between primary RP and SSc. Men reported lower median daily frequency of RP attacks (0.82 vs 1.93, p = 0.03). Perfusion using LSCI/IRT was higher in men for the majority of assessments. Objective and subjective methods provide differing information on microvascular function in RP. There is good convergent validity of LSCI with IRT and acceptable reproducibility of both modalities. Neither subjective nor objective assessments could differentiate between primary RP and SSc. Influence of sex on subjective and objective assessment of RP warrants further evaluation.

Optimal timing of early versus delayed adjuvant radiotherapy following radical prostatectomy for locally advanced prostate cancer.

PubMed

Kowalczyk, Keith J; Gu, Xiangmei; Nguyen, Paul L; Lipsitz, Stuart R; Trinh, Quoc-Dien; Lynch, John H; Collins, Sean P; Hu, Jim C

2014-04-01

Although post-radical prostatectomy (RP) adjuvant radiation therapy (ART) benefits disease that is staged as pT3 or higher, the optimal ART timing remains unknown. Our objective is to characterize the outcomes and optimal timing of early vs. delayed ART. From the Surveillance, Epidemiology and End Results-Medicare data from 1995 to 2007, we identified 963 men with pT3N0 disease receiving early (<4 mo after RP, n = 419) vs. delayed (4-12 mo after RP, n = 544) ART after RP. Utilizing propensity score methods, we compared overall mortality, prostate cancer-specific mortality (PCSM), bone-related events (BRE), salvage hormonal therapy utilization, and intervention for urethral stricture. We then used the maximal statistic approach to determine at what time post-RP ART had the most significant effect on outcomes of interest in men with pT3N0 disease. When compared with delayed ART in men with pT3 disease, early ART was associated with improved PCSM (0.47 vs. 1.02 events per 100 person-years; P = 0.038) and less salvage hormonal therapy (2.88 vs. 4.59 events per 100 person-years; P = 0.001). Delaying ART beyond 5 months is associated with worse PCSM (hazard ratio [HR] 2.3; P = 0.020), beyond 3 months is associated with more BRE (HR 1.6; P = 0.025), and beyond 4 months is associated higher rates of salvage hormonal therapy (HR 1.6; P = 0.002). ART performed after 9 months was associated with fewer urethral strictures (HR 0.6; P = 0.042). Initiating ART less than 5 months after RP for pT3 is associated with improved PCSM. Early ART is also associated with fewer BRE and less use of salvage hormonal therapy if administered earlier than 3 and 4 months after RP, respectively. However, ART administered later than 9 months after RP is associated with fewer urethral strictures. Our population-based findings complement randomized trials designed with fixed ART timing. © 2013 Published by Elsevier Inc.

Erectile Dysfunction after Radical Prostatectomy: Prevalence, Medical Treatments, and Psychosocial Interventions

PubMed Central

Emanu, Jessica C.; Avildsen, Isabelle K.; Nelson, Christian J.

2016-01-01

Purpose of review This review will discuss erectile dysfunction (ED) in prostate cancer patients following radical prostatectomy (RP). It will focus on the prevalence and current treatments for ED as well as the emotional impact of ED and the current psychosocial interventions designed to help patients cope with this side effect. Recent findings While there is a large discrepancy in prevalence rates of ED after RP, several recent studies have cited rates as high as 85%. The concept of “penile rehabilitation” is now the standard of practice to treat ED following RP. However, many men avoid seeking help or utilizing ED treatments. This avoidance is related to the shame, frustration, and distress many men with ED and their partners experience. Recent psychosocial interventions have been developed to facilitate the use of treatments and help men cope with ED. These interventions have shown initial promise, however, continued intervention development is needed to reduce distress and improve long-term erectile function (EF) outcomes. Summary ED is a significant problem following prostate cancer surgery. While there are effective medical treatments, the development of psychosocial interventions should continue to evolve to maximize the assistance we can give to men and their partners. PMID:26808052

Men's Experience with Penile Rehabilitation Following Radical Prostatectomy: A Qualitative Study with the Goal of Informing a Therapeutic Intervention

PubMed Central

Nelson, Christian J.; Lacey, Stephanie; Kenowitz, Joslyn; Pessin, Hayley; Shuk, Elyse; Mulhall, John P.

2016-01-01

Objectives Erectile rehabilitation (ER) following radical prostatectomy (RP) is considered an essential component to help men regain erectile functioning; however many men have difficulty adhering to this type of a program. This qualitative study explored men's experience with ER, erectile dysfunction (ED), and ED treatments to inform a psychological intervention designed to help men adhere to ER post-RP. Methods Thirty men, one to three years post-RP, who took part in an ER program, participated in one of four focus groups. Thematic analysis was used to identify the primary themes. Results Average age was 59 (SD=7); mean time since surgery was 26 months (SD=6). Six primary themes emerged: 1) frustration with the lack of information about post-surgery ED; 2) negative emotional impact of ED and avoidance of sexual situations; 3) negative emotional experience with penile injections and barriers leading to avoidance; 4) the benefit of focusing on the long-term advantage of ER versus short-term anxiety; 5) using humor to help cope; and 6) the benefit of support from partners and peers. Conclusions Men's frustration surrounding ED can lead to avoidance of sexual situations and ED treatments, which negatively impact men's adherence to an ER program. The theoretical construct of Acceptance and Commitment Therapy (ACT) was used to place the themes into a framework to conceptualize the mechanisms underlying both avoidance and adherence in this population. As such, ACT has the potential to serve as a conceptual underpinning of a psychological intervention to help men reduce avoidance to penile injections and adhere to an ER program. PMID:25707812

Predictors of inguinal hernia after radical prostatectomy.

PubMed

Rabbani, Farhang; Yunis, Luis Herran; Touijer, Karim; Brady, Mary S

2011-02-01

To determine the significant independent predictors of inguinal hernia development after radical prostatectomy (RP) so that prophylactic measures can be undertaken in those at increased risk. Although inguinal hernia is a recognized complication after RP, the risk factors have not been well elucidated. From January 1999 to June 2007, 4592 consecutive patients underwent open retropubic RP or laparoscopic RP without previous radiotherapy. The median follow-up was 36.9 months (interquartile range 20.3, 60.6). Comorbidities were recorded, as well as the occurrence of inguinal hernia, wound infection, and bladder neck contracture. Cox proportional hazards analysis was performed for the predictors of inguinal hernia after RP on multivariate analysis. Inguinal hernia developed after RP in 68 men (1.5%) men at a median follow-up of 7.9 months (interquartile range 4.3, 18.1). The laterality was bilateral in 7, right in 27, left in 24, and not documented in 10 patients. The significant independent predictors of inguinal hernia included age (hazard ratio [HR] 1.05, 95% confidence interval [CI] 1.01-1.09, P = .016), body mass index (HR 0.91, 95% CI 0.85-0.98, P = .011), history of inguinal hernia repair (HR 3.9, 95% CI 1.8-8.2, P <.001), and bladder neck contracture (HR 2.8, 95% CI 1.3-5.9, P = .007) but not the RP approach (HR 1.08, 95% CI 0.60-1.96, P = .80 for laparoscopic RP vs retropubic RP). The results of our study have indicated that older patients, thinner patients, those with previous inguinal hernia repair, and those developing bladder neck contracture are at increased risk of developing an inguinal hernia. These factors might identify a subset for whom evaluation for subclinical hernia might allow prophylactic inguinal hernia repair at RP. Copyright © 2011 Elsevier Inc. All rights reserved.

Prevalence of different pain categories based on pain spreading on the bodies of older adults in Sweden: a descriptive-level and multilevel association with demographics, comorbidities, medications, and certain lifestyle factors (PainS65+)

PubMed Central

Dragioti, E; Larsson, B; Bernfort, L; Levin, LÅ; Gerdle, B

2016-01-01

Background and objective There is limited knowledge about the prevalence of pain and its relation to comorbidities, medication, and certain lifestyle factors in older adults. To address this limitation, this cross-sectional study examined the spreading of pain on the body in a sample of 6611 subjects ≥65 years old (mean age = 75.0 years; standard deviation [SD] = 7.7) living in southeastern Sweden. Methods Sex, age, comorbidities, medication, nicotine, alcohol intake, and physical activity were analyzed in relation to the following pain categories: local pain (LP) (24.1%), regional pain medium (RP-Medium) (20.3%), regional pain heavy (RP-Heavy) (5.2%), and widespread pain (WSP) (1.7%). Results RP-Medium, RP-Heavy, and WSP were associated more strongly with women than with men (all p<0.01). RP-Heavy was less likely in the 80–84 and >85 age groups compared to the 65–69 age group (both p<0.01). Traumatic injuries, rheumatoid arthritis/osteoarthritis, and analgesics were associated with all pain categories (all p<0.001). An association with gastrointestinal disorders was found in LP, RP-Medium, and RP-Heavy (all p<0.01). Depressive disorders were associated with all pain categories, except for LP (all p<0.05). Disorders of the central nervous system were associated with both RP-Heavy and WSP (all p<0.05). Medication for peripheral vascular disorders was associated with RP-Medium (p<0.05), and hypnotics were associated with RP-Heavy (p<0.01). Conclusion More than 50% of older adults suffered from different pain spread categories. Women were more likely to experience greater spreading of pain than men. A noteworthy number of common comorbidities and medications were associated with increased likelihood of pain spread from LP to RP-Medium, RP-Heavy, and WSP. Effective management plans should consider these observed associations to improve functional deficiency and decrease spreading of pain-related disability in older adults. PMID:27942232

Definition and preoperative predictors of persistently elevated prostate-specific antigen after radical prostatectomy: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database.

PubMed

Moreira, Daniel M; Presti, Joseph C; Aronson, William J; Terris, Martha K; Kane, Christopher J; Amling, Christopher L; Freedland, Stephen J

2010-06-01

To define a level of persistently elevated prostate-specific antigen (PSA) after radical prostatectomy (RP) that equates with high-risk for disease progression, and to identify preoperative predictors of PSA persistence among men from the Shared Equal Access Regional Cancer Hospital (SEARCH) database. A total of 901 men treated with RP between 2001 and 2008 were separated into groups based upon PSA nadir within 6 months after RP. We explored the association between nadir groups and time to biochemical recurrence (BCR) using multivariate Cox proportional hazards and determined the preoperative predictors of PSA persistence using logistic regression. Relative to men with undetectable PSA levels, those with a PSA nadir of 0.03 (hazard ratio [HR] 3.88, P < 0.001), 0.04 (HR 4.87, P < 0.001), 0.05-0.09 (HR 12.69, P < 0.001), 0.1-0.19 (HR 13.17, P < 0.001), and 0.2 ng/mL (HR 13.23, P < 0.001) were at increased risk of BCR while men with a nadir of 0.01 (HR 1.36, P = 0.400) and 0.02 (HR 1.64, P = 0.180) were not. Using the PSA persistence definition of a PSA nadir > or = 0.03 ng/mL, 230 men (26%) had persistence. The independent preoperative predictors of PSA persistence were higher body mass index (BMI, P = 0.002), pathological Gleason score (relative to 2-6: 4 + 3-10, P = 0.001) and preoperative PSA level (P < 0.001). Men with a PSA nadir > or = 0.03 ng/mL after RP were at higher risk for BCR. Using a PSA persistence definition of a PSA nadir > or = 0.03 ng/mL, persistence was predicted by known factors associated with aggressive disease (tumour grade, PSA level and BMI). Validation of the present definition in different populations using later end-points remains necessary to assess its prognostic usefulness.

[Socioeconomic factors associated with overweight in a low-income population of northeast Brazil].

PubMed

Barbosa, Janine Maciel; Cabral, Poliana Coelho; de Lira, Pedro Israel Cabral; Florêncio, Telma Maria de Menezes Toledo

2009-03-01

The purpose of this research was to describe the overweight prevalence and factors potentially associated to it in adults residents in areas of social exclusion. The sample consisted of 3214 individuals, aged 20 to 69 years, in shanty town in Maceió-AL, northeast of Brazil. Body mass index (BMI) was used in the nutritional evaluation. Overweight prevalence of 41.2% was found (46.2% females vs. 32.6% males, p < 0.001). The analysis indicated there is higher chance of getting overweight, both for males and females, in higher age ranges (Prevalence Ratio [RP] = 1.62, CI 95% 1.37-1.90 and RP = 1.55, CI 95% 1.41-1.69, respectively), and among those from rural areas (RP = 1.27, CI 95% 1.07-1.51 and RP = 2.23, CI 95% 2.01-2.47, respectively). In males, the overweight risk is directly associated to the schooling level (RP = 0.78, CI 95% 0.63-0.97), whereas, in females it is inversely associated (RP = 1.40, CI 95% 1.17-1.66). A higher overweight risk was evidenced among men of higher income (RP = 1.29, CI 95% 1.09-1.53). In general, small improvements in variables related to housing conditions and consumption goods are associated to higher overweight risk. Even in populations of low socioeconomic level, improvement in housing conditions can become an overweight risk factor in adults for both genders, whereas education is a protective factor for women and the income a risk factor in men.

Radical Prostatectomy Findings in White Hispanic/Latino Men With NCCN Very Low-risk Prostate Cancer Detected by Template Biopsy.

PubMed

Kryvenko, Oleksandr N; Lyapichev, Kirill; Chinea, Felix M; Prakash, Nachiketh Soodana; Pollack, Alan; Gonzalgo, Mark L; Punnen, Sanoj; Jorda, Merce

2016-08-01

Radical prostatectomy (RP) outcomes have been studied in White and Black non-Hispanic men qualifying for Epstein active surveillance criteria (EASC). Herein, we first analyzed such outcomes in White Hispanic men. We studied 70 men with nonpalpable Gleason score 3+3=6 (Grade Group [GG] 1) prostate cancer (PCa) with ≤2 positive cores on biopsy who underwent RP. In 18 men, prostate-specific antigen (PSA) density (PSAD) was >0.15 ng/mL/g. Three of these had insignificant and 15 had significant PCa. The remaining 52 men qualified for EASC. One patient had no PCa identified at RP. Nineteen (37%) had significant PCa defined by volume (n=7), grade (n=7), and volume and grade (n=5). Nine cases were 3+4=7 (GG 2) (5/9 [56%] with pattern 4 <5%), 2 were 3+5=8 (GG 4), and 1 was 4+5=9 (GG 5). Patients with significant PCa more commonly had anterior dominant disease (11/19, 58%) versus patients with insignificant cancer (7/33, 21%) (P=0.01). In 12 cases with higher grade at RP, the dominant tumor nodule was anterior in 6 (50%) and posterior in 6 (median volumes: 1.1 vs. 0.17 cm, respectively; P=0.01). PSA correlated poorly with tumor volume (r=0.28, P=0.049). Gland weight significantly correlated with PSA (r=0.54, P<0.001). While PSAD and PSA mass density correlated with tumor volume, only PSA mass density distinguished cases with significant disease (median, 0.008 vs. 0.012 μg/g; P=0.03). In summary, a PSAD threshold of 0.15 works well in predicting significant tumor volume in Hispanic men. EASC appear to perform better in White Hispanic men than previously reported outcomes for Black non-Hispanic and worse than in White non-Hispanic men. Significant disease is often Gleason score 3+3=6 (GG 1) PCa >0.5 cm. Significant PCa is either a larger-volume anterior disease that may be detected by multiparametric magnetic resonance imaging-targeted biopsy or anterior sampling of the prostate or higher-grade smaller-volume posterior disease that in most cases should not pose immediate harm and may be detected by repeat template biopsies.

Radical prostatectomy, sparing of the seminal vesicles, and painful orgasm.

PubMed

Mogorovich, Andrea; Nilsson, Andreas E; Tyritzis, Stavros I; Carlsson, Stefan; Jonsson, Martin; Haendler, Leif; Nyberg, Tommy; Steineck, Gunnar; Wiklund, N Peter

2013-05-01

Erectile dysfunction has been widely investigated as the major factor responsible for sexual bother in patients after radical prostatectomy (RP); painful orgasm (PO) is one element of this bother, but little is known about its prevalence and its effects on sexual health. This study aims to investigate the prevalence of PO and to identify potential risk factors. A total of 1,411 consecutive patients underwent open (radical retropubic prostatectomy) or robot-assisted laparoscopic RP between 2002 and 2006. The patients were asked to complete a study-specific questionnaire. Of a total of 145 questions, 5 dealt with the orgasmic characteristics. The questionnaire was also administered to a comparison group of 442 persons, matched for age and area of residency. The response rate was 91% (1,288 patients). A total of 143 (11%) patients reported PO. Among the 834 men being able to have an orgasm, the prevalence was 18% vs. 6% in the comparison group (relative risk [RR] 2.8, 95% confidence interval [CI] 1.7-4.5). When analyzed as independent variables, bilateral seminal vesicle (SV)-sparing approach (RR 2.33, 95% CI 1.0-5.3, P = 0.045) and age <60 years were significantly related to the presence of PO (95% CI 0.5-0.9, P = 0.019). After adjustment for age, bilateral SV-sparing still remained a significant predictor for occurrence of PO. We found that PO occurs significantly more often in patients undergoing bilateral SV-sparing RP when compared with age-matched comparison population. © 2013 International Society for Sexual Medicine.

Robot-assisted laparoscopic prostatectomy is not associated with early postoperative radiation therapy.

PubMed

Chino, Junzo; Schroeck, Florian R; Sun, Leon; Lee, W Robert; Albala, David M; Moul, Judd W; Koontz, Bridget F

2009-11-01

To compare open radical prostatectomy (RP) and robot-assisted laparoscopic prostatectomy (RALP), and to determine whether RALP is associated with a higher risk of features that determine recommendations for postoperative radiation therapy (RT). Patients undergoing RP from 2003 to 2007 were stratified into two groups: open RP and RALP. Preoperative (PSA level, T stage and Gleason score), pathological factors (T stage, Gleason score, extracapsular extension [ECE] and the status of surgical margins and seminal vesicle invasion [SVI]) and early treatment with RT or referral for RT within 6 months were compared between the groups. Multivariate analysis was used to control for selection bias in the RALP group. In all, 904 patients were identified; 368 underwent RALP and 536 underwent open RP (retropubic or perineal). Patients undergoing open RP had a higher pathological stage with ECE present in 24.8% vs 19.3% in RALP (P = 0.05) and SVI in 10.3% vs 3.8% (P < 0.001). In the RALP vs open RP group, there were positive surgical margins in 31.5% vs 31.9% (P = 0.9) and there were postoperative PSA levels of (3) 0.2 ng/mL in 5.7% vs 6.3% (P = 0.7), respectively. On multivariate analysis to control for selection bias, RALP was not associated with indication for RT (odds ratio (OR) 1.10, P = 0.55), or referral for RT (OR 1.04, P = 0.86). RALP was not associated with an increase in either indication or referral for early postoperative RT.

Long-term decision regret after post-prostatectomy image-guided intensity-modulated radiotherapy.

PubMed

Shakespeare, Thomas P; Chin, Stephen; Manuel, Lucy; Wen, Shelly; Hoffman, Matthew; Wilcox, Shea W; Aherne, Noel J

2017-02-01

Decision regret (DR) may occur when a patient believes their outcome would have been better if they had decided differently about their management. Although some studies investigate DR after treatment for localised prostate cancer, none report DR in patients undergoing surgery and post-prostatectomy radiotherapy. We evaluated DR in this group of patients overall, and for specific components of therapy. We surveyed 83 patients, with minimum 5 years follow-up, treated with radical prostatectomy (RP) and post-prostatectomy image-guided intensity-modulated radiotherapy (IG-IMRT) to 64-66 Gy following www.EviQ.org.au protocols. A validated questionnaire identified DR if men either indicated that they would have been better off had they chosen another treatment, or they wished they could change their mind about treatment. There was an 85.5% response rate, with median follow-up post-IMRT 78 months. Adjuvant IG-IMRT was used in 28% of patients, salvage in 72% and ADT in 48%. A total of 70% of patients remained disease-free. Overall, 16.9% of patients expressed DR for treatment, with fourfold more regret for the RP component of treatment compared to radiotherapy (16.9% vs 4.2%, P = 0.01). DR for androgen deprivation was 14.3%. Patients were regretful of surgery due to toxicity, not being adequately informed about radiotherapy as an alternative, positive margins and surgery costs (83%, 33%, 25% and 8% of regretful patients respectively). Toxicity caused DR in the three radiotherapy-regretful and four ADT-regretful patients. Patients were twice as regretful overall, and of surgery, for salvage vs adjuvant approaches (both 19.6% vs 10.0%). Decision regret after RP and post-prostatectomy IG-IMRT is uncommon, although patients regret RP more than post-operative IG-IMRT. This should reassure urologists referring patients for post-prostatectomy IG-IMRT, particularly in the immediate adjuvant setting. Other implications include appropriate patient selection for RP (and obtaining clear margins), and ensuring adequately discussing definitive radiotherapy as an alternative to surgery. © 2016 The Royal Australian and New Zealand College of Radiologists.

Adverse pathology and undetectable ultrasensitive prostate-specific antigen after radical prostatectomy: is adjuvant radiation warranted?

PubMed

Simon, Ross M; Howard, Lauren E; Freedland, Stephen J; Aronson, William J; Terris, Martha K; Kane, Christopher J; Amling, Christopher L; Cooperberg, Matthew R; Vidal, Adriana C

2016-06-01

To determine if men with adverse pathology but undetectable ultrasensitive (<0.01 ng/mL) PSA are at high-risk for biochemical recurrence (BCR), or if there is a subset of patients at low-risk for whom the benefit of adjuvant radiation therapy might be limited. We evaluated 411 patients treated with RP from 2001 to 2013 without adjuvant radiation who had an undetectable (<0.01 ng/mL) PSA level after RP but with adverse pathology [positive surgical margins (PSMs), extraprostatic extension (EPE), and/or seminal vesicle invasion (SVI)]. Multivariable Cox regression analyses tested the relationship between pathological characteristics and BCR to identify groups of men at highest risk of early BCR. On multivariable analysis, only pathological Gleason 7 (4 + 3), Gleason ≥8, and SVI independently predicted BCR (P = 0.019, P < 0.001, and P = 0.001, respectively), although on two-way analysis men with Gleason 7 (4 + 3) did not have significantly higher rates of BCR compared with patients with Gleason ≤6 (log-rank, P = 0.074). Men with either Gleason ≥8 (with PSMs or EPE) or SVI (15% of the cohort) defined a high-risk group vs men without these characteristics (3-year BCR risk of 50.4% vs 11.9%, log-rank, P < 0.001). Among men with adverse pathology but an undetectable (<0.01 ng/mL) PSA level after RP, the benefits of adjuvant radiation are probably limited except for men with Gleason 8-10 (with PSMs or EPE) or SVI who are at high-risk of early BCR. © 2015 The Authors BJU International © 2015 BJU International Published by John Wiley & Sons Ltd.

Recurrent Pneumonia in Children: A Reasoned Diagnostic Approach and a Single Centre Experience.

PubMed

Montella, Silvia; Corcione, Adele; Santamaria, Francesca

2017-01-29

Recurrent pneumonia (RP), i.e., at least two episodes of pneumonia in one year or three episodes ever with intercritical radiographic clearing of densities, occurs in 7.7%-9% of children with community-acquired pneumonia. In RP, the challenge is to discriminate between children with self-limiting or minor problems, that do not require a diagnostic work-up, and those with an underlying disease. The aim of the current review is to discuss a reasoned diagnostic approach to RP in childhood. Particular emphasis has been placed on which children should undergo a diagnostic work-up and which tests should be performed. A pediatric case series is also presented, in order to document a single centre experience of RP. A management algorithm for the approach to children with RP, based on the evidence from a literature review, is proposed. Like all algorithms, it is not meant to replace clinical judgment, but it should drive physicians to adopt a systematic approach to pediatric RP and provide a useful guide to the clinician.

The retinitis pigmentosa-mutated RP2 protein exhibits exonuclease activity and translocates to the nucleus in response to DNA damage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yoon, Jung-Hoon; Qiu Junzhuan; Cai Sheng

2006-05-01

Retinitis pigmentosa (RP) is a genetically heterogeneous disease characterized by degeneration of the retina. Mutations in the RP2 gene are linked to the second most frequent form of X-linked retinitis pigmentosa. RP2 is a plasma membrane-associated protein of unknown function. The N-terminal domain of RP2 shares amino acid sequence similarity to the tubulin-specific chaperone protein co-factor C. The C-terminus consists of a domain with similarity to nucleoside diphosphate kinases (NDKs). Human NDK1, in addition to its role in providing nucleoside triphosphates, has recently been described as a 3' to 5' exonuclease. Here, we show that RP2 is a DNA-binding proteinmore » that exhibits exonuclease activity, with a preference for single-stranded or nicked DNA substrates that occur as intermediates of base excision repair pathways. Furthermore, we show that RP2 undergoes re-localization into the nucleus upon treatment of cells with DNA damaging agents inducing oxidative stress, most notably solar simulated light and UVA radiation. The data suggest that RP2 may have previously unrecognized roles as a DNA damage response factor and 3' to 5' exonuclease.« less

Ninety-Day Postoperative Mortality after Robot-assisted Laparoscopic Prostatectomy and Retropubic Radical Prostatectomy. Nation-wide population-based study

PubMed Central

Björklund, Johan; Folkvaljon, Yasin; Cole, Alexander; Carlsson, Stefan; Robinson, David; Loeb, Stacy; Stattin, Pär; Akre, Olof

2016-01-01

Objective To assess 90-day postoperative mortality after Robot assisted laparoscopic Radical prostatectomy (RARP) and retropubic radical prostatectomy (RRP) by use of nationwide population-based registry data. Patients and methods Cohort study in the National Prostate Cancer Register (NPCR) of Sweden of 22 344 men with prostate cancer in clinical local stage T1-T3, PSA <50 μg/ml who had undergone primary RP in 1998 - 2012. Vital status was ascertained through the Total Population Register. 90-day postoperative mortality was analysed by use of logistic regression analysis and comparison of 90-day mortality with the background population were made using standardised mortality ratios (SMR). Results 29 out of 14820 men (0.20%) died after RRP and 10 out of 7524 men (0.13%) died after RARP. Mortality during the 90-day postoperative period in the cohort was lower than in an age-matched background population, SMR 0.57 (CI 95% 0.39-0.75). There was no statistically significant difference in 90-day mortality according to surgical method, RARP vs. RRP (odds ratio, OR 1.14; 95% CI, 0.46-2.81). Postoperative 90-day mortality decreased over time, 2008-2012 vs. 1998-2007 (OR 0.44; 95% CI, 0.21-0.95), mainly due to decreased mortality after RARP. Limitations of our study include the non-randomised design and that more RARP were performed in recent years compared to RRP. Conclusion 90-day postoperative mortality was low after RARP and RRP and there was nostatistically significant difference between the methods. Given the long life expectancy among men with low and intermediate risk prostate cancer, very low postoperative mortality is a prerequisite for RP which was fulfilled by both RRP and RARP. The selection of healthy men for RP is highlighted by the lower 90-day mortality after RP compared to the background population. PMID:26762928

Quality of Life, Psychological Functioning, and Treatment Satisfaction of Men Who Have Undergone Penile Prosthesis Surgery Following Robot-Assisted Radical Prostatectomy.

PubMed

Pillay, Brindha; Moon, Daniel; Love, Christopher; Meyer, Denny; Ferguson, Emma; Crowe, Helen; Howard, Nicholas; Mann, Sarah; Wootten, Addie

2017-12-01

Penile prosthesis surgery is last-line treatment to regaining erectile function after radical prostatectomy (RP) for localized prostate cancer. To assess quality of life, psychological functioning, and treatment satisfaction of men who underwent penile implantation after RP; the psychosocial correlates of treatment satisfaction and sexual function after surgery; and the relation between patients' and partners' ratings of treatment satisfaction. 98 consecutive patients who underwent penile implantation after RP from 2010 and 2015 and their partners were invited to complete a series of measures at a single time point. Of these, 71 patients and 43 partners completed measures assessing sexual function, psychological functioning, and treatment satisfaction. Proportions of patients who demonstrated good sexual function and satisfaction with treatment and clinical levels of anxiety and depression were calculated. Hierarchical regression analyses were conducted to determine psychosocial factors associated with patient treatment satisfaction and sexual function and patient-partner differences in treatment satisfaction. Patients completed the Expanded Prostate Cancer Index Composite Short Form (EPIC-26), Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS), Prostate Cancer-Related Quality of Life Scale, Self-Esteem and Relationship Questionnaire (SEAR), Generalized Anxiety Disorder-7 (GAD-7), and Patient Health Questionnaire-9 (PHQ-9). Partners completed the GAD-7, PHQ-9, EDITS (partner version), and SEAR. 94% of men reported satisfaction with treatment (EDITS score > 50). 77% of men reported good sexual function (EPIC-26 score > 60). Lower depression scores were associated with higher sexual confidence and sexual intimacy, and these were correlated with better treatment satisfaction and sexual function. Patients experienced higher sexual relationship satisfaction (median score = 90.6) than their partners (median score = 81.2), but there was no difference in treatment satisfaction between groups. Higher patient treatment satisfaction was more likely to be reported for couples whose depression scores were more similar. It is important to provide preoperative penile implant counseling and encourage patients to seek postoperative counseling if needed. This is one of the first Australian-based studies comprehensively assessing treatment satisfaction and psychosocial health of men after penile prosthesis surgery after RP. This was a retrospective cross-sectional study, so there is a possibility of recall bias, and causal associations could not be determined. Men in this Australian series who underwent penile prosthesis surgery after RP generally reported good sexual function and treatment satisfaction. Nevertheless, patient and partner mental health influenced their reported experience of the treatment. Pillay B, Moon D, Love C, et al. Quality of Life, Psychological Functioning, and Treatment Satisfaction of Men Who Have Undergone Penile Prosthesis Surgery Following Robot-Assisted Radical Prostatectomy. J Sex Med 2017;14:1612-1620. Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Evaluation of the Prostate Bed for Local Recurrence After Radical Prostatectomy Using Endorectal Magnetic Resonance Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liauw, Stanley L., E-mail: sliauw@radonc.uchicago.edu; Pitroda, Sean P.; Eggener, Scott E.

Purpose: To summarize the results of a 4-year period in which endorectal magnetic resonance imaging (MRI) was considered for all men referred for salvage radiation therapy (RT) at a single academic center; to describe the incidence and location of locally recurrent disease in a contemporary cohort of men with biochemical failure after radical prostatectomy (RP), and to identify prognostic variables associated with MRI findings in order to define which patients may have the highest yield of the study. Methods and Materials: Between 2007 and 2011, 88 men without clinically palpable disease underwent eMRI for detectable prostate-specific antigen (PSA) after RP.more » The median interval between RP and eMRI was 32 months (interquartile range, 14-57 months), and the median PSA level was 0.30 ng/mL (interquartile range, 0.19-0.72 ng/mL). Magnetic resonance imaging scans consisting of T2-weighted, diffusion-weighted, and dynamic contrast-enhanced imaging were evaluated for features consistent with local recurrence. The prostate bed was scored from 0-4, whereby 0 was definitely normal, 1 probably normal, 2 indeterminate, 3 probably abnormal, and 4 definitely abnormal. Local recurrence was defined as having a score of 3-4. Results: Local recurrence was identified in 21 men (24%). Abnormalities were best appreciated on T2-weighted axial images (90%) as focal hypointense lesions. Recurrence locations were perianastomotic (67%) or retrovesical (33%). The only risk factor associated with local recurrence was PSA; recurrence was seen in 37% of men with PSA >0.3 ng/mL vs 13% if PSA {<=}0.3 ng/mL (P<.01). The median volume of recurrence was 0.26 cm{sup 3} and was directly associated with PSA (r=0.5, P=.02). The correlation between MRI-based tumor volume and PSA was even stronger in men with positive margins (r=0.8, P<.01). Conclusions: Endorectal MRI can define areas of local recurrence after RP in a minority of men without clinical evidence of disease, with yield related to PSA. Further study is necessary to determine whether eMRI can improve patient selection and success of salvage RT.« less

Prostate Biopsy Specimens With Gleason 3+3=6 and Intraductal Carcinoma: Radical Prostatectomy Findings and Clinical Outcomes.

PubMed

Khani, Francesca; Epstein, Jonathan I

2015-10-01

Although intraductal carcinoma of the prostate (IDC-P) is typically present on biopsies in which there is also invasive prostate carcinoma of Gleason pattern 4 or 5 and an associated unfavorable outcome, there are limited studies on IDC-P in needle core biopsies or transurethral resections (TURP) with only a concomitant low-grade invasive component. There are differing opinions on incorporating IDC-P into the Gleason score in such cases. The aim of this study was to investigate clinical outcomes and radical prostatectomy (RP) findings in patients with Gleason 3+3=6 and IDC-P on biopsy or TURP. We identified 73 patients in our consult files (2001 to 2014) who had IDC-P and Gleason score 6 carcinoma on biopsy or TURP with no invasive higher Gleason grade component. Clinical follow-up information was available in 62 patients. Treatment was RP in 14 patients, radiation therapy in 31 patients, androgen deprivation therapy in 1 patient, and cryotherapy in 1 patient. Four patients were found to have metastatic disease at the time of diagnosis and were treated with chemotherapy. Eleven patients underwent active surveillance after diagnosis, of which 6 were eventually treated for progressive disease. The 14 RP specimens were centrally reviewed, and 86% had extensive IDC-P present. The Gleason grades in these 14 RP cases were 3+3=6 in 21%, 3+4=7 in 36%, 4+3=7 in 29%, and 4+4=8 in 14%. Pathologic stage was pT2 in 36%, pT3a in 36%, and pT3b in 28%. After 3 years, there was a 20% actuarial rate of disease progression in men who underwent either RP or radiation therapy. In summary, most men with IDC-P on biopsy/TURP have aggressive tumors, even when the invasive tumor on biopsy is Gleason score 6. As a minority of men may only have Gleason 6 invasive cancer at RP and a favorable prognosis, we recommend that IDC-P on biopsy/TURP be reported separately and not assigned a Gleason score.

Testosterone therapy in men with prostate cancer: literature review, clinical experience, and recommendations

PubMed Central

Morgentaler, Abraham; Conners III, William P

2015-01-01

For several decades any diagnosis of prostate cancer (PCa) has been considered an absolute contraindication to the use of testosterone (T) therapy in men. Yet this prohibition against T therapy has undergone recent re-examination with refinement of our understanding of the biology of androgens and PCa, and increased appreciation of the benefits of T therapy. A reassuringly low rate of negative outcomes has been reported with T therapy after radical prostatectomy (RP), radiation treatments, and in men on active surveillance. Although the number of these published reports are few and the total number of treated men is low, these experiences do provide a basis for consideration of T therapy in selected men with PCa. For clinicians considering offering this treatment, we recommend first selecting patients with low grade cancers and undetectable prostate-specific antigen following RP. Further research is required to define the safety of T therapy in men with PCa. However, many patients symptomatic from T deficiency are willing to accept the potential risk of PCa progression or recurrence in return for the opportunity to live a fuller and happier life with T therapy. PMID:25652633

Physical activity and quality of life after radical prostatectomy

PubMed Central

Mina, Daniel Santa; Matthew, Andrew G.; Trachtenberg, John; Tomlinson, George; Guglietti, Crissa L.; Alibhai, Shabbir M.H.; Ritvo, Paul

2010-01-01

Background: There are significant post-surgical reductions in health-related quality of life (HRQOL) in prostate cancer (PCa) patients undergoing radical prostatectomy (RP). Physical activity (PA) interventions have improved treatment outcomes for PCa patients undergoing radiation and hormone therapy, but PA effects have not previously been examined in the RP setting. This study examined the relationship between preoperative PA levels and postoperative HRQOL outcomes in PCa patients treated with RP. Methods: Sixty patients were interviewed regarding lifetime PA and completed preoperative (2 weeks prior to surgery) and postoperative (4 weeks after surgery) HRQOL questionnaires. Aerobic fitness testing was conducted on a subsample of 22 patients. Results: Higher levels of total past-year PA and occupational PA significantly correlated with lesser HRQOL declines from presurgery to 4 weeks post-surgery (Beta = −0.364, p = 0.037 and Beta = −0.243, p = 0.089, respectively) in models adjusted for age, postoperative questionnaire completion date, Gleason score and education. Past-year occupational PA was highly positively correlated with past-year total PA (r = 0.785, p < 0.001). Lifetime total PA was correlated with estimated VO2 max (r = 0.486, p = 0.026) in the 22 patients who were aerobically tested. Lifetime and past-year PA volumes were not correlated with waist circumference or body mass index. Interpretation: Declines in HRQOL after RP may be reduced in patients with higher preoperative levels of self-reported PA. These findings require further study with larger samples to confirm results. If confirmed, findings suggest exercise preoperatively may improve HRQOL outcomes after RP. PMID:20514281

Case-Matched comparison of contemporary radiation therapy to surgery in patients with locally advanced prostate cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fletcher, Sophie G.; Mills, Stacey E.; Smolkin, Mark E.

2006-11-15

Purpose: Few studies critically compare current radiotherapy techniques to surgery for patients with locally advanced prostate cancer, despite an urgent need to determine which approach offers superior cancer control. Our objective was to compare rates of biochemical relapse-free survival (BFS) and surrogates of disease specific survival among men with high risk adenocarcinoma of the prostate as a function of treatment modality. Methods and Materials: Retrospective data from 409 men with prostate-specific antigen (PSA) {>=}10 or Gleason 7-10 or Stage {>=}T2b cancer treated uniformly at one university between March 1988 and December 2000 were analyzed. Patients had undergone radical prostatectomy (RP),more » brachytherapy implant alone (BTM), or external beam radiotherapy with brachytherapy boost with short-term neoadjuvant and adjuvant androgen deprivation therapy (BTC). From the total study population a 1:1 matched-cohort analysis (208 patients matched via prostate-specific antigen, Gleason score) comparing RP with BTC was performed as well. Results: Estimated 4-year BFS rates were superior for patients treated with BTC (BTC 72%, BTM 25%, RP 53%; p < 0.001). Matched analysis of BTC vs. RP confirmed these results (BTC 73%, BTM 55%; p = 0.010). Relative risk (RR) of biochemical relapse for BTM and BTC compared with RP were 2.92 (1.95-4.36) and 0.56 (0.36-0.87) (p < 0.001, p = 0.010). RR for BTC from the matched cohort analysis was 0.44 (0.26-0.74; p = 0.002). Conclusions: High-risk prostate cancer patients receiving multimodality radiation therapy (BTC) display apparently superior BFS compared with those receiving surgery (RP) or brachytherapy alone (BTM)« less

Improved retinal and visual function following panmacular subthreshold diode micropulse laser for retinitis pigmentosa.

PubMed

Luttrull, Jeffrey K

2018-06-01

To examine the effect of subthreshold diode micropulse laser (SDM) on pattern electroretinography (PERG) and visual function in retinitis pigmentosa (RP). The records of all patients (pts) undergoing SDM in a vitreoretinal subspecialty practice were reviewed. Inclusion criteria included the presence of RP evaluated before and after SDM by PERG. As a secondary outcome measure, the results of automated omnifield resolution perimetry (ORP) were also reviewed. All eyes undergoing SDM for RP were eligible study, including 26 eyes of 15 pts; seven male and eight female, aged 16-69 (avg. 47) years. Retinal function by PERG improved by all indices, with significant improvements in the 24° field signal latency measures; the MagD(µV)/ Mag(µV) ratio (P < 0.0001) and the MagD(µV) amplitude (P = 0.0003). ORP significantly improved by all indices (p = 0.02-0.002). Average best-corrected chart visual acuities improved from 0.6 to 0.4 logMAR units (p = 0.02). There were no adverse treatment effects. SDM significantly improved chart visual acuity, mesopic logMAR visual acuity perimetry, and retinal function by PERG in RP without adverse treatment effects. Treatment responses indicate a significant capacity for rescue of dysfunctional retina. These results suggest that early and periodic treatment with SDM might slow disease progression and reduce long-term vision loss.

Prognostic value of the new Grade Groups in Prostate Cancer: a multi-institutional European validation study.

PubMed

Mathieu, R; Moschini, M; Beyer, B; Gust, K M; Seisen, T; Briganti, A; Karakiewicz, P; Seitz, C; Salomon, L; de la Taille, A; Rouprêt, M; Graefen, M; Shariat, S F

2017-06-01

We aimed to assess the prognostic relevance of the new Grade Groups in Prostate Cancer (PCa) within a large cohort of European men treated with radical prostatectomy (RP). Data from 27 122 patients treated with RP at seven European centers were analyzed. We investigated the prognostic performance of the new Grade Groups (based on Gleason score 3+3, 3+4, 4+3, 8 and 9-10) on biopsy and RP specimen, adjusted for established clinical and pathological characteristics. Multivariable Cox proportional hazards regression models assessed the association of new Grade Groups with biochemical recurrence (BCR). Prognostic accuracies of the models were assessed using Harrell's C-index. Median follow-up was 29 months (interquartile range, 13-54). The 4-year estimated BCR-free survival (bRFS) for biopsy Grade Groups 1-5 were 91.3, 81.6, 69.8, 60.3 and 44.4%, respectively. The 4-year estimated bRFS for RP Grade Groups 1-5 were 96.1%, 86.7%, 67.0%, 63.1% and 41.0%, respectively. Compared with Grade Group 1, all other Grade Groups based both on biopsy and RP specimen were independently associated with a lower bRFS (all P<0.01). Adjusted pairwise comparisons revealed statistically differences between all Grade Groups, except for group 3 and 4 on RP specimen (P=0.10). The discriminations of the multivariable base prognostic models based on the current three-tier and the new five-tier systems were not clinically different (0.3 and 0.9% increase in discrimination for clinical and pathological model). We validated the independent prognostic value of the new Grade Groups on biopsy and RP specimen from European PCa men. However, it does not improve the accuracies of prognostic models by a clinically significant margin. Nevertheless, this new classification may help physicians and patients estimate disease aggressiveness with a user-friendly, clinically relevant and reproducible method.

Multiple cores of Gleason score 6 correlate with favourable findings at radical prostatectomy

PubMed Central

Ellis, Carla L.; Walsh, Patrick C.; Partin, Alan W.; Epstein, Jonathan I.

2014-01-01

Objective To establish whether the good prognosis of Gleason score 6 (GS6) is maintained in the setting of multiple involved cores. Patients and Methods In total, 6156 men (from 1 April 2000 to 30 April 2007) with GS6 on biopsy underwent radical prostatectomy (RP) at our institution. The number of positive cores was correlated with the outcome at RP. Results More positive cores correlated with less organ-confined disease (P < 0.001), positive margins (P < 0.012), increasing RP grade (P < 0.001) and increased seminal vesicles/lymph node involvement (P = 0.012). For men with data available, the actuarial risk of being biochemically free of disease at 5 years was 93.2% when ≤6 cores were positive (812 men followed to 5 years) vs 89.1% if >6 cores were positive (41 men followed to 2 years) (P = 0.6). Although the predicted ‘cure rate’ of >75% probability of a tumour showing no evidence of biochemical recurrence at 10 years after RP was statistically different between cases with ≤6 vs >6 positive cores (P < 0.0001), the outcome in both groups was still favourable (90.5% vs 84%). Partin-like tables were generated factoring in the number of positive cores to predict organ-confined disease as a guide for urologists to perform nerve-sparing surgery. For example, with T1c disease, there was a ≥75% probability of organ-confined disease with one to three positive cores regardless of prostate-specific antigen (PSA) level, and the same probability was present with four to six positive cores and a PSA level of 0–4 ng/mL. Conclusion A low Gleason score on biopsy is a powerful prognostic finding, such that this favourable outcome is maintained even in the setting of multiple positive cores with GS6. PMID:23350787

Multiple cores of Gleason score 6 correlate with favourable findings at radical prostatectomy.

PubMed

Ellis, Carla L; Walsh, Patrick C; Partin, Alan W; Epstein, Jonathan I

2013-06-01

To establish whether the good prognosis of Gleason score 6 (GS6) is maintained in the setting of multiple involved cores. In total, 6156 men (from 1 April 2000 to 30 April 2007) with GS6 on biopsy underwent radical prostatectomy (RP) at our institution. The number of positive cores was correlated with the outcome at RP. More positive cores correlated with less organ-confined disease (P < 0.001), positive margins (P < 0.012), increasing RP grade (P < 0.001) and increased seminal vesicles/lymph node involvement (P = 0.012). For men with data available, the actuarial risk of being biochemically free of disease at 5 years was 93.2% when ≤6 cores were positive (812 men followed to 5 years) vs 89.1% if >6 cores were positive (41 men followed to 2 years) (P = 0.6). Although the predicted 'cure rate' of >75% probability of a tumour showing no evidence of biochemical recurrence at 10 years after RP was statistically different between cases with ≤6 vs >6 positive cores (P < 0.0001), the outcome in both groups was still favourable (90.5% vs 84%). Partin-like tables were generated factoring in the number of positive cores to predict organ-confined disease as a guide for urologists to perform nerve-sparing surgery. For example, with T1c disease, there was a ≥75% probability of organ-confined disease with one to three positive cores regardless of prostate-specific antigen (PSA) level, and the same probability was present with four to six positive cores and a PSA level of 0-4 ng/mL. A low Gleason score on biopsy is a powerful prognostic finding, such that this favourable outcome is maintained even in the setting of multiple positive cores with GS6. © 2013 BJU International.

Urodynamic assessment of bladder and urethral function among men with lower urinary tract symptoms after radical prostatectomy: A comparison between men with and without urinary incontinence.

PubMed

Lee, Hansol; Kim, Ki Bom; Lee, Sangchul; Lee, Sang Wook; Kim, Myong; Cho, Sung Yong; Oh, Seung-June; Jeong, Seong Jin

2015-12-01

We compared bladder and urethral functions following radical prostatectomy (RP) between men with and without urinary incontinence (UI), using a large-scale database from SNU-experts-of-urodynamics-leading (SEOUL) Study Group. Since July 2004, we have prospectively collected data on urodynamics from 303 patients with lower urinary tract symptoms (LUTS) following RP at three affiliated hospitals of SEOUL Study Group. After excluding 35 patients with neurogenic abnormality, pelvic irradiation after surgery, or a history of surgery on the lower urinary tract, 268 men were evaluated. We compared the urodynamic findings between men who had LUTS with UI (postprostatectomy incontinence [PPI] group) and those who had LUTS without UI (non-PPI group). The mean age at an urodynamic study was 68.2 years. Overall, a reduced bladder compliance (≤20 mL/cmH2O) was shown in 27.2% of patients; and 31.3% patients had idiopathic detrusor overactivity. The patients in the PPI group were older (p=0.001) at an urodynamic study and had a lower maximum urethral closure pressure (MUCP) (p<0.001), as compared with those in the non-PPI group. Bladder capacity and detrusor pressure during voiding were also significantly lower in the PPI group. In the logistic regression, only MUCP and maximum cystometric capacity were identified as the related factor with the presence of PPI. In our study, significant number of patients with LUTS following RP showed a reduced bladder compliance and detrusor overactivity. PPI is associated with both impairment of the urethral closuring mechanism and bladder storage dysfunction.

On the intracellular trafficking of mouse S5 ribosomal protein from cytoplasm to nucleoli.

PubMed

Matragkou, Ch; Papachristou, H; Karetsou, Z; Papadopoulos, G; Papamarcaki, T; Vizirianakis, I S; Tsiftsoglou, A S; Choli-Papadopoulou, T

2009-10-09

The non-ribosomal functions of mammalian ribosomal proteins have recently attracted worldwide attention. The mouse ribosomal protein S5 (rpS5) derived from ribosomal material is an assembled non-phosphorylated protein. The free form of rpS5 protein, however, undergoes phosphorylation. In this study, we have (a) investigated the potential role of phosphorylation in rpS5 protein transport into the nucleus and then into nucleoli and (b) determined which of the domains of rpS5 are involved in this intracellular trafficking. In vitro PCR mutagenesis of mouse rpS5 cDNA, complemented by subsequent cloning and expression of rpS5 truncated recombinant forms, produced in fusion with green fluorescent protein, permitted the investigation of rpS5 intracellular trafficking in HeLa cells using confocal microscopy complemented by Western blot analysis. Our results indicate the following: (a) rpS5 protein enters the nucleus via the region 38-50 aa that forms a random coil as revealed by molecular dynamic simulation. (b) Immunoprecipitation of rpS5 with casein kinase II and immobilized metal affinity chromatography analysis complemented by in vitro kinase assay revealed that phosphorylation of rpS5 seems to be indispensable for its transport from nucleus to nucleoli; upon entering the nucleus, Thr-133 phosphorylation triggers Ser-24 phosphorylation by casein kinase II, thus promoting entrance of rpS5 into the nucleoli. Another important role of rpS5 N-terminal region is proposed to be the regulation of protein's cellular level. The repetitively co-appearance of a satellite C-terminal band below the entire rpS5 at the late stationary phase, and not at the early logarithmic phase, of cell growth suggests a specific degradation balancing probably the unassembled ribosomal protein molecules with those that are efficiently assembled to ribosomal subunits. Overall, these data provide new insights on the structural and functional domains within the rpS5 molecule that contribute to its cellular functions.

Stunning and Right Ventricular Dysfunction Is Induced by Coronary Balloon Occlusion and Rapid Pacing in Humans: Insights From Right Ventricular Conductance Catheter Studies.

PubMed

Axell, Richard G; Giblett, Joel P; White, Paul A; Klein, Andrew; Hampton-Til, James; O'Sullivan, Michael; Braganza, Denise; Davies, William R; West, Nick E J; Densem, Cameron G; Hoole, Stephen P

2017-06-06

We sought to determine whether right ventricular stunning could be detected after supply (during coronary balloon occlusion [BO]) and supply/demand ischemia (induced by rapid pacing [RP] during transcatheter aortic valve replacement) in humans. Ten subjects with single-vessel right coronary artery disease undergoing percutaneous coronary intervention with normal ventricular function were studied in the BO group. Ten subjects undergoing transfemoral transcatheter aortic valve replacement were studied in the RP group. In both, a conductance catheter was placed into the right ventricle, and pressure volume loops were recorded at baseline and for intervals over 15 minutes after a low-pressure BO for 1 minute or a cumulative duration of RP for up to 1 minute. Ischemia-induced diastolic dysfunction was seen 1 minute after RP (end-diastolic pressure [mm Hg]: 8.1±4.2 versus 12.1±4.1, P <0.001) and BO (end-diastolic pressure [mm Hg]: 8.1 ± 4.0 versus 8.7±4.0, P =0.03). Impairment of systolic and diastolic function after BO remained at 15-minutes recovery (ejection fraction [%]: 55.7±9.0 versus 47.8±6.3, P <0.01; end-diastolic pressure [mm Hg]: 8.1±4.0 versus 9.2±3.9, P <0.01). Persistent diastolic dysfunction was also evident in the RP group at 15-minutes recovery (end-diastolic pressure [mm Hg]: 8.1±4.1 versus 9.9±4.4, P =0.03) and there was also sustained impairment of load-independent indices of systolic function at 15 minutes after RP (end-systolic elastance and ventriculo-arterial coupling [mm Hg/mL]: 1.25±0.31 versus 0.85±0.43, P <0.01). RP and right coronary artery balloon occlusion both cause ischemic right ventricular dysfunction with stunning observed later during the procedure. This may have intraoperative implications in patients without right ventricular functional reserve. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Comprehensive quality-of-life outcomes in the setting of a multidisciplinary, equal access prostate cancer clinic.

PubMed

Rice, Kevin; Hudak, Jane; Peay, Kimberly; Elsamanoudi, Sally; Travis, Judith; Lockhart, Robbin; Cullen, Jennifer; Black, Libby; Houge, Susan; Brassell, Stephen

2010-11-01

To identify racial and demographic factors that influence treatment choice and its resulting impact on health-related quality of life (HRQoL) for prostate cancer patients. Patients presenting to an equal access, military, multidisciplinary prostate cancer clinic composed the study group. The Expanded Prostate Cancer Index Composite (EPIC), EPIC Demographic, and Medical Outcomes Study Short Form 36 were the instruments used. Evaluation was performed before treatment and every 3 months after treatment. The study group comprised 665 patients. Caucasians were 3-fold more likely to choose surgery (radical prostatectomy [RP]) over external beam radiation therapy (EBRT). Patients who earned more than $100,000 annually disproportionately chose RP (P < .0001). Similarly, those having a graduate school degree disproportionally chose RP (P < .0001). Patients undergoing RP had the greatest risk of urinary function decline (P < .0001) and sexual bother (P = .0003). African Americans (AA) had a greater risk of urinary function decline irrespective of treatment choice. Patients undergoing EBRT had equivalent urinary function to expectant management (EM) at 12 months (P < .0001). Brachytherapy was the only treatment that posed an increased risk of urinary bother decline when compared with EM (P = .0217). EBRT alone did not show significant decrement in sexual function when compared with EM. RP was chosen by patients of Caucasian ethnicity and patients with higher income and education level, despite providing the greatest risk of HRQoL decline. EBRT had no significant impact on urinary function, sexual function, or sexual bother scores at 12 months. EBRT may be offered to older patients with minimal HRQoL impact. Pretreatment counseling of HRQoL outcomes is essential to overall prostate cancer management. Published by Elsevier Inc.

Association of statin and nonsteroidal anti-inflammatory drug use with prostate cancer outcomes: results from CaPSURE.

PubMed

Katz, Matthew S; Carroll, Peter R; Cowan, Janet E; Chan, June M; D'Amico, Anthony V

2010-09-01

To determine whether 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) and nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with the risk of prostate cancer and improved survival in men with prostate cancer. We retrospectively examined the association between NSAID and statin use among 7042 men who underwent radical prostatectomy (RP, 4611) or radiotherapy (RT, 2431) for prostate cancer between 1990 and 2003 identified in the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE), a primarily community-based national prostate cancer registry. We compared clinical and sociodemographic variables by statin and NSAID use, using chi-square tests and multinomial logistic regression. We examined associations between medications and comorbid illness with mortality using unadjusted and adjusted Cox proportional hazard models. The median (range) follow-up from treatment was 4 (0-16) years. In multivariate survival analysis, statin 'ever-use' was associated with a reduced risk of all-cause mortality (ACM) after RP (hazard ratio, HR, 0.35, 95% confidence interval, CI, 0.21-0.58) and RT (0.59, 0.37-0.94). NSAID ever-use was also associated with a reduced risk of ACM after RP (HR 0.47, 95% CI 0.30-0.75) and RT (0.39, 0.25-0.59). In a population of men with prostate cancer, statin and NSAID ever-use were associated with a reduced risk of ACM. Our study highlights the importance of multidisciplinary survivorship care for men with prostate cancer. © 2010 THE AUTHORS. JOURNAL COMPILATION © 2010 BJU INTERNATIONAL.

Association between surgeon and hospital characteristics and lymph node counts from radical prostatectomy and pelvic lymph node dissection.

PubMed

Wang, Elyn H; Yu, James B; Gross, Cary P; Abouassaly, Robert; Cherullo, Edward E; Smaldone, Marc C; Shah, Nilay D; Kiechle, Jonathon; Trinh, Quoc-Dien; Sun, Maxine; Kim, Simon P

2015-04-01

To assess whether surgical approach and hospital characteristics independently determine the number of lymph nodes (LNs) removed from prostate cancer patients undergoing radical prostatectomy (RP) and pelvic LN dissection (PLND). Using the National Cancer Database, we identified all surgically treated patients diagnosed with pretreatment intermediate- or high-risk prostate cancer from 2010 to 2011. The primary outcome was the number of LNs retrieved at the time of RP. Generalized estimating equations were used to assess for differences in the adjusted number of LNs retrieved after accounting for patient and hospital characteristics and surgical approach. Overall, 35,876 patients were diagnosed with intermediate-risk (61.2%) and high-risk (38.8%) prostate cancer and underwent RP and PLND.On multivariate analysis, open RP and high-volume and academic hospitals were independently associated with greater LN counts compared with robotic-assisted RP and medium or low and community hospitals, respectively (all P <.001). After adjusting for patient and hospital variables, higher adjusted LN counts were observed for open RP compared with robotic-assisted RP (7.1 vs 6.1; P <.001). Adjusted counts were also higher for high-volume hospitals compared with medium- or low-volume hospitals (7.8 vs 5.9; P <.001), and academic compared with community hospitals (7.3 vs 5.6; P <.001). Among patients with aggressive prostate cancer treated with RP and PLND, retrieval of LN counts varied by surgical approach and hospital characteristics. Copyright © 2015 Elsevier Inc. All rights reserved.

Reference Pricing with Endogenous or Exogenous Payment Limits: Impacts on Insurer and Consumer Spending.

PubMed

Brown, Timothy T; Robinson, James C

2016-06-01

Reference pricing (RP) theories predict different outcomes when reference prices are fixed (exogenous) versus being a function of market prices (MPs) (endogenous). Exogenous RP results in MPs at both high-price and low-price firms converging towards the reference price from above and below, respectively. Endogenous RP results in MPs at both high-price and low-price firms decreasing, with low-price firms acting strategically to decrease the reference price in order to gain market share. We extend these models to a hospital context focusing on insurer and consumer payments. Under exogenous RP, insurer and consumer payments to low-price hospitals increase, and insurer payments to high-price hospitals decrease, but predictions regarding consumer payments are ambiguous for high-price hospitals. Under endogenous RP, insurer payments to high-price and low-price hospitals decrease, and consumer payments to low-price hospitals decrease, but predictions regarding consumer payments are ambiguous for high-price hospitals. We test these predictions with difference-in-differences specifications using 2008-2013 data on patients undergoing joint replacement. For 2 years following RP implementation, insurer payments to high-price and low-price hospitals moved downward, consistent with endogenous RP. However, when the reference price was not reset to account for changes in MPs, insurer payments to low-price hospitals reverted to pre-implementation levels, consistent with exogenous RP. Copyright © 2015 John Wiley & Sons, Ltd. Copyright © 2015 John Wiley & Sons, Ltd.

Health-related quality of life following radical prostatectomy: long-term outcomes.

PubMed

Matthew, Andrew G; Alibhai, Shabbir M H; Davidson, Tal; Currie, Kristen L; Jiang, Haiyan; Krahn, Murray; Fleshner, Neil E; Kalnin, Robin; Louis, Alyssa S; Davison, B Joyce; Trachtenberg, John

2014-10-01

To identify the health-related quality of life (HRQoL) domains that radical prostatectomy (RP) impacts most negatively and to define the recovery of these domains over 30 months of observation. A total of 1,200 RP patients completed the Patient-Oriented Prostate Utility Scale-Psychometric (PORPUS-P; range 0-100, higher is better), a prostate cancer-specific HRQoL measure, prior to RP and at 0-3 (T1), 3-9 (T2), 9-18 (T3) and 18-30 (T4) months post-RP. HRQoL changes were examined using paired t tests and a mixed-effect growth curve model. Multivariable analyses were performed to investigate demographic and treatment factors predicting the change in HRQoL. Mean baseline PORPUS-P score, 83.1, fell to 66.5 (p < 0.001) at T1. Over time HRQoL improved but did not return to baseline (T4 mean 76.4, p < 0.001). Domain analysis revealed that sexual function (p < 0.001), sexual drive (p < 0.001), energy (p = 0.001) and bladder control (p < 0.001) failed to return to baseline at T4. Sexual function demonstrated the greatest impairment overall. The multivariable model revealed Black men experienced greater losses in global HRQoL compared with White men (coefficient -2.77, 95% CI -5.00 to -0.54, p = 0.015). High baseline HRQoL, pro-erectile aid use and bilateral nerve-sparing were significantly associated with smaller reductions in HRQoL post-RP. Overall HRQoL, sexual drive, sexual function, energy and bladder control do not return to preoperative levels within 30 months post-RP. Black patients experience the greatest reductions in HRQoL. HRQoL losses may be ameliorated by use of pro-erectile aids. These findings help to identify at-risk patient populations and inform survivorship programs.

National estimated costs of never events following radical prostatectomy.

PubMed

Deibert, Christopher M; Kates, Max; McKiernan, James M; Spencer, Benjamin A

2015-09-01

To examine the Centers for Medicare and Medicaid Services, which since 2008 has identified and not reimbursed 10 common postoperative complications deemed "never events" or hospital-acquired conditions (HACs). Prostate cancer, the most frequent cancer among U.S. men, is most often treated with radical prostatectomy (RP). Therefore, its complications in total may represent significant costs to hospitals and providers if not reimbursed. We evaluated the potential effect of these unreimbursed HACs following RP on clinical outcomes and costs. Using the Nationwide Inpatient Sample, we selected a weighed, national, estimated sample of 451,707 men with prostate cancer who underwent RP between 2002 and 2009. Baseline sociodemographic and hospital characteristics are described. We calculated estimated frequencies and costs of HACs and the predictors of in-hospital mortality, prolonged length of stay, and increased total hospital costs. Overall, HACs were infrequent at 0.08%, with pressure ulcer development (0.02%) and foreign object retained at surgery (0.02%) being the most common. HAC occurrence was not affected by hospital teaching status or surgical volume, but larger hospital size was related to more HACs. Those experiencing an HAC were much more likely to have a prolonged length of stay (odds ratio = 6.68, 95% CI: 5.34-8.36) and increased hospital costs (odds ratio = 5.03, 95% CI: 4.05-6.24). HACs after RP cost an estimated nearly $1 million annually in the United States. In a robust sample of patients who underwent RP in the United States, HACs were very uncommon and contributed approximately $1 million in additional expenditures. As the U.S. government continues to expand quality improvement programs and develop incentives to avoid complications, efforts to monitor unnecessary complications should continue as well. Copyright © 2015. Published by Elsevier Inc.

Usher Syndrome

MedlinePlus

... or hearing loss and an eye disease called retinitis pigmentosa (RP) [re-tin-EYE-tis pig-men-TOE- ... 27. 6 Berson, E.L. (1998). Treatment of retinitis pigmentosa with vitamin A . Digital Journal of Ophthalmology, 4( ...

Phenotypic modulation of corpus cavernosum smooth muscle cells in a rat model of cavernous neurectomy.

PubMed

Yang, Fan; Zhao, Jian F; Shou, Qi Y; Huang, Xiao J; Chen, Gang; Yang, Ke B; Zhang, Shi G; Lv, Bo D; Fu, Hui Y

2014-01-01

Patients undergoing radical prostatectomy (RP) are at high risk for erectile dysfunction (ED) due to potential cavernous nerve (CN) damage during surgery. Penile hypoxia after RP is thought to significantly contribute to ED pathogenesis. We previously showed that corpora cavernosum smooth muscle cells (CCSMCs) undergo phenotypic modulation under hypoxic conditions in vitro. Here, we studied such changes in an in vivo post-RP ED model by investigating CCSMCs in bilateral cavernous neurectomy (BCN) rats. Sprague-Dawley rats underwent sham (n = 12) or BCN (n = 12) surgery. After 12 weeks, they were injected with apomorphine to determine erectile function. The penile tissues were harvested and assessed for fibrosis using Masson trichrome staining and for molecular markers of phenotypic modulation using immunohistochemistry and western blotting. CCSMC morphological structure was evaluated by hematoxylin-eosin (H&E) staining and transmission electron microscopy (TEM). Erectile function was significantly lower in BCN rats than in sham rats. BCN increased hypoxia-inducible factor-1α and collagen protein expression in corpora cavernous tissue. H&E staining and TEM showed that CCSMCs in BCN rats underwent hypertrophy and showed rough endoplasmic reticulum formation. The expression of CCSMC phenotypic markers, such as smooth muscle α-actin, smooth muscle myosin heavy chain, and desmin, was markedly lower, whereas vimentin protein expression was significantly higher in BCN rats than in control rats. CCSMCs undergo phenotype modulation in rats with cavernous neurectomy. The results have unveiled physiological transformations that occur at the cellular and molecular levels and have helped characterize CN injury-induced ED.

Reporting in vitro fertilization cycles to the Society for Assisted Reproductive Technology database: where have all the cycles gone?

PubMed

Kulak, David; Jindal, Sangita K; Oh, Cheongeun; Morelli, Sara S; Kratka, Scott; McGovern, Peter G

2016-04-01

To assess the relationship between live birth rates (LBRs) and the incidence of under-reported cycles by IVF clinics. Cohort study. Not applicable. All patients undergoing IVF cycles in the aforementioned clinics. Not applicable. The reporting percentage (RP), defined as number of cycles with reported pregnancy rates divided by total cycles performed. Results from cryopreservation cycles are only presented by SART if an embryo transfer occurs. Thus, RP decreases as incidence of embryo or oocyte banking cycles increases. The LBRs in women aged <35 years were compared between clinics. The median RP of all clinics was 93%-97%. Clinics with RP <80% increased from 2 in 2004 to 30 in 2012. Twenty-one clinics had an RP that fell 2 standard deviations below the mean in any year. Over the 9 years, there was a negative correlation between RP and LBR of -0.17, but for the 21 outlier clinics the correlation increased to -0.26. In 2012 alone, in outlier clinics, for every 10% drop in RP there was an associated rise in LBR of 4.3%; some clinics reported 40% fewer cycles than the median. In clinics with very low RP, the cycles that are reported have higher success rates. Regardless of intent, the reduction of reported data to SART makes it increasingly difficult for clinicians and patients to accurately assess a clinic's success rates. Copyright © 2016 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

The effects of hedonically acceptable red pepper doses on thermogenesis and appetite

PubMed Central

Ludy, Mary-Jon; Mattes, Richard D.

2010-01-01

Previous studies suggest consumption of red pepper (RP) promotes negative energy balance. However, the RP dose provided in these studies (up to 10 g/meal) usually exceeded the amount preferred by the general population in the United States (mean = ~ 1 g/meal). The objective of this study was to evaluate the effects of hedonically acceptable RP doses served at a single meal in healthy, lean individuals on thermogenesis and appetite. Twenty-five men and women (aged 23.0 ± 0.5 y, BMI 22.6 ± 0.3 kg/m2, 13 spicy food users and 12 non-users) participated in a randomized crossover trial during which they consumed a standardized quantity (1 g); their preferred quantity (regular spicy foods users 1.8 ± 0.3 g/meal, non-users 0.3 ± 0.1 g/meal); or no RP. Energy expenditure, core body and skin temperature, and appetite were measured. Postprandial energy expenditure and core body temperature were greater, and skin temperature was lower, after test loads with 1 g RP than no RP. Respiratory quotient was lower after the preferred RP dose was ingested orally, compared to in capsule form. These findings suggest that RP’s effects on energy balance stem from a combination of metabolic and sensory inputs, and that oral exposure is necessary to achieve RP’s maximum benefits. Energy intake was lower after test loads with 1 g RP than no RP in non-users, but not in users. Preoccupation with food, and the desire to consume fatty, salty, and sweet foods were decreased more (or tended to be decreased more) in non-users than users after a 1 g RP test load, but did not vary after a test load with no RP. This suggests that individuals may become desensitized to the effects of RP with long-term spicy food intake. PMID:21093467

Gleason grade grouping of prostate cancer is of prognostic value in Asian men.

PubMed

Yeong, Joe; Sultana, Rehena; Teo, Jonathan; Huang, Hong Hong; Yuen, John; Tan, Puay Hoon; Khor, Li Yan

2017-09-01

The International Society of Urological Pathology made recommendations for the use of Grade Groups (GG) originally described by Epstein and colleagues over Gleason score (GS) alone in 2014, which was subsequently adopted by the WHO classification in 2016. The majority of studies validating this revision have been in Caucasian populations. We therefore asked whether the new GG system was retrospectively associated with biochemical disease-free survival in a mixed-ethnicity cohort of Asian men. A total of 680 radical prostatectomies (RPs) from 2005 to 2014 were included. GS from initial biopsy and RP were compared and used to allocate cases to GG, defined as: 1 (GS≤6); 2 (GS 3+4=7); 3 (GS 4+3=7); 4 (GS 4+4=8/5+3=8/3+5=8) and 5 (GS 9-10). Biochemical recurrence was defined as two consecutive post-RP prostate-specific antigen (PSA) levels of >0.2 ng/mL after post-RP PSA reaching the nadir of <0.1 ng/mL. Our data showed that Kaplan-Meier analysis revealed significant differences in biochemical recurrence within Gleason GG based on either biopsy or prostatectomy scoring. Multivariate analysis further confirmed that a higher GG was significantly associated with risk of biochemical recurrence. This GG system had a higher prognostic discrimination for both initial biopsy and RP than GS. Our study validates the use of the revised and updated GG system in a mixed-ethnicity population of Asian men. Higher GG was significantly associated with increased risk of biochemical recurrence. We therefore recommend its use to inform clinical management for patients with prostate cancer. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Prospective, Randomized Controlled Trial Exploring the Effect of TachoSil® on Lymphocele Formation after Extended Pelvic Lymph Node Dissection in Prostate Cancer.

PubMed

Buelens, Sarah; Van Praet, Charles; Poelaert, Filip; Van Huele, Andries; Decaestecker, Karel; Lumen, Nicolaas

2018-05-15

To explore whether TachoSil®, a hemostatic patch, can reduce the incidence of lymphocele formation. Development of a lymphocele is a frequent complication after pelvic lymph node dissection (PLND) for nodal staging in prostate cancer. From 2013 - 2017, 100 patients with prostate cancer who were set to undergo a staging PLND before external beam radiotherapy (n = 50) or PLND concomitant with radical prostatectomy (RP) (n = 50) were prospectively randomized 1:1 between bilateral TachoSil® placement or not. Primary end points were radiographic lymphocele development, lymphocele volume (one week and one month postoperatively), the duration and volume of postoperative catheter drainage. Patient, tumor and surgical characteristics of the TachoSil® and control group did not differ significantly. In total 65 (65%) patients experienced a radiographic lymphocele up to three months after surgery, 29 (58%) in the TachoSil® and 36 (72%) in the control group (p = 0.34). Significantly less radiographic lymphoceles were observed one week postoperatively for patients undergoing sole PLND and one month postoperatively for PLND with RP in the TachoSil® compared to control group (16% versus 48%, p = 0.024 and 24% versus 52%, p = 0.047, respectively). The other postoperative characteristics presented no significant differences between both groups neither for patients undergoing sole PLND nor PLND with RP. Patients receiving bilateral TachoSil® placement after PLND seem less likely to develop a radiographic lymphocele early postoperative. Nevertheless, the clinical relevance of the use of TachoSil® remains highly debatable. Copyright © 2018 Elsevier Inc. All rights reserved.

Prostate-Specific Antigen Persistence After Radical Prostatectomy as a Predictive Factor of Clinical Relapse-Free Survival and Overall Survival: 10-Year Data of the ARO 96-02 Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wiegel, Thomas, E-mail: thomas.wiegel@uniklinik-ulm.de; Bartkowiak, Detlef; Bottke, Dirk

2015-02-01

Objective: The ARO 96-02 trial primarily compared wait-and-see (WS, arm A) with adjuvant radiation therapy (ART, arm B) in prostate cancer patients who achieved an undetectable prostate-specific antigen (PSA) after radical prostatectomy (RP). Here, we report the outcome with up to 12 years of follow-up of patients who retained a post-RP detectable PSA and received salvage radiation therapy (SRT, arm C). Methods and Materials: For the study, 388 patients with pT3-4pN0 prostate cancer with positive or negative surgical margins were recruited. After RP, 307 men achieved an undetectable PSA (arms A + B). In 78 patients the PSA remained above thresholds (median 0.6,more » range 0.05-5.6 ng/mL). Of the latter, 74 consented to receive 66 Gy to the prostate bed, and SRT was applied at a median of 86 days after RP. Clinical relapse-free survival, metastasis-free survival, and overall survival were determined by the Kaplan-Meier method. Results: Patients with persisting PSA after RP had higher preoperative PSA values, higher tumor stages, higher Gleason scores, and more positive surgical margins than did patients in arms A + B. For the 74 patients, the 10-year clinical relapse-free survival rate was 63%. Forty-three men had hormone therapy; 12 experienced distant metastases; 23 patients died. Compared with men who did achieve an undetectable PSA, the arm-C patients fared significantly worse, with a 10-year metastasis-free survival of 67% versus 83% and overall survival of 68% versus 84%, respectively. In Cox regression analysis, Gleason score ≥8 (hazard ratio [HR] 2.8), pT ≥ 3c (HR 2.4), and extraprostatic extension ≥2 mm (HR 3.6) were unfavorable risk factors of progression. Conclusions: A persisting PSA after prostatectomy seems to be an important prognosticator of clinical progression for pT3 tumors. It correlates with a higher rate of distant metastases and with worse overall survival. A larger prospective study is required to determine which patient subgroups will benefit most from which treatment option.« less

Multigene interactions and the prediction of depression in the Wisconsin Longitudinal Study

PubMed Central

Roetker, Nicholas S; Yonker, James A; Lee, Chee; Chang, Vicky; Basson, Jacob J; Roan, Carol L; Hauser, Taissa S; Hauser, Robert M

2012-01-01

Objectives Single genetic loci offer little predictive power for the identification of depression. This study examined whether an analysis of gene–gene (G × G) interactions of 78 single nucleotide polymorphisms (SNPs) in genes associated with depression and age-related diseases would identify significant interactions with increased predictive power for depression. Design A retrospective cohort study. Setting A survey of participants in the Wisconsin Longitudinal Study. Participants A total of 4811 persons (2464 women and 2347 men) who provided saliva for genotyping; the group comes from a randomly selected sample of Wisconsin high school graduates from the class of 1957 as well as a randomly selected sibling, almost all of whom are non-Hispanic white. Primary outcome measure Depression as determine by the Composite International Diagnostic Interview–Short-Form. Results Using a classification tree approach (recursive partitioning (RP)), the authors identified a number of candidate G × G interactions associated with depression. The primary SNP splits revealed by RP (ANKK1 rs1800497 (also known as DRD2 Taq1A) in men and DRD2 rs224592 in women) were found to be significant as single factors by logistic regression (LR) after controlling for multiple testing (p=0.001 for both). Without considering interaction effects, only one of the five subsequent RP splits reached nominal significance in LR (FTO rs1421085 in women, p=0.008). However, after controlling for G × G interactions by running LR on RP-specific subsets, every split became significant and grew larger in magnitude (OR (before) → (after): men: GNRH1 novel SNP: (1.43 → 1.57); women: APOC3 rs2854116: (1.28 → 1.55), ACVR2B rs3749386: (1.11 → 2.17), FTO rs1421085: (1.32 → 1.65), IL6 rs1800795: (1.12 → 1.85)). Conclusions The results suggest that examining G × G interactions improves the identification of genetic associations predictive of depression. 4 of the SNPs identified in these interactions were located in two pathways well known to impact depression: neurotransmitter (ANKK1 and DRD2) and neuroendocrine (GNRH1 and ACVR2B) signalling. This study demonstrates the utility of RP analysis as an efficient and powerful exploratory analysis technique for uncovering genetic and molecular pathway interactions associated with disease aetiology. PMID:22761283

Reduction in PSA messenger-RNA expression and clinical recurrence in patients with prostatic cancer undergoing neoadjuvant therapy before radical prostatectomy

PubMed Central

Grasso, Marco; Lania, Caterina; Blanco, Salvatore; Baruffi, Marco; Mocellin, Simone

2004-01-01

Background We assessed the incidence of micro-metastases at surgical margins (SM) and pelvic lymph nodes (LN) in patients submitted to radical retropubic prostatectomy (RP) after neoadjuvant therapy (NT) or to RP alone. We compared traditional staging to molecular detection of PSA using Taqman-based quantitative real-time PCR (qrt-PCR) never used before for this purpose. Methods 29 patients were assigned to NT plus RP (arm A) or RP alone (arm B). Pelvic LN were dissected for qrt-PCR analysis, together with right and left lateral SM. Results 64,3% patients of arm B and 26.6% of arm A had evidence of PSA mRNA expression in LN and/or SM. 17,2% patients, all of arm B, had biochemical recurrence. Conclusions Qrt-PCR may be more sensitive, compared to conventional histology, in identifying presence of viable prostate carcinoma cells in SM and LN. Gene expression of PSA in surgical periprostatic samples might be considered as a novel and reliable indicator of minimal residual disease after NT. PMID:15104791

Return to work following robot-assisted laparoscopic and open retropubic radical prostatectomy: A single-center cohort study to compare duration of sick leave.

PubMed

von Mechow, Stefanie; Graefen, Markus; Haese, Alexander; Tennstedt, Pierre; Pehrke, Dirk; Friedersdorff, Frank; Beyer, Burkhard

2018-06-01

To compare the duration of sick leave in patients with localized prostate cancer after robot-assisted radical prostatectomy (RARP) and open retropubic RP (ORP) at a German high-volume prostate cancer center. The data of 1,415 patients treated with RP at Martini Klinik, Prostate Cancer Center between 2012 and 2016 were, retrospectively, analyzed. Information on employment status, monthly revenues and days of work missed due to sickness were assessed via online questionnaire. Additional data were retrieved from our institutional database. Medians and interquartile ranges (IQR) were reported for continuous data. Cox proportional hazard analysis was performed to compare both surgical techniques for return to work time after RP. Median time elapsed between surgery and return to work comprised 42 days in patients undergoing RARP (IQR: 21-70) and ORP (IQR: 28-84, P = 0.05). In Cox regression analysis, surgical approach showed no impact on return to work time (RARP vs. ORP hazard ratio = 1, 95% CI: 0.91-1.16, P = 0.69). Return to work time was significantly associated with employment status, physical workload and monthly income (all P<0.001). Limitation of this study is the nonrandomized design in a single-center. As the surgical approach did not show any influence on the number of days missed from work in patients undergoing RP, no superiority of either RARP or ORP could be identified for return to work time in a German cohort. Both surgical approaches are safe options usually allowing the patients to resume normal activities including work after an appropriate convalescence period. Copyright © 2018 Elsevier Inc. All rights reserved.

Impact of initial local therapy on survival in men later receiving chemotherapy for prostate cancer: a population-based, propensity-weighted multivariable analysis.

PubMed

Zabell, Joseph R; Adejoro, Oluwakayode; Jarosek, Stephanie L; Elliott, Sean P; Konety, Badrinath R

2016-10-01

Prostate cancer remains a common disease that is frequently treated with multimodal therapy. The goal of this study was to assess the impact of treatment of the primary tumor on survival in men who go onto receive chemotherapy for prostate cancer. Using surveillance, epidemiology and end results (SEER)-Medicare data from 1992 to 2009, we identified a cohort of 1614 men who received chemotherapy for prostate cancer. Primary outcomes were prostate cancer-specific mortality (PCSM) and all-cause mortality (ACM). We compared survival among men who had previously undergone radical prostatectomy (RP), radiation therapy (RT), or neither of these therapies. Propensity score adjusted Cox proportional hazard models and weighted Kaplan-Meier curves were used to assess survival. Compared to men who received no local treatment, PCSM was lower for men who received RP ± RT (HR 0.65, p < 0.01) and for those who received RT only (HR 0.79, p < 0.05). Patients receiving neither RP nor RT demonstrated higher PCSM and ACM than those receiving treatment in a weighted time-to-event analysis. Men who received RP + RT had longer mean time from diagnosis to initiation of chemotherapy (100.7 ± 47.7 months) than men with no local treatment (48.8 ± 35.0 months, p < 0.05). In patients who go on to receive chemotherapy, treatment of the primary tumor for prostate cancer appears to confer a survival advantage over those who do not receive primary treatment. These data suggest continued importance for local treatment of prostate cancer, even in patients at high risk of failing local therapy.

Ligand-regulated peptides: a general approach for modulating protein-peptide interactions with small molecules.

PubMed

Binkowski, Brock F; Miller, Russell A; Belshaw, Peter J

2005-07-01

We engineered a novel ligand-regulated peptide (LiRP) system where the binding activity of intracellular peptides is controlled by a cell-permeable small molecule. In the absence of ligand, peptides expressed as fusions in an FKBP-peptide-FRB-GST LiRP scaffold protein are free to interact with target proteins. In the presence of the ligand rapamycin, or the nonimmunosuppressive rapamycin derivative AP23102, the scaffold protein undergoes a conformational change that prevents the interaction of the peptide with the target protein. The modular design of the scaffold enables the creation of LiRPs through rational design or selection from combinatorial peptide libraries. Using these methods, we identified LiRPs that interact with three independent targets: retinoblastoma protein, c-Src, and the AMP-activated protein kinase. The LiRP system should provide a general method to temporally and spatially regulate protein function in cells and organisms.

Radical Prostatectomy, External Beam Radiotherapy, or External Beam Radiotherapy With Brachytherapy Boost and Disease Progression and Mortality in Patients With Gleason Score 9-10 Prostate Cancer.

PubMed

Kishan, Amar U; Cook, Ryan R; Ciezki, Jay P; Ross, Ashley E; Pomerantz, Mark M; Nguyen, Paul L; Shaikh, Talha; Tran, Phuoc T; Sandler, Kiri A; Stock, Richard G; Merrick, Gregory S; Demanes, D Jeffrey; Spratt, Daniel E; Abu-Isa, Eyad I; Wedde, Trude B; Lilleby, Wolfgang; Krauss, Daniel J; Shaw, Grace K; Alam, Ridwan; Reddy, Chandana A; Stephenson, Andrew J; Klein, Eric A; Song, Daniel Y; Tosoian, Jeffrey J; Hegde, John V; Yoo, Sun Mi; Fiano, Ryan; D'Amico, Anthony V; Nickols, Nicholas G; Aronson, William J; Sadeghi, Ahmad; Greco, Stephen; Deville, Curtiland; McNutt, Todd; DeWeese, Theodore L; Reiter, Robert E; Said, Johnathan W; Steinberg, Michael L; Horwitz, Eric M; Kupelian, Patrick A; King, Christopher R

2018-03-06

The optimal treatment for Gleason score 9-10 prostate cancer is unknown. To compare clinical outcomes of patients with Gleason score 9-10 prostate cancer after definitive treatment. Retrospective cohort study in 12 tertiary centers (11 in the United States, 1 in Norway), with 1809 patients treated between 2000 and 2013. Radical prostatectomy (RP), external beam radiotherapy (EBRT) with androgen deprivation therapy, or EBRT plus brachytherapy boost (EBRT+BT) with androgen deprivation therapy. The primary outcome was prostate cancer-specific mortality; distant metastasis-free survival and overall survival were secondary outcomes. Of 1809 men, 639 underwent RP, 734 EBRT, and 436 EBRT+BT. Median ages were 61, 67.7, and 67.5 years; median follow-up was 4.2, 5.1, and 6.3 years, respectively. By 10 years, 91 RP, 186 EBRT, and 90 EBRT+BT patients had died. Adjusted 5-year prostate cancer-specific mortality rates were RP, 12% (95% CI, 8%-17%); EBRT, 13% (95% CI, 8%-19%); and EBRT+BT, 3% (95% CI, 1%-5%). EBRT+BT was associated with significantly lower prostate cancer-specific mortality than either RP or EBRT (cause-specific HRs of 0.38 [95% CI, 0.21-0.68] and 0.41 [95% CI, 0.24-0.71]). Adjusted 5-year incidence rates of distant metastasis were RP, 24% (95% CI, 19%-30%); EBRT, 24% (95% CI, 20%-28%); and EBRT+BT, 8% (95% CI, 5%-11%). EBRT+BT was associated with a significantly lower rate of distant metastasis (propensity-score-adjusted cause-specific HRs of 0.27 [95% CI, 0.17-0.43] for RP and 0.30 [95% CI, 0.19-0.47] for EBRT). Adjusted 7.5-year all-cause mortality rates were RP, 17% (95% CI, 11%-23%); EBRT, 18% (95% CI, 14%-24%); and EBRT+BT, 10% (95% CI, 7%-13%). Within the first 7.5 years of follow-up, EBRT+BT was associated with significantly lower all-cause mortality (cause-specific HRs of 0.66 [95% CI, 0.46-0.96] for RP and 0.61 [95% CI, 0.45-0.84] for EBRT). After the first 7.5 years, the corresponding HRs were 1.16 (95% CI, 0.70-1.92) and 0.87 (95% CI, 0.57-1.32). No significant differences in prostate cancer-specific mortality, distant metastasis, or all-cause mortality (≤7.5 and >7.5 years) were found between men treated with EBRT or RP (cause-specific HRs of 0.92 [95% CI, 0.67-1.26], 0.90 [95% CI, 0.70-1.14], 1.07 [95% CI, 0.80-1.44], and 1.34 [95% CI, 0.85-2.11]). Among patients with Gleason score 9-10 prostate cancer, treatment with EBRT+BT with androgen deprivation therapy was associated with significantly better prostate cancer-specific mortality and longer time to distant metastasis compared with EBRT with androgen deprivation therapy or with RP.

Intraindividual Comparison of 18F-PSMA-1007 PET/CT, Multiparametric MRI, and Radical Prostatectomy Specimens in Patients with Primary Prostate Cancer: A Retrospective, Proof-of-Concept Study.

PubMed

Kesch, Claudia; Vinsensia, Maria; Radtke, Jan P; Schlemmer, Heinz P; Heller, Martina; Ellert, Elena; Holland-Letz, Tim; Duensing, Stefan; Grabe, Nils; Afshar-Oromieh, Ali; Wieczorek, Kathrin; Schäfer, Martin; Neels, Oliver C; Cardinale, Jens; Kratochwil, Clemens; Hohenfellner, Markus; Kopka, Klaus; Haberkorn, Uwe; Hadaschik, Boris A; Giesel, Frederik L

2017-11-01

68 Ga-prostate-specific membrane antigen (PSMA)-11 PET/CT represents an advanced method for the staging of primary prostate cancer (PCa) and diagnosis of recurrent or metastatic PCa. However, because of the narrow availability of 68 Ga the development of alternative tracers is of high interest. The objective of this study was to examine the value of the new PET tracer 18 F-PSMA-1007 for the staging of local disease by comparing it with multiparametric MRI (mpMRI) and radical prostatectomy (RP) histopathology. Methods: In 2016, 18 F-PSMA-1007 PET/CT was performed in 10 men with biopsy-confirmed high-risk PCa. Nine patients underwent mpMRI in the process of primary diagnosis. Consecutively, RP was performed in all 10 men. Agreement analysis was performed retrospectively. PSMA staining was added for representative sections in RP specimen slices. Localization and agreement analysis of 18 F-PSMA-1007 PET/CT, mpMRI, and RP specimens was performed by dividing the prostate into 38 sections as described in the prostate imaging reporting and data system (PI-RADS) (version 2). Sensitivity, specificity, positive predictive values, negative predictive values (NPVs), and accuracy were calculated for total and near-total agreement. Results: 18 F-PSMA-1007 PET/CT had an NPV of 68% and an accuracy of 75%, and mpMRI had an NPV of 88% and an accuracy of 73% for total agreement. Near-total agreement analysis resulted in an NPV of 91% and an accuracy of 93% for 18 F-PSMA-1007 PET/CT and 91% and 87% for mpMRI, respectively. Retrospective combination of mpMRI and PET/CT had an accuracy of 81% for total and 93% for near-total agreement. Conclusion: Comparison with RP histopathology demonstrates that 18 F-PSMA-1007 PET/CT is promising for accurate local staging of PCa. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Prostate-specific Antigen Mass Density--A Measure Predicting Prostate Cancer Volume and Accounting for Overweight and Obesity-related Prostate-specific Antigen Hemodilution.

PubMed

Kryvenko, Oleksandr N; Diaz, Mireya; Matoso, Andres; Kates, Max; Cohen, Jason; Swanson, Gregory P; Epstein, Jonathan I

2016-04-01

To test prostate-specific antigen mass density (PSAMD) as a predictor of total tumor volume (TTV) at radical prostatectomy (RP). We conducted a detailed pathologic analysis of 469 RP from men with NCCN low-risk prostate cancer who had Gleason score of 3 + 3 = 6 (grade group 1) at RP. We then compared the ability of PSA, PSA density (PSAD), PSA mass (PSAM-absolute amount of PSA in patient's circulation), and PSAM density (PSAM divided by prostate weight without seminal vesicles) to predict TTV at RP. PSAM was calculated by multiplying plasma volume (estimated body surface [weight, kg(0.425) × height, m(0.72) × 0.007184] × 1.67) by PSA. Performance of the above measures in different BMI categories was assessed. Kruskal-Wallis test was used to compare the means and Spearman's rank correlation coefficient to assess the correlations. The 469 men were normal weight (n = 129), overweight (n = 253), and obese (n = 87). Mean age of the patients' was 57.4 years and PSA of 4.53 ng/ml. Increase of prostate weight with body mass index (BMI) was reflected in PSAM (both P <.001) but not in other measures. BMI did not correlate with TTV and PSA. Among PSA, PSAD, PSAM, and PSAMD, PSAMD had the highest correlation with TTV (r = 0.336; P <.001). Prostate weight had stronger (negative) association with PSAMD (r = -0.394; <.001) than TTV. PSAMD is the biochemical measure with the best correlation with TTV at RP. Unlike other measures, it is not affected by BMI-related hemodilution. Thresholds should be established to use this more objective measure clinically in surveillance algorithms and in planning radical prostatectomy. Copyright © 2016 Elsevier Inc. All rights reserved.

Early incontinence after radical prostatectomy: a community based retrospective analysis in 911 men and implications for preoperative counseling.

PubMed

Khoder, Wael Y; Trottmann, Matthias; Stuber, Andrea; Stief, Christian G; Becker, Armin J

2013-10-01

Radical prostatectomy (RP) is curative for localized prostatic cancer. Incontinence after RP (P-RP-I) varies widely (2% to <60%) according to the definition and quantification of incontinence, timing of evaluation, and who evaluates (physician or patient). Conservative treatments, including pelvic floor muscle training (PFMT), anal electrical stimulation (AES), lifestyle adjustment, or combination are usually recommended at first for P-RP-I. Between January 2002 and December 2004, a total of 911 patients, median age 63 years (46-78), with different grades of P-RP-I have been retrospectively examined for perioperative risk factors and effect of rehabilitation procedures. These consecutive patients were from 67 clinics with median postoperative interval of 26 days. Incontinence was graded by Stamey classification, number of used pads and pads' consistency (dry, lightly wet, and wet). Therapeutic measures were done by team of specialists in rehabilitation, psycho-oncology, physiotherapy, internal medicine, and urology. Ninety-six percent of patients suffered different grades of incontinence at beginning of hospitalization. This was reported as Stamey first grade (49.4%), second grade (36.4%), and third grade (10.3%). Analysis included patients' age, body mass index (BMI), prostate volume, surgical approach, nerve sparing, pelvic lymphadenectomy, previous therapy, and catheterization time. Analysis showed age, nerve sparing, and BMI as significant risk factors for P-RP-I. Conservative therapy, including PFMT, AES, or combinations has been performed on all patients. Grade of P-RP-I showed significant improvement after 3 weeks rehabilitation period. Preoperative counseling of patients should provide them with realistic expectations for P-RP-I and motivate them to conservative therapy, as it reduces the duration and degree of urinary incontinence. Copyright © 2013 Elsevier Inc. All rights reserved.

Correlative analysis of social support with anxiety and depression in men undergoing in vitro fertilization embryo transfer for the first time.

PubMed

Dong, Yue-Zhi; Yang, Xiao-Xia; Sun, Ying-Pu

2013-08-01

To explore the correlation between the level of social support and the extent of anxiety and depression in Chinese men undergoing in vitro fertilization embryo transfer (IVF-ET) for the first time, in order to provide a basis for male mental health counselling. Self-administered questionnaires covering general health status, anxiety (self-rating anxiety scale), depression (self-rating depression scale) and social support (social support rating scale) were completed by men undergoing their first round of IVF-ET. A total of 502 completed questionnaires were considered valid and were analysed. The anxiety, depression and social support scores for men undergoing their first round of IVF-ET were significantly higher than those for Chinese normative data. Social support was inversely correlated with anxiety and depression. These findings suggest that health care professionals should provide specific psychological counselling to Chinese men undergoing their first round of IVF-ET, in order to improve their psychological health and to facilitate increased levels of social support.

Randomized Clinical Trial of Brewed Green and Black Tea in Men with Prostate Cancer Prior to Prostatectomy

PubMed Central

Henning, Susanne M.; Wang, Piwen; Said, Jonathan W.; Huang, Min; Grogan, Tristan; Elashoff, David; Carpenter, Catherine L.; Heber, David; Aronson, William J.

2014-01-01

Background Preclinical and epidemiologic studies suggest chemopreventive effects of green tea (GT) and black tea (BT) in prostate cancer. In the current study we determined the effect of GT and BT consumption on biomarkers related to prostate cancer development and progression. Methods In this exploratory, open label, phase II trial 113 men diagnosed with prostate cancer were randomized to consume six cups daily of brewed GT, BT or water (control) prior to radical prostatectomy (RP). The primary endpoint was prostate tumor markers of cancer development and progression determined by tissue immunostaining of proliferation (Ki67), apoptosis (Bcl-2, Bax, Tunel), inflammation [nuclear and cytoplasmic nuclear factor kappa B (NFκB)] and oxidation [8-hydroxydeoxy- guanosine (8OHdG)]. Secondary endpoints of urinary oxidation, tea polyphenol uptake in prostate tissue, and serum prostate specific antigen (PSA) were evaluated by high performance liquid chromatography and ELISA analysis. Results Ninety three patients completed the intervention. There was no significant difference in markers of proliferation, apoptosis and oxidation in RP tissue comparing GT and BT to water control. Nuclear staining of NFkB was significantly decreased in RP tissue of men consuming GT (p=0.013) but not BT (p=0.931) compared to water control. Tea polyphenols were detected in prostate tissue from 32 of 34 men consuming GT but not in the other groups. Evidence of a systemic antioxidant effect was observed (reduced urinary 8OHdG) only with GT consumption (p=0.03). GT, but not BT or water, also led to a small but statistically significant decrease in serum prostate-specific antigen (PSA) levels (p=0.04). Conclusion Given the GT-induced changes in NFkB and systemic oxidation, and uptake of GT polyphenols in prostate tissue, future longer-term studies are warranted to further examine the role of GT for prostate cancer prevention and treatment, and possibly for other prostate conditions such as prostatitis. PMID:25545744

3-DIMENSIONAL EXTERNAL BEAM RADIOTHERAPY FOR PROSTATE CANCER INCREASES THE RISK OF HIP FRACTURE

PubMed Central

Elliott, Sean P.; Jarosek, Stephanie L.; Alanee, Shaheen R.; Konety, Badrinath R.; Dusenbery, Kathryn E.; Virnig, Beth A.

2011-01-01

Background Hip fracture is associated with high morbidity and mortality. Pelvic external beam radiotherapy (EBRT) is known to increase the risk of hip fractures in women but the effect in men is unknown. Methods 45,662 men aged ≥66 years, diagnosed with prostate cancer in 1992–2004 were identified from the SEER-Medicare database. Using Kaplan-Meier methods and Cox proportional hazards models, the primary outcome of hip fracture risk was compared among men who received radical prostatectomy (RP), EBRT, EBRT+androgen suppression therapy (AST) or AST alone, controlling for age, osteoporosis, race and other comorbidities. A secondary outcome was distal forearm fractures as an indicator of fragility fracture risk outside the radiation field. Results After controlling for covariates, EBRT increased the risk of hip fractures by 76% (HR 1.76, 95% CI 1.38–2.40) without increasing the risk of distal forearm fractures (HR 0.80, 95% CI 0.56–1.14). Combination therapy with EBRT+AST increased the risk of hip fracture 145% relative to RP (HR 2.45, 95% CI 1.88–3.19) and by 40% relative to EBRT (HR 1.40, 95% CI 1.17–1.68). EBRT+AST increased the risk of distal forearm fracture by 43% relative to RP (HR 1.43, 95% CI 0.97–2.10). The number needed to treat to result in 1 hip fracture through 10 years was 51 (95% CI 31–103). Conclusion In men with prostate cancer, pelvic 3-D conformal EBRT is associated with a 76% increased risk of hip fracture. This risk is slightly increased further by the addition of short-course AST to EBRT. This risk associated with EBRT is site-specific as there is no increase in the risk of fall-related fractures outside the radiation field. PMID:21412999

Association between preoperative erectile dysfunction and prostate cancer features--an analysis from the Duke Prostate Center Database.

PubMed

Kimura, Masaki; Bañez, Lionel L; Gerber, Leah; Qi, Jim; Tsivian, Matvey; Freedland, Stephen J; Satoh, Takefumi; Polascik, Thomas J; Baba, Shiro; Moul, Judd W

2012-04-01

Erectile dysfunction (ED) is related to several co-morbidities including obesity, metabolic syndrome, cigarette smoking, and low testosterone, all of which have been reported to be associated with adverse prostate cancer features. To examine whether preoperative ED has a relationship with adverse prostate cancer features in patients who underwent radical prostatectomy (RP). We analyzed data from our institution on 676 patients who underwent RP between 2001 and 2010. Crude and adjusted logistic regression models were used to investigate the association between preoperative ED and several pathological parameters. The log-rank test and multivariate proportional hazards model were conducted to determine the association of preoperative ED with biochemical recurrence (BCR). The expanded prostate cancer index composite (EPIC) instrument was used to evaluate preoperative erectile function (EF). Preoperative normal EF was defined as EPIC-SF ≥ 60 points while ED was defined as preoperative EPIC-SF lower than 60 points. Preoperatively, a total of 343 (50.7%) men had normal EF and 333 (49.3%) men had ED. After adjusting for covariates, preoperative ED was identified a risk factor for positive extracapsular extension (OR 1.57; P = 0.029) and high percentage of tumor involvement (OR 1.56; P = 0.047). In a Kaplan-Meier curve, a trend was identified that patients with ED had higher incidence of BCR than men with normal EF (P = 0.091). Moreover, using a multivariate Cox model, higher preoperative EF was negatively associated with BCR (HR 0.99; P = 0.014). These results suggest that the likelihood for adverse pathological outcomes as well as BCR following prostatectomy is higher among men with preoperative ED, though these results require validation in larger datasets. The present study indicates that preoperative ED might be a surrogate for adverse prostate cancer outcomes following RP. © 2011 International Society for Sexual Medicine.

Female Partner Acceptance as a Predictor of Men's Readiness to Undergo Voluntary Medical Male Circumcision in Zambia: The Spear and Shield Project.

PubMed

Cook, Ryan; Jones, Deborah; Redding, Colleen A; Zulu, Robert; Chitalu, Ndashi; Weiss, Stephen M

2016-11-01

The World Health Organization has recommended the scale-up of voluntary medical male circumcision (VMMC) for HIV prevention in sub-Saharan Africa; however, men are often uninterested in undergoing VMMC. The Spear & Shield project enrolled 668 men and female partners from ten Zambian community health centers into parallel interventions promoting VMMC for HIV prevention or time-matched control conditions. A mediation model was utilized to examine the relationships between changes in women's acceptance of VMMC and men's readiness to undergo the procedure. Results demonstrated that, at 12 months post-intervention, a 5.9 % increase in the likelihood of undergoing VMMC among men in the experimental condition could be attributed to increased women's acceptance. From a public health perspective, involving women in VMMC promotion interventions such as the Spear & Shield project could significantly impact the demand for VMMC in Zambia.

Acceptability, Knowledge, Beliefs, and Partners as Determinants of Zambian Men's Readiness to Undergo Medical Male Circumcision

PubMed Central

Jones, Deborah; Cook, Ryan; Arheart, Kris; Redding, Colleen A.; Zulu, Robert; Castro, Jose; Weiss, Stephen M.

2013-01-01

There is limited information about the influence of partners on medical male circumcision (MMC) uptake. This study aimed to evaluate attitudes, knowledge, and preferences about MMC among men and their partners, and their relative impact on male readiness to undergo the MMC procedure. Male participants (n = 354) and their partners (n = 273) were recruited from community health centers in Lusaka, Zambia. Men reported their readiness to undergo MMC, and both men and women were assessed regarding their attitudes and knowledge regarding MMC. Men who had discussed MMC with their partners, those who endorsed MMC for HIV risk reduction, and those viewing MMC as culturally acceptable reported increased readiness to undergo MMC. Additionally, endorsement of MMC by female partners was associated with increased men’s readiness. Results support promotion of cultural acceptability of MMC, and efforts to increase MMC uptake may benefit from incorporating partners in the decision making process. PMID:23757123

RP-2 Thermal Stability and Heat Transfer Investigation for Hydrocarbon Boost Engines

NASA Technical Reports Server (NTRS)

VanNoord, J. L.; Stiegemeier, B. R.

2010-01-01

A series of electrically heated tube tests were performed at the NASA Glenn Research Center s Heated Tube Facility to investigate the use of RP-2 as a fuel for next generation regeneratively cooled hydrocarbon boost engines. The effect that test duration, operating condition and test piece material have on the overall thermal stability and materials compatibility characteristics of RP-2 were evaluated using copper and 304 stainless steel test sections. The copper tests were run at 1000 psia, heat flux up to 6.0 Btu/in.2-sec, and wall temperatures up to 1180 F. Preliminary results, using measured wall temperature as an indirect indicator of the carbon deposition process, show that in copper test pieces above approximately 850 F, RP-2 begins to undergo thermal decomposition resulting in local carbon deposits. Wall temperature traces show significant local temperature increases followed by near instantaneous drops which have been attributed to the carbon deposition/shedding process in previous investigations. Data reduction is currently underway for the stainless steel test sections and carbon deposition measurements will be performed in the future for all test sections used in this investigation. In conjunction with the existing thermal stability database, these findings give insight into the feasibility of cooling a long life, high performance, high-pressure liquid rocket combustor and nozzle with RP-2.

Does the tibial remnant of the anterior cruciate ligament promote ligamentization?

PubMed

Lee, Byung Ill; Kim, Byoung Min; Kho, Duk Hwan; Kwon, Sai Won; Kim, Hyeung June; Hwang, Hyun Ryong

2016-12-01

The purpose of this study was to clarify the difference in ligamentization between the remnant-preserving (RP) and remnant-sacrificing (RS) techniques in anterior cruciate ligament (ACL) reconstruction using magnetic resonance imaging (MRI). A retrospective comparative study was carried out on 98 patients undergoing ACL reconstruction using either an RP (n=56) or RS (n=42) technique. MRI was performed at one of four time points postoperatively, and the signal intensity of the ACL graft was analyzed using the signal to noise quotient (SNQ) ratio and inter-bundle high signal intensity, along with an analysis of the survival rate of remnant tissue. The mean SNQ ratio of grafted tendons in the RP group was significantly higher than that seen in the RS group in the proximal and middle regions two to four months after surgery (P<0.05) and was significantly lower than that seen in the RS group in all regions at 12 -18months (P<0.05). The inter-bundle high signal intensity was observed more frequently in the RP group (73.7%) at two to four months. Tibial remnants were observed on postoperative MRI regardless of when MRI was conducted. The ACL graft of the RP group showed higher signal intensity in the early stage and lower signal intensity in the late stage compared to that of the RS group. The ligamentization of grafts in the RP group proceeded more quickly. Preserving the remnant in ACL reconstruction appears to have a positive effect on ligamentization. Copyright © 2016 Elsevier B.V. All rights reserved.

Effects of Nonlinear Aerobic Training on Erectile Dysfunction and Cardiovascular Function Following Radical Prostatectomy for Clinically Localized Prostate Cancer

PubMed Central

Jones, Lee W.; Hornsby, Whitney E.; Freedland, Stephen J.; Lane, Amy; West, Miranda J.; Moul, Judd W.; Ferrandino, Michael N.; Allen, Jason D.; Kenjale, Aarti A.; Thomas, Samantha M.; Herndon, James E.; Koontz, Bridget F.; Chan, June M.; Khouri, Michel G.; Douglas, Pamela S.; Eves, Neil D.

2014-01-01

Erectile dysfunction (ED) is a major adverse effect of radical prostatectomy (RP). We conducted a randomized controlled trial to examine the efficacy of aerobic training (AT) compared with usual care (UC) on ED prevalence in 50 men (n = 25 per group) after RP. AT consisted of five walking sessions per week at 55– 100% of peak oxygen uptake (VO2peak) for 30–60 min per session following a nonlinear prescription. The primary outcome was change in the prevalence of ED, as measured by the International Index of Erectile Function (IIEF), from baseline to 6 mo. Secondary outcomes were brachial artery flow–mediated dilation (FMD), VO2peak, cardiovascular (CV) risk profile (eg, lipid profile, body composition), and patient-reported outcomes (PROs). The prevalence of ED (IIEF score ≤21) decreased by 20% in the AT group and by 24% in the UC group (difference: p = 0.406). There were no significant between-group differences in any erectile function subscale (p > 0.05). Significant between-group differences were observed for changes in FMD and VO2peak, favoring AT. There were no group differences in other markers of CV risk profile or PROs. In summary, nonlinear AT does not improve ED in men with localized prostate cancer in the acute period following RP. PMID:24315706

Men's body mass index in relation to embryo quality and clinical outcomes in couples undergoing in vitro fertilization.

PubMed

Colaci, Daniela S; Afeiche, Myriam; Gaskins, Audrey J; Wright, Diane L; Toth, Thomas L; Tanrikut, Cigdem; Hauser, Russ; Chavarro, Jorge E

2012-11-01

To evaluate the association between men's body mass index (BMI), early embryo quality, and clinical outcomes in couples undergoing in vitro fertilization (IVF). Prospective cohort study. Fertility clinic in an academic medical center. 114 couples who underwent 172 assisted reproduction cycles. None. Fertilization rate, embryo quality, implantation rate, clinical pregnancy rate, and live birth rate. The fertilization rate was higher among obese men than among normal weight men in conventional IVF cycles. No statistically significant associations were found between men's BMI and the proportion of poor-quality embryos on day 3, slow embryo cleavage rate, or accelerated embryo cleavage rate. Men's BMI was unrelated to positive β-human chorionic gonadotropin rate, clinical pregnancy rate, or live-birth rate per embryo transfer. Among couples undergoing intracytoplasmic sperm injection, the odds of live birth in couples with obese male partners was 84% lower than the odds in couples with men with normal BMI. Our data suggest a possible deleterious effect of male obesity on the odds of having a live birth among couples undergoing intracytoplasmic sperm injection. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Treatment Outcomes from 68Ga-PSMA PET/CT-Informed Salvage Radiation Treatment in Men with Rising PSA After Radical Prostatectomy: Prognostic Value of a Negative PSMA PET.

PubMed

Emmett, Louise; van Leeuwen, Pim J; Nandurkar, Rohan; Scheltema, Matthijs J; Cusick, Thomas; Hruby, George; Kneebone, Andrew; Eade, Thomas; Fogarty, Gerald; Jagavkar, Raj; Nguyen, Quoc; Ho, Bao; Joshua, Anthony M; Stricker, Phillip

2017-12-01

68 Ga-PSMA (prostate-specific membrane antigen) PET/CT is increasingly used in men with prostate-specific antigen (PSA) failure after radical prostatectomy (RP) to triage those who will benefit from salvage radiation treatment (SRT). This study examines the value of PSMA-informed SRT in improving treatment outcomes in the context of biochemical failure after RP. Methods: We analyzed men with rising PSA after RP with PSA readings between 0.05 and 1.0 ng/mL, considered eligible for SRT at the time of PSMA. For each patient, clinical and pathologic features as well as scan results, including site of PSMA-positive disease, number of lesions, and a certainty score, were documented. Subsequent management, including SRT, and most recent PSA were recorded using medical records. Treatment response was defined as both PSA ≤ 0.1 ng/mL and >50% reduction in PSA. Multivariate logistic regression analysis was performed for association of clinical variables and treatment response to SRT. Results: One hundred sixty-four men were included. PSMA was positive in 62% ( n = 102/164): 38 of 102 in the prostatic fossa, 41 of 102 in pelvic nodes, and 23 of 102 distantly. Twenty-four patients received androgen-deprivation therapy (ADT) and were excluded for outcomes analysis. In total, 99 of 146 received SRT with a median follow-up after radiation treatment of 10.5 mo (interquartile range, 6-14 mo). Overall treatment response after SRT was 72% ( n = 71/99). Forty-five percent ( n = 27/60) of patients with a negative PSMA underwent SRT whereas 55% (33/60) did not. In men with a negative PSMA who received SRT, 85% ( n = 23/27) demonstrated a treatment response, compared with a further PSA increase in 65% (22/34) in those not treated. In 36 of 99 patients with disease confined to the prostate fossa on PSMA, 81% ( n = 29/36) responded to SRT. In total, 26 of 99 men had nodal disease on PSMA, of whom 61% ( n = 16/26) had treatment response after SRT. On multivariate logistic regression analysis, PSMA and serum PSA significantly correlated with treatment response, whereas pT stage, Gleason score, and surgical margin status did not. Conclusion: PSMA PET is independently predictive of treatment response to SRT and stratifies men into a high treatment response to SRT (negative or fossa-confined PSMA) versus men with poor response to SRT (nodes or distant-disease PSMA). In particular, a negative PSMA PET result predicts a high response to salvage fossa radiotherapy. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Psychotherapy and phosphodiesterase-5 inhibitor in early rehabilitation after radical prostatectomy: a prospective randomised controlled trial.

PubMed

Naccarato, A M E P; Reis, L O; Ferreira, U; Denardi, F

2016-12-01

The aim of this study was to evaluate the impact of group psychotherapy and the use of a phosphodiesterase-5 inhibitor (PDE-5i) in the early rehabilitation stage of patients with prostate cancer undergoing radical prostatectomy (RP). Fifty-six patients undergoing RP for prostate cancer were randomised into four groups, and 53 completed the protocol: Group 1 - control (n = 11), Group 2 - group psychotherapy (n = 16), Group 3 - lodenafil 80 mg/one tablet per week (n = 12) and Group 4 - group psychotherapy + lodenafil 80 mg/one tablet per week (n = 14). The groups were individually evaluated for erectile function (IIEF-5) and quality of life - QoL (SF-36) weekly, with two meetings held a week apart before the RP and 12 weekly meetings after surgery. The ages ranged from 39 to 76 years, average 61.84. There were no significant medication side effects. Only Group 4 showed improvement in intimacy with a partner and satisfaction with their sex life (P = 0.045 and P = 0.013 respectively), and with no significant worsening of the IIEF-5 (P = 0.250) reported. All groups showed worsening in the final result of the role limitations caused by physical problems (P = 0.009) and role limitations caused by emotional problems (P = 0.002) of the SF-36, but Group 4 had a significantly higher score for the role limitations caused by physical problems (P = 0.009) than the other groups. In conclusion, precocious integral treatment involving group psychotherapy and PDE-5i before and after RP led to less deterioration of erectile function and other domains related to physical aspects (SF-36), with improvement in intimacy with their partner and satisfaction in their sex life, being superior to single treatments. © 2016 Blackwell Verlag GmbH.

Urinary and sexual outcomes in long-term (5+ years) prostate cancer disease free survivors after radical prostatectomy

PubMed Central

2009-01-01

Background After long term disease free follow up (FUp) patients reconsider quality of life (QOL) outcomes. Aim of this study is assess QoL in prostate cancer patients who are disease-free at least 5 years after radical prostatectomy (RP). Methods 367 patients treated with RP for clinically localized pCa, without biochemical failure (PSA ≤ 0.2 ng/mL) at the follow up ≥ 5 years were recruited. Urinary (UF) and Sexual Function (SF), Urinary (UB) and Sexual Bother (SB) were assessed by using UCLA-PCI questionnaire. UF, UB, SF and SB were analyzed according to: treatment timing (age at time of RP, FUp duration, age at time of FUp), tumor characteristics (preoperative PSA, TNM stage, pathological Gleason score), nerve sparing (NS) procedure, and hormonal treatment (HT). We calculated the differences between 93 NS-RP without HT (group A) and 274 non-NS-RP or NS-RP with HT (group B). We evaluated the correlation between function and bother in group A according to follow-up duration. Results Time since prostatectomy had a negative effect on SF and a positive effect SB (both p < 0.001). Elderly men at follow up experienced worse UF and SF (p = 0.02 and p < 0.001) and better SB (p < 0.001). Higher stage PCa negatively affected UB, SF, and SB (all: p ≤ 0.05). NS was associated with better UB, SF and SB (all: p ≤ 0.05); conversely, HT was associated with worse UF, SF and SB (all: p ≤ 0.05). More than 8 years after prostatectomy SF of group A and B were similar. Group A subjects (NS-RP without HT) demonstrated worsening SF, but improved SB, suggesting dissociation of the correlation between SF and SB over time. Conclusion Older age at follow up and higher pathological stage were associated with worse QoL outcomes after RP. The direct correlation between UF and age at follow up, with no correlation between UF and age at time of RP suggests that other issues (i.e: vascular or neurogenic disorders), subsequent to RP, are determinant on urinary incontinence. After NS-RP without HT the correlation between SF and SB is maintained for 7 years, after which function and bother appear to have divergent trajectories. PMID:19912640

A cone beam CT-Based Study for Clinical Target Definition Using Pelvic Anatomy During Postprostatectomy Radiotherapy.

PubMed

Showalter, Timothy N; Nawaz, A Omer; Xiao, Ying; Galvin, James M; Valicenti, Richard K

2008-02-01

There are no accepted guidelines for target volume definition for online image-guided radiation therapy (IGRT) after radical prostatectomy (RP). This study used cone beam CT (CBCT) imaging to generate information for use in post-RP IGRT. The pelvic anatomy of 10 prostate cancer patients undergoing post-RP radiation therapy (RT) to 68.4 Gy was studied using CBCT images obtained immediately before treatment. Contoured bladder and rectal volumes on CBCT images were compared with planning CT (CT(ref)) volumes from seminal vesicle stump (SVS) to bladder-urethral junction. This region was chosen to approximate the prostatic fossa (PF) during a course of post-RP RT. Anterior and posterior planning target volume margins were calculated using ICRU report 71 guidelines, accounting for systematic and random error based on bladder and rectal motion, respectively. A total of 176 CBCT study sets obtained 2 to 5 times weekly were analyzed. The rectal and bladder borders were reliably identified in 166 of 176 (94%) of CBCT images. Relative to CT(ref), mean posterior bladder wall position was anterior by 0.1 to 1.5 mm, and mean anterior rectum wall position was posterior by 1.6 to 2.7 mm. Calculated anterior margin as derived from bladder motion ranged from 5.9 to 7.1 mm. Calculated posterior margin as derived from rectal motion ranged from 8.6 to 10.2 mm. Normal tissue anatomy was definable by CBCT imaging throughout the course of post-RP RT, and the interfraction anteroposterior motion of the bladder and rectum was studied. This information should be considered in devising post-RP RT techniques using image guidance.

Outcomes of breast cancer patients with triple negative receptor status treated with accelerated partial breast irradiation.

PubMed

Wilkinson, J Ben; Reid, Robert E; Shaitelman, Simona F; Chen, Peter Y; Mitchell, Christine K; Wallace, Michelle F; Marvin, Kimberly S; Grills, Inga S; Margolis, Jeffrey M; Vicini, Frank A

2011-11-01

Triple negative receptor status (TNRS) of patients undergoing breast-conserving therapy treated with whole-breast irradiation has been associated with increased distant metastasis and decreased disease-free and overall survival. This paper reports the outcomes of TNRS patients treated with accelerated partial breast irradiation (APBI). We studied 455 patients who received APBI at our institution, using interstitial, intracavitary, and three-dimensional conformal radiation therapy. TNRS was assigned if a patient tested negative for all three (ER [estrogen receptor], PR [progesterone receptor], and HER2/neu) receptors. Of 202 patients with all receptor results available, 20 patients were designated TNRS, and 182 patients had at least one receptor positive (RP). We analyzed ipsilateral breast tumor recurrence (IBTR), regional nodal failure (RNF), distant metastasis (DM), and overall survival (OS). Mean follow-up was 4.1 years for the TNRS group and 5.1 years for the RP cohort (p = 0.11). TNRS patients had a higher histologic grade (59% TNRS vs. 13% RP; p < 0.001). Mean tumor size, stage N1 disease, and margin status were similar. Based on a 5-year actuarial analysis, the TNRS cohort experienced no IBTR, RNF, or DM, with an OS of 100% versus rates of 1.4% IBTR, 1.5% RNF, and 2.8% DM in the RP cohort (p > 0.52). OS for the RP cohort was 93% at 5 years (p > 0.28). In our patient population, TNRS conferred a clinical outcome similar to that of patients with RP disease treated with APBI. Further investigation with larger patient populations and longer follow-up periods is warranted to confirm that APBI is a safe and effective treatment for patients with localized TNRS breast cancer. Copyright © 2011 Elsevier Inc. All rights reserved.

Biosimilars in Inflammatory Bowel Disease: Facts and Fears of Extrapolation.

PubMed

Ben-Horin, Shomron; Vande Casteele, Niels; Schreiber, Stefan; Lakatos, Peter Laszlo

2016-12-01

Biologic drugs such as infliximab and other anti-tumor necrosis factor monoclonal antibodies have transformed the treatment of immune-mediated inflammatory conditions such as Crohn's disease and ulcerative colitis (collectively known as inflammatory bowel disease [IBD]). However, the complex manufacturing processes involved in producing these drugs mean their use in clinical practice is expensive. Recent or impending expiration of patents for several biologics has led to development of biosimilar versions of these drugs, with the aim of providing substantial cost savings and increased accessibility to treatment. Biosimilars undergo an expedited regulatory process. This involves proving structural, functional, and biological biosimilarity to the reference product (RP). It is also expected that clinical equivalency/comparability will be demonstrated in a clinical trial in one (or more) sensitive population. Once these requirements are fulfilled, extrapolation of biosimilar approval to other indications for which the RP is approved is permitted without the need for further clinical trials, as long as this is scientifically justifiable. However, such justification requires that the mechanism(s) of action of the RP in question should be similar across indications and also comparable between the RP and the biosimilar in the clinically tested population(s). Likewise, the pharmacokinetics, immunogenicity, and safety of the RP should be similar across indications and comparable between the RP and biosimilar in the clinically tested population(s). To date, most anti-tumor necrosis factor biosimilars have been tested in trials recruiting patients with rheumatoid arthritis. Concerns have been raised regarding extrapolation of clinical data obtained in rheumatologic populations to IBD indications. In this review, we discuss the issues surrounding indication extrapolation, with a focus on extrapolation to IBD. Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.

Outcomes of Breast Cancer Patients With Triple Negative Receptor Status Treated With Accelerated Partial Breast Irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wilkinson, J. Ben; Reid, Robert E.; Shaitelman, Simona F.

2011-11-01

Purpose: Triple negative receptor status (TNRS) of patients undergoing breast-conserving therapy treated with whole-breast irradiation has been associated with increased distant metastasis and decreased disease-free and overall survival. This paper reports the outcomes of TNRS patients treated with accelerated partial breast irradiation (APBI). Methods and Materials: We studied 455 patients who received APBI at our institution, using interstitial, intracavitary, and three-dimensional conformal radiation therapy. TNRS was assigned if a patient tested negative for all three (ER [estrogen receptor], PR [progesterone receptor], and HER2/neu) receptors. Of 202 patients with all receptor results available, 20 patients were designated TNRS, and 182 patientsmore » had at least one receptor positive (RP). We analyzed ipsilateral breast tumor recurrence (IBTR), regional nodal failure (RNF), distant metastasis (DM), and overall survival (OS). Results: Mean follow-up was 4.1 years for the TNRS group and 5.1 years for the RP cohort (p = 0.11). TNRS patients had a higher histologic grade (59% TNRS vs. 13% RP; p < 0.001). Mean tumor size, stage N1 disease, and margin status were similar. Based on a 5-year actuarial analysis, the TNRS cohort experienced no IBTR, RNF, or DM, with an OS of 100% versus rates of 1.4% IBTR, 1.5% RNF, and 2.8% DM in the RP cohort (p > 0.52). OS for the RP cohort was 93% at 5 years (p > 0.28). Conclusions: In our patient population, TNRS conferred a clinical outcome similar to that of patients with RP disease treated with APBI. Further investigation with larger patient populations and longer follow-up periods is warranted to confirm that APBI is a safe and effective treatment for patients with localized TNRS breast cancer.« less

Pattern of retinal morphological and functional decay in a light-inducible, rhodopsin mutant mouse.

PubMed

Gargini, Claudia; Novelli, Elena; Piano, Ilaria; Biagioni, Martina; Strettoi, Enrica

2017-07-18

Hallmarks of Retinitis Pigmentosa (RP), a family of genetic diseases, are a typical rod-cone-degeneration with initial night blindness and loss of peripheral vision, followed by decreased daylight sight and progressive visual acuity loss up to legal blindness. Great heterogeneity in nature and function of mutated genes, variety of mutations for each of them, variability in phenotypic appearance and transmission modality contribute to make RP a still incurable disease. Translational research relies on appropriate animal models mimicking the genetic and phenotypic diversity of the human pathology. Here, we provide a systematic, morphological and functional analysis of Rho Tvrm4 /Rho + rhodopsin mutant mice, originally described in 2010 and portraying several features of common forms of autosomal dominant RP caused by gain-of-function mutations. These mice undergo photoreceptor degeneration only when exposed briefly to strong, white light and allow controlled timing of induction of rod and cone death, which therefore can be elicited in adult animals, as observed in human RP. The option to control severity and retinal extent of the phenotype by regulating intensity and duration of the inducing light opens possibilities to exploit this model for multiple experimental purposes. Altogether, the unique features of this mutant make it an excellent resource for retinal degeneration research.

Application of 3D printing rapid prototyping-assisted percutaneous fixation in the treatment of intertrochanteric fracture.

PubMed

Zheng, Sheng-Nai; Yao, Qing-Qiang; Mao, Feng-Yong; Zheng, Peng-Fei; Tian, Shu-Chang; Li, Jia-Yi; Yu, Yi-Fan; Liu, Shuai; Zhou, Jin; Hu, Jun; Xu, Yan; Tang, Kai; Lou, Yue; Wang, Li-Ming

2017-10-01

The aim of the present study was to investigate the application of 3D printing (3DP) rapid prototyping (RP) technique-assisted percutaneous fixation in the treatment of femoral intertrochanteric fracture (ITF) using proximal femoral nail anti-rotation (PFNA). A total of 39 patients with unstable ITF were included in the current study. Patients were divided into two groups: 19 patients were examined using computed tomography scanning and underwent PFNA with SDP-RP whereas the other 20 patients underwent conventional PFNA treatment. Anatomical data were converted from the Digital Imaging and Communications in Medicine format to the stereolithography format using M3D software. The 3DP-RP model was established using the fused deposition modeling technique and the length and diameter of the main screw blade was measured during the simulation. The postoperative femoral neck-shaft angle (NSA), surgery duration, intraoperative and postoperative blood loss, and the duration of hospital stay were recorded and compared with the corresponding values in conventional surgery. No significant differences were observed in mean PFNA size between the implants used and the preoperative planning estimates. It was demonstrated that the 3DP-RP assisted procedure resulted in more effective reduction of the NSA. Furthermore, patients undergoing 3DP-RP experienced a significant reduction in duration of surgery (P<0.01), as well as reductions in intraoperative (P=0.02) and postoperative (P=0.03) blood loss, compared with conventional surgery. At 6 months post-surgery, no cases of hip varus/vague deformities or implant failure were observed in patients that underwent either the 3DP-RP-assisted or conventional procedure. The results of the present study suggest that the 3DP-RP technique is able to create an accurate model of the ITF, which facilitates surgical planning and fracture reduction, thus improving the efficiency of PFNA surgery for ITFs.

Three-dimensional external beam radiotherapy for prostate cancer increases the risk of hip fracture.

PubMed

Elliott, Sean P; Jarosek, Stephanie L; Alanee, Shaheen R; Konety, Badrinath R; Dusenbery, Kathryn E; Virnig, Beth A

2011-10-01

Hip fracture is associated with high morbidity and mortality. Pelvic external beam radiotherapy (EBRT) is known to increase the risk of hip fractures in women, but the effect in men is unknown. From the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, 45,662 men who were aged ≥66 years and diagnosed with prostate cancer in 1992-2004 were identified. By using Kaplan-Meier methods and Cox proportional hazards models, the primary outcome of hip fracture risk was compared among men who received radical prostatectomy (RP), EBRT, EBRT plus androgen suppression therapy (AST), or AST alone. Age, osteoporosis, race, and other comorbidities were statistically controlled. A secondary outcome was distal forearm fracture as an indicator of the risk of fall-related fracture outside the radiation field. After covariates were statistically controlled, the findings showed that EBRT increased the risk of hip fractures by 76% (hazards ratio [HR], 1.76; 95% confidence interval [CI], 1.38-2.40) without increasing the risk of distal forearm fractures (HR, 0.80; 95% CI, 0.56-1.14). Combination therapy with EBRT plus AST increased the risk of hip fracture 145% relative to RP alone (HR, 2.45; 95% CI, 1.88-3.19) and by 40% relative to EBRT alone (HR, 1.40; 95% CI, 1.17-1.68). EBRT plus AST increased the risk of distal forearm fracture by 43% relative to RP alone (HR, 1.43; 95% CI, 0.97-2.10). The number needed to treat to result in 1 hip fracture during a 10-year period was 51 patients (95% CI, 31-103). In men with prostate cancer, pelvic 3-D conformal EBRT was associated with a 76% increased risk of hip fracture. This risk was slightly increased further by the addition of short-course AST to EBRT. This risk associated with EBRT must be site-specific as there was no increase in the risk of fall-related fractures in bones that were outside the radiation field. Copyright © 2011 American Cancer Society.

Transrectal ultrasonography-guided biopsy does not reliably identify dominant cancer location in men with low-risk prostate cancer.

PubMed

Washington, Samuel L; Bonham, Michael; Whitson, Jared M; Cowan, Janet E; Carroll, Peter R

2012-07-01

Study Type - Diagnostic (exploratory cohort) Level of Evidence 2b What's known on the subject? and What does the study add? The widespread use of serum PSA testing followed by TRUS-guided biopsy have resulted in profound prostate cancer stage migration with many patients presenting with focal rather than multifocal disease. There is increasing interest in the use of focal rather than whole-gland treatment. However, current biopsy schemes may still miss cancer or, even when cancer is identified, its extent or grade might not be accurately characterized. In order for focal therapy to be effective, the area of highest tumour volume and/or grade needs to localized accurately. The aim of this study was to assess how well biopsy, as currently performed, locates the focus of highest prostate cancer volume and/or grade. To evaluate the ability of transrectal ultrasonography (TRUS)-guided extended core biopsy to identify the dominant tumour accurately in men with early stage prostate cancer. Patients with early stage, low-risk prostate cancer who subsequently underwent radical prostatectomy (RP) and had complete surgical specimens were identified. Re-review was performed by a single uropathologist using ImageJ software to identify tumour location, dominant grade (DG) and dominant volume (DV). Pathology findings were then compared with biopsy results. A total of 51 men with early stage, low-risk prostate cancer, who had undergone RP, had complete specimens for review and a median of 15 biopsy cores taken for diagnosis and grading. Sixteen men had a single diagnostic biopsy, 21 had one repeat biopsy, and 14 had two or more repeat biopsies. Compared with surgical findings, biopsy correctly identified the sextant with the largest tumour volume in 55% (95% CI 0.5-0.6) of specimens and the highest grade in 37% (95 CI 0.3-0.5). No demographic or clinical factors were significantly associated with identification of DG. Interval between last biopsy and RP, total tissue length taken and total length of tumour identified were significantly associated with correct identification of DV. Our findings show that TRUS-guided biopsy detects and localizes DV better than it does DG. Even with an extended scheme, TRUS-guided biopsy does not reliably identify dominant cancer location in this low-risk cohort of men with early stage prostate cancer. TRUS-guided biopsy may perform better in similar men with low stage, but higher volume disease. © 2011 BJU INTERNATIONAL.

Persistent Atrial Fibrillation Ablation in Females: Insight from the MAGIC-AF Trial.

PubMed

Singh, Sheldon M; D'Avila, Andre; Aryana, Arash; Kim, Young-Hoon; Mangrum, J Michael; Michaud, Gregory F; Dukkipati, Srinivas R; Heist, E Kevin; Barrett, Conor D; Thorpe, Kevin E; Reddy, Vivek Y

2016-07-27

Atrial fibrillation (AF) ablation is less frequently performed in women when compared to men. There are conflicting data on the safety and efficacy of AF ablation in women. The objective of this study was to compare the clinical characteristics and outcomes in a contemporary cohort of men and women undergoing persistent AF ablation procedures. A total of 182 men and 53 women undergoing a first-ever persistent AF catheter ablation procedure in The Modified Ablation Guided by Ibutilide Use in Chronic Atrial Fibrillation (MAGIC-AF) trial were evaluated. Clinical and procedural characteristics were compared between each gender. The primary efficacy endpoint was the 1-year single procedure freedom from atrial arrhythmia off anti-arrhythmic drugs. Women undergoing catheter ablation procedures were older than men (P < 0.001). The duration of AF and associated co-morbidities were similar between both genders. Single procedure drug-free atrial arrhythmia recurrence occurred in 53% of the cohort with no difference based on gender (men = 54%, women = 53%; P = 1.0). Procedural (P = 0.04), fluoroscopic (P = 0.02), and ablation times (P = 0.003) were shorter in women compared to men. Periprocedural complications and postablation improvement in quality of life were similar between men and women. Women undergoing a first-ever persistent AF ablation procedure were older but had similar clinical outcomes and complications when compared with men. © 2016 Wiley Periodicals, Inc.

Do Angiotensin-Converting Enzyme Inhibitors Reduce the Risk of Symptomatic Radiation Pneumonitis in Patients With Non-Small Cell Lung Cancer After Definitive Radiation Therapy? Analysis of a Single-Institution Database

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Hongmei; Liao, Zhongxing, E-mail: zliao@mdanderson.org; Zhuang, Yan

2013-12-01

Purpose: Preclinical studies have suggested that angiotensin-converting enzyme inhibitors (ACEIs) can mitigate radiation-induced lung injury. We sought here to investigate possible associations between ACEI use and the risk of symptomatic radiation pneumonitis (RP) among patients undergoing radiation therapy (RT) for non–small cell lung cancer (NSCLC). Methods and Materials: We retrospectively identified patients who received definitive radiation therapy for stages I to III NSCLC between 2004 and 2010 at a single tertiary cancer center. Patients must have received a radiation dose of at least 60 Gy for a single primary lung tumor and have had imaging and dosimetric data available formore » analysis. RP was quantified according to Common Terminology Criteria for Adverse Events, version 3.0. A Cox proportional hazard model was used to assess potential associations between ACEI use and risk of symptomatic RP. Results: Of 413 patients analyzed, 65 were using ACEIs during RT. In univariate analysis, the rate of RP grade ≥2 seemed lower in ACEI users than in nonusers (34% vs 46%), but this apparent difference was not statistically significant (P=.06). In multivariate analysis of all patients, ACEI use was not associated with the risk of symptomatic RP (hazard ratio [HR] = 0.66; P=.07) after adjustment for sex, smoking status, mean lung dose (MLD), and concurrent carboplatin and paclitaxel chemotherapy. Subgroup analysis showed that ACEI use did have a protective effect from RP grade ≥2 among patients who received a low (≤20-Gy) MLD (P<.01) or were male (P=.04). Conclusions: A trend toward reduction in symptomatic RP among patients taking ACEIs during RT for NSCLC was not statistically significant on univariate or multivariate analyses, although certain subgroups may benefit from use (ie, male patients and those receiving low MLD). The evidence at this point is insufficient to establish whether the use of ACEIs does or does not reduce the risk of RP.« less

An analysis of sexual health information on radical prostatectomy websites.

PubMed

Mulhall, John P; Rojaz-Cruz, Cesar; Müller, Alexander

2010-01-01

To define the nature of information posted on websites related to radical prostatectomy (RP), specifically its accuracy and comprehensiveness, as RP is associated with erectile dysfunction (ED). We reviewed 70 robotic RP (RARP) and 20 open RP (ORP) medical centres. Their websites were reviewed for various factors, by two separate reviewers whose reviews were not seen by each other. Websites were graded based on accuracy and comprehensiveness of information by the senior investigator. Of the academic and community-based RARP centres, 55% and 79% had specific websites (P < 0.05); 45% of RARP sites had generic information copied directly from the website of Intuitive Surgical (Sunnyvale, CA, USA; the manufacturer of the robotic system). ED was mentioned by only 54% of RARP sites and 45% of ORP sites; 17% of RARP sites were deemed accurate, compared with 30% of ORP sites (P < 0.05). Just over 1% of RARP sites were considered comprehensive, vs 10% of ORP sites (P < 0.05). A third of RARP sites had a direct link to the Intuitive Surgical website (16% academic vs 53% community, P < 0.05), compared to 10% of open sites (P < 0.05). Of most interest was that half of the RARP sites suggested that ED rates were lower for RARP than for ORP; this compared to ED rates being cited as lower for ORP on 5% of the ORP sites (P < 0.05). Despite the stature of RP as a treatment option for men with prostate cancer, and the recent increase in the use of RARP, the accuracy of information pertaining to sexual health on RP websites is poor, with many making false statements about the long-term outcomes for erectile function. This inadequacy appears to be greater on RARP than on ORP websites.

Health related quality of life patterns in patients treated with interstitial prostate brachytherapy for localized prostate cancer--data from CaPSURE.

PubMed

Downs, Tracy M; Sadetsky, Natalia; Pasta, David J; Grossfeld, Gary D; Kane, Christopher J; Mehta, Shilpa S; Carroll, Peter R; Lubeck, Deborah P

2003-11-01

We measured the impact brachytherapy monotherapy (BMT) has on general and disease specific health related quality of life (HRQOL) compared to patients treated with radical prostatectomy (RP). We studied 419 men with newly diagnosed prostate cancer who enrolled in CaPSURE (Cancer of the Prostate Strategic Urological Research Endeavor) data base whose primary treatment was brachytherapy monotherapy (92) or radical prostatectomy (327). The validated RAND 36-Item Health Survey and the UCLA Prostate Cancer Index were used to measure HRQOL before treatment and at 6-month intervals during the first 2 years after treatment. Patients treated with BMT or RP did not differ greatly in general HRQOL after treatment. Both treatment groups showed early functional impairment in most general domains with scores returning to or approaching baseline in most domains 18 to 24 months after treatment. Patients treated with BMT had significantly higher urinary function scores at 0 to 6 months after treatment (84.5, SD 18.7) than patients treated with RP (63.3, SD 26.6). Urinary bother scores at 0 to 6 months after treatment were not significantly different between patients treated with BMT (67.7, SD 31.2) and those treated with RP (67.4, SD 29.1). Both treatment groups had decreases in sexual function that did not return to pretreatment levels. Overall BMT and RP are well tolerated procedures that cause mild changes in general HRQOL. Disease specific HRQOL patterns are different in patients treated with BMT or RP. Baseline and serial HRQOL measurements after treatment can provide valuable information regarding expected quality of life outcome after treatment for localized prostate cancer.

Patient-reported outcome (PRO) questionnaires for men who have radical surgery for prostate cancer: a conceptual review of existing instruments.

PubMed

Protopapa, Evangelia; van der Meulen, Jan; Moore, Caroline M; Smith, Sarah C

2017-10-01

To critically review conceptual frameworks for available patient-reported outcome (PRO) questionnaires in men having radical prostatectomy (RP), psychometrically evaluate each questionnaire, and identify whether each is appropriate for use at the level of the individual patient. We searched PubMed, the Reports and Publications database of the University of Oxford Patient-Reported Outcomes Measurement Group and the website of the International Consortium for Health Outcomes Measurement (ICHOM) for psychometric reviews of prostate cancer-specific PRO questionnaires. From these we identified relevant questionnaires and critically appraised the conceptual content, guided by the Wilson and Cleary framework and psychometric properties, using well established criteria. The searches found four reviews and one recommendation paper. We identified seven prostate cancer-specific PROs: the Expanded Prostate Cancer Index Composite-26 (EPIC-26), Expanded Prostate Cancer Index Composite-50 (EPIC-50), University of California-Los Angeles Prostate Cancer Index (UCLA-PCI), Functional Assessment of Cancer Therapy - Prostate Cancer Subscale (FACT-P PCS), European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - prostate specific 25-item (EORTC QLQ-PR25), Prostate Cancer - Quality of Life (PC-QoL), and Symptom Tracking and Reporting (STAR). Six out of seven measures purported to measure health-related quality of life (HRQL), but items focused strongly on urinary and sexual symptoms/functioning. The remaining questionnaire (STAR) claimed to assess functional recovery after RP. The psychometric evidence for these questionnaires was incomplete and variable in quality; none had evidence that they were appropriate for use with individual patients. Several questionnaires provide the basis of measures of urinary and/or sexual symptoms/functioning. Further work should explore other aspects of HRQL that are important for men having RP. Further psychometric work is also needed to determine whether they can be used at the individual level. © 2017 The Authors BJU International © 2017 BJU International Published by John Wiley & Sons Ltd.

Near-Infrared Monitoring of Volatiles in Frozen Lunar Simulants While Drilling

NASA Technical Reports Server (NTRS)

Roush, Ted L.; Colaprete, Anthony; Elphic, Richard C.; Forgione, Joshua; White, Bruce; McMurray, Robert; Cook, Amanda M.; Bielawski, Richard; Fritzler, Erin L.; Thompson, Sarah J.;

The influence of physician recommendation on prostate-specific antigen screening.

PubMed

Pucheril, Daniel; Dalela, Deepansh; Sammon, Jesse; Sood, Akshay; Sun, Maxine; Trinh, Quoc-Dien; Menon, Mani; Abdollah, Firas

2015-10-01

Prostate-specific antigen (PSA) screening is controversial, and little is known regarding a physician's effect on a patient's decision to undergo screening. This study's objective was to evaluate the effect of a patient's understanding of the risks and benefits of screening compared to the final recommendation of the provider on the patient's decision to undergo PSA screening. Using the 2012 Behavioral Risk Factor Surveillance System, men older than 55 years who did not have a history of prostate cancer/prostate "problem" and who reported a PSA test within the preceding year were considered to have undergone screening. The percentages of men informed and not informed of the risks and benefits of screening and the percentage men receiving recommendations for PSA screening from their provider were reported. Multivariable complex-sample logistic regression calculated the odds of undergoing screening. In all, 75% of men were informed of screening benefits; however, 32% were informed of screening risks. After being informed of both, 56% of men opted for PSA screening if the provider recommended it, compared with only 21% when not recommended. Men receiving a recommendation to undergo PSA testing had higher odds of undergoing screening (odds ratio [OR] = 4.98, 95% CI: 4.53-5.48) compared with those who were only informed about screening benefits (OR = 2.40, 95% CI: 2.18-2.65) or risks (OR = 0.92, 95% CI: 0.86-0.98). Significant limitations include recall and nonresponse bias. Patients' decision to undergo or forgo PSA screening is heavily influenced by the recommendation of their physician; it is imperative that physicians are cognizant of their biases and facilitate a shared decision-making process. Copyright © 2015 Elsevier Inc. All rights reserved.

Brachytherapy versus prostatectomy in localized prostate cancer: Results of a French multicenter prospective medico-economic study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Buron, Catherine; Le Vu, Beatrice; Cosset, Jean-Marc

2007-03-01

Purpose: To prospectively compare health-related quality of life (HRQOL), patient-reported treatment-related symptoms, and costs of iodine-125 permanent implant interstitial brachytherapy (IB) with those of radical prostatectomy (RP) during the first 2 years after these treatments for localized prostate cancer. Methods and Materials: A total of 435 men with localized low-risk prostate cancer, from 11 French hospitals, treated with IB (308) or RP (127), were offered to complete the European Organization for Research and Treatment of Cancer core Quality of Life Questionnaire QLQ-C30 version 3 (EORTC QLQ-C30) and the prostate cancer specific EORTC QLQ-PR25 module before and at the end ofmore » treatment, 2, 6, 12, 18, and 24 months after treatment. Repeated measures analysis of variance and analysis of covariance were conducted on HRQOL changes. Comparative cost analysis covered initial treatment, hospital follow-up, outpatient and production loss costs. Results: Just after treatment, the decrease of global HRQOL was less pronounced in the IB than in the RP group, with a 13.5 points difference (p < 0.0001). A difference slightly in favor of RP was observed 6 months after treatment (-7.5 points, p = 0.0164) and was maintained at 24 months (-8.2 points, p = 0.0379). Impotence and urinary incontinence were more pronounced after RP, whereas urinary frequency, urgency, and urination pain were more frequent after IB. Mean societal costs did not differ between IB ( Euro 8,019 at T24) and RP ( Euro 8,715 at T24, p = 0.0843) regardless of the period. Conclusions: This study suggests a similar cost profile in France for IB and RP but with different HRQOL and side effect profiles. Those findings may be used to tailor localized prostate cancer treatments to suit individual patients' needs.« less

Personality, treatment choice and satisfaction in patients with localized prostate cancer.

PubMed

Block, Craig A; Erickson, Brad; Carney-Doebbling, Caroline; Gordon, Susanna; Fallon, Bernard; Konety, Badrinath R

2007-11-01

Radical prostatectomy (RP), external beam radiation (XRT) and brachytherapy (BTX) are the most commonly used treatments for localized prostate cancer. We studied whether patient personality influences treatment choice and overall treatment satisfaction. From 1998 to 2002, 219 consecutive patients treated with RP (n = 74), XRT (n = 73), or BTX (n = 72) at our institution who remained free of biochemical recurrence were sent the Big Five Inventory (BFI) and a satisfaction/treatment participation questionnaire. We compared personality, satisfaction and participation scores between the three groups. Correlation between personality and satisfaction was determined. Multivariate regression was used to determine association between personality and satisfaction/participation after controlling for patient- and disease-related factors. Higher mean satisfaction and participation scores were observed within the RP and XRT groups, respectively (P = NS). No significant differences in personality were observed between groups. XRT patients tended to have higher extroversion, openness and agreeability scores, while RP patients tended to be more neurotic and conscientious (all P = NS). After controlling for other factors, a negative correlation was found between openness scores and satisfaction and a positive correlation between conscientiousness scores and satisfaction. Specific personality traits were associated with interest in participation in care for both RP and BTX patients but not for XRT patients. There are mild variations in personality as measured by the BFI between patients undergoing treatment for localized prostate cancer. Certain BFI-measured personality traits may be associated with levels of satisfaction following therapy. Disease concerns and provider recommendations may override the influence of personality in the decision-making process.

A Distinct Phenotype of Eyes Shut Homolog (EYS)-Retinitis Pigmentosa Is Associated With Variants Near the C-Terminus.

PubMed

Sengillo, Jesse D; Lee, Winston; Nagasaki, Takayuki; Schuerch, Kaspar; Yannuzzi, Lawrence A; Freund, K Bailey; Sparrow, Janet R; Allikmets, Rando; Tsang, Stephen H

2018-06-01

Mutations in the eyes shut homolog (EYS) gene are a frequent cause of autosomal recessive retinitis pigmentosa (arRP). This study used multimodal retinal imaging to elucidate genotype-phenotype correlations in EYS-related RP (EYS-RP). Cross-sectional study. Multimodal retinal imaging and electrophysiologic testing were assessed for 16 patients with genetic confirmation of EYS-RP. A total of 27 unique EYS variants were identified in 16 patients. Seven patients presented with an unusual crescent-shaped hyperautofluorescent (hyperAF) ring on fundus autofluorescence (FAF) imaging encompassing a large nasal-superior area of the posterior pole. Three patients had a typical circular or oval perifoveal hyperAF ring and 6 patients had no hyperAF ring. Spectral-domain (SD) and en face optical coherence tomography (OCT) showed preserved ellipsoid zone and retinal thickness spatially corresponding to areas within the hyperAF rings. Eleven patients presented with a rod-cone dystrophy on full-field electroretinogram (ffERG), 1 patient presented with cone-rod dystrophy, and 4 patients did not undergo ffERG testing. A significant spatial association was found between EYS variant position and FAF phenotype, with variants occurring at a nucleotide position greater than GRCh37 6:65300137 (c.5617C) being more associated with patients exhibiting hyperAF rings at presentation. EYS-RP is a heterogeneous manifestation. Variants occurring in positions closer to the C-terminus of EYS are more common in patients presenting with hyperAF rings on FAF imaging. Copyright © 2018 Elsevier Inc. All rights reserved.

The "Kiel Concept" of Long-Term Administration of Daily Low-Dose Sildenafil Initiated in the Immediate Post-Prostatectomy Period: Evaluation and Comparison With the International Literature on Penile Rehabilitation.

PubMed

Osmonov, Daniar K; Jünemann, Klaus P; Bannowsky, Andreas

2017-07-01

Radical prostatectomy (RP) is the most common definitive invasive treatment option for localized prostate cancer. Although the different surgical procedures-open RP, laparoscopic RP, and robot-assisted laparoscopic RP-do not differ significantly for the results of postoperative erectile dysfunction (ED) and continence, the fear of losing erectile function (EF) is often an important factor for preoperatively sexually active men when deciding for or against a procedure. To review the available literature on rehabilitation of EF after RP and to evaluate the value of the "Kiel concept" against different strategies of phosphodiesterase type 5 inhibitor (PDE5i) low-dose treatments. A review of the available literature up to January 2017 was undertaken using the key terms postsurgical ED, penile rehabilitation," PDE5i rehabilitation, and PDE5i daily dose treatment. As a main outcome measure we chose reviewed different concepts on the rehabilitation of EF after RP, taking into account the clinical background of the Kiel concept. The different therapeutic concepts for rehabilitation of EF after nerve-sparing RP are surprising. The most frequently applied method is application of different PDE5is. Despite different studies on efficacy, the issue of an optimal concept remains unresolved. The reason for this, among others, can be found in the difficulty of comparing different studies, which can vary with respect to the degree of nerve sparing, postoperative preservation of nocturnal erections, concomitant morbidity, and the number and experience of surgeons. In 86% of patients, the Kiel concept has been shown to support rehabilitation of EF after nerve-sparing RP with some form of therapeutic method. The Kiel concept is one therapeutic option among other comparable therapeutic options. Osmonov DK, Jünemann KP, Bannowsky A. The "Kiel Concept" of Long-Term Administration of Daily Low-Dose Sildenafil Initiated in the Immediate Post-Prostatectomy Period: Evaluation and Comparison With the International Literature on Penile Rehabilitation. Sex Med Rev 2017;5:387-392. Copyright © 2017 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Diagnosis of varicoceles in men undergoing vasectomy may lead to earlier detection of hypogonadism.

PubMed

Liu, Joceline S; Jones, Madeline; Casey, Jessica T; Fuchs, Amanda B; Cashy, John; Lin, William W

2014-06-01

To determine the temporal relationship between vasectomy, varicocele, and hypogonadism diagnosis. Many young men undergo their first thorough genitourinary examination in their adult lives at the time of vasectomy consultation, providing a unique opportunity for diagnosis of asymptomatic varicoceles. Varicoceles have recently been implicated as a possible reversible contributor to hypogonadism. Hypogonadism may be associated with significant adverse effect, including decreased libido, impaired cognitive function, and increased cardiovascular events. Early diagnosis and treatment of hypogonadism may prevent these adverse sequelae. Data were collected from the Truven Health Analytics MarketScan database, a large outpatient claims database. We reviewed records between 2003 and 2010 for male patients between the ages of 25 and 50 years with International Classification of Diseases, Ninth Revision codes for hypogonadism, vasectomy, and varicocele, and queried dates of first claim. A total of 15,679 men undergoing vasectomies were matched with 156,790 men with nonvasectomy claims in the same year. Vasectomy patients were diagnosed with varicocele at an earlier age (40.9 vs 42.5 years; P=.009). We identified 224,817 men between the ages of 25 and 50 years with a claim of hypogonadism, of which 5883 (2.6%) also had a claim of varicocele. Men with hypogonadism alone were older at presentation compared with men with an accompanying varicocele (41.3 [standard deviation±6.5] vs 34.9 [standard deviation±6.1]; P<.001). Men undergoing vasectomies are diagnosed with varicoceles at a younger age than age-matched controls. Men with varicoceles present with hypogonadism earlier than men without varicoceles. Earlier diagnosis of varicocele at the time of vasectomy allows for earlier detection of hypogonadism. Copyright © 2014 Elsevier Inc. All rights reserved.

Racial Disparities Differ for African Americans and Hispanics in the Diagnosis and Treatment of Penile Cancer.

PubMed

Slopnick, Emily A; Kim, Simon P; Kiechle, Jonathan E; Gonzalez, Christopher M; Zhu, Hui; Abouassaly, Robert

2016-10-01

To evaluate racial disparities in the diagnosis and treatment of penile cancer among a contemporary series of men from a large diverse national data base. Using the 1998-2012 National Cancer Data Base, all men with squamous cell carcinoma (SCC) were stratified by race and ethnicity. Demographic and disease characteristics were compared between groups. Likelihood of undergoing surgery and type of surgery were compared among patients with nonmetastatic disease. Factors influencing disease stage and treatment type were analyzed with univariate and multivariable logistic regressions. Overall survival was examined with Kaplan-Meier and adjusted Cox proportional hazard models. We identified 12,090 men with penile SCC with median age 66 years (range 18-90). Distribution of patients is as follows: 76.8% Caucasian, 10.2% African American (AA), 8.7% Hispanic. On multivariable analysis, Hispanic men are more likely to present with high-risk (≥T1G3) penile SCC (odds ratio [OR] 1.6; confidence interval [CI] 1.20-2.00; P = .001) and tend to undergo penectomy rather than penile-sparing surgery (OR 1.46; CI 1.15-1.85; P = .002) for equal stage SCC compared to Caucasian patients. Whereas AA men are less likely to undergo surgery of any type (OR 0.67; CI 0.51-0.87; P = .003) and have higher mortality rates than Caucasian patients (hazard ratio 1.25; CI 1.10-1.42; P < .001). Hispanic men with penile SCC are more likely to present with high-risk disease and undergo more aggressive treatment than Caucasian patients but have comparable survival. AA men are less likely to undergo surgical management of their disease and have higher mortality rates. Copyright © 2016 Elsevier Inc. All rights reserved.

The Impact of Magnetic Resonance Imaging on Prediction of Extraprostatic Extension and Prostatectomy Outcome in Patients with Low-, Intermediate- and High-Risk Prostate Cancer: Try to Find a Standard.

PubMed

Radtke, Jan Philipp; Hadaschik, Boris A; Wolf, Maya B; Freitag, Martin T; Schwab, Constantin; Alt, Celine; Roth, Wilfried; Duensing, Stefan; Pahernik, Sascha A; Roethke, Matthias C; Schlemmer, Heinz-Peter; Hohenfellner, Markus; Teber, Dogu

2015-12-01

To investigate the value of multiparametric magnetic resonance imaging (mpMRI) and to predict extracapsular extension (ECE), seminal vesicle (SV) infiltration, and a negative surgical margin (SM) status at radical prostatectomy (RP) for different prostate cancer (PC) risk groups. In the study, 805 men underwent 3 tesla mpMRI without endorectal coil before MRI/transrectal ultrasonography-fusion guided prostate biopsy. MRIs were analyzed using the prostate imaging reporting and data system. The cohort was classified into risk groups according to National Comprehensive Cancer Network (NCCN) criteria. Of 132 men who subsequently underwent RP, pathologic stage and SM status at RP were used as reference. Retrospectively, we investigated a European Society of Urogenital Radiology (ESUR) score for ECE and SV-infiltration. Statistical analyses included regression analyses, receiver operating characteristics (ROC), and Youden Index to assess an ESUR-score cutoff. Area under the curve in ROC curve analyses was 0.82 for ESUR-ECE score to detect pT(3a)-disease and 0.77 for ESUR-SV score for pT(3b). Using a cutoff of 4 for ECE and of 2 for SV, the positive predictive value of the ECE-score for harboring pT(3) was 50.0%, 90.0%, and 88.8% for the low-, intermediate- and high-risk cohort. Retrospectively, the use of the ESUR-ECE score preoperatively would have changed the initial surgical plan, according to NCCN criteria, in 31.1% of patients. In the high-risk subgroup, 9/35 (25.7%) patients were correctly assessed as not harboring pT(3) by imaging (ECE score <4), and would have allowed secure robot-assisted radical prostatectomy and nerve-sparing surgery (NSS). When T3 suspicion on preoperative MRI would be taken into account, intraoperative frozen-sections (IFS) might avoid positive SM in 12/18 high-risk patients and an oncologic secure NSS in 8/20 intermediate-risk patients. Prediction of pT(3) disease is crucial to plan NSS and to achieve negative SM in RP. Standardized ECE scoring on mpMRI is an independent predictor of pT(3) and may help to plan RP with oncologic security, even in high-risk patients. In addition, it allows more accurate selection of a subgroup of patients for systematic and MRI-guided IFS.

Extreme Gleason Upgrading From Biopsy to Radical Prostatectomy: A Population-based Analysis.

PubMed

Winters, Brian R; Wright, Jonathan L; Holt, Sarah K; Lin, Daniel W; Ellis, William J; Dalkin, Bruce L; Schade, George R

2016-10-01

To examine the risk factors associated with the odds of extreme Gleason upgrading at radical prostatectomy (RP) (defined as a Gleason prognostic group score increase of ≥2), we utilized a large, population-based cancer registry. The Surveillance, Epidemiologic, and End Results database was queried (2010-2011) for all patients diagnosed with Gleason 3 + 3 or 3 + 4 on prostate needle biopsy. Available clinicopathologic factors and the odds of upgrading and extreme upgrading at RP were evaluated using multivariate logistic regression. A total of 12,459 patients were identified, with a median age of 61 (interquartile range: 56-65) and a diagnostic prostate-specific antigen (PSA) of 5.5 ng/mL (interquartile range: 4.3-7.5). Upgrading was observed in 34% of men, including 44% of 7402 patients with Gleason 3 + 3 and 19% of 5057 patients with Gleason 3 + 4 disease. Age, clinical stage, diagnostic PSA, and % prostate needle biopsy cores positive were independently associated with odds of any upgrading at RP. In baseline Gleason 3 + 3 disease, extreme upgrading was observed in 6%, with increasing age, diagnostic PSA, and >50% core positivity associated with increased odds. In baseline Gleason 3 + 4 disease, extreme upgrading was observed in 4%, with diagnostic PSA and palpable disease remaining predictive. Positive surgical margins were significantly higher in patients with extreme upgrading at RP (P < .001). Gleason upgrading at RP is common in this large population-based cohort, including extreme upgrading in a clinically significant portion. Copyright © 2016 Elsevier Inc. All rights reserved.

The Effect of Salvage Radiotherapy and its Timing on the Health-related Quality of Life of Prostate Cancer Patients.

PubMed

van Stam, Marie-Anne; Aaronson, Neil K; Pos, Floris J; Bosch, J L H Ruud; Kieffer, Jacobien M; Tillier, Corinne N; van der Poel, Henk G

2016-11-01

The impact of salvage radiotherapy (SRT) and its timing on health-related quality of life (HRQoL) in prostate cancer patients is still unclear. To compare the HRQoL of patients who underwent SRT with that of patients who underwent radical prostatectomy (RP) only and to investigate whether SRT timing is associated with HRQoL. All SRT patients (n=241) and all RP-only patients (n=1005) were selected from a prospective database (2004-2015). The database contained HRQoL and prostate problem assessments up to 2 yr after last treatment. Mixed effects growth modelling adjusting for significant differences in patient characteristics and baseline HRQoL was used to analyze the association between: (1) "treatment" (RP-only vs SRT) and (2) "timing of SRT" with changes in HRQoL. SRT patients showed significantly (p<0.05) poorer recovery from urinary, bowel, and erectile function after their last treatment (clinically meaningful difference for urinary and erectile function). Patients with a longer interval (≥ 7 mo) between RP and SRT reported significantly better sexual satisfaction after SRT (p=0.02), and a better urinary function recovery (p=0.03). Limitations of the study include the nonrandom design and the variability in timing of HRQoL measurements. Up to 2 yr after treatment, SRT patients reported poorer HRQoL in several HRQoL domains compared with RP-only patients, but not in overall HRQoL. Delaying the start of SRT after RP may limit the incidence and duration of urinary and sexual problems. Nevertheless, decisions regarding SRT timing should also be based on the potential benefits in disease recurrence. Patients who receive radiotherapy after surgery may experience poorer urinary, bowel, and erectile function compared with patients who undergo surgery only. Although more research is needed, delaying radiotherapy seems to limit its impact on urinary and sexual functioning. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Theoretical description of spin-selective reactions of radical pairs diffusing in spherical 2D and 3D microreactors

NASA Astrophysics Data System (ADS)

Ivanov, Konstantin L.; Sadovsky, Vladimir M.; Lukzen, Nikita N.

2015-08-01

In this work, we treat spin-selective recombination of a geminate radical pair (RP) in a spherical "microreactor," i.e., of a RP confined in a micelle, vesicle, or liposome. We consider the microreactor model proposed earlier, in which one of the radicals is located at the center of the micelle and the other one undergoes three-dimensional diffusion inside the micelle. In addition, we suggest a two-dimensional model, in which one of the radicals is located at the "pole" of the sphere, while the other one diffuses on the spherical surface. For this model, we have obtained a general analytical expression for the RP recombination yield in terms of the free Green function of two-dimensional diffusion motion. In turn, this Green function is expressed via the Legendre functions and thus takes account of diffusion over a restricted spherical surface and its curvature. The obtained expression allows one to calculate the RP recombination efficiency at an arbitrary magnetic field strength. We performed a comparison of the two models taking the same geometric parameters (i.e., the microreactor radius and the closest approach distance of the radicals), chemical reactivity, magnetic interactions in the RP and diffusion coefficient. Significant difference between the predictions of the two models is found, which is thus originating solely from the dimensionality effect: for different dimensionality of space, the statistics of diffusional contacts of radicals becomes different altering the reaction yield. We have calculated the magnetic field dependence of the RP reaction yield and chemically induced dynamic nuclear polarization of the reaction products at different sizes of the microreactor, exchange interaction, and spin relaxation rates. Interestingly, due to the intricate interplay of diffusional contacts of reactants and spin dynamics, the dependence of the reaction yield on the microreactor radius is non-monotonous. Our results are of importance for (i) interpreting experimental data for magnetic field effects on RP recombination in confined space and (ii) for describing kinetics of chemical reactions, which occur predominantly on the surfaces of biomembranes, i.e., lipid peroxidation reactions.

Theoretical description of spin-selective reactions of radical pairs diffusing in spherical 2D and 3D microreactors

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ivanov, Konstantin L., E-mail: ivanov@tomo.nsc.ru; Lukzen, Nikita N.; Novosibirsk State University, Pirogova St. 2, Novosibirsk 630090

2015-08-28

In this work, we treat spin-selective recombination of a geminate radical pair (RP) in a spherical “microreactor,” i.e., of a RP confined in a micelle, vesicle, or liposome. We consider the microreactor model proposed earlier, in which one of the radicals is located at the center of the micelle and the other one undergoes three-dimensional diffusion inside the micelle. In addition, we suggest a two-dimensional model, in which one of the radicals is located at the “pole” of the sphere, while the other one diffuses on the spherical surface. For this model, we have obtained a general analytical expression formore » the RP recombination yield in terms of the free Green function of two-dimensional diffusion motion. In turn, this Green function is expressed via the Legendre functions and thus takes account of diffusion over a restricted spherical surface and its curvature. The obtained expression allows one to calculate the RP recombination efficiency at an arbitrary magnetic field strength. We performed a comparison of the two models taking the same geometric parameters (i.e., the microreactor radius and the closest approach distance of the radicals), chemical reactivity, magnetic interactions in the RP and diffusion coefficient. Significant difference between the predictions of the two models is found, which is thus originating solely from the dimensionality effect: for different dimensionality of space, the statistics of diffusional contacts of radicals becomes different altering the reaction yield. We have calculated the magnetic field dependence of the RP reaction yield and chemically induced dynamic nuclear polarization of the reaction products at different sizes of the microreactor, exchange interaction, and spin relaxation rates. Interestingly, due to the intricate interplay of diffusional contacts of reactants and spin dynamics, the dependence of the reaction yield on the microreactor radius is non-monotonous. Our results are of importance for (i) interpreting experimental data for magnetic field effects on RP recombination in confined space and (ii) for describing kinetics of chemical reactions, which occur predominantly on the surfaces of biomembranes, i.e., lipid peroxidation reactions.« less

Evaluation of positive surgical margins in patients undergoing robot-assisted and open radical prostatectomy according to preoperative risk groups.

PubMed

Suardi, Nazareno; Dell'Oglio, Paolo; Gallina, Andrea; Gandaglia, Giorgio; Buffi, Nicolò; Moschini, Marco; Fossati, Nicola; Lughezzani, Giovanni; Karakiewicz, Pierre I; Freschi, Massimo; Lucianò, Roberta; Shariat, Shahrokh F; Guazzoni, Giorgio; Gaboardi, Franco; Montorsi, Francesco; Briganti, Alberto

2016-02-01

Recent studies showed that robot-assisted radical prostatectomy (RARP) represents an oncologically safe procedure in patients with prostate cancer (PCa), where the rate of positive surgical margins (PSMs) might be lower in patients treated with RARP as compared with that of those undergoing the open approach (open RP [ORP]). The aim of this study is to analyze the rate of PSMs according to preoperative risk groups in a large cohort of patients treated with RARP and ORP in a single institution with standardized surgical technique and pathological examination. We evaluated 6,194 consecutive patients with PCa undergoing either ORP (71.1%) or RARP (28.9%) between 1992 and 2014. Logistic regression analyses were used to test the association between type of surgery and PSMs in each preoperative risk group (low vs. intermediate vs. high) after adjusting for confounders. Overall, 21.6% patients had PSMs. RARP was associated with a lower rate of PSMs in low-risk (11.5 vs. 15.4%, P = 0.01), intermediate-risk (18.9 vs. 23.5%, P = 0.008), and high-risk patients (19.7 vs. 30.1%, P<0.001). In multivariable analyses, after stratification according to risk group categories, no difference in PSMs between RARP and ORP was observed for low-risk (odds ratio [OR] = 0.87, P = 0.46) and intermediate-risk patients (OR = 0.84, P = 0.19). Conversely, RARP was associated with lower odds of PSMs in high-risk patients (OR = 0.69, P = 0.04). Similar results were observed when our analyses were repeated after accounting for pathological characteristics, in patients treated between 2006 and 2014 and in a cohort of men treated by high-volume surgeons (all P≤ 0.03). The introduction of RARP at our institution led to a significant reduction in the risk of PSMs in patients with PCa with high-risk disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Tobacco use and outcome in radical prostatectomy patients.

PubMed

Curtis, Alexandra; Ondracek, Rochelle Payne; Murekeyisoni, Christine; Kauffman, Eric; Mohler, James; Marshall, James

2017-04-01

Cigarette smoking has been consistently associated with increased risk of overall mortality, but the importance of smoking for patients with prostate cancer (CaP) who are candidates for curative radical prostatectomy (RP) has received less attention. This retrospectively designed cohort study investigated the association of smoking history at RP with subsequent CaP treatment outcomes and overall mortality. A total of 1981 patients who underwent RP at Roswell Park Cancer Institute (RPCI) between 1993 and 2014 were studied. Smoking history was considered as a risk factor for overall mortality as well as for currently accepted CaP treatment outcomes (biochemical failure, treatment failure, distant metastasis, and disease-specific mortality). The associations of smoking status with these outcomes were tested by Cox proportional hazard analyses. A total of 153 (8%) patients died during follow-up. Current smoking at diagnosis was a statistically significant predictor of overall mortality after RP (current smokers vs. former and never smokers, hazards ratio 2.07, 95% confidence interval [CI]: 1.36-3.14). This association persisted for overall mortality at 3, 5, and 10 years (odds ratios 2.07 [95% CI: 1.36-3.15], 2.05 [95% CI: 1.35-3.12], and 1.8 [95% CI: 1.18-2.74], respectively). Smoking was not associated with biochemical failure, treatment failure, distant metastasis, or CaP-specific mortality, and the association of smoking with overall mortality did not appear to be functionally related to treatment or biochemical failure, or to distant metastasis. Smoking is a non-negligible risk factor for death among CaP patients who undergo RP; patients who smoke are far more likely to die of causes other than CaP. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Histologic and cytologic bone marrow findings in dogs with suspected precursor-targeted immune-mediated anemia and associated phagocytosis of erythroid precursors.

PubMed

Lucidi, Cynthia de A; de Rezende, Christian L E; Jutkowitz, L Ari; Scott, Michael A

2017-09-01

Precursor-targeted immune-mediated anemia (PIMA) has been suspected in dogs with nonregenerative anemia and bone marrow findings varying from erythroid hyperplasia to pure red cell aplasia. Phagocytosis of erythroid precursors/rubriphagocytosis (RP) reported in some affected dogs suggests a destructive component to the pathogenesis of PIMA. The purpose of the study was to characterize laboratory and clinical findings in dogs with suspected PIMA and RP, with emphasis on cytologic and histologic bone marrow findings. Dogs with PIMA and RP were identified by review of paired bone marrow aspirate and core biopsy slides collected over a 4-year period. Samples were systematically assessed and characterized along with other pertinent laboratory data and clinical findings. Twenty-five dogs met criteria for PIMA and had RP that was relatively stage-selective. Erythropoiesis was expanded to the stage of erythroid precursors undergoing most prominent phagocytosis, yielding patterns characterized by a hypo-, normo-, or hypercellular erythroid lineage. A 4 th pattern involved severe collagen myelofibrosis, and there was a spectrum of mild to severe collagen myelofibrosis overall. Evidence of immune-mediated hemolysis was rare. Immunosuppressive therapy was associated with remission in 77% of dogs treated for at least the median response time of 2 months. Bone marrow patterns in dogs fulfilling criteria for PIMA were aligned with stage-selective phagocytosis of erythroid precursors and the development of collagen myelofibrosis, common in dogs with PIMA. Recognition of these patterns and detection of RP facilitates diagnosis of PIMA, and slow response to immunosuppressive therapy warrants further investigation into its pathogenesis. © 2017 American Society for Veterinary Clinical Pathology.

Ex vivo MRI evaluation of prostate cancer: Localization and margin status prediction of prostate cancer in fresh radical prostatectomy specimens.

PubMed

Heidkamp, Jan; Hoogenboom, Martijn; Kovacs, Iringo E; Veltien, Andor; Maat, Arie; Sedelaar, J P Michiel; Hulsbergen-van de Kaa, Christina A; Fütterer, Jurgen J

2018-02-01

To investigate the ability of high field ex vivo magnetic resonance imaging (MRI) to localize prostate cancer (PCa) and to predict the margin status in fresh radical prostatectomy (RP) specimens using histology as the reference standard. This Institutional Review Board (IRB)-approved study had written informed consent. Patients with biopsy-proved PCa and a diagnostic multiparametric 3T MRI examination of the prostate prior to undergoing RP were prospectively included. A custom-made container provided reference between the 7T ex vivo MRI obtained from fresh RP specimens and histological slicing. On ex vivo MRI, PCa was localized and the presence of positive surgical margins was determined in a double-reading session. These findings were compared with histological findings obtained from completely cut, whole-mount embedded, prostate specimens. In 12 RP specimens, histopathology revealed 36 PCa lesions, of which 17 (47%) and 20 (56%) were correlated with the ex vivo MRI in the first and second reading session, respectively. Nine of 12 (75%) index lesions were localized in the first session, in the second 10 of 12 (83%). Seven and 8 lesions of 11 lesions with Gleason score >6 and >0.5 cc were localized in the first and second session, respectively. In the first session none of the four histologically positive surgical margins (sensitivity 0%) and 9 of 13 negative margins (specificity 69%) were detected. In second session the sensitivity and specificity were 25% and 88%, respectively. Ex vivo MRI enabled accurate localization of PCa in fresh RP specimens, and the technique provided information on the margin status with high specificity. 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:439-448. © 2017 International Society for Magnetic Resonance in Medicine.

Patterns and Predictors of Early Biochemical Recurrence After Radical Prostatectomy and Adjuvant Radiation Therapy in Men With pT{sub 3}N{sub 0} Prostate Cancer: Implications for Multimodal Therapies

DOE Office of Scientific and Technical Information (OSTI.GOV)

Briganti, Alberto, E-mail: briganti.alberto@hsr.it; Joniau, Steven; Gandaglia, Giorgio

Purpose: The aim of our study was to evaluate patterns and predictors of early biochemical recurrence (eBCR) after radical prostatectomy (RP) and adjuvant radiation therapy (aRT) in order to identify which individuals might benefit from additional treatments. Methods and Materials: We evaluated 390 patients with pT{sub 3}N{sub 0} prostate cancer (PCa) receiving RP and aRT at 6 European centers between 1993 and 2006. Patients who were free from BCR at <2 years' follow-up were excluded. This resulted in 374 assessable patients. Early BCR was defined as 2 consecutive prostate-specific antigen (PSA) test values >0.2 ng/mL within 2 or 3 yearsmore » after aRT. Uni- and multivariable Cox regression analyses predicting overall and eBCR after aRT were fitted. Covariates consisted of preoperative PSA results, surgical margins, pathological stage, Gleason score, and aRT dose. Results: Overall, 5- and 8-year BCR-free survival rates were 77.1% and 70.8%, respectively. At a median follow-up of 86 months after aRT, 33 (8.8%) and 55 (14.6%) men experienced BCR within 2 or 3 years after aRT, respectively. In multivariable analyses, Gleason scores of 8 to 10 represented the only independent predictor of eBCR after aRT (all, P≤.01). The risk of BCR was significantly higher in patients with a Gleason score of 8 to 10 disease than in those with Gleason 2 to 6 within 24 months after treatment, after adjusting for all covariates (all, P≤.04). However, given a 24-month BCR free period, the risk of subsequent BCR for men with poorly differentiated disease was equal to that of men with less aggressive disease (all, P≥.3). Conclusions: High Gleason score represents the only predictor of eBCR after RP and aRT in patients affected by pT{sub 3}N{sub 0} PCa. Given the association between early PSA recurrence, clinical progression, and mortality, these patients might be considered candidates for adjuvant medical therapy and/or prophylactic whole-pelvis radiation therapy in addition to aRT, delivered to the prostatic bed.« less

Folding behavior of a T-shaped, ribosome-binding translation enhancer implicated in a wide-spread conformational switch

PubMed Central

Le, My-Tra; Kasprzak, Wojciech K; Kim, Taejin; Gao, Feng; Young, Megan YL; Yuan, Xuefeng; Shapiro, Bruce A; Seog, Joonil; Simon, Anne E

2017-01-01

Turnip crinkle virus contains a T-shaped, ribosome-binding, translation enhancer (TSS) in its 3’UTR that serves as a hub for interactions throughout the region. The viral RNA-dependent RNA polymerase (RdRp) causes the TSS/surrounding region to undergo a conformational shift postulated to inhibit translation. Using optical tweezers (OT) and steered molecular dynamic simulations (SMD), we found that the unusual stability of pseudoknotted element H4a/Ψ3 required five upstream adenylates, and H4a/Ψ3 was necessary for cooperative association of two other hairpins (H5/H4b) in Mg2+. SMD recapitulated the TSS unfolding order in the absence of Mg2+, showed dependence of the resistance to pulling on the 3D orientation and gave structural insights into the measured contour lengths of the TSS structure elements. Adenylate mutations eliminated one-site RdRp binding to the 3’UTR, suggesting that RdRp binding to the adenylates disrupts H4a/Ψ3, leading to loss of H5/H4b interaction and promoting a conformational switch interrupting translation and promoting replication. DOI: http://dx.doi.org/10.7554/eLife.22883.001 PMID:28186489

Screening Women Aged 50-59 for CRC Using Fecal Occult Blood Test Produces Outcomes Similar to Men Undergoing Screening Colonoscopy.

PubMed

Mooers, Harrison M; Holub, Jennifer L; Lieberman, David A

2018-06-13

Average-risk women aged 50-59 years have a lower incidence and mortality of colorectal cancer relative to age-matched men, calling into question the benefit of screening colonoscopy in this age group. We aimed to determine whether FOBT is an effective initial screening test in 50-59-year-old women. We conducted a cross-sectional study using a computerized endoscopic report generator. We identified 320,906 individuals who had average-risk screening colonoscopy and 32,369 who had colonoscopy for positive FOBT. The primary outcome was the positive predictive value (PPV) of FOBT for large polyp(s) greater than 9 mm, as a surrogate for advanced neoplasia. Among patients aged 50-59 years undergoing screening colonoscopy, men were more likely than women to have large polyps (6.3 vs 4.2%, p < 0.0001). Black women undergoing screening colonoscopy had higher rates of large polyps compared to non-Black women. The PPV in FOBT-positive men aged 50-54 (11.5%) and 55-59 (14.4%) was higher than in women aged 50-54 (6.1%) and 55-59 (5.4%). Despite this lower PPV, women aged 50-54 with a positive FOBT had a similar rate of large polyps as 50-54-year-old men undergoing screening colonoscopy (6.1 vs 6.3%, p = 0.626). CRC screening with FOBT identifies 50-59-year-old men and women with a higher risk of large polyps. Since younger women have a lower risk of large polyps than men, screening with FOBT in 50-59-year-old non-Black women could be an effective screening strategy, with outcomes similar to the use of screening colonoscopy in 50-59-year-old men.

Temporal changes in outcomes of women and men undergoing percutaneous coronary intervention for chronic total occlusion: 2005-2013.

PubMed

Toma, Aurel; Stähli, Barbara E; Gick, Michael; Ferenc, Miroslaw; Mashayekhi, Kambis; Buettner, Heinz Joachim; Neumann, Franz-Josef; Gebhard, Catherine

2018-06-01

Percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) has undergone impressive progress during the last decade, both in strategies and equipment. It is unknown whether technical refinement has translated into improved outcomes in women undergoing CTO-PCI. A total of 2002 consecutive patients (17% females, mean age 65.2 ± 10.7 years) undergoing PCI of at least one CTO lesion at our center between 01/2005 and 12/2013 were evaluated. The incidence of adverse events was compared between two time series (2005-2009 and 2010-2013). A significant increase in adverse lesion characteristics over time was noted in both, women and men (p < 0.001), while technical success rates significantly increased in men but not in women (p trend  < 0.001 in men and p trend =0.9 in women). The incidence of procedural complications was significantly higher in women as compared to men and increased over the study period in women (p < 0.05) but not in men. Accordingly, multivariate logistic regression analysis identified female sex as a strong predictor of PCI-related complications in recent years, while this was not the case in earlier years (adjusted HR 2.03, 95% CI 0.62-6.6, p = 0.2 and adjusted HR 4.7, 95% CI 1.8-12.3, p = 0.002, respectively, p < 0.001 for log LH ratio). In addition, major adverse cardiovascular events (MACE) after a 3-year follow-up significantly declined in men (log rank = 0.046), while no changes were observed in women. While higher success rates and a reduced rate of MACE have been achieved in men, the incidence of procedural complications in women undergoing CTO-PCI has increased over time.

Use of combined intracorporal injection and a phosphodiesterase-5 inhibitor therapy for men with a suboptimal response to sildenafil and/or vardenafil monotherapy after radical retropubic prostatectomy.

PubMed

Mydlo, Jack H; Viterbo, Rosalia; Crispen, Paul

2005-04-01

To report experience with combined therapy using intracorporal injection (ICI) of alprostadil and oral phosphodiesterase 5 (PDE-5) inhibitors for the minimally invasive treatment of erectile dysfunction (ED) after radical prostatectomy (RP), as PDE-5 inhibitors are effective but a few patients may have a suboptimal response. In a retrospective study, 34 men (aged 46-66 years) had a nerve-sparing retropubic RP and subsequent ED. Patients were titrated on sildenafil citrate or vardenafil to maximum doses. All had a suboptimal response after a maximum of eight doses of oral therapy and were then treated with ICI therapy using 15 or 20 microg alprostadil. Erectile function was assessed with the Sexual Health Inventory for Men (SHIM). Of the 32 patients who continued combined therapy, 22 (68%) had an improvement in erectile function after ICI therapy, as assessed by the SHIM score. On follow-up, 36% of these patients used ICI therapy only intermittently, instead of regularly, as they felt that this was adequate enough for good results. PDE-5 oral pharmacotherapy is the most commonly used effective therapy for ED but may not be as effective in patients who have radical surgery; the addition of testosterone patches may have side-effects or be considered a risk in patients with a history of prostate cancer. The use of ICI therapy as an adjunct or maintenance therapy to their oral medication may be another alternative in these patients.

Relapsing polychondritis and airway involvement.

PubMed

Ernst, Armin; Rafeq, Samaan; Boiselle, Phillip; Sung, Arthur; Reddy, Chakravarthy; Michaud, Gaetane; Majid, Adnan; Herth, Felix J F; Trentham, David

2009-04-01

To assess the prevalence and characteristics of airway involvement in relapsing polychondritis (RP). Retrospective chart review and data analysis of RP patients seen in the Rheumatology Clinic and the Complex Airway Center at Beth Israel Deaconess Medical Center from January 2004 through February 2008. RP was diagnosed in 145 patients. Thirty-one patients had airway involvement, a prevalence of 21%. Twenty-two patients were women (70%), and they were between 11 and 61 years of age (median age, 42 years) at the time of first symptoms. Airway symptoms were the first manifestation of disease in 17 patients (54%). Dyspnea was the most common symptom in 20 patients (64%), followed by cough, stridor, and hoarseness. Airway problems included the following: subglottic stenosis (n = 8; 26%); focal and diffuse malacia (n = 15; 48%); and focal stenosis in different areas of the bronchial tree in the rest of the patients. Twelve patients (40%) required and underwent intervention including balloon dilatation, stent placement, tracheotomy, or a combination of the above with good success. The majority of patients experienced improvement in airway symptoms after intervention. One patient died during the follow-up period from the progression of airway disease. The rest of the patients continue to undergo periodic evaluation and intervention. In this largest cohort described in the English language literature, we found symptomatic airway involvement in RP to be common and at times severe. The nature of airway problems is diverse, with tracheomalacia being the most common. Airway intervention is frequently required and in experienced hands results in symptom improvement.

Cross-cultural application of the Korean version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for patients with prostate cancer - EORTC QLQ-PR25.

PubMed

Park, Jinsung; Shin, Dong Wook; Yun, Seok Joong; Park, Sung-Woo; Jeon, Seong Soo; Kwak, Cheol; Kwon, Tae Gyun; Kim, Hyung Jin; Ahn, Hanjong

2013-01-01

We evaluated the psychometric properties of the Korean version of the European Organization for Research and Treatment of Cancer QLQ-PR25 when applied to Korean prostate cancer (PC) patients. A total of 172 patients who underwent curative radical prostatectomy (RP) with or without adjuvant androgen deprivation therapy were asked to complete the Korean version of the EORTC QLQ-C30 and PR25 questionnaires 3 times (before and 3 and 6 months after RP). Psychometric evaluation of the questionnaire was conducted. Multitrait scaling analysis showed satisfactory construct validity in most scales except for bowel symptoms and hormonal treatment-related symptoms. Internal consistency tested by Cronbach's α coefficient met the 0.70 criterion for the urinary symptom, sexual activity and sexual functioning scales at the all 3 time points. Known-group comparison analyses showed better quality-of-life (QOL) scores in patients with higher performance status, and higher hormonal treatment-related symptom scores in patients on hormonal treatment. Responsiveness to changes was in line with clinical implications over time after RP. Our results show that the EORTC QLQ-PR25 questionnaire has adequate levels in cross-cultural validity. The Korean version of the EORTC QLQ-PR25 is a generally reliable and robust instrument for the assessment of various QOL aspects that can be self-administered to Korean PC patients undergoing RP. © 2013 S. Karger AG, Basel.

Extraprostatic Extension Is Extremely Rare for Contemporary Gleason Score 6 Prostate Cancer.

PubMed

Anderson, Blake B; Oberlin, Daniel T; Razmaria, Aria A; Choy, Bonnie; Zagaja, Gregory P; Shalhav, Arieh L; Meeks, Joshua J; Yang, Ximing J; Paner, Gladell P; Eggener, Scott E

2017-09-01

A significant proportion of men with Gleason score 6 (GS6) prostate cancer undergo treatment with radiation or surgery. To assess pathologic stage of pure GS6 at radical prostatectomy (RP). In the period 2003-2014, 7817 patients underwent RP at two institutions. Of 2502 patients with GS6 at surgery, 60 were identified as stage pT3a-b on initial pathologic review, 55 with pT3a (extraprostatic extension, EPE), and five with pT3b (seminal vesicle invasion; SVI). All cases of GS6 with pT3 disease underwent contemporary pathologic evaluation for Gleason grade, stage, and extent of EPE. At one institution, all GS≥7 pT3b cases were re-reviewed for downgrading. The 2014 International Society of Urological Pathology (ISUP) Gleason grading criteria and 2009 ISUP recommendations on pT3 staging were applied. Calculated incidence (%) of pT3a, pT3b, pT4, and lymph node-positive disease. Of the 60 GS6 pT3a-b cases identified in the period 2003-2014, seven (0.28% of entire GS6 cohort) with GS6 and pT3a were identified after re-review, all focal EPE. Among the re-examined cohort, no cases of GS6 with pT3b were observed. None of the 132 GS≥7 pT3b cases were downgraded to GS6. Limitations include partial embedding of specimens and separate pathologic review at each institution. In a large prostatectomy cohort, GS6 never had seminal vesicle invasion (0%) and was very rarely (0.28%) associated with extraprostatic extension. GS6 prostate cancer rarely spreads outside the prostate. A new finding in this study was that GS6 prostate cancer never spread to the seminal vesicles. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Quantitative analyses of factors related to anxiety and depression in patients with retinitis pigmentosa.

PubMed

Sainohira, Mayumi; Yamashita, Takehiro; Terasaki, Hiroto; Sonoda, Shozo; Miyata, Kazunori; Murakami, Yusuke; Ikeda, Yasuhiro; Morimoto, Takeshi; Endo, Takao; Fujikado, Takashi; Kamo, Junko; Sakamoto, Taiji

2018-01-01

The purpose of this study is to determine the factors related to anxiety and depression in patients with retinitis pigmentosa (RP). The status of anxiety and depression was determined in RP patients with the Hospital Anxiety and Depression Scale (HADS) questionnaire which consisted of subscales for HADS-anxiety (HADS-A) and HADS-depression (HADS-D). The vision-specific quality of life (VSQOL) was assessed with the National Eye Institute Visual Function Questionnaire 25 (NEI-VFQ25). The correlations between the HADS-A or HADS-D scores and vision-related clinical parameters such as the best-corrected visual acuity (BCVA), Functional Acuity Score, Functional Field Score, Functional Vision Score, the NEI- VFQ25 subscale score were determined. The socioeconomic status, such as the work status and membership in the RP society, was investigated to determine the factors related to the HADS-A and HADS-D scores. One hundred and twelve RP patients (46 men and 66 women) with mean age of 60.7±15.4 (standard deviation) years were studied. The HADS-A score was not significantly correlated with any visual functions but was significantly correlated with the general health condition (r = -0.34, P<0.001) and the role limitation (r = -0.20, P = 0.03) of the NEI-VFQ25 subscale. The HADS-D score was significantly correlated with all the visual functions (r = -0.38 to 0.29, P<0.001), the NEI-VFQ25 subscale score (r = - 0.58 to -0.33, P<0.001) by Spearman's correlations. The HADS-A score was significantly higher in the members of the RP society than in non-members (P = 0.013). The mean HADS-D score of employed individuals was significantly lower than that of unemployed ones (P = 0.001) by the Mann-Whitney U test. The results indicate that visual function impairments and vision-related quality of life are associated with a depressive state, and the general health condition is related to anxiety in RP patients. Being employed may be strongly correlated with the degree of depression in RP patients.

Risk Behavior and Sexually Transmitted Infections Among Transgender Women and Men Undergoing Community-Based Screening for Acute and Early HIV Infection in San Diego.

PubMed

Green, Nella; Hoenigl, Martin; Morris, Sheldon; Little, Susan J

2015-10-01

The transgender community represents an understudied population in the literature. The objective of this study was to compare risk behavior, and HIV and sexually transmitted infection (STI) rates between transgender women and transgender men undergoing community-based HIV testing.With this retrospective analysis of a cohort study, we characterize HIV infection rates as well as reported risk behaviors and reported STI in 151 individual transgender women and 30 individual transgender men undergoing community based, voluntary screening for acute and early HIV infection (AEH) in San Diego, California between April 2008 and July 2014.HIV positivity rate was low for both, transgender women and transgender men undergoing AEH screening (2% and 3%, respectively), and the self-reported STI rate for the prior 12 months was 13% for both. Although transgender women appeared to engage in higher rates of risk behavior overall, with 69% engaged in condomless receptive anal intercourse (CRAI) and 11% engaged in sex work, it is important to note that 91% of transgender women reported recent sexual intercourse, 73% had more than 1 sexual partner, 63% reported intercourse with males, 37% intercourse with males and females, and 30% had CRAI.Our results indicate that in some settings rates of HIV infection, as well as rates of reported STIs and sexual risk behavior in transgender men may resemble those found in transgender women. Our findings support the need for comprehensive HIV prevention in both, transgender women and men.

The impact of race on prostate cancer detection and choice of treatment in men undergoing a contemporary extended biopsy approach.

PubMed

Swords, Kelly; Wallen, Eric M; Pruthi, Raj S

2010-01-01

African American men have a higher rate of prostate cancer mortality compared with their Caucasian American counterparts. However, it remains unclear as to whether such differences are due to biologic or socioeconomic influences. This study sought to determine if there are differences in demographic and clinical characteristics between African American and Caucasian American men in a modern cohort undergoing extended biopsy approach, and evaluated the subsequent choice of therapy in patients diagnosed with prostate cancer. A retrospective review was performed from a consecutive series of 500 men undergoing prostate biopsy at our institution between 2003 and 2005. All patients underwent a contemporary 10-12 biopsy scheme. Demographic, clinical, and pathologic variables as well as treatment choice (those with positive biopsy) were stratified and evaluated with regard to race-African American, Caucasian American, and other (Hispanic, Asian, American Indian). 65% were Caucasian American, 29% African American, and 7% other. The overall positive biopsy rate was 44%. African American men were significantly younger than Caucasian American but were not younger than "other" (61.6 vs. 64.3 vs. 61.5 years). No differences were observed with regard to prostate specific antigen density (PSAD), prostate volume, or rate of abnormal digital rectal exam (DRE). The positive biopsy rate was not different between Caucasian American and African American (46% vs. 46%), but significantly lower in other men (16%). These differences were maintained on odds ratio modeling, including age-adjusted and multivariate models. Of the 223 men with positive biopsies, information on treatment choice demonstrated that African American men had a significantly higher rate of choice of XRT (OR = 2.12) and rate of avoidance of surgery (OR = 0.35) than Caucasian American men. In men undergoing prostate biopsy using an extended (10-12 core) biopsy scheme, no differences were observed with regard to positive biopsy rate or other clinical or biochemical parameters [except for age and prostate specific antigen (PSA) level] between African American and Caucasian American men. Of those with a positive biopsy, African American men were more likely to avoid surgery and choose XRT in our population. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Cathepsin B expression in prostate cancer of native Japanese and Japanese-American patients: an immunohistochemical study.

PubMed

Sinha, Akhouri A; Morgan, Jenifer L; Betre, Konjit; Wilson, Michael J; Le, Chap; Marks, Leonard S

2008-01-01

Japanese-American (J-A) men who have immigrated to the U.S.A. and acquired the Western lifestyle usually have more invasive prostate cancer (PCa) than native Japanese (NJ) living in Japan. The specific reasons for these differences remain unknown. The objective of this study was to examine immunostainings of cathepsin B (CB) and its endogenous inhibitor stefin A (SA) in tissue microarray (TMA) and radical prostatectomy (RP) tissue sections in the hope of obtaining insights into the invasiveness of PCa in Japanese patients. TMA and RP sections were evaluated in 50 men (25 NJ and 25 J-A) for CB and SA reaction products. The CB and SA immunostainings were imaged directly from microscope slides to a computer using a high performance charge coupled device (CCD) digital camera, quantified using Metamorph software, analyzed using the two-sample t-test, and confirmed by multiple regression analysis. The CB and SA proteins were localized in the carcinomatous glands and isolated cancer cells in the TMA and RP sections. The Gleason scores and pre-surgery serum total prostate-specific antigen (PSA) levels did not differ significantly in the NJ and J-A patients (p = 0.14, p = 0.16, respectively). The Chi-square analysis of clinical stage versus place of birth showed that the NJ patients had significantly more T2a and T2b clinical stages than the J-A patients who had more advanced T2c and T3a stages (p = 0.003). The CB and SA immunostainings and their ratios in Gleason score 6 tumors did not show any difference, but the CB:SA ratios in score > or = 7 tumors approached significance levels. The overall matching of specimens according to the Gleason grade/score, pre-RP serum total PSA levels, clinical stage and age prior to evaluation of immunostainings greatly minimizes subjectivity associated with the evaluation of markers in this ethnic sub-population of PCa patients. CB and SA immunostaining is similar in Japanese patients who have organ-confined and moderately-differentiated PCa. Analysis of the reaction product data provides indirect evidence that invasiveness of PCa is similar in the two Japanese patient populations.

Pretreatment tables predicting pathologic stage of locally advanced prostate cancer.

PubMed

Joniau, Steven; Spahn, Martin; Briganti, Alberto; Gandaglia, Giorgio; Tombal, Bertrand; Tosco, Lorenzo; Marchioro, Giansilvio; Hsu, Chao-Yu; Walz, Jochen; Kneitz, Burkhard; Bader, Pia; Frohneberg, Detlef; Tizzani, Alessandro; Graefen, Markus; van Cangh, Paul; Karnes, R Jeffrey; Montorsi, Francesco; van Poppel, Hein; Gontero, Paolo

2015-02-01

Pretreatment tables for the prediction of pathologic stage have been published and validated for localized prostate cancer (PCa). No such tables are available for locally advanced (cT3a) PCa. To construct tables predicting pathologic outcome after radical prostatectomy (RP) for patients with cT3a PCa with the aim to help guide treatment decisions in clinical practice. This was a multicenter retrospective cohort study including 759 consecutive patients with cT3a PCa treated with RP between 1987 and 2010. Retropubic RP and pelvic lymphadenectomy. Patients were divided into pretreatment prostate-specific antigen (PSA) and biopsy Gleason score (GS) subgroups. These parameters were used to construct tables predicting pathologic outcome and the presence of positive lymph nodes (LNs) after RP for cT3a PCa using ordinal logistic regression. In the model predicting pathologic outcome, the main effects of biopsy GS and pretreatment PSA were significant. A higher GS and/or higher PSA level was associated with a more unfavorable pathologic outcome. The validation procedure, using a repeated split-sample method, showed good predictive ability. Regression analysis also showed an increasing probability of positive LNs with increasing PSA levels and/or higher GS. Limitations of the study are the retrospective design and the long study period. These novel tables predict pathologic stage after RP for patients with cT3a PCa based on pretreatment PSA level and biopsy GS. They can be used to guide decision making in men with locally advanced PCa. Our study might provide physicians with a useful tool to predict pathologic stage in locally advanced prostate cancer that might help select patients who may need multimodal treatment. Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Group Planning and Task Efficiency with Complex Problems. Final Report.

ERIC Educational Resources Information Center

Lawson, E. D.

One hundred eighty 4-man groups (90 of men and 90 of women) using 3 types of net (All-Channel, Wheel and Circle) under 3 conditions (Planning Period (PP), Rest Period (RP) and Control) were run in a single session with 5 complex problems to determine whether a single 2-minute planning period after solution of the first problem would result in…

Factors associated with disposition of cryopreserved reproductive tissue.

PubMed

Styer, Aaron K; Cekleniak, Natalie A; Legedza, Anna; Mutter, George L; Hornstein, Mark D

2003-09-01

To study patient characteristics associated with the preferences for the disposition of cryopreserved semen and embryos in the event of death or divorce. Retrospective exploratory study. Tertiary care academic medical center. One hundred twelve men banking sperm, 54 female patients (partners of men banking sperm) undergoing in vitro fertilization (IVF), and 112 women undergoing IVF who were not partners of men banking sperm. Male patients banking sperm and couples undergoing IVF completed a standard consent form detailing their desired dispositions (disposal or release to a surviving party) of cryopreserved sperm and embryos in the event of death or divorce. Effect of marital status, age, reason for sperm banking, infertility diagnosis, partner status (single or significant-other partner) on sperm, and embryo disposition choice. In the event of death, married men were 5.5 times more likely to release banked sperm to a surviving party than were single men. The estimated odds of giving sperm to a survivor were 1.07 times greater with every 1-year increase in age. The choice of sperm disposal was significantly related to the banking reason for the case of banking prior to chemotherapy and/or radiation for malignancy. In the case of male death, the decisions of couples undergoing IVF for embryo disposition agreed with choices of male patients for sperm disposition approximately 33% of the time more often than by chance alone. Decisions surrounding disposition of cryopreserved sperm are significantly associated with marital status, age, and reason for banking sperm. Respective choices of sperm and embryo disposition in couples undergoing IVF were similar in the situation of male death.

A Biopsy-based 17-gene Genomic Prostate Score as a Predictor of Metastases and Prostate Cancer Death in Surgically Treated Men with Clinically Localized Disease.

PubMed

Van Den Eeden, Stephen K; Lu, Ruixiao; Zhang, Nan; Quesenberry, Charles P; Shan, Jun; Han, Jeong S; Tsiatis, Athanasios C; Leimpeter, Amethyst D; Lawrence, H Jeffrey; Febbo, Phillip G; Presti, Joseph C

2018-01-01

A 17-gene biopsy-based reverse transcription polymerase chain reaction assay, which provides a Genomic Prostate Score (GPS-scale 0-100), has been validated as an independent predictor of adverse pathology and biochemical recurrence after radical prostatectomy (RP) in men with low- and intermediate-risk prostate cancer (PCa). To evaluate GPS as a predictor of PCa metastasis and PCa-specific death (PCD) in a large cohort of men with localized PCa and long-term follow-up. A retrospective study using a stratified cohort sampling design was performed in a cohort of men treated with RP within Kaiser Permanente Northern California. RNA from archival diagnostic biopsies was assayed to generate GPS results. We assessed the association between GPS and time to metastasis and PCD in prespecified uni- and multivariable statistical analyses, based on Cox proportional hazard models accounting for sampling weights. The final study population consisted of 279 men with low-, intermediate-, and high-risk PCa between 1995 and 2010 (median follow-up 9.8 yr), and included 64 PCD and 79 metastases. Valid GPS results were obtained for 259 (93%). In univariable analysis, GPS was strongly associated with time to PCD, hazard ratio (HR)/20 GPS units=3.23 (95% confidence interval [CI] 1.84-5.65; p<0.001), and time to metastasis, HR/20 units=2.75 (95% CI 1.63-4.63; p<0.001). The association between GPS and both end points remained significant after adjusting for National Comprehensive Cancer Network, American Urological Association, and Cancer of the Prostate Risk Assessment (CAPRA) risks (p<0.001). No patient with low- or intermediate-risk disease and a GPS of<20 developed metastases or PCD (n=31). In receiver operating characteristic analysis of PCD at 10 yr, GPS improved the c-statistic from 0.78 (CAPRA alone) to 0.84 (GPS+CAPRA; p<0.001). A limitation of the study was that patients were treated during an era when definitive treatment was standard of care with little adoption of active surveillance. GPS is a strong independent predictor of long-term outcomes in clinically localized PCa in men treated with RP and may improve risk stratification for men with newly diagnosed disease. Many prostate cancers are slow growing and unlikely to spread or threaten a man's life, while others are more aggressive and require treatment. Increasingly, doctors are using new molecular tests, such as the17-gene Genomic Prostate Score (GPS), which can be performed at the time of initial diagnosis to help determine how aggressive a given patient's cancer may be. In this study, performed in a large community-based healthcare network, GPS was shown to be a strong predictor as to whether a man's prostate cancer will spread and threaten his life after surgery, providing information that may help patients and their doctors decide on the best course of management of their disease. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Apparent diffusion coefficient value is a strong predictor of unsuspected aggressiveness of prostate cancer before radical prostatectomy.

PubMed

Renard Penna, Raphaele; Cancel-Tassin, Geraldine; Comperat, Eva; Mozer, Pierre; Léon, Priscilla; Varinot, Justine; Roupret, Morgan; Bitker, Marc-Olivier; Lucidarme, Olivier; Cussenot, Olivier

2016-10-01

To evaluate the use of multiparametric MRI (mp MRI) parameters in order to predict prostate cancer aggressiveness as defined by pathological Gleason score or molecular markers in a cohort of patients defined with a Gleason score of 6 at biopsy. Sixty-seven men treated by radical prostatectomy (RP) for a low grade (Gleason 6) on biopsy and mp MRI before biopsy were selected. The cycle cell proliferation (CCP) score assessed by the Prolaris test and Ki-67/PTEN expression assessed by immunohistochemistry were quantified on the RP specimens. 49.25 % of the cancers were undergraded on biopsy compared to the RP specimens. Apparent diffusion coefficient (ADC) < 0.80 × 10(-3) mm(2)/s (P value 0.003), Likert score >4 (P value 0.003) and PSA density >0.15 ng/ml/cc (P value 0.035) were significantly associated with a higher RP Gleason score. Regarding molecular markers of aggressiveness, ADC < 0.80 × 10(-3) mm(2)/s and Likert score >4 were also significantly associated with a positive staining for Ki-67 (P value 0.039 and 0.01, respectively). No association was found between any analyzed MRI or clinical parameter and the CCP score. Decreasing ADC value is a stronger indicator of aggressive prostate cancer as defined by molecular markers or postsurgical histology than biopsy characteristics.

Replacement of Atlantis', OV-104's, right orbital maneuvering system pod

NASA Technical Reports Server (NTRS)

1988-01-01

Atlantis', Orbiter Vehicle (OV) 104's, right orbital maneuvering system (OMS) pod (RP01) is placed in a checkout cell at Kennedy Space Center's (KSC's) Hypergolic Maintenance Facility (HMF). Technicians steady OMS mounted on ground handling cart as third technician, standing on ladder, secures support frame. At the HMF, a group of specially-equipped buildings in the KSC Industrial Area, the OMS pods are undergoing extensive processing, including removal of certain components that will undergo modification at vendor facilities prior to the Shuttle's return to flight. The OMS pods are bolted to the aft fuselage of the orbiter and contain the engines and thrusters used to maneuver the spaceship in orbit. View provided by KSC with alternate number KSC-87PC-93.

75 FR 25860 - Agency Forms Undergoing Paperwork Reduction Act Review

Federal Register 2010, 2011, 2012, 2013, 2014

2010-05-10

... diagnoses in 33 states. Black men who have sex with men (MSM) have been identified as the population with... interventions. Previous research indicates that 20% to 40% of Black MSM also have female sex partners. Interventions developed for gay men may not be relevant or appropriate for men who have sex with men and women...

Upper esophageal sphincter (UES) metrics on high-resolution manometry (HRM) differentiate achalasia subtypes.

PubMed

Blais, P; Patel, A; Sayuk, G S; Gyawali, C P

2017-12-01

The upper esophageal sphincter (UES) reflexively responds to bolus presence within the esophageal lumen, therefore UES metrics can vary in achalasia. Within consecutive patients undergoing esophageal high-resolution manometry (HRM), 302 patients (58.2±1.0 year, 57% F) with esophageal outflow obstruction were identified, and compared to 16 asymptomatic controls (27.7±0.7 year, 56% F). Esophageal outflow obstruction was segregated into achalasia subtypes 1, 2, and 3, and esophagogastric junction outflow obstruction (EGJOO with intact peristalsis) using Chicago Classification v3.0. UES and lower esophageal sphincter (LES) metrics were compared between esophageal outflow obstruction and normal controls using univariate and multivariate analysis. Linear regression excluded multicollinearity of pressure metrics that demonstrated significant differences across individual subtype comparisons. LES integrated relaxation pressure (IRP) had utility in differentiating achalasia from controls (P<.0001), but no utility in segregating between subtypes (P=.27). In comparison to controls, patients collectively demonstrated univariate differences in UES mean basal pressure, relaxation time to nadir, recovery time, and residual pressure (UES-RP) (P≤.049). UES-RP was highest in type 2 achalasia (P<.0001 compared to other subtypes and controls). In multivariate analysis, only UES-RP retained significance in comparison between each of the subgroups (P≤.02 for each comparison). Intrabolus pressure was highest in type 3 achalasia; this demonstrated significant differences across some but not all subtype comparisons. Nadir UES-RP can differentiate achalasia subtypes within the esophageal outflow obstruction spectrum, with highest values in type 2 achalasia. This metric likely represents a surrogate marker for esophageal pressurization. © 2017 John Wiley & Sons Ltd.

Tough, Microcracking-Resistant, High-Temperature Polymer

NASA Technical Reports Server (NTRS)

Pater, Ruth H.; Razon, Pert; Smith, Ricky; Working, Dennis; Chang, Alice; Gerber, Margaret

1990-01-01

Simultaneous synthesis from thermosetting and thermoplastic components yields polyimide with outstanding properties. Involves process in which one polymer cross-linked in immediate presence of other, undergoing simultaneous linear chain extension. New material, LaRC-RP40 synthesized from high-temperature thermosetting imide prepolymer and from thermoplastic monomer. Three significantly improved properties: toughness, resistance to microcracking, and glass-transition temperature. Shows promise as high-temperature matrix resin for variety of components of aircraft engines and for use in other aerospace structures.

Many Men with Penile Cancer Not Getting Recommended Treatments

Cancer.gov

Professional guidelines recommend that men with penile cancer that has not spread beyond nearby lymph nodes undergo lymph node dissection and receive chemotherapy. As this Cancer Currents blog post reports, that’s not happening for many men.

Risk factors for psychiatric disorders in infertile women and men undergoing in vitro fertilization treatment.

PubMed

Volgsten, Helena; Skoog Svanberg, Agneta; Ekselius, Lisa; Lundkvist, Orjan; Sundström Poromaa, Inger

2010-03-01

To identify risk factors associated with depression and anxiety in infertile women and men undergoing in vitro fertilization (IVF). Prospective study. A university hospital in Sweden during a 2-year period. 825 participants (413 women and 412 men). Primary Care Evaluation of Mental Disorders (PRIME-MD), based on the Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV), as the diagnostic tool for evaluating mood and anxiety disorders, and fertility history and outcome of IVF treatment collected from the patients' medical records. Risk factors associated with depression and anxiety disorders. A negative pregnancy test and obesity were the independent risk factors for any mood disorders in women. Among men, the only independent risk factor for depression was unexplained infertility. No IVF-related risk factors could be identified for any anxiety disorder. A negative pregnancy test is associated with an increased risk for depression in women undergoing IVF, but no risk of developing anxiety disorders is associated with the pregnancy test result after IVF. Pregnancy test results were not a risk factor for depression or anxiety among men. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

[Anxiety and its inducing factors in men undergoing in vitro fertilization and embryo transfer].

PubMed

Shu, Ling; Chen, Dan; Jiang, Ling; Zhang, Qiong; Jiang, Li-Ping

2016-11-01

To explore the prevalence of anxiety and its inducing factors in men undergoing in vitro fertilization and embryo transfer (IVF-ET). We randomly selected 202 men undergoing IVF-ET in the Infertility and Reproduction Center of the Second Xiangya Hospital of Central South University. On the first day of the IVF-ET cycle, we completed an investigation among the men using a self-designed questionnaire, Self-Rating Anxiety Scale (SAS), Social Support Rating Scale (SSRS), and 3 subscales (marital satisfaction, husband-wife communication, and sexual relationship) of Olson Marital Inventory. Mild anxiety was found in 55 (27.2%) of the included men while the other 147 (72.8%) were non-anxiety males. Compared with the non-anxiety group, the anxiety group showed significant decreases in the total SSRS score (38.65±4.87 vs 36.44±4.21), objective support score (9.22±1.82 vs 8.36±1.18), and utility degree of social support score (6.89±1.50 vs 6.24±1.61) on the first day of the treatment cycle (P<0.01) as well as in the total scores of marital satisfaction (103.04±9.97 vs 96.89±9.90), husband-wife communication (32.29±4.24 vs 30.56±5.43), and sexual relationship (38.03±5.27 vs 34.20±4.41) (P<0.05). There were statistically significant differences in the incidence rate of anxiety in the men with different housing conditions, monthly incomes, treatment costs, attitudes towards IVF-ET, pressure from social opinion, status of parenthood (P<0.01). Multivariate logistic regression analysis indicated that the major factors associated with anxiety included the attitude towards IVF-ET, pressure from social opinion, and sexual relationship in the men undergoing IVF-ET (P<0.05). The incidence rate of anxiety is high in males undergoing IVF-ET and it is associated with various factors. Psychological aid is needed to these male patients from the staff of the reproduction center.

The metabolic reactions in men and women during long-term head-down tilt

NASA Astrophysics Data System (ADS)

Markin, Andrey

We have demonstrated that dynamics of alterations of some biochemical blood indices during ling-term space flights and at a long duration head-down tilt (HDT) features that same directionality [Andrei Markin, Lubov Strogonova, Oleg Balashov et al, 1998]. A comparison between biochemical blood parameters at 120-day HDT was provided for groups consisting of nine men (MG1),six men (MG2) and four women (WG). All examined persons aged were exposed to "pure" HDT without resort to any prophylactic agents. Under investigations were concentrations of urea, uric acid, total cholesterol [CHO], HDL-cholesterol [HDL], triglycerides (TG), primary lipid peroxidation (LPO) products, final LPO products, tocopherol (TP) as well as activity of alanin aminotransferase (ALT), total creatin kinase (CK). For all the groups the investigated indices values were expressed as a percentage to background ones. ALT activity for the WG group had a tendency to decrease by 2-15 Women presented a moderate urea concentration lowering which ranged from 99 to 86 CHO level in WG was also elevated, and the extent to which elevated, for the most part, exceeded that of men, but beginning with the 72-nd - 84-th days of HDT an increase in MG1 become more pronounced with its retaining up to the RP. In all groups the tendency for decrease in HDL content was observed, however, it was more pronounced with men. In the RP the parameter value was increased in MG1 and MG2, but in WG it remained at the level which was observed at HDT. TG concentration women presented in the course of HDT increased, but beginning with the 49-th - 50-th day of experiment an increased in MG1 and MG2 became more pronounced. LPO products content dynamics in WG manifested as alternating increases and decreases relative to the background values (65 to 24 Comparative results of biochemical value dynamics investigation obtained in the course of a 120- day HDT demonstrated that women feature slower and less pronounced formation of metabolic response to experimental exposure as compared to men. In terms of some parameters (products of nitrogen and nucleic metabolism), men and women present dynamics of different direction, which is testimony to a woman body conservative reaction nature.

Association between Allogeneic or Autologous Blood Transfusion and Survival in Patients after Radical Prostatectomy: A Systematic Review and Meta-Analysis

PubMed Central

Yuan, Xiao-Hua

2017-01-01

Background A number of studies have investigated the effect of perioperative blood transfusion (PBT) for patients after radical prostatectomy (RP), with some reporting conflicting results. A systematic review of the literature and a meta-analysis were conducted to explore the association between PBT (autologous or allogeneic) and biochemical recurrence-free survival (BRFS), overall survival (OS) and cancer-specific survival (CSS) in patients undergoing RP. Methods The PubMed, Medline, Cochrane Library, and Embase databases were searched for published controlled clinical studies on perioperative allogeneic or autologous blood transfusion (BT) and patient survival after RP. STATA software version 12.0 was used for data analysis. We used hazard ratios (HRs) and 95% confidence intervals (CIs) to test the correlation between BT and patient survival after RP. Results Data from a total of 26,698 patients in ten published studies were included in the meta-analysis. The meta-analysis results showed that autologous BT was not associated with BRFS (HR: 1.06; 95% CI: 0.96–1.18; Z = 1.17; P = 0.24), OS (HR: 0.86; 95% CI: 0.71–1.04; Z = 1.58; P = 0.11), or CSS (HR: 0.98; 95% CI: 0.49–1.96; Z = 0.05; P = 0.96). Allogeneic BT exhibited a significant association with worse BRFS (HR: 1.09; 95% CI: 1.01–1.16; Z = 2.37; P = 0.02), OS (HR: 1.43; 95% CI: 1.24–1.64; Z = 4.95; P<0.01) and CSS (HR: 1.74; 95% CI: 1.18–2.56; Z = 2.81; P = 0.005). Conclusion Our data showed an association between allogeneic BT and reduced BRFS, OS and CSS in patients after RP. These findings indicate that perioperative blood conservation strategies are important for decreasing the allogeneic BT rate. PMID:28135341

Gender-based outcomes of bivalirudin versus heparin in patients undergoing percutaneous coronary interventions: Meta-analysis of randomized controlled trials.

PubMed

Mina, George S; Firouzbakht, Tina; Modi, Kalgi; Dominic, Paari

2017-11-01

We aimed to perform a gender-based meta-analysis of the outcome of bivalirudin versus heparin in patients undergoing percutaneous coronary interventions (PCI). Bivalirudin has been shown to decrease major bleeding when compared to heparin ± glycoprotein IIb/IIIa inhibitors (GPI) in patients undergoing PCI. It is unclear, however, if those differences in outcomes are the same for men and women. We included randomized controlled trials (RCTs) that compared bivalirudin to heparin with or without GPI in patients undergoing PCI and reported outcome data that were stratified by gender. Random effect model was used to pool odds ratio (OR) and 95% confidence intervals (CI). We included 9 trials with 33,224 patients. Bivalirudin decreased major bleeding when compared to heparin plus routine GPI in both men (OR: 0.51, P < 0.001) and women (OR: 0.55, P < 0.001). However, when GPI were used selectively with heparin, the bleeding lowering effect of bivalirudin was statistically significant in men (OR: 0.69, P = 0.02) but not in women (OR: 0.71, P = 0.21). When compared to heparin ± GPI, there was a nonstatistically significant trend toward lower all-cause mortality with bivalirudin in both men (OR: 0.76, P = 0.055) and women (OR: 0.79, P = 0.21). There were no significant differences in major adverse cardiovascular events between heparin and bivalirudin in both men and women. Bivalirudin decreases major bleeding in both men and women when compared to heparin plus routine GPI. However, when compared to heparin alone, the bleeding lowering benefit of bivalirudin is less evident in women. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Investigating CT to CBCT image registration for head and neck proton therapy as a tool for daily dose recalculation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Landry, Guillaume, E-mail: g.landry@lmu.de; Nijhuis, Reinoud; Thieke, Christian

2015-03-15

Purpose: Intensity modulated proton therapy (IMPT) of head and neck (H and N) cancer patients may be improved by plan adaptation. The decision to adapt the treatment plan based on a dose recalculation on the current anatomy requires a diagnostic quality computed tomography (CT) scan of the patient. As gantry-mounted cone beam CT (CBCT) scanners are currently being offered by vendors, they may offer daily or weekly updates of patient anatomy. CBCT image quality may not be sufficient for accurate proton dose calculation and it is likely necessary to perform CBCT CT number correction. In this work, the authors investigatedmore » deformable image registration (DIR) of the planning CT (pCT) to the CBCT to generate a virtual CT (vCT) to be used for proton dose recalculation. Methods: Datasets of six H and N cancer patients undergoing photon intensity modulated radiation therapy were used in this study to validate the vCT approach. Each dataset contained a CBCT acquired within 3 days of a replanning CT (rpCT), in addition to a pCT. The pCT and rpCT were delineated by a physician. A Morphons algorithm was employed in this work to perform DIR of the pCT to CBCT following a rigid registration of the two images. The contours from the pCT were deformed using the vector field resulting from DIR to yield a contoured vCT. The DIR accuracy was evaluated with a scale invariant feature transform (SIFT) algorithm comparing automatically identified matching features between vCT and CBCT. The rpCT was used as reference for evaluation of the vCT. The vCT and rpCT CT numbers were converted to stopping power ratio and the water equivalent thickness (WET) was calculated. IMPT dose distributions from treatment plans optimized on the pCT were recalculated with a Monte Carlo algorithm on the rpCT and vCT for comparison in terms of gamma index, dose volume histogram (DVH) statistics as well as proton range. The DIR generated contours on the vCT were compared to physician-drawn contours on the rpCT. Results: The DIR accuracy was better than 1.4 mm according to the SIFT evaluation. The mean WET differences between vCT (pCT) and rpCT were below 1 mm (2.6 mm). The amount of voxels passing 3%/3 mm gamma criteria were above 95% for the vCT vs rpCT. When using the rpCT contour set to derive DVH statistics from dose distributions calculated on the rpCT and vCT the differences, expressed in terms of 30 fractions of 2 Gy, were within [−4, 2 Gy] for parotid glands (D{sub mean}), spinal cord (D{sub 2%}), brainstem (D{sub 2%}), and CTV (D{sub 95%}). When using DIR generated contours for the vCT, those differences ranged within [−8, 11 Gy]. Conclusions: In this work, the authors generated CBCT based stopping power distributions using DIR of the pCT to a CBCT scan. DIR accuracy was below 1.4 mm as evaluated by the SIFT algorithm. Dose distributions calculated on the vCT agreed well to those calculated on the rpCT when using gamma index evaluation as well as DVH statistics based on the same contours. The use of DIR generated contours introduced variability in DVH statistics.« less

Orbital atherectomy for severely calcified lesions: More dissections in women but similar 30-day outcomes to men.

PubMed

Chandrasekhar, Jaya; Mehran, Roxana

2016-03-01

Calcified lesions are associated with lower rates of successful percutaneous coronary intervention (PCI), greater stent thrombosis, and increased target vessel revascularization. Women undergoing PCI are more often older than men and likely to present with severe lesion calcification. The ORBIT II study, for the first time compares the effect of the orbital atherectomy system (OAS) in men and women undergoing PCI for severely calcified lesions. Although the adjusted risk of severe dissections was higher in women, the incidence of in-hospital and 30-day outcomes was similar to men. Randomized comparisons of the OAS with rotational atherectomy and with stenting without atherectomy are needed to further elucidate sex-based differences in calcified lesion PCI. © 2016 Wiley Periodicals, Inc.

Effects of testosterone supplementation on clinical and rehabilitative outcomes in older men undergoing on-pump CABG.

PubMed

Maggio, Marcello; Nicolini, Francesco; Cattabiani, Chiara; Beghi, Cesare; Gherli, Tiziano; Schwartz, Robert S; Valenti, Giorgio; Ceda, Gian Paolo

2012-07-01

Testosterone levels decrease with age. This decline is steeper during "critical illnesses". Cardiac surgery is a particular representative model of major clinical condition producing stress responses similar to those observed during severe nonsurgical illness. Cardiac revascularization with extracorporeal circulation is characterized by marked postoperative complications such as insulin resistance, a pro-inflammatory state, acute anemia and renal dysfunction. These phenomena are more evident in older subjects, who are particularly vulnerable in the post-operative state, a condition that has been recently termed as "acute postoperative frailty". We recently showed that in older men with low ejection fraction undergoing cardiac revascularization with extracorporeal circulation, there is a profound decline in anabolic hormones, including testosterone. After surgery testosterone concentration frequently declines to less than 200 ng/dl, a situation suggestive of overt hypogonadism. Since men with low testosterone levels have a high probability of developing mobility limitations, we considered this a rationale for the perioperative use of testosterone treatment in older men undergoing cardiac revasularization surgery. We hypothesized that testosterone supplementation at this time might attenuate the impressive post-surgical catabolic hormonal milieu. The aim of this manuscript is to elucidate an ongoing randomized clinical trial in older men (70+ years old) undergoing elective cardiovascular revascularization with extracorporeal circulation. This randomized clinical trial will evaluate the effects of intramuscular testosterone administration on clinical and functional outcomes in this population. The study will also address potential mechanisms underlying the expected beneficial effects of testosterone supplementation including improvement of insulin sensitivity, markers of inflammatory status and improved hemoglobin levels. Copyright © 2012 Elsevier Inc. All rights reserved.

Independent surgical validation of the new prostate cancer grade-grouping system.

PubMed

Spratt, Daniel E; Cole, Adam I; Palapattu, Ganesh S; Weizer, Alon Z; Jackson, William C; Montgomery, Jeffrey S; Dess, Robert T; Zhao, Shuang G; Lee, Jae Y; Wu, Angela; Kunju, Lakshmi P; Talmich, Emily; Miller, David C; Hollenbeck, Brent K; Tomlins, Scott A; Feng, Felix Y; Mehra, Rohit; Morgan, Todd M

2016-11-01

To report the independent prognostic impact of the new prostate cancer grade-grouping system in a large external validation cohort of patients treated with radical prostatectomy (RP). Between 1994 and 2013, 3 694 consecutive men were treated with RP at a single institution. To investigate the performance of and validate the grade-grouping system, biochemical recurrence-free survival (bRFS) rates were assessed using Kaplan-Meier tests, Cox-regression modelling, and discriminatory comparison analyses. Separate analyses were performed based on biopsy and RP grade. The median follow-up was 52.7 months. The 5-year actuarial bRFS for biopsy grade groups 1-5 were 94.2%, 89.2%, 73.1%, 63.1%, and 54.7%, respectively (P < 0.001). Similarly, the 5-year actuarial bRFS based on RP grade groups was 96.1%, 93.0%, 74.0%, 64.4%, and 49.9% for grade groups 1-5, respectively (P < 0.001). The adjusted hazard ratios for bRFS relative to biopsy grade group 1 were 1.98, 4.20, 5.57, and 9.32 for groups 2, 3, 4, and 5, respectively (P < 0.001), and for RP grade groups were 2.09, 5.27, 5.86, and 10.42 (P < 0.001). The five-grade-group system had a higher prognostic discrimination compared with the commonly used three-tier system (Gleason score 6 vs 7 vs 8-10). In an independent surgical cohort, we have validated the prognostic benefit of the new prostate cancer grade-grouping system for bRFS, and shown that the benefit is maintained after adjusting for important clinicopathological variables. The greater predictive accuracy of the new system will improve risk stratification in the clinical setting and aid in patient counselling. © 2016 The Authors BJU International © 2016 BJU International Published by John Wiley & Sons Ltd.

Predicting participation in and successful outcome of a penile rehabilitation programme using a phosphodiesterase type 5 inhibitor with a vacuum erection device after radical prostatectomy.

PubMed

Kimura, Masaki; Caso, Jorge R; Bañez, Lionel L; Koontz, Bridget F; Gerber, Leah; Senocak, Cagri; Donatucci, Craig F; Vujaskovic, Zeljko; Moul, Judd W; Polascik, Thomas J

2012-12-01

Study Type--Therapy (case series) Level of Evidence 4. What's known on the subject? and What does the study add? The role of the vacuum erection device (VED) has increased with its use in combined therapy with a phosphodiesterase type 5 inhibitor (PDE5i) for penile rehabilitation after radical prostatectomy (RP) and radiotherapy. The advantages of the VED are non-invasive, cost-effective, and a possibility of preventing shrinkage of penis length. Albeit current widespread use of penile rehabilitation programmes for post-RP erectile dysfunction, independent predictors for the rehabilitation participants, as well as for its treatment success have not been fully investigated. In the present study, we have added several new predictors for rehabilitation participation, e.g. African-Americans and higher preoperative sexual function. Conversely, higher preoperative PSA concentrations and the presence of positive surgical margins were predictors for avoidance of rehabilitation. Notably, there was a primary surgeon difference, which had a trend for predicting outcome of the rehabilitation among the participants, implying their surgical technique and follow-up might influence success of the rehabilitation. • To investigate baseline demographic and clinicopathological characteristics of men who participate in our penile rehabilitation programme after radical prostatectomy (RP). • To determine predictors for participation in rehabilitation, as well as successful rehabilitation outcome using multivariable logistic regression analyses. • We analysed data on 2345 consecutive patients who underwent RP between 2001 and 2009 in our institution. • The decision to participate in penile rehabilitation using phosphodiesterase type 5 inhibitor (PDE5i) with a vacuum erection device (VED) was based on the patient's choice after post-RP discussions. • Rehabilitation success was defined using the following criteria: (i) patients who continued the penile rehabilitation programme and did not switch treatment from PDE5i to other erectile aids, (ii) success was noted in men who had an Expanded Prostate Cancer Index Composite (EPIC) sexual function (SF) score of >75% of the patient's baseline EPIC score, and (iii) patients who answered that they achieved adequate erections with a PDE5i. • Logistic regression analysis was used to identify factors associated with treatment participation and its success. • Of 676 patients, 354 (53.2%) men participated in a penile rehabilitation programme. Among 329 rehabilitation participants with available data, 96 (29.2%) had treatment success. • In multivariable regression analysis, African-Americans (odds ratio [OR] 3.47, P < 0.001), and higher preoperative SF (OR 1.02, P < 0.001) were associated with participation in rehabilitation. • Higher preoperative PSA concentration (OR 0.50, P = 0.004) and presence of positive surgical margins (OR 0.68, P = 0.042) were found to be independent predictors for non-participation in the rehabilitation. • For rehabilitation outcomes, being older at surgery (OR 0.93, P = 0.001) and adjuvant therapy (OR 0.34, P = 0.047) had a negative association with successful outcome. • There was a trend in the relationship between primary surgeon and rehabilitation success (OR 1.05, P = 0.053) • Those patients who have risk factors, e.g. adverse prostate cancer features, need to be carefully counselled and encouraged to participate in the penile rehabilitation programme. • Clinicians could lead patients toward successful outcomes if appropriate surgical techniques and rehabilitation are provided. © 2012 BJU INTERNATIONAL.

Urethroplasty After Radiation Therapy for Prostate Cancer

PubMed Central

Glass, Allison S.; McAninch, Jack W.; Zaid, Uwais B.; Cinman, Nadya M.; Breyer, Benjamin N.

2013-01-01

OBJECTIVE To report urethroplasty outcomes in men who developed urethral stricture after undergoing radiation therapy for prostate cancer. METHODS Our urethroplasty database was reviewed for cases of urethral stricture after radiation therapy for prostate cancer between June 2004 and May 2010. Patient demographics, prostate cancer therapy type, stricture length and location, and type of urethroplasty were obtained. All patients received clinical evaluation, including imaging studies post procedure. Treatment success was defined as no need for repeat surgical intervention. RESULTS Twenty-nine patients underwent urethroplasty for radiation-induced stricture. Previous radiation therapy included external beam radiotherapy (EBRT), radical prostatectomy (RP)/EBRT, EBRT/brachytherapy (BT) and BT alone in 11 (38%), 7 (24%), 7 (24%), and 4 (14%) patients, respectively. Mean age was 69 (±6.9) years. Mean stricture length was 2.6 (±1.6) cm. Anastomotic urethroplasty was performed in 76% patients, buccal mucosal graft in 17%, and perineal flap repair in 7%. Stricture was localized to bulbar urethra in 12 (41%), membranous in 12 (41%), vesicourethra in 3 (10%), and pan-urethral in 2 (7%) patients. Overall success rate was 90%. Median follow-up was 40 months (range 12-83). Time to recurrence ranged from 6-16 months. CONCLUSION Multiple forms of urethroplasty appear to be viable options in treating radiation-induced urethral stricture. Future studies are needed to examine the durability of repairs. PMID:22521189

Barriers and Facilitators to Digital Rectal Examination Screening among African-American and Afro-Caribbean Men

PubMed Central

Lee, Daniel J; Consedine, Nathan S; Spencer, Benjamin A

2011-01-01

Objective To examine the effect of race/ethnicity and fear characteristics on the initiation and maintenance of DRE screening. Methods 533 men from Brooklyn, NY, aged 45–70, were classified into four race/ethnic groups: US-born whites, US-born African-American, Jamaican, and Trinidadian/Tobagonian. Participants recorded the number of DRE’s in the past 10 years. Demographics and structural variables, as well as prostate cancer worry and screening fear were measured with validated tools. Results Overall, 30% of subjects reported never having a DRE and 24% reported annual DRE’s. African-American, Jamaican, and Trinidadian/Tobagonian men have higher prostate cancer worry and screening fear scores than white men (all p<0.05). African-American, Jamaican, and Trinidadian/Tobagonian men were less likely to maintain annual DRE’s than white males (ORs = 0.17, 0.26, and 0.16, respectively, all p<0.05). Men with low screening fear were more likely to have an initial DRE (OR=2.3, p<0.05 vs. high screening fear), but no more or less likely to have annual DRE’s. Having a regular physician, comprehensive physician discussion, and annual visits were also associated with undergoing DRE. Conclusion We identified several ethnically-varying barriers and facilitators to DRE screening. African-American and Afro-Caribbean men undergo DRE less often and have higher prostate cancer worry and screening fear scores than white men. Screening fear predicts the likelihood of undergoing an initial, but not annual, DRE screen. Access to a physician and annual visits facilitate DRE screening. Interventions that include both culturally-sensitive education and patient navigation, and consider whether patients should be initiating or maintaining screening, may facilitate guideline-consistent screening. PMID:21477716

Age-stratified outcomes after robotic-assisted laparoscopic radical prostatectomy.

PubMed

Zorn, Kevin C; Mendiola, Frederick P; Rapp, David E; Mikhail, Albert A; Lin, Shang; Orvieto, Marcelo A; Zagaja, Gregory P; Shalhav, Arieh L

2007-01-01

We sought to evaluate post-operative return of urinary and sexual function in men undergoing robotic-assisted laparoscopic radical prostatectomy (RLRP). Prospective assessment of urinary continence and sexual function was performed in patients undergoing RLRP. Subjective assessment involved the use of the validated RAND-36 Item Health Survey/UCLA Prostate Cancer Index questionnaire. Questionnaires were completed pre-operatively and at 1, 3, 6 and 12 months post-operatively. Subset analyses were performed to assess the effect of age on functional outcomes. A total of 338 consecutive patients underwent RLRP between February 2003 and August 2005. Included patients for evaluation comprised of 21, 129, and 150 patients, aged <50, 50-59, and ≥60 years old, respectively. Kaplan-Meier curve analysis demonstrated that younger men (<60 years) achieved subjective continence significantly earlier than older age group (≥60 years) (P = 0.02). Continence rates, however, equalized among all age groups at 1 year follow-up. Younger men (<50 years) also demonstrated a quicker and greater return of sexual function (P = 0.01), which persisted through assessment at 1 year post-operatively. Our results suggest that younger men may have an earlier return of continence and potency when compared to men > 60 years. Despite this finding, continence outcomes appear to be equal among age groups after 1 year of follow-up. Moreover, men < 60 years continue to report superior potency outcomes compared to men > 60 years at 1 year post-operatively. Such findings are valuable in counseling patients undergoing RLRP.

In situ structures of the segmented genome and RNA polymerase complex inside a dsRNA virus

NASA Astrophysics Data System (ADS)

Zhang, Xing; Ding, Ke; Yu, Xuekui; Chang, Winston; Sun, Jingchen; Hong Zhou, Z.

2015-11-01

Viruses in the Reoviridae, like the triple-shelled human rotavirus and the single-shelled insect cytoplasmic polyhedrosis virus (CPV), all package a genome of segmented double-stranded RNAs (dsRNAs) inside the viral capsid and carry out endogenous messenger RNA synthesis through a transcriptional enzyme complex (TEC). By direct electron-counting cryoelectron microscopy and asymmetric reconstruction, we have determined the organization of the dsRNA genome inside quiescent CPV (q-CPV) and the in situ atomic structures of TEC within CPV in both quiescent and transcribing (t-CPV) states. We show that the ten segmented dsRNAs in CPV are organized with ten TECs in a specific, non-symmetric manner, with each dsRNA segment attached directly to a TEC. The TEC consists of two extensively interacting subunits: an RNA-dependent RNA polymerase (RdRP) and an NTPase VP4. We find that the bracelet domain of RdRP undergoes marked conformational change when q-CPV is converted to t-CPV, leading to formation of the RNA template entry channel and access to the polymerase active site. An amino-terminal helix from each of two subunits of the capsid shell protein (CSP) interacts with VP4 and RdRP. These findings establish the link between sensing of environmental cues by the external proteins and activation of endogenous RNA transcription by the TEC inside the virus.

Functional Evolution in Orthologous Cell-encoded RNA-dependent RNA Polymerases.

PubMed

Qian, Xinlei; Hamid, Fursham M; El Sahili, Abbas; Darwis, Dina Amallia; Wong, Yee Hwa; Bhushan, Shashi; Makeyev, Eugene V; Lescar, Julien

2016-04-22

Many eukaryotic organisms encode more than one RNA-dependent RNA polymerase (RdRP) that probably emerged as a result of gene duplication. Such RdRP paralogs often participate in distinct RNA silencing pathways and show characteristic repertoires of enzymatic activities in vitro However, to what extent members of individual paralogous groups can undergo functional changes during speciation remains an open question. We show that orthologs of QDE-1, an RdRP component of the quelling pathway in Neurospora crassa, have rapidly diverged in evolution at the amino acid sequence level. Analyses of purified QDE-1 polymerases from N. crassa (QDE-1(Ncr)) and related fungi, Thielavia terrestris (QDE-1(Tte)) and Myceliophthora thermophila (QDE-1(Mth)), show that all three enzymes can synthesize RNA, but the precise modes of their action differ considerably. Unlike their QDE-1(Ncr) counterpart favoring processive RNA synthesis, QDE-1(Tte) and QDE-1(Mth) produce predominantly short RNA copies via primer-independent initiation. Surprisingly, a 3.19 Å resolution crystal structure of QDE-1(Tte) reveals a quasisymmetric dimer similar to QDE-1(Ncr) Further electron microscopy analyses confirm that QDE-1(Tte) occurs as a dimer in solution and retains this status upon interaction with a template. We conclude that divergence of orthologous RdRPs can result in functional innovation while retaining overall protein fold and quaternary structure. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Functional Evolution in Orthologous Cell-encoded RNA-dependent RNA Polymerases*

PubMed Central

Qian, Xinlei; Hamid, Fursham M.; El Sahili, Abbas; Darwis, Dina Amallia; Wong, Yee Hwa; Bhushan, Shashi; Makeyev, Eugene V.; Lescar, Julien

2016-01-01

Many eukaryotic organisms encode more than one RNA-dependent RNA polymerase (RdRP) that probably emerged as a result of gene duplication. Such RdRP paralogs often participate in distinct RNA silencing pathways and show characteristic repertoires of enzymatic activities in vitro. However, to what extent members of individual paralogous groups can undergo functional changes during speciation remains an open question. We show that orthologs of QDE-1, an RdRP component of the quelling pathway in Neurospora crassa, have rapidly diverged in evolution at the amino acid sequence level. Analyses of purified QDE-1 polymerases from N. crassa (QDE-1Ncr) and related fungi, Thielavia terrestris (QDE-1Tte) and Myceliophthora thermophila (QDE-1Mth), show that all three enzymes can synthesize RNA, but the precise modes of their action differ considerably. Unlike their QDE-1Ncr counterpart favoring processive RNA synthesis, QDE-1Tte and QDE-1Mth produce predominantly short RNA copies via primer-independent initiation. Surprisingly, a 3.19 Å resolution crystal structure of QDE-1Tte reveals a quasisymmetric dimer similar to QDE-1Ncr. Further electron microscopy analyses confirm that QDE-1Tte occurs as a dimer in solution and retains this status upon interaction with a template. We conclude that divergence of orthologous RdRPs can result in functional innovation while retaining overall protein fold and quaternary structure. PMID:26907693

Role of information in preparing men for transrectal ultrasound guided prostate biopsy: a qualitative study embedded in the ProtecT trial.

PubMed

Wade, Julia; Rosario, Derek J; Howson, Joanne; Avery, Kerry N L; Salter, C Elizabeth; Goodwin, M Louise; Blazeby, Jane M; Lane, J Athene; Metcalfe, Chris; Neal, David E; Hamdy, Freddie C; Donovan, Jenny L

2015-02-28

The histological diagnosis of prostate cancer requires a prostate needle biopsy. Little is known about the relationship between information provided to prepare men for transrectal ultrasound guided biopsy (TRUS-Bx) and how men experience biopsy. The objectives were a) to understand men's experiences of biopsy as compared to their expectations; and b) to propose current evidence-based information for men undergoing TRUS-Bx. Between February 2006 and May 2008, 1,147 men undergoing a standardised 10-core transrectal ultrasound guided biopsy protocol under antibiotic cover following a PSA 3.0-19.9 ng/ml in the Prostate Testing for Cancer and Treatment (ProtecT) trial, completed questionnaires about biopsy symptoms. In this embedded qualitative study, in-depth interviews were undertaken with 85 men (mean age 63.6 yrs, mean PSA 4.5 ng/ml) to explore men's experiences of prostate biopsy and how the experience might be improved. Interview data were analysed thematically using qualitative research methods. Findings from the qualitative study were used to guide selection of key findings from the questionnaire study in developing a patient information leaflet preparing men for biopsy. Although most men tolerated TRUS-Bx, a quarter reported problematic side-effects and anxiety. Side effects were perceived as problematic and anxiety arose most commonly when experiences deviated from information provided. Men who were unprepared for elements of TRUS-Bx procedure or its sequelae responded by contacting health professionals for reassurance and voiced frustration that pre-biopsy information had understated the possible severity or duration of pain/discomfort and bleeding. Findings from questionnaire and interview data were combined to propose a comprehensive, evidence-based patient information leaflet for TRUS-Bx. Men reported anxiety associated with TRUS-Bx or its side-effects most commonly if they felt inadequately prepared for the procedure. Data from this qualitative study and the previous questionnaire study have been used to propose an updated, comprehensive evidence-based set of information for men undergoing TRUS-Bx.

Gender differences in risk profile and outcome of Middle Eastern patients undergoing percutaneous coronary intervention.

PubMed

Jarrah, Mohamad I; Hammoudeh, Ayman J; Al-Natour, Dalal B; Khader, Yousef S; Tabbalat, Ramzi A; Alhaddad, Imad A; Kullab, Susan M

2017-02-01

To determine the gender differences in cardiovascular risk profile and outcomes among patients undergoing percutaneous coronary intervention (PCI). Methods: In a prospective multicenter study of consecutive Middle Eastern patients managed with PCI from January 2013 to February 2014 in 12 tertiary care centers in Amman and Irbid, Jordan. Clinical and coronary angiographic features, and major cardiovascular events were assessed for both genders from hospital stay to 1 year. Results: Women comprised 20.6% of 2426 enrolled patients, were older (mean age 62.9 years versus 57.2 years), had higher prevalence of hypertension (81% versus 57%), diabetes (66% versus 44%), dyslipidemia (58% versus 46%), and obesity (44% versus 25%) compared with men, p less than 0.001. The PCI for ST-segment elevation myocardial infarction was indicated for fewer women than men (23% versus 33%; p=0.001). Prevalence of single or multi-vessel coronary artery disease was similar in women and men. More women than men had major bleeding during hospitalization (2.2% versus 0.6%; p=0.003) and at one year (2.5% versus 0.9%; p=0.007). There were no significant differences between women and men in mortality (3.1% versus 1.7%) or stent thrombosis (2.1% versus 1.8%) at 1 year. Conclusion: Middle Eastern women undergoing PCI had worse baseline risk profile compared with men.Except for major bleeding, no gender differences in the incidence of major adverse cardiovascular events were demonstrated.

Clinical presentation and initial management of Black men and White men with prostate cancer in the United Kingdom: the PROCESS cohort study

PubMed Central

Evans, S; Metcalfe, C; Patel, B; Ibrahim, F; Anson, K; Chinegwundoh, F; Corbishley, C; Gillatt, D; Kirby, R; Muir, G; Nargund, V; Popert, R; Wilson, P; Persad, R; Ben-Shlomo, Y

2009-01-01

Background: In the United States, Black men have a higher risk of prostate cancer and worse survival than do White men, but it is unclear whether this is because of differences in diagnosis and management. We re-examined these differences in the United Kingdom, where health care is free and unlikely to vary by socioeconomic status. Methods: This study is a population-based retrospective cohort study of men diagnosed with prostate cancer with data on ethnicity, prognostic factors, and clinical care. A Delphi panel considered the appropriateness of investigations and treatments received. Results: At diagnosis, Black men had similar clinical stage and Gleason scores but higher age-adjusted prostate-specific antigen levels (geometric mean ratio 1.41, 95% confidence interval (95% CI): 1.15–1.73). Black men underwent more investigations and were more likely to undergo radical treatment, although this was largely explained by their younger age. Even after age adjustment, Black men were more likely to undergo a bone scan (odds ratio 1.37, 95% CI: 1.05–1.80). The Delphi analysis did not suggest differential management by ethnicity. Conclusions: This UK-based study comparing Black men with White men found no evidence of differences in disease characteristics at the time of prostate cancer diagnosis, nor of under-investigation or under-treatment in Black men. PMID:19935788

No increased risk of carcinogenesis with mesh-based hernia repairs.

PubMed

Chughtai, Bilal; Sedrakyan, Art; Thomas, Dominique; Mao, Jialin; Eilber, Karyn S; Clemens, J Quentin; Anger, Jennifer T

2017-12-06

The use of synthetic mesh has been placed under considerable scrutiny. We sought to evaluate whether there is a link between placement of synthetic polypropylene mesh for hernia repair and a subsequent cancer diagnosis. Adult men undergoing mesh-based hernia repair from January 2008-December 2009 in New York State were identified and followed through December 2014. Control cohorts of men undergoing cholecystectomy and total knee replacement were control cohorts. 1894 patients undergoing hernia repair, 912 patients in the cholecystectomy control cohort, and 1099 in the TKA control cohort with a cancer diagnosis. In the matched analyses of mesh-based hernia repair and cholecystectomy patients 6.5% vs. 7.1% developed cancer. In the matched analysis of hernia patients and TKA patients, 9.3% vs. 9.1% developed cancer. No association between mesh-based hernia surgery and increased risk of cancer was found. Mesh-based hernia repair was not associated with an increased risk of subsequent development of cancer in men. Copyright © 2017 Elsevier Inc. All rights reserved.

Sex inequality in kidney transplantation rates.

PubMed

Schaubel, D E; Stewart, D E; Morrison, H I; Zimmerman, D L; Cameron, J I; Jeffery, J J; Fenton, S S

Men in the United States undergoing renal replacement therapy are more likely than women to receive a kidney transplant. However, the ability to pay may, in part, be responsible for this finding. To compare adult male and female transplantation rates in a setting in which equal access to medical treatment is assumed. Using data from the Canadian Organ Replacement Register, the rate of first transplantations was computed for the 20, 131 men and the 13,458 women aged 20 years or older who initiated renal replacement therapy between January 1, 1981, and December 31, 1996. Poisson regression analysis was used to estimate the male-female transplantation rate ratio, adjusting for age, race, province, calendar period, underlying disease leading to renal failure, and dialytic modality. Actuarial survival methods were used to compare transplantation probability for covariable-matched cohorts of men and women. Men experienced 20% greater covariable-adjusted kidney transplantation rates relative to women (rate ratio, 1.20; 95% confidence interval, 1.13-1.27). The sex disparity was stronger for cadaveric transplants (rate ratio, 1.23) compared with those from living donors (rate ratio, 1.10). The 5-year probability of receiving a transplant was 47% for men and 39% for women within covariable-matched cohorts (P<.001). The sex disparity in transplantation rates increased with increasing age. The sex effect was weaker among whites and Oriental persons (Chinese, Japanese, Vietnamese, Cambodian, Laotian, Filipino, Malaysian, Indonesian, and Korean) and stronger among blacks, Asian Indians (Indian, Pakistani, and Sri Lankan), and North American Indians (aboriginal). Since survival probability and quality of life are superior for patients who undergo transplantation relative to those who undergo dialysis, an increased effort should be made to distribute kidneys available for transplantation more equitably by sex among patients undergoing renal replacement therapy.

Adult Attachment and Male Aggression in Couple Relationships: The Demand-Withdraw Communication Pattern and Relationship Satisfaction as Mediators

ERIC Educational Resources Information Center

Fournier, Benoit; Brassard, Audrey; Shaver, Phillip R.

2011-01-01

This study examines men's domestic aggression as a function of attachment insecurities, considering the mediating roles of the demand-withdraw communication pattern and relationship satisfaction. The sample included 55 Canadian men undergoing counseling for relationship difficulties including aggression. The men completed questionnaires assessing…

Projected Effects of Radiation-Induced Cancers on Life Expectancy in Patients Undergoing CT Surveillance for Limited-Stage Hodgkin Lymphoma: A Markov Model.

PubMed

Lowry, Kathryn P; Turan, Ekin A; Eisenberg, Jonathan; Kong, Chung Y; Barnes, Jeffrey A; Pandharipande, Pari Vijay

2015-06-01

Patients with limited-stage Hodgkin lymphoma (HL) undergo frequent posttreatment surveillance CT examinations, raising concerns about the cumulative magnitude of radiation exposure. The purpose of this study was to project radiation-induced cancer risks relative to competing risks of HL and account for the differential timing of each. We adapted a previously developed Markov model to project lifetime mortality risks and life expectancy losses due to HL versus radiation-induced cancers in HL patients undergoing surveillance CT. In the base case, we modeled 35-year-old men and women undergoing seven CT examinations of the chest, abdomen, and pelvis over 5 years. Radiation-induced cancer risks and deaths for 17 organ systems were modeled using an organ-specific approach, accounting for specific anatomy exposed at CT. Cohorts of 20-, 50-, and 65-year-old men and women were evaluated in secondary analyses. Markov chain Monte Carlo methods were used to estimate the uncertainty of radiation risk projections. For 35-year-old adults, we projected 3324/100,000 (men) and 3345/100,000 (women) deaths from recurrent lymphoma and 245/100,000 (men, 95% uncertainty interval [UI]: 121-369) and 317/100,000 (women, 95% UI: 202-432) radiation-induced cancer deaths. Discrepancies in life expectancy losses between HL (428 days in men, 482 days in women) and radiation-induced cancers (11.6 days in men, [95% UI: 5.7-17.5], 15.6 days in women [95% UI: 9.8-21.4]) were proportionately greater because of the delayed timing of radiation-induced cancers relative to recurrent HL. Deaths and life expectancy losses from radiation-induced cancers were highest in the youngest cohorts. Given the low rate of radiation-induced cancer deaths associated with CT surveillance, modest CT benefits would justify its use in patients with limited-stage HL.

Male factor infertility and lack of openness about infertility as risk factors for depressive symptoms in males undergoing assisted reproductive technology treatment in Italy.

PubMed

Babore, Alessandra; Stuppia, Liborio; Trumello, Carmen; Candelori, Carla; Antonucci, Ivana

2017-04-01

To investigate the association between male factor infertility and openness to discussing assisted reproductive technology (ART) treatment with levels of depression among men undergoing infertility treatment. Cross-sectional. Not applicable. Three hundred forty participants (170 men and their partners) undergoing ART treatments. Administration of a set of questionnaires. Depressive symptoms were detected by means of the Zung Depression Self-Rating Scale. Participants' willingness to share their infertility treatment experience with other people was assessed by means of self-report questionnaires. In this study, 51.8% of males chose not to discuss their ART treatments with people other than their partner. In addition, the decision to discuss or not discuss the ART treatments with others was significantly associated with men's depressive symptoms. Male factor infertility was significantly associated with depression when considered together with the decision not to discuss ART treatments with others. A general disposition characterized by a lack of openness with others seemed to be a significant predictor of depression. There is a need for routine fertility care to pay greater attention to men's emotional needs. Before commencing reproductive treatment, male patients may benefit from undergoing routine screening for variables (i.e., male factor infertility and openness to others about ART) that may affect their risk of depression. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Predicting survival of men with recurrent prostate cancer after radical prostatectomy.

PubMed

Dell'Oglio, Paolo; Suardi, Nazareno; Boorjian, Stephen A; Fossati, Nicola; Gandaglia, Giorgio; Tian, Zhe; Moschini, Marco; Capitanio, Umberto; Karakiewicz, Pierre I; Montorsi, Francesco; Karnes, R Jeffrey; Briganti, Alberto

2016-02-01

To develop and externally validate a novel nomogram aimed at predicting cancer-specific mortality (CSM) after biochemical recurrence (BCR) among prostate cancer (PCa) patients treated with radical prostatectomy (RP) with or without adjuvant external beam radiotherapy (aRT) and/or hormonal therapy (aHT). The development cohort included 689 consecutive PCa patients treated with RP between 1987 and 2011 with subsequent BCR, defined as two subsequent prostate-specific antigen values >0.2 ng/ml. Multivariable competing-risks regression analyses tested the predictors of CSM after BCR for the purpose of 5-year CSM nomogram development. Validation (2000 bootstrap resamples) was internally tested. External validation was performed into a population of 6734 PCa patients with BCR after treatment with RP at the Mayo Clinic from 1987 to 2011. The predictive accuracy (PA) was quantified using the receiver operating characteristic-derived area under the curve and the calibration plot method. The 5-year CSM-free survival rate was 83.6% (confidence interval [CI]: 79.6-87.2). In multivariable analyses, pathologic stage T3b or more (hazard ratio [HR]: 7.42; p = 0.008), pathologic Gleason score 8-10 (HR: 2.19; p = 0.003), lymph node invasion (HR: 3.57; p = 0.001), time to BCR (HR: 0.99; p = 0.03) and age at BCR (HR: 1.04; p = 0.04), were each significantly associated with the risk of CSM after BCR. The bootstrap-corrected PA was 87.4% (bootstrap 95% CI: 82.0-91.7%). External validation of our nomogram showed a good PA at 83.2%. We developed and externally validated the first nomogram predicting 5-year CSM applicable to contemporary patients with BCR after RP with or without adjuvant treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

KSC-05pd2558

NASA Image and Video Library

2005-12-05

KENNEDY SPACE CENTER, FLA. - The Lockheed Martin Atlas V rocket (center) undergoes a tanking test on Launch Complex 41 at Cape Canaveral Air Force Station in Florida. The rocket was fully fueled with liquid hydrogen, liquid oxygen and RP 1 kerosene fuel. Seen surrounding the rocket are lightning towers that support the catenary wire that provides lightning protection. The Atlas V is the launch vehicle for NASA’s New Horizons spacecraft, scheduled to launch during a 35-day window that opens Jan. 11, and fly through the Pluto system as early as summer 2015.

KSC-05pd2559

NASA Image and Video Library

2005-12-05

KENNEDY SPACE CENTER, FLA. - The Lockheed Martin Atlas V rocket (center) undergoes a tanking test on Launch Complex 41 at Cape Canaveral Air Force Station in Florida. The rocket was fully fueled with liquid hydrogen, liquid oxygen and RP 1 kerosene fuel. Seen surrounding the rocket are lightning towers that support the catenary wire that provides lightning protection. The Atlas V is the launch vehicle for NASA’s New Horizons spacecraft, scheduled to launch during a 35-day window that opens Jan. 11, and fly through the Pluto system as early as summer 2015.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Slad, George William; Merchant, Bion J.

The Seismo - Hydroacoustic Data Acquisition System (SHDAS) is undergoing evaluation in preparation for its engineering, development, and deployment by the U.S Navy as an ocean bottom seismic monitoring system. At the current stage of development, the production seismometers are being evaluated to confirm their performance prior to packaging and assembly for deployment. The testing of the seismometers is being conducted at the Pinon Flats Observatory (PFO) , supervised by Sandia National Laboratories, U.S Navy, and RP Kromer Consulting. SNL will conduct evaluation of the collected seismometer data and comment on the performance of the seismometers.

Gender differences in health-related quality of life in patients undergoing coronary angiography.

PubMed

Gijsberts, Crystel M; Agostoni, Pierfrancesco; Hoefer, Imo E; Asselbergs, Folkert W; Pasterkamp, Gerard; Nathoe, Hendrik; Appelman, Yolande E; de Kleijn, Dominique P V; den Ruijter, Hester M

2015-01-01

Health-related quality of life (HRQOL) reflects the general well-being of individuals. In patients with coronary artery disease (CAD), HRQOL is compromised. Female patients with CAD have been reported to have lower HRQOL. In this study, we investigate gender differences in HRQOL and in associations of patient characteristics with HRQOL in patients with coronary angiography (CAG). We cross-sectionally analysed patients from the Utrecht Coronary Biobank undergoing CAG. All patients filled in an HRQOL questionnaire (RAND-36 and EuroQoL) on inclusion. RAND-36 and EuroQoL HRQOL measures were compared between the genders across indications for CAG, CAD severity and treatment of CAD. RAND-36 HRQOL measures were compared with the general Dutch population. Additionally, we assessed interactions of gender with patient characteristics in their association with HRQOL (EuroQoL). We included 1421 patients (1020 men and 401 women) with a mean age of 65 in our analysis. Women reported lower HRQOL measures than men (mean EuroQoL self-rated health grade 6.84±1.49 in men, 6.46±1.40 in women, p<0.001). The reduction in RAND-36 HRQOL as compared with the general Dutch population was larger in women than in men. From regression analysis, we found that diabetes, a history of cardiovascular disease and symptoms of shortness of breath determined HRQOL (EuroQoL) more strongly in men than in women. Women reported lower HRQOL than men throughout all indications for CAG and regardless of CAD severity or treatment. As compared with the general population, the reduction in HRQOL was more extreme in women than in men. Evident gender differences were found in determinants of HRQOL in patients undergoing CAG, which deserve attention in future research. NCT02304744 (clinicaltrials.gov).

Gender disparities in the utilization of laparoscopic groin hernia repair.

PubMed

Thiels, Cornelius A; Holst, Kimberly A; Ubl, Daniel S; McKenzie, Travis J; Zielinski, Martin D; Farley, David R; Habermann, Elizabeth B; Bingener, Juliane

2017-04-01

Clinical treatment guidelines have suggested that laparoscopic hernia repair should be the preferred approach in both men and women with bilateral or recurrent elective groin hernias. Anecdotal evidence suggests, however, that women are less likely to undergo a laparoscopic repair than men, and therefore, we aimed to delineate if these disparities persisted after controlling for patient factors and comorbidities. The American College of Surgeons National Surgical Quality Improvement Project data were abstracted for all elective groin hernia repairs between 2005 and 2014. Univariate analysis was used to compare rates of laparoscopic surgery between men and women. Multivariable analysis was performed, controlling for patient demographics, preoperative comorbidities, and year of surgery. Over the 10-y period, 141,490 patients underwent elective groin hernia repair, of which 13,325 were women (9.4%). The rate of general anesthesia utilization was high in both men (81.3%) and women (77.2%) with 75.1% of open repairs being performed under general anesthesia. Overall, 20.2% of women underwent laparoscopic repair compared with 28.0% of men (P < 0.01). Women tended to be older, had a lesser body mass index, and slightly greater American Anesthesia Association (all P < 0.05). On multivariable regression, women had decreased odds of undergoing a laparoscopic approach compared with men (odds ratio: 0.70; 95% confidence interval, 0.67-0.73, P < 0.01). In the elective setting, women were less likely to undergo laparoscopic repair of groin hernias than men. Although we are unable to ascertain underlying causes for these gender disparities, these data suggest that there remains a disparity in the management of groin hernias in women. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparison of 68Ga-PSMA-11 PET-CT with mpMRI for preoperative lymph node staging in patients with intermediate to high-risk prostate cancer.

PubMed

Zhang, Qing; Zang, Shiming; Zhang, Chengwei; Fu, Yao; Lv, Xiaoyu; Zhang, Qinglei; Deng, Yongming; Zhang, Chuan; Luo, Rui; Zhao, Xiaozhi; Wang, Wei; Wang, Feng; Guo, Hongqian

2017-11-07

To evaluate the diagnostic value of 68 Ga-PSMA-11 PET-CT with multiparametric magnetic resonance imaging (mpMRI) for lymph node (LN) staging in patients with intermediate- to high-risk prostate cancer (PCa) undergoing radical prostatectomy (RP) with pelvic lymph node dissection (PLND). We retrospectively identified 42 consecutive patients with intermediate- to high-risk PCa according to D'Amico and without concomitant cancer. Preoperative 68 Ga-PSMA-11 PET-CT, pelvic mpMRI and subsequent robot assisted laparoscopic RP with PLND were performed in all patients. Among 42 patients assessed, the preoperative PSA value, Gleason score, pT stage and intraprostatic PCa volume of patients with LN metastases were all significantly higher than those without metastases (P = 0.029, 0.028, 0.004, respectively). The average maximum standardized uptake value (SUV) of 68 Ga-PSMA-11 PET-CT positive PCa of patients with or without LN metastases were 13.10 (range 6.12-51.75) and 7.22 (range 5.4-11.2), respectively (P < 0.001). 68 Ga-PSMA-11 PET-CT and pelvic mpMRI had the ability of succeed on preoperative definite accurate diagnosis and accurate localization of primary PCa in all 42 patients. Fifteen patients (35.71%) had a pN1 stage. 51 positive LN were found. Both 68 Ga-PSMA-11 PET-CT and pelvic mpMRI displayed brillient patient-based and region-based sensitivity, specificity, negative predictive value and positive predictive value. There was no statistical difference for the detection of LNMs according to the diameter of the LNMs between 68 Ga-PSMA-11 PET-CT and mpMRI in this study. Both 68 Ga-PSMA-11 PET-CT and mpMRI performed great value for LN staging in patients with intermediate- to high-risk PCa undergoing RP with PLND. However, despite excellent performance of 68 Ga-PSMA-11 PET-CT, it cannot replace mpMRI that remains excellent for lymph node staging.

Autosomal recessive retinitis pigmentosa with RP1 mutations is associated with myopia.

PubMed

Chassine, Thomas; Bocquet, Béatrice; Daien, Vincent; Avila-Fernandez, Almudena; Ayuso, Carmen; Collin, Rob Wj; Corton, Marta; Hejtmancik, J Fielding; van den Born, L Ingeborgh; Klevering, B Jeroen; Riazuddin, S Amer; Sendon, Nathacha; Lacroux, Annie; Meunier, Isabelle; Hamel, Christian P

2015-10-01

To determine the refractive error in patients with autosomal recessive retinitis pigmentosa (arRP) caused by RP1 mutations and to compare it with that of other genetic subtypes of RP. Twenty-six individuals had arRP with RP1 mutations, 25 had autosomal dominant RP (adRP) with RP1 mutation, 8 and 33 had X-linked RP (xlRP) with RP2 and RPGR mutations, respectively, 198 and 93 had Usher syndrome and arRP without RP1 mutations, respectively. The median of the spherical equivalent (SE) and the IQR (Q25-Q75) was determined and multiple comparisons were performed. arRP patients with RP1 mutations had SE median at -4.0 dioptres (D) OD (Ocula Dextra); -3.88 D OS (Ocula Sinistra), whereas arRP patients without RP1 mutations (-0.50 D OD; -0.75 D OS) and Usher syndrome patients (-0.50 D OD; -0.38 D OS) were significantly less myopic (p<0.0001). Conversely, myopia of xlRP patients with either an RPGR mutation (-4.50 D OD; -5.25 D OS) or an RP2 mutation (-6.25 D OD; -6.88 D OS) was not significantly different from the arRP group with RP1 mutations. arRP without RP1 mutations, Usher syndrome and adRP with RP1 mutation had a narrow IQR (-9.06 to -1.13 D), whereas arRP with RP1 mutations and xlRP with RP2 or RPGR mutations had a larger range (-9.06; -1.13 D). arRP patients with RP1 mutations have myopia not different from patients with xlRP with RP2 or RPGR mutations, while RP patients from other genetic subgroups were emmetropic or mildly myopic. We suggest that arRP patients with high myopic refractive error should be preferentially analysed for RP1 mutations. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Relationship of postprandial nonesterified fatty acids, adipokines, and insulin across gender in human immunodeficiency virus-positive patients undergoing highly active antiretroviral therapy.

PubMed

Lu, Guijing; Thomas-Geevarghese, Asha; Anuurad, Erdembileg; Raghavan, Subhashree; Minolfo, Robert; Ormsby, Bernard; Karmally, Wahida; El-Sadr, Wafaa M; Albu, Jeanine; Berglund, Lars

2009-06-01

Metabolic derangements are common in human immunodeficiency virus (HIV)-positive subjects undergoing antiretroviral therapy, but little is known about postprandial conditions. We investigated the relationship between leptin, adiponectin, nonesterified fatty acids (NEFA), and insulin in response to a day-long meal pattern and evaluated gender differences in HIV-positive men (n = 12) and women (n = 13) undergoing highly active antiretroviral therapy (HAART). For both men and women, a significant decrease in postprandial NEFA levels was observed following breakfast (0.53 vs. 0.22 mmol/L, P < 0.001, baseline and at 3 hours, respectively), whereas day-long postprandial leptin and adiponectin levels showed small nonsignificant oscillations. In contrast to NEFA and adiponectin, postprandial leptin levels were significantly higher among women compared to men (P < 0.05). Postprandial NEFA levels correlated positively with fasting insulin levels (r(2) = 0.25, P = 0.016), and the postbreakfast decrease in NEFA levels correlated significantly with the postbreakfast increase in insulin levels (r(2) = 0.17, P = 0.038). No significant association between postprandial adipokines and insulin was observed. In HAART-treated, HIV-infected men and women, levels of NEFA, but not adipokines, showed significant postprandial variation. Furthermore, food intake resulted in significant NEFA suppression in proportion to the food-stimulated insulin increase.

Polygamy and Risk of Coronary Artery Disease in Men Undergoing Angiography: An Observational Study.

PubMed

Daoulah, Amin; Lotfi, Amir; Al-Murayeh, Mushabab; Al-Kaabi, Salem; Al-Faifi, Salem M; Elkhateeb, Osama E; Alama, Mohamed N; Hersi, Ahmad S; Dixon, Ciaran M; Ahmed, Waleed; Al-Shehri, Mohamed; Youssef, Ali; Elimam, Ahmed Moustafa; Abougalambou, Ayman S; Murad, Waheed; Alsheikh-Ali, Alawi A

2017-01-01

Epidemiologic evidence suggests a link between psychosocial risk factors such as marital status and coronary artery disease (CAD). Polygamy (multiple concurrent wives) is a distinct marital status practiced in many countries in Asia and the Middle East, but its association with CAD is not well defined. We conducted a multicenter, observational study of consecutive patients undergoing coronary angiography during the period from April 1, 2013, to March 30, 2014. Of 1,068 enrolled patients, 687 were married men. Polygamy was reported in 32% of married men (1 wife: 68%, 2 wives: 19%, 3 wives: 10%, and 4 wives: 3%). When stratified by number of wives, significant baseline differences were observed in age, type of community (rural versus urban), prior coronary artery bypass grafting (CABG), and household income. After adjusting for baseline differences, there was a significant association between polygamy and CAD (adjusted OR 4.6 [95% CI 2.5, 8.3]), multivessel disease (MVD) (adjusted OR 2.6 [95% CI 1.8, 3.7]), and left main disease (LMD) (adjusted OR 3.5 [95% CI 2.1, 5.9]). Findings were consistent when the number of wives was analyzed as a continuous variable. In conclusion, among married men undergoing coronary angiography for clinical indications, polygamy is associated with the presence of significant CAD, MVD, and LMD.

Toxicity and dosimetric analysis of non-small cell lung cancer patients undergoing radiotherapy with 4DCT and image-guided intensity modulated radiotherapy: a regional centre's experience.

PubMed

Livingston, Gareth C; Last, Andrew J; Shakespeare, Thomas P; Dwyer, Patrick M; Westhuyzen, Justin; McKay, Michael J; Connors, Lisa; Leader, Stephanie; Greenham, Stuart

2016-09-01

For patients receiving radiotherapy for locally advance non-small cell lung cancer (NSCLC), the probability of experiencing severe radiation pneumonitis (RP) appears to rise with an increase in radiation received by the lungs. Intensity modulated radiotherapy (IMRT) provides the ability to reduce planned doses to healthy organs at risk (OAR) and can potentially reduce treatment-related side effects. This study reports toxicity outcomes and provides a dosimetric comparison with three-dimensional conformal radiotherapy (3DCRT). Thirty curative NSCLC patients received radiotherapy using four-dimensional computed tomography and five-field IMRT. All were assessed for early and late toxicity using common terminology criteria for adverse events. All plans were subsequently re-planned using 3DCRT to the same standard as the clinical plans. Dosimetric parameters for lungs, oesophagus, heart and conformity were recorded for comparison between the two techniques. IMRT plans achieved improved high-dose conformity and reduced OAR doses including lung volumes irradiated to 5-20 Gy. One case each of oesophagitis and erythema (3%) were the only Grade 3 toxicities. Rates of Grade 2 oesophagitis were 40%. No cases of Grade 3 RP were recorded and Grade 2 RP rates were as low as 3%. IMRT provides a dosimetric benefit when compared to 3DCRT. While the clinical benefit appears to increase with increasing target size and increasing complexity, IMRT appears preferential to 3DCRT in the treatment of NSCLC.

Map refinement of locus RP13 to human chromosome 17p13.3 in a second family with autosomal dominant retinitis pigmentosa

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kojis, T.L.; Heinzmann, C.; Ngo, J.T.

1996-02-01

In order to elucidate the genetic basis of autosomal dominant retinitis pigmentosa (adRP) in a large eight-generation family (UCLA-RP09) of British descent, we assessed linkage between the UCLA-RP09 adRP gene and numerous genetic loci, including eight adRP candidate genes, five anonymous adRP-linked DNA loci, and 20 phenotypic markers. Linkage to the UCLA-RP09 disease gene was excluded for all eight candidate genes analyzed, including rhodopsin (RP4) and peripherin/RDS (RP7), for the four adRP loci RP1, RP9, RP10 and RP11, as well as for 17 phenotypic markers. The anonymous DNA marker locus D17S938, linked to adRP locus RP13 on chromosome 17p13.1, yieldedmore » a suggestive but not statistically significant positive lod score. Linkage was confirmed between the UCLA-RP09 adRP gene and markers distal to D17S938 in the chromosomal region 17p13.3. A reanalysis of the original RP13 data from a South African adRP family of British descent, in conjunction with our UCLA-RP09 data, suggests that only one adRP locus exists on 17p but that it maps to a more telomeric position, at band 17p13.3, than previously reported. Confirmation of the involvement of RP13 in two presumably unrelated adRP families, both of British descent, suggests that this locus is a distinct adRP gene in a proportion of British, and possibly other, adRP families. 39 refs., 4 figs., 3 tabs.« less

The effects of thoracic surgery operations on quality of life: a multicenter study.

PubMed

Öz, Gürhan; Solak, Okan; Metin, Muzaffer; Esme, Hıdır; Sayar, Adnan

2015-10-01

Some treatment modalities may cause losses in patients' life comfort because of the treatment process. Our aim is to determine the effects of thoracic surgery operations on patients' quality of life. This is a multicenter and prospective study. A hundred patients, who had undergone posterolateral thoracotomy (PLT) and/or lateral thoracotomy (LT), were included in the study. A quality of life questionnaire (SF-36) was used to determine the changes in life comfort. SF-36 was performed before the operation, on the first month, third month, sixth month and twelfth month after the operation. Seventy-two percent (n = 72) of the patients were male. PLT was performed in 66% (n = 66) of the patients, and LT was performed in 34% (n = 34) of the patients. The types of resections in patients were pneumonectomy in four patients, lobectomy in 59 patients and wedge resection in 11 patients. No resection was performed in 26 patients. Thoracotomy caused deteriorations in physical function (PF), physical role (RP), bodily pain (BP), health, vitality and social function scores. The deteriorations observed in the third month improved in the sixth and twelfth months. The PF, RP, BP and MH scores of the patients with lung resection were much more worsened compared with the patients who did not undergo lung resection. Thoracic surgery operations caused substantial dissatisfaction in life comfort especially in the third month postoperatively. The worsening in physical function, physical role, pain and mental health is much more in patients with resection compared with the patients who did not undergo resection. © 2014 John Wiley & Sons Ltd.

Significance of preoperatively observed detrusor overactivity as a predictor of continence status early after robot-assisted radical prostatectomy

PubMed Central

Yanagiuchi, Akihiro; Miyake, Hideaki; Tanaka, Kazushi; Fujisawa, Masato

2014-01-01

Several recent studies have reported the involvement of bladder dysfunction in the delayed recovery of urinary continence following radical prostatectomy (RP). The objective of this study was to investigate the significance of detrusor overactivity (DO) as a predictor of the early continence status following robot-assisted RP (RARP). This study included 84 consecutive patients with prostate cancer undergoing RARP. Urodynamic studies, including filling cystometry, pressure flow study, electromyogram of the external urethral sphincter and urethral pressure profile, were performed in these patients before surgery. Urinary continence was defined as the use of either no or one pad per day as a precaution only. DO was preoperatively observed in 30 patients (35.7%), and 55 (65.5%) and 34 (40.5%) were judged to be incontinent 1 and 3 months after RARP, respectively. At both 1 and 3 months after RARP, the incidences of incontinence in patients with DO were significantly higher than in those without DO. Of several demographic and urodynamic parameters, univariate analyses identified DO and maximal urethral closure pressure (MUCP) as significant predictors of the continence status at both 1 and 3 months after RARP. Furthermore, DO and MUCP appeared to be independently associated with the continence at both 1 and 3 months after RARP on multivariate analysis. These findings suggest that preoperatively observed DO could be a significant predictor of urinary incontinence early after RARP; therefore, it is recommended to perform urodynamic studies for patients who are scheduled to undergo RARP in order to comprehensively evaluate their preoperative vesicourethral functions. PMID:25038181

Sex-related differences in outcomes among men and women under 55 years of age with acute coronary syndrome undergoing percutaneous coronary intervention: Results from the PROMETHEUS study.

PubMed

Chandrasekhar, Jaya; Baber, Usman; Sartori, Samantha; Faggioni, Michela; Aquino, Melissa; Kini, Annapoorna; Weintraub, William; Rao, Sunil; Kapadia, Samir; Weiss, Sandra; Strauss, Craig; Toma, Catalin; Muhlestein, Brent; DeFranco, Anthony; Effron, Mark; Keller, Stuart; Baker, Brian; Pocock, Stuart; Henry, Timothy; Mehran, Roxana

2017-03-01

Young women undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) experience greater adverse events than men, potentially due to under-treatment. We sought to compare the 1-year outcomes by sex in patients ≤55 years of age from a contemporary PCI cohort. PROMETHEUS was a retrospective multicenter observational US study comparing outcomes in clopidogrel and prasugrel treated patients following ACS PCI. MACE was defined as a composite of death, myocardial infarction, stroke or unplanned revascularization. Clinically significant bleeding was defined as bleeding requiring transfusion or hospitalization. Hazard ratios were generated using multivariable Cox proportional hazards regression. The study cohort included 4,851 patients of which 1,162 (24.0%) were women and 3,689 (76.0%) were men. In this cohort, the prevalence of diabetes (41.0 vs. 27.9%) and chronic kidney disease (12.7 vs. 7.2%) was higher among women compared with men. Irrespective of sex, prasugrel was used in less than one-third of patients (31.8% in men vs. 28.1% in women, P = 0.01). Unadjusted, 1-year MACE (21.1% vs. 16.2%, P < 0.001) and bleeding (3.6% vs. 2.2%, P = 0.01) was significantly higher in women compared with men, but these results were no longer significant after adjustment for risk (HR 1.13, 95% CI 0.94-1.36 for MACE and HR 1.31, 95% CI 0.85-2.04 for bleeding). Women ≤ 55 years of age undergoing ACS PCI have significantly greater comorbidities than young men. Despite a higher risk clinical phenotype in women, prasugrel use was significantly lower in women than men. Female sex was associated with a significantly higher risk of 1-year MACE and bleeding than male sex, findings that are attributable to baseline differences. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Controlling the orientation of spin-correlated radical pairs by covalent linkage to nanoporous anodic aluminum oxide membranes.

PubMed

Chen, Hsiao-Fan; Gardner, Daniel M; Carmieli, Raanan; Wasielewski, Michael R

2013-10-07

Ordered multi-spin assemblies are required for developing solid-state molecule-based spintronics. A linear donor-chromophore-acceptor (D-C-A) molecule was covalently attached inside the 150 nm diam. nanopores of an anodic aluminum oxide (AAO) membrane. Photoexcitation of D-C-A in a 343 mT magnetic field results in sub-nanosecond, two-step electron transfer to yield the spin-correlated radical ion pair (SCRP) (1)(D(+)˙-C-A(-)˙), which then undergoes radical pair intersystem crossing (RP-ISC) to yield (3)(D(+)˙-C-A(-)˙). RP-ISC results in S-T0 mixing to selectively populate the coherent superposition states |S'> and |T'>. Microwave-induced transitions between these states and the unpopulated |T(+1)> and |T(-1)> states result in spin-polarized time-resolved EPR (TREPR) spectra. The dependence of the electron spin polarization (ESP) phase of the TREPR spectra on the orientation of the AAO membrane pores relative to the externally applied magnetic field is used to determine the overall orientation of the SCRPs within the pores at room temperature.

Salivary testosterone and a trinucleotide (CAG) length polymorphism in the androgen receptor gene predict amygdala reactivity in men.

PubMed

Manuck, Stephen B; Marsland, Anna L; Flory, Janine D; Gorka, Adam; Ferrell, Robert E; Hariri, Ahmad R

2010-01-01

In studies employing functional magnetic resonance imaging (fMRI), reactivity of the amygdala to threat-related sensory cues (viz., facial displays of negative emotion) has been found to correlate positively with interindividual variability in testosterone levels of women and young men and to increase on acute administration of exogenous testosterone. Many of the biological actions of testosterone are mediated by intracellular androgen receptors (ARs), which exert transcriptional control of androgen-dependent genes and are expressed in various regions of the brain, including the amygdala. Transactivation potential of the AR decreases (yielding relative androgen insensitivity) with expansion a polyglutamine stretch in the N-terminal domain of the AR protein, as encoded by a trinucleotide (CAG) repeat polymorphism in exon 1 of the X-chromosome AR gene. Here we examined whether amygdala reactivity to threat-related facial expressions (fear, anger) differs as a function of AR CAG length variation and endogenous (salivary) testosterone in a mid-life sample of 41 healthy men (mean age=45.6 years, range: 34-54 years; CAG repeats, range: 19-29). Testosterone correlated inversely with participant age (r=-0.39, p=0.012) and positively with number of CAG repeats (r=0.45, p=0.003). In partial correlations adjusted for testosterone level, reactivity in the ventral amygdala was lowest among men with largest number of CAG repeats. This inverse association was seen in both the right (r(p)=-0.34, p<0.05) and left (r(p)=-0.32, p<0.05) hemisphere. Activation of dorsal amygdala, correlated positively with individual differences in salivary testosterone, also in right (r=0.40, p<0.02) and left (r=0.32, p<0.05) hemisphere, but was not affected by number of CAG repeats. Hence, androgenic influences on threat-related reactivity in the ventral amygdala may be moderated partially by CAG length variation in the AR gene. Because individual differences in salivary testosterone also predicted dorsal amygdala reactivity and did so independently of CAG repeats, it is suggested that androgenic influences within this anatomically distinct region may be mediated, in part, by non-genomic or AR-independent mechanisms.

A single-cell assay for telomere DNA content shows increasing telomere length heterogeneity, as well as increasing mean telomere length in human spermatozoa with advancing age.

PubMed

Antunes, Danielle M F; Kalmbach, Keri H; Wang, Fang; Dracxler, Roberta C; Seth-Smith, Michelle L; Kramer, Yael; Buldo-Licciardi, Julia; Kohlrausch, Fabiana B; Keefe, David L

2015-11-01

The effect of age on telomere length heterogeneity in men has not been studied previously. Our aims were to determine the relationship between variation in sperm telomere length (STL), men's age, and semen parameters in spermatozoa from men undergoing in vitro fertilization (IVF) treatment. To perform this prospective cross-sectional pilot study, telomere length was estimated in 200 individual spermatozoa from men undergoing IVF treatment at the NYU Fertility Center. A novel single-cell telomere content assay (SCT-pqPCR) measured telomere length in individual spermatozoa. Telomere length among individual spermatozoa within an ejaculate varies markedly and increases with age. Older men not only have longer STL but also have more variable STL compared to younger men. STL from samples with normal semen parameters was significantly longer than that from samples with abnormal parameters, but STL did not differ between spermatozoa with normal versus abnormal morphology. The marked increase in STL heterogeneity as men age is consistent with a role for ALT during spermatogenesis. No data have yet reported the effect of age on STL heterogeneity. Based on these results, future studies should expand this modest sample size to search for molecular evidence of ALT in human testes during spermatogenesis.

Development and Testing of The Lunar Resource Prospector Drill

NASA Astrophysics Data System (ADS)

Zacny, K.; Paulsen, G.; Kleinhenz, J.; Smith, J. T.; Quinn, J.

2017-12-01

The goal of the Lunar Resource Prospector (RP) mission is to capture and identify volatiles species within the top one meter layer of the lunar surface. The RP drill has been designed to 1. Generate cuttings and place them on the surface for analysis by the Near InfraRed Volatiles Spectrometer Subsystem (NIRVSS), and 2. Capture cuttings and transfer them to the Oxygen and Volatile Extraction Node (OVEN) coupled with the Lunar Advanced Volatiles Analysis (LAVA) subsystem. The RP drill is based on the TRL4 Mars Icebreaker drill and TRL5 LITA drill developed for capturing samples of ice and ice cemented ground on Mars, and represents over a decade of technology development effort. The TRL6 RP drill weighs approximately 15 kg and is rated at just over 500 Watt. The drill consists of: 1. Rotary-Percussive Drill Head, 2. Sampling Auger, 3. Brushing Station, 4. Feed Stage, and 5. Deployment Stage. To reduce sample handling complexity, the drill auger is designed to capture cuttings as opposed to cores. High sampling efficiency is possible through a dual design of the auger. The lower section has deep and low pitch flutes for retaining of cuttings. The upper section has been designed to efficiently move the cuttings out of the hole. The drill uses a "bite" sampling approach where samples are captured in 10 cm depth intervals. The first generation, TRL4 Icebreaker drill was tested in Mars chamber as well as in Antarctica and the Arctic. It demonstrated drilling at 1-1-100-100 level (1 meter in 1 hour with 100 Watt and 100 N Weight on Bit) in ice, ice cemented ground, soil, and rocks. The second generation, TRL5 LITA drill was deployed on a Carnegie Mellon University rover, called Zoe, and tested in Atacama, Antarctica, the Arctic, and Greenland. The tests demonstrated fully autonomous sample acquisition and delivery to a carousel. The modified LITA drill was tested in NASA GRC's lunar vacuum chamber at <10^-5 torr and <200 K. It demonstrated successful capture and transfer of volatile rich frozen samples to a crucible for analysis. The modified LITA drill has also been successfully vibration tested at NASA KSC. The drill was integrated with RP rover at NASA JSC and successfully tested in a lab and in the field, as well as on a large vibration table and steep slope. The latest TRL6 RP drill is currently undergoing testing at NASA GRC lunar chamber facilities.

SU-E-J-251: Incorporation of Pre-Therapy 18F-FDG Uptake with CT Texture Features in a Predictive Model for Radiation Pneumonitis Development

DOE Office of Scientific and Technical Information (OSTI.GOV)

Anthony, G; Cunliffe, A; Armato, S

2015-06-15

Purpose: To determine whether the addition of standardized uptake value (SUV) statistical variables to CT lung texture features can improve a predictive model of radiation pneumonitis (RP) development in patients undergoing radiation therapy. Methods: Anonymized data from 96 esophageal cancer patients (18 RP-positive cases of Grade ≥ 2) were retrospectively collected including pre-therapy PET/CT scans, pre-/posttherapy diagnostic CT scans and RP status. Twenty texture features (firstorder, fractal, Laws’ filter and gray-level co-occurrence matrix) were calculated from diagnostic CT scans and compared in anatomically matched regions of the lung. The mean, maximum, standard deviation, and 50th–95th percentiles of the SUV valuesmore » for all lung voxels in the corresponding PET scans were acquired. For each texture feature, a logistic regression-based classifier consisting of (1) the average change in that texture feature value between the pre- and post-therapy CT scans and (2) the pre-therapy SUV standard deviation (SUV{sub SD}) was created. The RP-classification performance of each logistic regression model was compared to the performance of its texture feature alone by computing areas under the receiver operating characteristic curves (AUCs). T-tests were performed to determine whether the mean AUC across texture features changed significantly when SUV{sub SD} was added to the classifier. Results: The AUC for single-texturefeature classifiers ranged from 0.58–0.81 in high-dose (≥ 30 Gy) regions of the lungs and from 0.53–0.71 in low-dose (< 10 Gy) regions. Adding SUVSD in a logistic regression model using a 50/50 data partition for training and testing significantly increased the mean AUC by 0.08, 0.06 and 0.04 in the low-, medium- and high-dose regions, respectively. Conclusion: Addition of SUVSD from a pre-therapy PET scan to a single CT-based texture feature improves RP-classification performance on average. These findings demonstrate the potential for more accurate prediction of RP using information from multiple imaging modalities. Supported, in part, by the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health under grant number T32 EB002103; SGA receives royalties and licensing fees through the University of Chicago for computer-aided diagnosis technology. HA receives royalties through the University of Chicago for computer-aided diagnosis technology.« less

Differences in clinical characteristics and disease-free survival for Latino, African American, and non-Latino white men with localized prostate cancer: data from CaPSURE.

PubMed

Latini, David M; Elkin, Eric P; Cooperberg, Matthew R; Sadetsky, Natalia; Duchane, Janeen; Carroll, Peter R

2006-02-15

Few studies of ethnicity and prostate cancer have included Latino men in analyses of baseline clinical characteristics, treatment selection, and disease-free survival (DFS). The present study examines the impact of Latino ethnicity on these parameters in a large, multiinstitutional database of men with prostate cancer. We compared baseline disease characteristics and clinical outcomes for Latino (N = 138), non-Latino White (NLW, N = 5619), and African-American (AA, N = 608) men with localized prostate cancer by using chi-square and ANOVA for baseline variables and survival analysis to examine differences in time to recurrence. Latino men resembled AA men more than NLW on sociodemographic characteristics. AA men had higher Gleason scores and prostate-specific antigen (PSA) at diagnosis than Latino or NLW men (both P < 0.01). 10% of both Latino and AA men presented with advanced disease (T3b/T4/N+/M+) versus 4% of NLW (P < 0.01). Latino men did not receive different treatments than NLW or AA men after controlling for clinical and demographic factors; however, AA men were more likely to receive external beam radiation (OR = 1.51, 95% confidence interval [CI] = 0.99-2.31) and hormone treatment (OR = 1.56, 95% CI = 1.05-2.32) then NLW men. For prostatectomy patients, 3-year actuarial DFS rates were 83% for NLW men and 86% for Latino men versus 69% for AA men (P < 0.01). After controlling for clinical and sociodemographic variables, AA men were somewhat more likely than NLW to experience disease recurrence after radical prostatectomy (RP) (HR = 1.38, 95% CI = 0.98-1.94, P = 0.06). Latinos are more similar to African Americans on sociodemographic characteristics but more similar to NLW on clinical presentation, treatments received, and DFS. Copyright 2006 American Cancer Society.

Low acceptability of medical male circumcision as an HIV/AIDS prevention intervention within a South African community that practises traditional circumcision.

PubMed

Mark, Daniella; Middelkoop, Keren; Black, Samantha; Roux, Surita; Fleurs, Llewellyn; Wood, Robin; Bekker, Linda-Gail

2012-05-23

Traditional circumcision is practised among some indigenous tribes in South Africa (SA) such as the Xhosa. Recent experimental evidence has demonstrated the benefits of male circumcision for the prevention of HIV infection in heterosexual men. The acceptability of circumcision as a biomedical intervention mirroring an ingrained cultural practice, as well as the age and extent of the procedure, are poorly understood. Men aged 15 - 42 years were recruited in a peri-urban settlement near Cape Town. Participants completed an interviewer-administered questionnaire assessing self-reported circumcision status, context and reasons for previous or planned circumcision, and willingness to undergo medical circumcision for themselves or their sons. Results were confirmed by clinical examination. The most recent HIV test result was compared with circumcision status. Of the 199 men enrolled, 148 (74%) reported being traditionally circumcised; of the 51 not circumcised, 50 were planning the traditional procedure. Among men self-reporting circumcision, 40 (27%) had some or all of the foreskin remaining. The median age at traditional circumcision was 21 years (interquartile range 19 - 22 years). While knowledge of the preventive benefit of circumcision was reported by 128 men (66%), most were unwilling to undergo medical circumcision or allow their sons to do so, because of religion/culture, notions of manhood, and social disapproval. Almost all men in this study had undergone or were planning to undergo traditional circumcision and were largely opposed to the medically performed procedure. In the majority, traditional circumcision had occurred after the mean age of sexual debut and almost a quarter were found to have only partial foreskin removal. To ensure optimal HIV prevention benefits, strategies to facilitate complete foreskin removal prior to sexual debut within traditional circumcision practices require further attention.

Excess mortality in women compared to men after PCI in STEMI: an analysis of 11,931 patients during 2000-2009.

PubMed

de Boer, Sanneke P M; Roos-Hesselink, Jolien W; van Leeuwen, Maarten A H; Lenzen, Mattie J; van Geuns, Robert-Jan; Regar, Evelyn; van Mieghem, Nicolas M; van Domburg, Ron; Zijlstra, Felix; Serruys, Patrick W; Boersma, Eric

2014-09-20

Ambiguity exists whether gender affects outcome in patients undergoing percutaneous coronary intervention (PCI). To evaluate the relationship between gender and outcome in a large cohort of PCI patients, 11,931 consecutive patients who underwent PCI for various indications during 2000-2009 were studied using survival analyses and Cox regression models. Most patients (n=8588; 72%) were men. Women were older and more often had a history of hypertension and diabetes mellitus. Men smoked more frequently, had a more extensive cardiovascular history (previous MI, PCI and CABG), a higher prevalence of renal impairment and multi-vessel disease. In STEMI patients, women had higher 31-day mortality rates than men (11.6% vs. 6.5%, respectively, p<0.001). This difference remained after adjustment for confounders (aHR at 30-days 1.54 and 95% CI 1.22-1.96). Likewise, higher mortality was observed at 1-year (15.1% vs. 9.3%) and 4-year follow-up (21.6% vs. 15.0%, aHR 1.30 and 95% CI 1.10-1.53). There were no differences in mortality between women and men in NSTE-ACS (aHR at 4-years 1.05 and 95% CI 0.85-1.28) or stable angina (HR at 4-years 0.85 and 95% CI 0.68-1.08). Women undergoing PCI for STEMI had higher mortality than men. The excess mortality in women appeared in the first month after PCI and could only partially be explained by a difference in baseline characteristics. No gender differences in outcome in patients undergoing PCI for NSTE-ACS and stable angina were observed. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Pre-operative training induces changes in the histomorphometry and muscle function of the pelvic floor in patients with indication of radical prostatectomy.

PubMed

Ocampo-Trujillo, A; Carbonell-González, J; Martínez-Blanco, A; Díaz-Hung, A; Muñoz, C A; Ramírez-Vélez, R

2014-01-01

To evaluate the efficacy of preoperative pelvic floor muscle training (PFMT) on histomorphometry, muscle function, urinary continence and quality of life of patients undergoing radical prostatectomy (RP). A prospective intervention clinical study was designed in 16 patients with indication of RP who were randomized into two groups. The Control Group received routine pre-surgical education (hygienic-dietary measures). The intervention group received a training session with supervised PFMT, three times a day, for four weeks, 30 days before the PR. Muscle function of the external urethral sphincter, contraction pressure of the levator ani, urinary continence and quality of life related to health (HRQoL) were evaluated before and after the intervention. At the end of the intervention and day of the surgery, samples of residual muscle tissue were obtained from the external sphincter muscle of the urethra for histomorphometric analysis. After the intervention, those participants who carried out PFMT showed an increase in the cross-sectional area of the muscle fibers of the external urethral sphincter (1,313 ± 1,075 μm(2)vs. 1,056 ± 844 μm(2), P=.03) and higher pressure contraction of the levator ani (F=9.188; P=.010). After catheter removal, 62% of patients in the experimental group and 37% in the control group showed no incontinence. After removal of the catheter, 75% of the experimental group did not require any pad compared to 25% in the control group (p=NS). There were no significant differences between the two groups in any of the HRQoL domains studied. Pre-surgical PFMT in patients with RP indication induces changes in the histology and function of the pelvic floor muscles, without changes in urogenital function and HRQoL. These results provide new evidence regarding the benefit of PFMT in preventing RP associated complications. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

The Impact of Definitive Local Therapy for Lymph Node-Positive Prostate Cancer: A Population-Based Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rusthoven, Chad G., E-mail: chad.rusthoven@ucdenver.edu; Carlson, Julie A.; Waxweiler, Timothy V.

2014-04-01

Purpose: To evaluate the survival outcomes for patients with lymph node-positive, nonmetastatic prostate cancer undergoing definitive local therapy (radical prostatectomy [RP], external beam radiation therapy [EBRT], or both) versus no local therapy (NLT) in the US population in the modern prostate specific antigen (PSA) era. Methods and Materials: The Surveillance, Epidemiology, and End Results database was queried for patients with T1-4N1M0 prostate cancer diagnosed from 1995 through 2005. To allow comparisons of equivalent datasets, patients were analyzed in separate clinical (cN+) and pathologically confirmed (pN+) lymph node-positive cohorts. Kaplan-Meier overall survival (OS) and prostate cancer-specific survival (PCSS) estimates were generated,more » with accompanying univariate log-rank and multivariate Cox proportional hazards comparisons. Results: A total of 796 cN+ and 2991 pN+ patients were evaluable. Among cN+ patients, 43% underwent EBRT and 57% had NLT. Outcomes for cN+ patients favored EBRT, with 10-year OS rates of 45% versus 29% (P<.001) and PCSS rates of 67% versus 53% (P<.001). Among pN+ patients, 78% underwent local therapy (RP 57%, EBRT 10%, or both 11%) and 22% had NLT. Outcomes for pN+ also favored local therapy, with 10-year OS rates of 65% versus 42% (P<.001) and PCSS rates of 78% versus 56% (P<.001). On multivariate analysis, local therapy in both the cN+ and pN+ cohorts remained independently associated with improved OS and PCSS (all P<.001). Local therapy was associated with favorable hazard ratios across subgroups, including patients aged ≥70 years and those with multiple positive lymph nodes. Among pN+ patients, no significant differences in survival were observed between RP versus EBRT and RP with or without adjuvant EBRT. Conclusions: In this large, population-based cohort, definitive local therapy was associated with significantly improved survival in patients with lymph node-positive prostate cancer.« less

Postprostatectomy Erectile Dysfunction: A Review

PubMed Central

Salonia, Andrea; Briganti, Alberto; Montorsi, Francesco

2016-01-01

In the current era of the early diagnosis of prostate cancer (PCa) and the development of minimally invasive surgical techniques, erectile dysfunction (ED) represents an important issue, with up to 68% of patients who undergo radical prostatectomy (RP) complaining of postoperative erectile function (EF) impairment. In this context, it is crucial to comprehensively consider all factors possibly associated with the prevention of post-RP ED throughout the entire clinical management of PCa patients. A careful assessment of both oncological and functional baseline characteristics should be carried out for each patient preoperatively. Baseline EF, together with age and the overall burden of comorbidities, has been strongly associated with the chance of post-RP EF recovery. With this goal in mind, internationally validated psychometric instruments are preferable for ensuring proper baseline EF evaluations, and questionnaires should be administered at the proper time before surgery. Careful preoperative counselling is also required, both to respect the patient's wishes and to avoid false expectations regarding eventual recovery of baseline EF. The advent of robotic surgery has led to improvements in the knowledge of prostate surgical anatomy, as reflected by the formal redefinition of nerve-sparing techniques. Overall, comparative studies have shown significantly better EF outcomes for robotic RP than for open techniques, although data from prospective trials have not always been consistent. Preclinical data and several prospective randomized trials have demonstrated the value of treating patients with oral phosphodiesterase 5 inhibitors (PDE5is) after surgery, with the concomitant potential benefit of early re-oxygenation of the erectile tissue, which appears to be crucial for avoiding the eventual penile structural changes that are associated with postoperative neuropraxia and ultimately result in severe ED. For patients who do not properly respond to PDE5is, proper counselling regarding intracavernous treatment should be considered, along with the further possibility of surgical treatment for ED involving the implantation of a penile prosthesis. PMID:27574591

Increasing sex differences in the use of cardiac resynchronization therapy with or without implantable cardioverter-defibrillator

PubMed Central

Chatterjee, Neal A.; Borgquist, Rasmus; Chang, Yuchiao; Lewey, Jennifer; Jackson, Vicki A.; Singh, Jagmeet P.; Metlay, Joshua P.; Lindvall, Charlotta

2017-01-01

Aims Previous studies have identified sex disparities in the use of cardiac resynchronization therapy (CRT) and implantable cardioverter defibrillators (ICD), although the basis of underutilization in women remains poorly understood. The aim of this study was to assess sex differences in patterns of CRT use with our without ICD. Methods and results In this cross-sectional study using the National Inpatient Sample database we identified 311 009 patients undergoing CRT implantation in the United States between 2006 and 2012. Demographic and clinical characteristics were compared between men and women undergoing CRT implantation, with special attention to clinical predictors of left ventricular reverse remodelling (CRT response, score range: 0–4) and reduced ICD efficacy (score range: 0–7). When compared to men, women undergoing CRT implantation were significantly more likely to have ≥ 3 predictors of CRT response (47.3 vs. 33.2%, P < 0.001) and less likely to have ≥3 predictors of reduced ICD efficacy (27.0 vs. 37.3%, P < 0.001). Despite this, men were significantly more likely to undergo CRT with ICD (CRT-D) as the type of CRT (88.6 vs. 80.1% of all CRT implants). Compared to those with the greatest likelihood of CRT response (score ≥ 3), those with the least likelihood of CRT response had a significant decreased odds of CRT-D implant (adj odds ratio 0.27 [0.24–0.31], P < 0.001), with a greater decreased odds in women compared to men (P, for sex interaction <0.001). The difference in the % of CRT-D implant in men vs. women increased over the study period (P, sex Δ time trend = 0.012). Conclusion In this large, contemporary cohort, sex differences in CRT-D implantation were inversely related to predicted CRT efficacy and have increased over time. Future efforts to narrow the gap in CRT-D implantation in men and women may help better align device selection with those most likely to benefit. PMID:28065904

Understanding of multigene test results among males undergoing germline testing for inherited prostate cancer: Implications for genetic counseling.

PubMed

Giri, Veda N; Obeid, Elias; Hegarty, Sarah E; Gross, Laura; Bealin, Lisa; Hyatt, Colette; Fang, Carolyn Y; Leader, Amy

2018-04-14

Genetic testing (GT) for prostate cancer (PCA) is rising, with limited insights regarding genetic counseling (GC) needs of males. Genetic Evaluation of Men (GEM) is a prospective multigene testing study for inherited PCA. Men undergoing GC were surveyed on knowledge of cancer risk and genetics (CRG) and understanding of personal GT results to identify GC needs. GEM participants with or high-risk for PCA were recruited. Pre-test GC was in-person, with video and handout, or via telehealth. Post-test disclosure was in-person, by phone, or via telehealth. Clinical and family history data were obtained from participant surveys and medical records. Participants completed measures of knowledge of CRG, literacy, and numeracy pre-test and post-test. Understanding of personal genetic results was assessed post-test. Factors associated with knowledge of CRG and understanding of personal genetic results were examined using multivariable linear regression or McNemar's test. Among 109 men who completed pre- and post-GT surveys, multivariable analysis revealed family history meeting hereditary cancer syndrome (HCS) criteria was significantly predictive of higher baseline knowledge (P = 0.040). Of 101 men who responded definitively regarding understanding of results, 13 incorrectly reported their result (McNemar's P < 0.001). Factors significantly associated with discordance between reported and actual results included having a variant of uncertain significance (VUS) (P < 0.001) and undergoing GC via pre-test video and post-test phone disclosure (P = 0.015). While meeting criteria for HCS was associated with higher knowledge of CRG, understanding of personal GT results was lacking among a subset of males with VUS. A more exploratory finding was lack of understanding of results among men who underwent GC utilizing video and phone. Studies optimizing GC strategies for males undergoing multigene testing for inherited PCA are warranted. © 2018 Wiley Periodicals, Inc.

Regional Radiation Pneumonitis After SIRT of a Subcapsular Liver Metastasis: What is the Effect of Direct Beta Irradiation?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dobrocky, Tomas, E-mail: tomas.dobrocky@insel.ch; Fuerstner, Markus, E-mail: markus.fuerstner@insel.ch; Klaeser, Bernd, E-mail: bernd.klaeser@insel.ch

2015-08-15

We herein present a patient undergoing selective internal radiation therapy with an almost normal lung shunt fraction of 11.5 %, developing histologically proven radiation pneumonitis. Due to a predominance of pulmonary consolidations in the right lower lung and its proximity to a large liver metastases located in the dome of the right liver lobe a Monte Carlo simulation was performed to estimate the effect of direct irradiation of the lung parenchyma. According to our calculations direct irradiation seems negligible and RP is almost exclusively due to ectopic draining of radioactive spheres.

The Patient Burden of Bladder Outlet Obstruction after Prostate Cancer Treatment.

PubMed

Liberman, Daniel; Jarosek, Stephanie; Virnig, Beth A; Chu, Haitao; Elliott, Sean P

2016-05-01

Bladder outlet obstruction after prostate cancer therapy imposes a significant burden on health and quality of life in men. Our objective was to describe the burden of bladder outlet obstruction after prostate cancer therapy by detailing the type of procedures performed and how often those procedures were repeated in men with recurrent bladder outlet obstruction. Using SEER (Surveillance, Epidemiology and End Results)-Medicare linked data from 1992 to 2007 with followup through 2009 we identified 12,676 men who underwent at least 1 bladder outlet obstruction procedure after prostate cancer therapy, including external beam radiotherapy in 3,994, brachytherapy in 1,485, brachytherapy plus external beam radiotherapy in 1,847, radical prostatectomy in 4,736, radical prostatectomy plus external beam radiotherapy in 369 and cryotherapy in 245. Histogram, incidence rates and Cox proportional hazards models with repeat events analysis were done to describe the burden of repeat bladder outlet obstruction treatments stratified by prostate cancer therapy type. We describe the type of bladder outlet obstruction surgery grouped by level of invasiveness. At a median followup of 8.8 years 44.6% of men underwent 2 or more bladder outlet obstruction procedures. Compared to men who underwent radical prostatectomy those treated with brachytherapy and brachytherapy plus external beam radiotherapy were at increased adjusted risk for repeat bladder outlet obstruction treatment (HR 1.2 and 1.32, respectively, each p <0.05). After stricture incision the men treated with radical prostatectomy or radical prostatectomy plus external beam radiotherapy were most likely to undergo dilation at a rate of 34.7% to 35.0%. Stricture resection/ablation was more common after brachytherapy, external beam radiotherapy or brachytherapy plus external beam radiotherapy at a rate of 28.9% to 41.2%. Almost half of the men with bladder outlet obstruction after prostate cancer therapy undergo more than 1 procedure. Furthermore men with bladder outlet obstruction after radiotherapy undergo more invasive endoscopic therapies and are at higher risk for multiple treatments than men with bladder outlet obstruction after radical prostatectomy. Copyright © 2016 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Expression of Wild-Type Rp1 Protein in Rp1 Knock-in Mice Rescues the Retinal Degeneration Phenotype

PubMed Central

Liu, Qin; Collin, Rob W. J.; Cremers, Frans P. M.; den Hollander, Anneke I.; van den Born, L. Ingeborgh; Pierce, Eric A.

2012-01-01

Mutations in the retinitis pigmentosa 1 (RP1) gene are a common cause of autosomal dominant retinitis pigmentosa (adRP), and have also been found to cause autosomal recessive RP (arRP) in a few families. The 33 dominant mutations and 6 recessive RP1 mutations identified to date are all nonsense or frameshift mutations, and almost exclusively (38 out of 39) are located in the 4th and final exon of RP1. To better understand the underlying disease mechanisms of and help develop therapeutic strategies for RP1 disease, we performed a series of human genetic and animal studies using gene targeted and transgenic mice. Here we report that a frameshift mutation in the 3rd exon of RP1 (c.686delC; p.P229QfsX35) found in a patient with recessive RP1 disease causes RP in the homozygous state, whereas the heterozygous carriers are unaffected, confirming that haploinsufficiency is not the causative mechanism for RP1 disease. We then generated Rp1 knock-in mice with a nonsense Q662X mutation in exon 4, as well as Rp1 transgenic mice carrying a wild-type BAC Rp1 transgene. The Rp1-Q662X allele produces a truncated Rp1 protein, and homozygous Rp1-Q662X mice experience a progressive photoreceptor degeneration characterized disorganization of photoreceptor outer segments. This phenotype could be prevented by expression of a normal amount of Rp1 protein from the BAC transgene without removal of the mutant Rp1-Q662X protein. Over-expression of Rp1 protein in additional BAC Rp1 transgenic lines resulted in retinal degeneration. These findings suggest that the truncated Rp1-Q662X protein does not exert a toxic gain-of-function effect. These results also imply that in principle gene augmentation therapy could be beneficial for both recessive and dominant RP1 patients, but the levels of RP1 protein delivered for therapy will have to be carefully controlled. PMID:22927954

Polygamy and Risk of Coronary Artery Disease in Men Undergoing Angiography: An Observational Study

PubMed Central

Lotfi, Amir; Al-Murayeh, Mushabab; Al-kaabi, Salem; Al-Faifi, Salem M.; Alama, Mohamed N.; Hersi, Ahmad S.; Dixon, Ciaran M.; Ahmed, Waleed; Al-Shehri, Mohamed; Youssef, Ali; Elimam, Ahmed Moustafa; Abougalambou, Ayman S.; Murad, Waheed; Alsheikh-Ali, Alawi A.

2017-01-01

Epidemiologic evidence suggests a link between psychosocial risk factors such as marital status and coronary artery disease (CAD). Polygamy (multiple concurrent wives) is a distinct marital status practiced in many countries in Asia and the Middle East, but its association with CAD is not well defined. We conducted a multicenter, observational study of consecutive patients undergoing coronary angiography during the period from April 1, 2013, to March 30, 2014. Of 1,068 enrolled patients, 687 were married men. Polygamy was reported in 32% of married men (1 wife: 68%, 2 wives: 19%, 3 wives: 10%, and 4 wives: 3%). When stratified by number of wives, significant baseline differences were observed in age, type of community (rural versus urban), prior coronary artery bypass grafting (CABG), and household income. After adjusting for baseline differences, there was a significant association between polygamy and CAD (adjusted OR 4.6 [95% CI 2.5, 8.3]), multivessel disease (MVD) (adjusted OR 2.6 [95% CI 1.8, 3.7]), and left main disease (LMD) (adjusted OR 3.5 [95% CI 2.1, 5.9]). Findings were consistent when the number of wives was analyzed as a continuous variable. In conclusion, among married men undergoing coronary angiography for clinical indications, polygamy is associated with the presence of significant CAD, MVD, and LMD. PMID:28250991

5-Year Downstream Outcomes Following Prostate-Specific Antigen (PSA) Screening in Older Men

PubMed Central

Walter, Louise C.; Fung, Kathy Z.; Kirby, Katharine A.; Shi, Ying; Espaldon, Roxanne; O'Brien, Sarah; Freedland, Stephen J.; Powell, Adam A.; Hoffman, Richard M.

2013-01-01

Background Despite ongoing controversies surrounding PSA screening, large numbers of men age 65+ undergo screening. However, there are few data quantifying the chain of events following screening in clinical practice to better inform decisions. The objective of this study is to quantify 5-year downstream outcomes following a PSA screening result > 4 ng/ml in older men. Methods Longitudinal cohort study of 295,645 men age 65+ who underwent PSA screening in the VA healthcare system in 2003 and were followed for 5 years using national VA and Medicare data. Among men whose index screening PSA was > 4 ng/ml we determined the number who underwent biopsy, were diagnosed with prostate cancer, were treated and survived 5-years, according to baseline characteristics. Biopsy and treatment complications were also assessed. Results 25,208 (8.5%) men had an index PSA > 4 ng/ml. During 5-year follow-up, 8,313 (33%) men underwent at least one biopsy, 5,220 (63%) of men biopsied were diagnosed with prostate cancer of whom 4,284 (82%) were treated. Receipt of biopsy decreased with advancing age and worsening comorbidity (P<0.001), whereas the percentage treated for biopsy-detected cancer exceeded 75% even among men age 85+, those with Charlson score 3+, and those with low-risk cancer. Among men with biopsy-detected cancer, the risk of dying of non-prostate cancer causes increased with advancing age and comorbidity (P<0.001). 468 (6%) of men had 7-day biopsy complications. Treatment complications included 584 (14%) men with new incontinence and 588 (14%) men with new erectile dysfunction. Conclusions Receipt of biopsy is low in older men with abnormal screening PSA and decreases with advancing age and comorbidity. However, once biopsy detects cancer most men undergo immediate treatment regardless of advancing age, comorbidity, or low-risk cancer. Understanding downstream outcomes in clinical practice should better inform individualized decisions among older men considering PSA screening. PMID:23588999

SU-F-J-102: Lower Esophagus Margin Implications Based On Rapid Computational Algorithm for SBRT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cardenas, M; Mazur, T; Li, H

2016-06-15

Purpose: To quantify inter-fraction esophagus-variation. Methods: Computed tomography and daily on-treatment 0.3-T MRI data sets for 7 patients were analyzed using a novel Matlab-based (Mathworks, Natick, MA) rapid computational method. Rigid registration was performed from the cricoid to the gastro-esophageal junction. CT and MR-based contours were compared at slice intervals of 3mm. Variation was quantified by “expansion,” defined as additional length in any radial direction from CT contour to MR contour. Expansion computations were performed with 360° of freedom in each axial slice. We partitioned expansions into left anterior, right anterior, right posterior, and left posterior quadrants (LA, RA, RP,more » and LP, respectively). Sample means were compared by analysis of variance (ANOVA) and Fisher’s Protected Least Significant Difference test. Results: Fifteen fractions and 1121 axial slices from 7 patients undergoing SBRT for primary lung cancer (3) and metastatic lung disease (4) were analyzed, generating 41,970 measurements. Mean LA, RA, RP, and LP expansions were 4.30±0.05 mm, 3.71±0.05mm, 3.17±0.07, and 3.98±0.06mm, respectively. 50.13% of all axial slices showed variation > 5 mm in one or more directions. Variation was greatest in lower esophagus with mean LA, RA, RP, and LP expansion (5.98±0.09 mm, 4.59±0.09 mm, 4.04±0.16 mm, and 5.41±0.16 mm, respectively). The difference was significant compared to mid and upper esophagus (p<.0001). The 95th percentiles of expansion for LA, RA, RP, LP were 13.36 mm, 9.97 mm, 11.29 mm, and 12.19 mm, respectively. Conclusion: Analysis of on-treatment MR imaging of the lower esophagus during thoracic SBRT suggests margin expansions of 13.36 mm LA, 9.97 mm RA, 11.29 mm RP, 12.19 mm LP would account for 95% of measurements. Our novel algorithm for rapid assessment of margin expansion for critical structures with 360° of freedom in each axial slice enables continuously adaptive patient-specific margins which may reduce overlap with high-dose regions.« less

[To cognize retinitis pigmentosa with scientific view].

PubMed

Li, Gen-lin

2009-03-01

Retinitis pigmentosa (RP) is the most common inherited eye disease that usually leads into blind, and is high simplex and clinical heterogeneity. Recent years, some new hereditary forms have been found, such as digenic RP, mitochondrial RP, incomplete dominant inheritance RP. The phenotype of RP is multiplicity. Incompatible phenomenon between genotype and phenotypes was shown in some genes such as peripherin/RDS, RHO, RP2 and RP3. The complicated phenotype was shown in the rare RP forms, such as centricity RP, stemma RP, retinitis pigmentosa sine pigmento, and retinal degeneration slow. Retinal transplantation, retinal implantation, drug and neurotrophic factor therapy, and gene therapy have been well studied worldwide and presented some hopeful efficacy. Ophthalmologists and practitioners should cognize the new advance and new knowledge on RP therapy with a scientific view for better serving the RP patients.

Phase Variation of NadA in Invasive Neisseria meningitidis Isolates Impacts on Coverage Estimates for 4C-MenB, a MenB vaccine.

PubMed

Green, Luke R; Lucidarme, Jay; Dave, Neelam; Chan, Hannah; Clark, Stephen; Borrow, Ray; Bayliss, Christopher D

2018-06-27

A recombinant NadA protein is one of the four major protective antigens of 4C-MenB (Bexsero®), a vaccine developed for serogroup B Neisseria meningitidis (MenB). The Meningococcal Antigen Typing System (MATS) is utilised as a high throughput assay for assessing the invasive MenB strain coverage of 4C-MenB. Where present, the nadA gene is subject to phase variable changes in transcription due to a 5'TAAA repeat tract located in a regulatory region. The promoter-containing intergenic region sequences (IGR) and 5'TAAA repeat numbers were determined for 906 invasive meningococcal disease isolates possessing the nadA gene. Exclusion of the 5'TAAA repeats reduced the number of IGR alleles from 82 to 23. Repeat numbers were associated with low and high levels of NadA expression by Western blotting and ELISA. Low expression repeat numbers were present in 83% of 179 MenB isolates with NadA-2/3 or Nad-1 peptide variants and 68% of 480 MenW ST-11 complex isolates with Nad-2/3 peptide variants. For isolates with vaccine-compatible NadA variants, 93% of MATS negative isolates were associated with low expression repeat numbers whereas 63% of isolates with MATS RP scores above the 95% confidence interval for the positive bactericidal threshold had high expression repeat numbers. Analysis of the 5'TAAA repeat number has potential as a rapid, high throughput method for assessing strain coverage for the NadA-component of 4C-MenB. A key application will be assessing coverage in meningococcal disease cases where confirmation is by PCR only and MATS cannot be applied. Copyright © 2018 Green et al.

Prognostic Importance of Small Prostate Size in Men Receiving Definitive Prostate Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taira, Al V.; Merrick, Gregory S., E-mail: gmerrick@urologicresearchinstitute.org; Galbreath, Robert W.

Purpose: To assess whether small prostate size is an adverse prognostic factor in men undergoing brachytherapy in the same manner in which it seems to be for men undergoing radical prostatectomy. Methods and Materials: From April 1995 to June 2008, 2024 patients underwent brachytherapy by a single brachytherapist. Median follow-up was 7.4 years. The role of small prostate size ({<=}20 cm{sup 3}) as a prognostic factor for biochemical progression-free survival, cause-specific survival, and all-cause mortality was investigated. The differences in survival between men with small and larger prostates were compared using Kaplan-Meier curves and log-rank tests. Results: Median prostate sizemore » for the entire cohort was 32.7 cm{sup 3}. For the 167 men with small prostates, median prostate size was 17.4 cm{sup 3}. There was no difference in biochemical progression-free survival (95.2% vs 96.2%, P=.603), cause-specific survival (97.7% vs 98.3%, P=.546), or all-cause mortality (78.0% vs 77.2%, P=.838) at 10 years for men with small prostates compared with men with larger prostates. On univariate and multivariate analysis, small prostate size was not associated with any of the primary outcome measures. Conclusion: Men with small prostates treated with brachytherapy have excellent outcomes and are at no higher risk of treatment failure than men with larger glands. High-quality implants with adequate margins seem sufficient to address the increased adverse risk factors associated with small prostate size.« less

Transcription of four Rhopalosiphum padi (L.) heat shock protein genes and their responses to heat stress and insecticide exposure.

PubMed

Li, Yuting; Zhao, Qi; Duan, Xinle; Song, Chunman; Chen, Maohua

2017-03-01

The bird cherry-oat aphid, Rhopalosiphum padi (L.), a worldwide destructive pest, is more heat tolerant than other wheat aphids, and it has developed resistance to different insecticides. Heat shock proteins (HSPs) play an important role in coping with environmental stresses. To investigate Hsp transcriptional responses to heat and insecticide stress, four full-length Hsp genes from R. padi (RpHsp60, RpHsc70, RpHsp70-1, and RpHsp70-2) were cloned. Four RpHsps were expressed during all R. padi developmental stages, but at varying levels. The mRNA levels of RpHsps were increased under thermal stress and reached maximal induction at a lower temperature (36°C) in the alate morph than in the apterous morph (37°C or 38°C). RpHsp expressions under heat stress suggest that RpHsp70-1 and RpHsp70-2 are inducible in both apterous and alate morphs, RpHsc70 is only heat-inducible in apterous morph, and RpHsp60 exhibits poor sensitivity to heat stress. The pretreatment at 37°C significantly increase both the survival rate and the RpHsps expression level of R. padi at subsequent lethal temperature. Under exposure to two sublethal concentrations (LC 10 and LC 30 ) of beta-cypermethrin, both RpHsp70-1 and RpHsp70-2 expressions were induced and reached a maximum 24h after exposure. In contrast, expression of RpHsp60 was not induced by either sublethal concentration of beta-cypermethrin. Moreover, the responses of RpHsp70-1 and RpHsp70-2 to heat shock were more sensitive than those to beta-cypermethrin. These results suggest that induction of RpHsp expression is related to thermal tolerance, and that RpHsp70-1 and RpHsp70-2 are the primary genes involved in the response to both heat and pesticide stress. Copyright © 2016 Elsevier Inc. All rights reserved.

Lymph node yield during radical prostatectomy does not impact rate of biochemical recurrence in patients with seminal vesicle invasion and node-negative disease.

PubMed

Badani, Ketan K; Reddy, Balaji N; Moskowitz, Eric J; Paulucci, David J; Beksac, Alp Tuna; Martini, Alberto; Whalen, Michael J; Skarecky, Douglas W; Huynh, Linda My; Ahlering, Thomas E

2018-06-01

Seminal vesicle invasion (SVI) is a risk factor for poor oncologic outcome in patients with prostate cancer. Modifications to the pelvic lymph node dissection (PLND) during radical prostatectomy (RP) have been reported to have a therapeutic benefit. The present study is the first to determine if lymph node yield (LNY) is associated with a lower risk of biochemical recurrence (BCR) for men with SVI. A total of 220 patients from 2 high-volume institutions who underwent RP without adjuvant treatment between 1990 and 2015 and had prostate cancer with SVI (i.e., pT3b) were identified, and 21 patients did not undergo lymph node dissection. BCR was defined as a postoperative PSA>0.2ng/mL, or use of salvage androgen deprivation therapy (ADT) or radiation. Multivariable Cox proportional hazards models were used to determine whether LNY was predictive of BCR, controlling for PSA, pathologic Gleason Score, pathologic lymph node status, NCCN risk category, etc. The Kaplan-Meier method was used to determine 3-year freedom from BCR. Median number of lymph nodes sampled were 7 (IQR: 3-12; range: 0-35) and 90.5% underwent PLND. The estimated 3-year BCR rate was 43.9%. Results from multivariable analysis demonstrated that LNY was not significantly associated with risk of BCR overall (HR = 1.00, 95% CI: 0.98-1.03; P = 0.848) for pN0 (HR = 0.99, 95% CI: 0.97-1.03; P = 0.916) or pN1 patients (HR = 0.96, 95% CI: 0.88-1.06; P = 0.468). Overall, PSA (HR = 1.02, P<0.001) and biopsy Gleason sum ≥ 8 (HR = 1.81, P = 0.001) were associated with an increased risk of BCR, and increasing LNY increased the likelihood of detecting>2 positive lymph nodes (OR = 1.27, 95% CI: 1.06-1.65, P = 0.023). Seminal vesicle invasion is associated with an increased risk of BCR at 3 years, primarily due to pathologic Gleason score and PSA. Although greater lymph node yield is diagnostic and facilitates more accurate pathologic staging, our data do not show a therapeutic benefit in reducing BCR. Copyright © 2018 Elsevier Inc. All rights reserved.

Collagen content in the bladder of men with LUTS undergoing open prostatectomy: A pilot study.

PubMed

Averbeck, Marcio A; De Lima, Nelson G; Motta, Gabriela A; Beltrao, Lauro F; Abboud Filho, Nury J; Rigotti, Clarice P; Dos Santos, William N; Dos Santos, Steven K J; Da Silva, Luis F B; Rhoden, Ernani L

2018-03-01

To evaluate the collagen content in the bladder wall of men undergoing open prostate surgery. From July 2014 to August 2016, men aged ≥ 50 years, presenting LUTS and undergoing open prostate surgery due to benign prostatic enlargement (BPE) or prostate cancer were prospectively enrolled. Preoperative assessment included validated questionnaires (IPSS and OAB-V8), lower urinary tract ultrasound, and urodynamics. Bladder biopsies were obtained during open prostatectomy for determination of collagen content (sirius red-picric acid stain; polarized light analysis). Collagen to smooth muscle ratio (C/M) in the detrusor was measured and its relationship with preoperative parameters was investigated. The level of significance was P < 0.05. Thirty-eight consecutive patients were included in this pilot study. Mean age was 66.36 ± 6.44 years and mean IPSS was 11.05 ± 8.72 points. Men diagnosed with diabetes mellitus (DM2) were found to have higher collagen content in the bladder wall when compared to non-diabetic patients (17.71 ± 6.82% vs 12.46 ± 5.2%, respectively; P = 0.024). Reduced bladder compliance was also marker for higher collagen content (P = 0.042). Bladder outlet obstruction (BOO) was not a predictor of increased collagen deposition in the bladder wall (P = 0.75). Patients with PVR ≥ 200 mL showed a higher collagen to smooth muscle ratio in the bladder wall (P = 0.036). DM2 and urodynamic parameters, such as increased PVR and reduced bladder compliance, were associated with higher collagen content in the bladder wall of men with LUTS. © 2017 Wiley Periodicals, Inc.

The association of lymph node dissection with 30-day perioperative morbidity among men undergoing minimally invasive radical prostatectomy: analysis of the National Surgical Quality Improvement Program (NSQIP).

PubMed

Brito, Joseph; Pereira, Jorge; Moreira, Daniel M; Pareek, Gyan; Tucci, Christopher; Guo, Ruiting; Zhang, Zheng; Amin, Ali; Mega, Anthony; Renzulli, Joseph; Golijanin, Dragan; Gershman, Boris

2018-06-01

The incremental morbidity of lymph node dissection (LND) among men undergoing radical prostatectomy remains uncertain. We therefore evaluated  the association of LND with perioperative morbidity among men undergoing minimally invasive radical prostatectomy (MIRP). We identified 29,012 men aged 35-89 who underwent MIRP from 2010-2015 in the National Surgical Quality Improvement Program (NSQIP) database, of whom 47% underwent concomitant LND. The associations of LND with 30-day perioperative morbidity and mortality were evaluated using logistic regression, adjusted for patient features. Median age at surgery was 63 (IQR 57, 67) years. There were statistically significant, but clinically insignificant, differences in several baseline characteristics stratified by performance of LND, including older age at surgery (p < 0.001), higher American Society of Anesthesiology (ASA) class (p < 0.001), and longer operative time (p < 0.001) for men who underwent LND. Overall, 30-day complications occurred in 4.3% of patients. There were no statistically significant differences in rates of 30-day complications (4.2 vs. 4.4%, p = 0.44), perioperative blood transfusion (1.7 vs. 1.7%, p = 0.99), hospital readmission (3.6 vs. 4.0%, p = 0.09), reoperation (1.1 vs. 1.1%, p = 0.80), or 30-day mortality (0.1 vs. 0.2%, p = 0.56) between patients who underwent MIRP alone or MIRP with LND, respectively. On multivariable analysis, LND was not significantly associated with an increased risk of perioperative morbidity or 30-day mortality. LND at the time of MIRP does not appear to be associated with an increased risk of perioperative morbidity.

Does infertility history affect the emotional adjustment of couples undergoing assisted reproduction? the mediating role of the importance of parenthood.

PubMed

Moura-Ramos, Mariana; Gameiro, Sofia; Canavarro, Maria Cristina; Soares, Isabel; Almeida-Santos, Teresa

2016-05-01

The emotional adjustment of couples undergoing assisted reproductive technology (ART) treatments has been widely studied; however, it remains unclear whether infertility history contributes to couples' adjustment. This study examined the impact of infertility history (duration of infertility and number of previous ART treatment cycles) on the emotional adjustment of couples undergoing an ART cycle and the mediating effect of importance of parenthood on that association. In this cross-sectional study, 70 infertile couples (70 women and 70 men) completed self-report questionnaires assessing emotional adjustment and infertility stress during the hormonal stimulation phase of an ART cycle. Path models accounting for the dyadic nature of the data examined the direct and indirect effects (by affecting representations about parenthood and childlessness) of infertility history on emotional adjustment. The number of previous cycles affected men's, but not women's, emotional adjustment by affecting the representations on the importance of parenthood and of childlessness. Duration of infertility had the opposite effect, as couples with longer infertility reported heightened importance of parenthood, which negatively affected their emotional adjustment. Infertility history was associated with emotional adjustment in men and women, although these associations were complex. The results suggest that progression through treatment is harder for those men and women who attribute higher importance to being parents, which is aggravated by longer infertility. What is already known about the subject? Infertility is an unexpected and stressful life event Assisted reproductive treatments (ART) are emotionally demanding What does this study add? The influence of infertility history on adjustment is mediated by the importance of parenthood Men and women are affected by their past history of infertility differently. © 2015 The Authors. British Journal of Health Psychology published by John Wiley & Sons Ltd on behalf of British Psychological Society.

Smoking, body weight, physical exercise, and risk of lower limb total joint replacement in a population-based cohort of men.

PubMed

Mnatzaganian, George; Ryan, Philip; Norman, Paul E; Davidson, David C; Hiller, Janet E

2011-08-01

To assess the associations of smoking, body weight, and physical activity with risk of undergoing total joint replacement (TJR) in a population-based cohort of men. A cohort study of 11,388 men that integrated clinical data with hospital morbidity data and mortality records was undertaken. The risk of undergoing TJR was modeled on baseline weight, height, comorbidity, socioeconomic status, years of smoking, and exercise in 3 separate age groups, using Cox proportional hazards regressions and competing risk regressions (CRRs). Dose-response relationships between weight and risk of TJR and between smoking and risk of TJR were observed. Being overweight independently increased the risk of TJR, while smoking lowered the risk. The decreased risk among smokers was demonstrated in both Cox and CRR models and became apparent after 23 years of exposure. Men who were in the highest quartile (≥48 years of smoking) were 42-51% less likely to undergo TJR than men who had never smoked. Tests for trend in the log hazard ratios (HRs) across both smoking and weight quantiles yielded significant P values. Vigorous exercise increased the hazard of TJR; however, the association reached statistical significance only in the 70-74-year-old age group (adjusted HR 1.64 [95% confidence interval 1.19-2.24]). Adjusting for Deyo-Charlson Index or Elixhauser's comorbidity measures did not eliminate these associations. Our findings indicate that being overweight and reporting vigorous physical activity increase the risk of TJR. This study is the first to demonstrate a strong inverse dose-response relationship between duration of smoking and risk of TJR. More research is needed to better understand the role of smoking in the pathogenesis of osteoarthritis. Copyright © 2011 by the American College of Rheumatology.

Absolute and relative risk of cardiovascular disease in men with prostate cancer: results from the Population-Based PCBaSe Sweden.

PubMed

Van Hemelrijck, Mieke; Garmo, Hans; Holmberg, Lars; Ingelsson, Erik; Bratt, Ola; Bill-Axelson, Anna; Lambe, Mats; Stattin, Pär; Adolfsson, Jan

2010-07-20

Cardiovascular disease (CVD) is a potential adverse effect of endocrine treatment (ET) for prostate cancer (PC). We investigated absolute and relative CVD risk in 76,600 patients with PC undergoing ET, curative treatment, or surveillance. PCBaSe Sweden is based on the National Prostate Cancer Register, which covers more than 96% of PC cases. Standardized incidence ratios (SIRs) and standardized mortality ratios (SMRs) of ischemic heart disease (IHD), acute myocardial infarction (MI), arrhythmia, heart failure, and stroke were calculated to compare observed and expected (using total Swedish population) numbers of CVD, taking into account age, calendar time, and previous CVD. Between 1997 and 2007, 30,642 patients with PC received primary ET, 26,432 curative treatment, and 19,527 surveillance. SIRs for CVD were elevated in all men with the highest for those undergoing ET, independent of circulatory disease history (SIR MI for men without circulatory disease history: 1.40 [95% CI, 1.31 to 1.49], 1.15 [95% CI, 1.01 to 1.31], and 1.20 [95% CI, 1.11 to 1.30] for men undergoing ET, curative treatment, and surveillance, respectively). Absolute risk differences (ARD) showed that two (arrhythmia) to eight (IHD) extra cases of CVD would occur per 1,000 person-years. SMRs showed similar patterns, with ARD of zero (arrhythmia) to three (IHD) per 1,000 person-years. Increased relative risks of nonfatal and fatal CVD were found among all men with PC, especially those treated with ET. Because ET is currently the only effective treatment for metastatic disease and the ARDs were rather small, our findings indicate that CVD risk should be considered when prescribing ET but should not constitute a contraindication when the expected gain is tangible.

Out of the black box: expansion of a theory-based intervention to self-manage the uncertainty associated with active surveillance (AS) for prostate cancer.

PubMed

Kazer, Meredith Wallace; Bailey, Donald E; Whittemore, Robin

2010-01-01

Active surveillance (AS) (sometimes referred to as watchful waiting) is an alternative approach to managing low-risk forms of prostate cancer. This management approach allows men to avoid expensive prostate cancer treatments and their well-documented adverse events of erectile dysfunction and incontinence. However, AS is associated with illness uncertainty and reduced quality of life (QOL; Wallace, 2003). An uncertainty management intervention (UMI) was developed by Mishel et al. (2002) to manage uncertainty in women treated for breast cancer and men treated for prostate cancer. However, the UMI was not developed for men undergoing AS for prostate cancer and has not been adequately tested in this population. This article reports on the expansion of a theory-based intervention to manage the uncertainty associated with AS for prostate cancer. Intervention Theory (Sidani & Braden, 1998) is discussed as a framework for revising the UMI intervention for men undergoing AS for prostate cancer (UMI-AS). The article concludes with plans for testing of the expanded intervention and implications for the extended theory.

Relationship of Postprandial Nonesterified Fatty Acids, Adipokines, and Insulin Across Gender in Human Immunodeficiency Virus–Positive Patients Undergoing Highly Active Antiretroviral Therapy

PubMed Central

Lu, Guijing; Thomas-Geevarghese, Asha; Anuurad, Erdembileg; Raghavan, Subhashree; Minolfo, Robert; Ormsby, Bernard; Karmally, Wahida; El-Sadr, Wafaa M.; Albu, Jeanine

2009-01-01

Abstract Background Metabolic derangements are common in human immunodeficiency virus (HIV)-positive subjects undergoing antiretroviral therapy, but little is known about postprandial conditions. Methods We investigated the relationship between leptin, adiponectin, nonesterified fatty acids (NEFA), and insulin in response to a day-long meal pattern and evaluated gender differences in HIV-positive men (n = 12) and women (n = 13) undergoing highly active antiretroviral therapy (HAART). Results For both men and women, a significant decrease in postprandial NEFA levels was observed following breakfast (0.53 vs. 0.22 mmol/L, P < 0.001, baseline and at 3 hours, respectively), whereas day-long postprandial leptin and adiponectin levels showed small nonsignificant oscillations. In contrast to NEFA and adiponectin, postprandial leptin levels were significantly higher among women compared to men (P < 0.05). Postprandial NEFA levels correlated positively with fasting insulin levels (r2 = 0.25, P = 0.016), and the postbreakfast decrease in NEFA levels correlated significantly with the postbreakfast increase in insulin levels (r2 = 0.17, P = 0.038). No significant association between postprandial adipokines and insulin was observed. Conclusions In HAART-treated, HIV-infected men and women, levels of NEFA, but not adipokines, showed significant postprandial variation. Furthermore, food intake resulted in significant NEFA suppression in proportion to the food-stimulated insulin increase. PMID:19320559

Site-specific association between distal aortic pulse wave velocity and peripheral arterial stenosis severity: a prospective cardiovascular magnetic resonance study.

PubMed

van den Bosch, Harrie C M; Westenberg, Jos J M; Setz-Pels, Wikke; Wondergem, John; Wolterbeek, Ron; Duijm, Lucien E M; Teijink, Joep A W; de Roos, Albert

2015-01-20

Vascular disease expression in one location may not be representative for disease severity in other vascular territories, however, strong correlation between disease expression and severity within the same vascular segment may be expected. Therefore, we hypothesized that aortic stiffening is more strongly associated with disease expression in a vascular territory directly linked to that aortic segment rather than in a more remote segment. We prospectively compared the association between aortic wall stiffness, expressed by pulse wave velocity (PWV), sampled in the distal aorta, with the severity of peripheral arterial occlusive disease (PAOD) as compared to atherosclerotic markers sampled in remote vascular territories such as PWV in the proximal aorta and the normalized wall index (NWI), representing the vessel wall thickness, of the left common carotid artery. Forty-two patients (23 men; mean age 64±10 years) underwent velocity-encoded cardiovascular magnetic resonance (CMR) in the proximal and distal aorta, whole-body contrast-enhanced MR angiography (CE-MRA) and carotid vessel wall imaging with black-blood CMR in the work-up for PAOD. Strength of associations between aortic stiffness, carotid NWI and peripheral vascular stenosis grade were assessed and evaluated with multiple linear regression. Stenosis severity correlated well with PWV in the distal aorta (Pearson rP=0.64, p<0.001, Spearman rS=0.65, p<0.001) but to a lesser extent with PWV in the proximal aorta (rP=0.48, p=0.002, rS=0.22, p=0.18). Carotid NWI was not associated with peripheral stenosis severity (rP=0.17, p=0.28, rS=0.14, p=0.37) nor with PWV in the proximal aorta (rP=0.22, p=0.17) nor in the distal aorta (rP=0.21, p=0.18). Correlation between stenosis severity and distal aortic PWV remained statistically significant after correction for age and gender. Distal aortic wall stiffness is more directly related to peripheral arterial stenosis severity than markers from more remote vascular territories such as proximal aortic wall stiffness or carotid arterial wall thickness. Site-specific evaluation of vascular disease may be required for full vascular risk estimation.

Metabolic syndrome and low high-density lipoprotein cholesterol are associated with adverse pathological features in patients with prostate cancer treated by radical prostatectomy.

PubMed

Lebdai, Souhil; Mathieu, Romain; Leger, Julie; Haillot, Olivier; Vincendeau, Sébastien; Rioux-Leclercq, Nathalie; Fournier, Georges; Perrouin-Verbe, Marie-Aimée; Doucet, Laurent; Azzouzi, Abdel Rahmene; Rigaud, Jérome; Renaudin, Karine; Charles, Thomas; Bruyere, Franck; Fromont, Gaelle

2018-02-01

Previous studies have suggested a link between metabolic syndrome (MetS) and prostate cancer (PCa). In the present study, we aimed to assess the association between MetS and markers of PCa aggressiveness on radical prostatectomy (RP). All patients consecutively treated for PCa by RP in 6 academic institutions between August 2013 and July 2016 were included. MetS was defined as at least 3 of 5 components (obesity, elevated blood pressure, diabetes, low high-density lipoprotein (HDL)-cholesterol, and hypertriglyceridemia). Demographic, biological, and clinical parameters were prospectively collected, including: age, biopsy results, preoperative serum prostate-specific antigen, surgical procedure, and pathological data of RP specimen. Locally advanced disease was defined as a pT-stage ≥3. International Society of Urological Pathology (ISUP) groups were used for pathological grading. Qualitative and quantitative variables were compared using chi-square and Wilcoxon tests; logistic regression analyses assessed the association of MetS and its components with pathological data. Statistical significance was defined as a P<0.05. Among 567 men, 249 (44%) had MetS. In a multivariate model including preoperative prostate-specific antigen, biopsy ISUP-score, clinical T-stage, age, and ethnicity: we found that MetS was an independent risk factor for positive margins, and ISUP group ≥4 on the RP specimen (odds ratio [OR] = 1.5; 95% CI: 1.1-2.3; P = 0.035; OR = 2.0; 95% CI: 1.1-4.0; P = 0.044, respectively). In addition, low HDL-cholesterol level was associated with locally advanced PCa (OR = 1.6; 95% CI: 1.1-2.4; P = 0.024). Risks of adverse pathological features increased with the number of MetS components: having ≥ 4 MetS components was significantly associated with higher risk of ISUP group ≥ 4 and higher risk of positive margins (OR = 1.9; 95% CI: 1.1-3.3; P = 0.017; OR = 1.8; 95% CI: 1.1-2.8; P = 0.007, respectively). MetS was an independent predictive factor for higher ISUP group and positive margins at RP. Low HDL-cholesterol alone, and having 4 and more MetS components were also associated with higher risk of adverse pathological features. Copyright © 2018. Published by Elsevier Inc.

Assessment of nailfold capillaroscopy by x 30 digital epiluminescence (dermoscopy) in patients with Raynaud phenomenon.

PubMed

Beltrán, E; Toll, A; Pros, A; Carbonell, J; Pujol, R M

2007-05-01

Dermoscopy is a useful tool for dermatologists to study melanocytic lesions. Its possible usefulness in the assessment of capillary nailfold morphological changes (capillaroscopy) has recently been advocated. To assess the practical utility of digital epiluminescence microscopy as a capillaroscopic instrument in patients with Raynaud phenomenon (RP). To compare the sensitivity and specificity rates obtained by epiluminescence microscopy with those previously reported with conventional capillaroscopic devices. Fifty-six consecutive patients with primary RP (PRP; n = 5) or secondary RP (SRP; n = 51) (11 men and 45 women in total) were included in the study. A control group of 10 healthy subjects was also evaluated. Twenty-six patients (46%) had systemic sclerosis (SS), 12 (21%) presystemic sclerosis (pre-SS), one (2%) dermatopolymyositis-SS, one (2%) mixed connective tissue disease, two (4%) Sjögren syndrome, two (4%) an overlap syndrome, one (2%) rheumatoid arthritis and six (11%) other connective tissue diseases. Capillary nailfold changes were studied using a nonportable digital epiluminescence device (magnification x 30). Following a systematized protocol, capillary nailfold morphology, density and distribution were evaluated. Several capillaroscopic patterns were identified (normal, sclerodermic, nonspecific, nondiagnostic) as previously defined. A possible relationship between capillary nailfold changes and the intensity of RP or the presence of associated autoimmune diseases was assessed. The sclerodermic pattern showed a sensitivity of 76.9% and a specificity of 90.9% in SS. A typical capillaroscopic SS pattern was observed in 73% of cases of limited SS and in 82% of cases of diffuse SS. Patients with Sjögren syndrome and dermatopolymyositis-SS showed a nonspecific capillaroscopic pattern. All patients with PRP presented a normal capillaroscopic pattern. A normal capillaroscopic pattern was also observed in 11 of 12 patients with pre-SS. In one of two patients presenting severe sclerodactyly and in all patients showing hand oedema (three of 56), capillaroscopic changes could not be evaluated. Avascular areas correlated significantly with severe RP (P < 0.002), bone resorption (P < 0.007) and diffuse SS (P < 0.008). Digital epiluminescence seems to be a useful and reliable technique in the evaluation of capillary nailfold morphological changes. This technical variation allows the identification of specific capillaroscopic patterns associated with connective tissue diseases. It also permits us to differentiate PRP from SRP. The results obtained with this technique are similar to those previously reported using standard capillaroscopy devices.

Women undergoing aortic surgery are at higher risk for unplanned readmissions compared with men especially when discharged home.

PubMed

Flink, Benjamin J; Long, Chandler A; Duwayri, Yazan; Brewster, Luke P; Veeraswamy, Ravi; Gallagher, Katherine; Arya, Shipra

2016-06-01

Women undergoing vascular surgery have higher morbidity and mortality. Our study explores gender-based differences in patient-centered outcomes such as readmission, length of stay (LOS), and discharge destination (home vs nonhome facility) in aortic aneurysm surgery. Patients were identified from the American College of Surgeons National Surgical Quality Improvement Project database (2011-2013) undergoing abdominal, thoracic, and thoracoabdominal aortic aneurysms (N = 17,763), who were discharged and survived their index hospitalization. The primary outcome was unplanned readmission, and secondary outcomes were discharge to a nonhome facility, LOS, and reasons for unplanned readmission. Univariate, multivariate, and stratified analyses based on gender and discharge destination were used. Overall, 1541 patients (8.7%) experienced an unplanned readmission, with a significantly higher risk in women vs men (10.8% vs 8%; P < .001) overall (Procedure subtypes: abdominal aortic aneurysm [10.1% vs 7.7%; P < .001], thoracic aortic aneurysm [14.1% vs 13.5%; P = .8], and thoracoabdominal aortic aneurysm [14.8% vs 10%; P = .051]). The higher odds of readmission in women compared with men persisted in multivariate analysis after controlling for covariates (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.05-1.4). Similarly, the rate of discharge to a nonhome facility was nearly double in women compared with men (20.6% vs 10.7%; P < .001), but discharge to a nonhome facility was not a significant predictor of unplanned readmission. Upon stratification by discharge destination, the higher odds of readmissions in women compared with men occurred in patients who were discharged home (OR, 1.2; 95% CI, 1.02-1.4) but not in those who were discharged to a nonhome facility (OR, 1.06; 95% CI, 0.8-1.4). Significant differences in LOS were seen in patients who were discharged home. No gender differences were found in reasons for readmission with the three most common reasons being thromboembolic events, wound infections, and pneumonia. Gender disparity exists in the risk of unplanned readmission among aortic aneurysm surgery patients. Women who were discharged home have a higher likelihood of unplanned readmission despite longer LOS than men. These data suggest that further study into the discharge planning processes, social factors, and use of rehabilitation services is needed for women undergoing aortic procedures to decrease readmissions. Published by Elsevier Inc.

Superoxide Dismutase and Transcription Factor sox9 as Mediators of Tumor Suppression by mac25 (IGFBP-rp1) in Prostate Cancer Cells

DTIC Science & Technology

2006-10-01

6 SSC, 5 Denhardt’s solution, 0.1M NaPO4 (pH 7.2), 10mM sodium pyrophosphate, and 50mg/ml sonicated herring sperm DNA (Ulrich et al., 1984). 32P... retention of SOX9 expression. Apoptosis assay Apoptosis was assessed by demonstrating cleavage of PARP by Western blotting (Drivdahl et al., 2001...is the second leading cause of cancer deaths in men and the seventh cause of all cancer deaths (30,000 per year) [1]. From a treatment perspective

Is computed tomography a necessary part of a metastatic evaluation for castration-resistant prostate cancer? Results from the Shared Equal Access Regional Cancer Hospital Database.

PubMed

Hanyok, Brian T; Howard, Lauren E; Amling, Christopher L; Aronson, William J; Cooperberg, Matthew R; Kane, Christopher J; Terris, Martha K; Posadas, Edwin M; Freedland, Stephen J

2016-01-15

Metastatic lesions in prostate cancer beyond the bone have prognostic importance and affect clinical therapeutic decisions. Few data exist regarding the prevalence of soft-tissue metastases at the initial diagnosis of metastatic castration-resistant prostate cancer (mCRPC). This study analyzed 232 men with nonmetastatic (M0) castration-resistant prostate cancer (CRPC) who developed metastases detected by a bone scan or computed tomography (CT). All bone scans and CT scans within the 30 days before or after the mCRPC diagnosis were reviewed. The rate of soft-tissue metastases among those undergoing CT was determined. Then, predictors of soft-tissue metastases and visceral and lymph node metastases were identified. Compared with men undergoing CT (n = 118), men undergoing only bone scans (n = 114) were more likely to have received primary treatment (P = .048), were older (P = .013), and less recently developed metastases (P = .018). Among those undergoing CT, 52 (44%) had soft-tissue metastases, including 20 visceral metastases (17%) and 41 lymph node metastases (35%), whereas 30% had no bone involvement. In a univariable analysis, only prostate-specific antigen (PSA) predicted soft-tissue metastases (odds ratio [OR], 1.27; P = .047), and no statistically significant predictors of visceral metastases were found. A higher PSA level was associated with an increased risk of lymph node metastases (OR, 1.38; P = .014), whereas receiving primary treatment was associated with decreased risk (OR, 0.36; P = .015). The data suggest that there is a relatively high rate of soft-tissue metastasis (44%) among CRPC patients undergoing CT at the initial diagnosis of metastases, including some men with no bone involvement. Therefore, forgoing CT during a metastatic evaluation may lead to an underdiagnosis of soft-tissue metastases and an underdiagnosis of metastases in general. Cancer 2015. © 2015 American Cancer Society. Cancer 2016;122:222-229. © 2015 American Cancer Society. © 2015 American Cancer Society.

In vitro antioxidant activity of rice protein affected by alkaline degree and gastrointestinal protease digestion.

PubMed

Liu, Ye; Wang, Zhengxuan; Li, Hui; Liang, Mingcai; Yang, Lin

2016-12-01

To elucidate whether and how alkali treatment, which is a common process for rice protein (RP) extraction, affects antioxidant activity of RP, the different degree of alkali (from 0.1% to 0.4% of NaOH) was used to extract RP (RP-1, RP-2, RP-3, RP-4). The antioxidant capacities of scavenging free radicals [2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid] diammonium salt, ABTS; 1,1-diphenyl-2-picrylhydrazyl, DPPH), chelating metals (iron, copper) and reducing power investigated in the hydrolysates of RPs (RP-1, RP-2, RP-3, RP-4) during in vitro pepsin-pancreatin digestion were effectively affected by alkali treatment. The present study demonstrated that the weakest antioxidant responses to ABTS radical-scavenging activity, DPPH radical-scavenging activity, iron chelating activity, copper chelating activity and reducing power were produced by RP-4 extracted by the highest alkali proportion (0.4% NaOH). The present study indicates that antioxidant capacity of RP could be more readily depressed by strict alkali degree and affected by gastrointestinal proteases. Results suggest that alkali extraction is a vital process to regulate the antioxidant activity of RP through modifying the compositions of amino acids, which are dependent on alkali magnitude. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Initial effect of controlled release chlorhexidine on subgingival microorganisms.

PubMed

Daneshmand, Nazanin; Jorgensen, Michael G; Nowzari, Hessam; Morrison, John L; Slots, Jørgen

2002-10-01

Little or no data exist on the ability of subgingival application of PerioChip (2.5 mg chlorhexidine gluconate in a biodegradable chip; Astra Pharmaceuticals, Westborough, MA, USA) to suppress periodontopathic microorganisms. The present study compared the subgingival microbiota of periodontitis sites receiving the chlorhexidine chip plus scaling and root planing (Sc/Rp) or Sc/Rp alone. Seven males and six females, mean age 49 years, with moderate to advanced periodontitis participated in the study. In each patient, two bilateral pockets probing 6-7 mm were randomly assigned to treatment by chlorhexidine chip + Sc/Rp, or by Sc/Rp alone. Subgingival placement of chlorhexidine chips was carried out according to the manufacturer's instructions. Sc/Rp was performed with hand instruments for at least 10 min in each study tooth. Subgingival samples were collected by paper-points at baseline, at 2 weeks and at 4 weeks post-treatment. Anaerobic culture methods were used for microbial isolation and identification. The microbiologic examination was carried out blindly. Microbiological data were evaluated by a repeated measures analysis of variance. No statistical difference was found in total colony counts between subgingival sites treated with chlorhexidine chip + Sc/Rp and those treated with Sc/Rp alone. Also, the percentage of major periodontal pathogens (Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis and Bacteroides forsythus) and the percentage of total periodontal pathogens (A. actinomycetemcomitans, P. gingivalis, B. forsythus, Prevotella intermedia-group, Fusobacterium, Eubacterium, Campylobacter rectus, Peptostreptococcus micros, Eikenella corrodens, enteric rods) were not significantly different between the chlorhexidine chip + Sc/Rp group and the Sc/Rp group. At baseline, A. actinomycetemcomitans was recovered from 4 chlorhexidine chip + Sc/Rp sites and 2 Sc/Rp sites, P. gingivalis from 5 chlorhexidine chip + Sc/Rp sites and 4 Sc/Rp sites, and B. forsythus from 9 chlorhexidine chip + Sc/Rp and 7 Sc/Rp sites. At 4 weeks, A. actinomycetemcomitans was detected in 2 chlorhexidine chip + Sc/Rp sites but not in any site receiving Sc/Rp, P. gingivalis in 2 chlorhexidine chip + Sc/Rp sites but not in any Sc/Rp site, and B. forsythus in 1 chlorhexidine chip + Sc/Rp and in 2 Sc/Rp sites. The present data obtained from bilateral periodontitis lesions of 13 adults suggest that chlorhexidine chip treatment of adult periodontitis lesions provides little or no additional antimicrobial benefits compared to thorough Sc/Rp alone.

Bacteriuria and antibiotic resistance in catheter urine specimens following radical prostatectomy.

PubMed

Banks, Jessica A; McGuire, Barry B; Loeb, Stacy; Shrestha, Sanjina; Helfand, Brian T; Catalona, William J

2013-10-01

There are increasing reports of infectious complications following prostate biopsy due to fluoroquinolone resistance. To determine infectious complications at catheter removal following radical prostatectomy (RP), another setting in daily urological practice where fluoroquinolone prophylaxis is frequently used. We prospectively examined urine culture results collected from 334 RP patients immediately prior to catheter removal. Patients received prophylactic antibiotics 1 day before, the day of, and for 5 days after catheter removal. Culture results were reviewed for bacterial species and antimicrobial susceptibilities. Patients with positive urine cultures resistant to the prophylactic antibiotic were switched to culture-specific antibiotic therapy and underwent follow-up culture. The frequency of urinary tract infection (UTI), complications, additional antibiotic therapy, and repeat urine cultures was determined within 60 days. Of the 334 patients identified, 203 (61%) had cultures with no bacterial growth, and 48 (14%) had colony counts of <1,000 bacteria or Candida albicans and received no further antibiotics. The remaining 83 (25%) had positive culture results, of which 7% were resistant to ciprofloxacin. Twenty-four bacterial species were identified, with Pseudomonas aeruginosa (5%) Escherichia coli (4%), and Staphylococcus epidermidis (3%) being the most frequent. Only two (0.6%) men developed clinical symptoms consistent with UTI (i.e., suprapubic pain, fever) prior to catheter removal, and no serious complications occurred. A substantial proportion of RP patients have positive urine cultures at the time of catheter removal, despite the administration of prophylactic fluoroquinolone antibiotics. Potentially virulent organisms are commonly cultured, and ciprofloxacin resistance is frequent. However, outcomes are favorable when culture-specific oral antibiotic therapy is initiated. Copyright © 2013 Elsevier Inc. All rights reserved.

Variations in the open market costs for prostate cancer surgery: a survey of US hospitals.

PubMed

Pate, Scott C; Uhlman, Matthew A; Rosenthal, Jaime A; Cram, Peter; Erickson, Bradley A

2014-03-01

To examine variation in the open market cost of a radical prostatectomy (RP) procedure in the US hospitals for an uninsured patient, as many proposals for health care reform highlight the importance of individuals actively participating in selecting care. However, reports suggest that obtaining procedure prices remains challenging and highly variable. We used 2011-2012 US News and World Report rankings to identify a cohort of 100 hospitals making an effort to include an equal distribution of both academic and private centers, city size, and geographic region. Each hospital was called and the essence of the script included a caller stating he was a healthy, uninsured 55-year-old man recently diagnosed with Gleason 3 + 4 prostatic adenocarcinoma with no metastases. Facility, surgeon, and anesthesia fees were solicited. Seventy hospitals provided facility prices. Facility estimates averaged $34,720 (±20,335; range, $10,100-$135,000), which was statistically higher at academics centers. No significant differences were seen by region, population, or hospital ranking. Surgeon and anesthesia fees were provided by 10%, averaging $8280 (±$4282; range, $4028-$18,720). Thirty-three hospitals provided discounted fees for prompt payment averaging 34% (±16%; range, 10%-80%). There is wide variation in pricing for RP, with higher rates found in academic centers. Wide variation in facility costs were observed, and nearly all were unable to provide surgeon and/or anesthesia fees. Currently, it appears to be unacceptably difficult for men with prostate cancer without insurance to obtain prices for an RP procedure. Copyright © 2014 Elsevier Inc. All rights reserved.

Influence of cataract surgery on optical coherence tomography and neurophysiology measurements in patients with retinitis pigmentosa.

PubMed

Garcia-Martin, Elena; Rodriguez-Mena, Diego; Dolz, Isabel; Almarcegui, Carmen; Gil-Arribas, Laura; Bambo, Maria P; Larrosa, Jose M; Polo, Vicente; Pablo, Luis E

2013-08-01

To evaluate the effect of uncomplicated cataract phacoemulsification on the measurements of visual evoked potentials (VEP), pattern electroretinogram (PERG), and macular and retinal nerve fiber layer (RNFL) using 2 spectral-domain optical coherence tomography (OCT) instruments, the Cirrus OCT (Carl Zeiss Meditech) and Spectralis OCT (Heidelberg Engineering), in patients with retinitis pigmentosa (RP), and to assess the reliability of the OCT measurements before and after cataract surgery. Observational cross-sectional study. Thirty-five eyes of 35 patients with RP (20 men and 15 women, 45-66 years) who underwent cataract phacoemulsification were studied. At 1 month before and 1 month after surgery, visual acuity, VEP, PERG, and 3 repetitions of scans using the RNFL and macular analysis protocols of the Cirrus and Spectralis OCT instruments were performed. The differences in measurements between the 2 visits were analyzed. Repeatability of OCT measurements was evaluated by calculating the coefficients of variation. VEP amplitude, RNFL thicknesses provided by Cirrus and Spectralis, and macular measurements provided by Cirrus OCT differed between the 2 visits. VEP latency, PERG measurements, and macular thicknesses provided by the Spectralis OCT before surgery did not differ significantly from those after surgery. The OCT repeatability was better after surgery, with lower coefficients of variation for scans performed after surgical removal of the cataract. The nuclear, cortical, and posterior subcapsular types of cataracts did not show different repeatability. The presence of cataracts affects VEP amplitude, RNFL, and macular measurements performed with OCT in eyes with RP. Image repeatability significantly improves after cataract phacoemulsification. Copyright © 2013 Elsevier Inc. All rights reserved.

Serum microRNA expression patterns that predict early treatment failure in prostate cancer patients.

PubMed

Singh, Prashant K; Preus, Leah; Hu, Qiang; Yan, Li; Long, Mark D; Morrison, Carl D; Nesline, Mary; Johnson, Candace S; Koochekpour, Shahriar; Kohli, Manish; Liu, Song; Trump, Donald L; Sucheston-Campbell, Lara E; Campbell, Moray J

2014-02-15

We aimed to identify microRNA (miRNA) expression patterns in the serum of prostate cancer (CaP) patients that predict the risk of early treatment failure following radical prostatectomy (RP). Microarray and Q-RT-PCR analyses identified 43 miRNAs as differentiating disease stages within 14 prostate cell lines and reflectedpublically available patient data. 34 of these miRNA were detectable in the serum of CaP patients. Association with time to biochemical progression was examined in a cohort of CaP patients following RP. A greater than two-fold increase in hazard of biochemical progression associated with altered expression of miR-103, miR-125b and miR-222 (p<.0008) in the serum of CaP patients. Prediction models based on penalized regression analyses showed that the levels of the miRNAs and PSA together were better at detecting false positives than models without miRNAs, for similar level of sensitivity. Analyses of publically available data revealed significant and reciprocal relationships between changes in CpG methylation and miRNA expression patterns suggesting a role for CpG methylation to regulate miRNA. Exploratory validation supported roles for miR-222 and miR-125b to predict progression risk in CaP. The current study established that expression patterns of serum-detectable miRNAs taken at the time of RP are prognostic for men who are at risk of experiencing subsequent early biochemical progression. These non-invasive approaches could be used to augment treatment decisions.

Use of Age and Medical Comorbidity to Assess Long-term Other-cause Mortality Risk in a Cohort of Men Undergoing Prostate Biopsy at an Academic Medical Center.

PubMed

Kominsky, Hal D; Bashline, Michael; Eun, Daniel; Pontari, Michel A; Mydlo, Jack H; Reese, Adam C

2017-02-01

To assess life expectancy and biopsy outcomes in men undergoing prostate biopsy at an academic medical center. We analyzed men who underwent prostate biopsy at our medical center between July 2012 and June 2014. Long-term other-cause mortality risk was determined using survival tables. Indications for biopsy and biopsy outcomes were assessed, and compared among men with varying mortality risks. A total of 417 men underwent prostate biopsy, in whom 14-year other-cause mortality risk ranged from 9% to 74%. One hundred ninety-three men (46.3%) were considered low-mortality risk (<40% risk of 14-year mortality), 131 (31.4%) intermediate risk (41%-55% 14-year mortality), and 93 (22.3%) high risk (>55% 14-year mortality). Of the 417 patients who underwent biopsy, 149 (35.7%) were found to have prostate cancer. There was no significant difference in the rate of positive biopsies (P = .72), distribution of Gleason scores (P = .60), or percentage of positive biopsy cores (P = .74) between mortality risk groups. However, by UCSF Cancer of the Prostate Risk Assessment score, there was significant trend toward higher-risk prostate cancer in men with intermediate and high-mortality risk (P = .04). In this analysis, a large number of men with limited life expectancies underwent prostate biopsy. The majority of these men had negative biopsies or low-risk cancers, suggesting that they were unlikely to benefit from biopsy. To avoid potentially unnecessary prostate biopsies, the practitioner must give serious consideration to a patient's age and medical comorbidities before making a recommendation as to whether biopsy should be performed. Copyright © 2016 Elsevier Inc. All rights reserved.

The Severity of Retinal Degeneration in Rp1h Gene-Targeted Mice Is Dependent on Genetic Background

PubMed Central

Liu, Qin; Saveliev, Alexei; Pierce, Eric A.

2009-01-01

Purpose The severity of disease in patients with retinitis pigmentosa (RP) can vary significantly, even among patients with the same primary mutations. It is hypothesized that modifier genes play important roles in determining the severity of RP, including the retinitis pigmentosa 1 (RP1) form of disease. To investigate the basis of variation in disease expression for RP1 disease, the authors generated congenic mice with a gene-targeted retinitis pigmentosa 1 homolog (Rp1h) allele (Rp1htm1Eap) on several different genetic backgrounds and analyzed their retinal phenotypes. Methods The Rp1htm1Eap allele was placed onto the C57BL/6J, DBA1/J, and A/J backgrounds. Retinal function of the resultant congenic mice was evaluated using electroretino-graphic analyses. Retinal structure and ultrastructure were evaluated using light and electron microscopy. Rp1h protein location was determined with immunofluorescence microscopy. Results Analysis of the retinal phenotype of incipient congenic (N6) B6.129S-Rp1h+/tm1Eap, DBA.129S(B6)-Rp1h+/tm1Eap, and A.129S(B6)-Rp1h+/tm1Eap mice at 1 year of age showed retinal degeneration only in the A.129S(B6)-Rp1h+/tm1Eap mice. Further analyses revealed that the photoreceptors of the fully congenic A.129S(B6)-Rp1h+/tm1Eap mice show evidence of degeneration at 6 months of age and are almost completely lost by 18 months of age. In contrast, the photoreceptor cells in the fully congenic B6.129S-Rp1h+/tm1Eap mice remain healthy up to 18 months. Conclusions The severity of the retinal degeneration caused by the Rp1htm1Eap allele is notably dependent on genetic background. The development and characterization of the B6.129S-Rp1h+/tm1Eap and A.129S(B6)-Rp1h+/tm1Eap congenic mouse lines will facilitate identification of sequence alterations in genes that modify the severity of RP1 disease. PMID:19060274

The severity of retinal degeneration in Rp1h gene-targeted mice is dependent on genetic background.

PubMed

Liu, Qin; Saveliev, Alexei; Pierce, Eric A

2009-04-01

The severity of disease in patients with retinitis pigmentosa (RP) can vary significantly, even among patients with the same primary mutations. It is hypothesized that modifier genes play important roles in determining the severity of RP, including the retinitis pigmentosa 1 (RP1) form of disease. To investigate the basis of variation in disease expression for RP1 disease, the authors generated congenic mice with a gene-targeted retinitis pigmentosa 1 homolog (Rp1h) allele (Rp1h(tm1Eap)) on several different genetic backgrounds and analyzed their retinal phenotypes. The Rp1h(tm1Eap) allele was placed onto the C57BL/6J, DBA1/J, and A/J backgrounds. Retinal function of the resultant congenic mice was evaluated using electroretinographic analyses. Retinal structure and ultrastructure were evaluated using light and electron microscopy. Rp1h protein location was determined with immunofluorescence microscopy. Analysis of the retinal phenotype of incipient congenic (N6) B6.129S-Rp1h(+/tm1Eap), DBA.129S(B6)-Rp1h(+/tm1Eap), and A.129S(B6)-Rp1h(+/tm1Eap) mice at 1 year of age showed retinal degeneration only in the A.129S(B6)-Rp1h(+/tm1Eap) mice. Further analyses revealed that the photoreceptors of the fully congenic A.129S(B6)-Rp1h(+/tm1Eap) mice show evidence of degeneration at 6 months of age and are almost completely lost by 18 months of age. In contrast, the photoreceptor cells in the fully congenic B6.129S-Rp1h(+/tm1Eap) mice remain healthy up to 18 months. The severity of the retinal degeneration caused by the Rp1h(tm1Eap) allele is notably dependent on genetic background. The development and characterization of the B6.129S-Rp1h(+/tm1Eap) and A.129S(B6)-Rp1h(+/tm1Eap) congenic mouse lines will facilitate identification of sequence alterations in genes that modify the severity of RP1 disease.

New clinical trial opens to determine safety and efficacy of PROSTVAC, nivolumab and ipilimumab in men with localized prostate cancer | Center for Cancer Research

Cancer.gov

A new study is now open to evaluate the safety and effectiveness of a treatment regimen that combines PROSTVAC with ipilimumab and/or nivolumab in men with localized prostate cancer who have elected to undergo surgical resection (prostatectomy).  Learn more...

The R245X mutation of PCDH15 in Ashkenazi Jewish children diagnosed with nonsyndromic hearing loss foreshadows retinitis pigmentosa.

PubMed

Brownstein, Zippora; Ben-Yosef, Tamar; Dagan, Orit; Frydman, Moshe; Abeliovich, Dvorah; Sagi, Michal; Abraham, Fabian A; Taitelbaum-Swead, Riki; Shohat, Mordechai; Hildesheimer, Minka; Friedman, Thomas B; Avraham, Karen B

2004-06-01

Usher syndrome is a frequent cause of the combination of deafness and blindness due to retinitis pigmentosa (RP). Five genes are known to underlie different forms of Usher syndrome type I (USH1). In the Ashkenazi Jewish population, the R245X mutation of the PCDH15 gene may be the most common cause of USH1 (Ben-Yosef T, Ness SL, Madeo AC, Bar-Lev A, Wolfman JH, Ahmed ZM, Desnick RK, Willner JP, Avraham KB, Ostrer H, Oddoux C, Griffith AJ, Friedman TB N Engl J Med 348: 1664-1670, 2003). To estimate what percentage of Ashkenazi Jewish children born with profound hearing loss will develop RP due to R245X, we examined the prevalence of the R245X PCDH15 mutation and its carrier rate among Ashkenazi Jews in Israel. Among probands diagnosed with nonsyndromic hearing loss not due to mutations of connexin 26 (GJB2) and/or connexin 30 (GJB6), and below the age of 10, 2 of 20 (10%) were homozygous for the R245X mutation. Among older nonsyndromic deaf individuals, no homozygotes were detected, although one individual was heterozygous for R245X. The carrier rate of the R245X mutation among the normal hearing Ashkenazi population in Israel was estimated at 1%. Ashkenazi Jewish children with profound prelingual hearing loss should be evaluated for the R245X PCDH15 mutation and undergo ophthalmologic evaluation to determine whether they will develop RP. Rehabilitation can then begin before loss of vision. Early use of cochlear implants in such cases may rescue these individuals from a dual neurosensory deficit.

Predictors of outcomes in patients with primary retroperitoneal dedifferentiated liposarcoma undergoing surgery.

PubMed

Keung, Emily Z; Hornick, Jason L; Bertagnolli, Monica M; Baldini, Elizabeth H; Raut, Chandrajit P

2014-02-01

Although sarcoma histology is recognized as a prognostic factor, most studies of retroperitoneal sarcomas report results combining multiple histologies and are inadequately powered to identify prognostic factors specific to a particular histology. We reviewed our experience with retroperitoneal dedifferentiated liposarcoma (RP DDLPS) to identify factors predictive of outcomes. All patients with RP DDLPS treated at our institution between 1998 and 2008 were reviewed. Multivariable Cox regression analyses were performed to identify factors predictive of progression-free survival (PFS), local recurrence-free survival (LRFS), distant recurrence-free survival (DRFS), and overall survival (OS). We identified 119 patients with primary DDLPS. Median tumor size was 20.5 cm; 21% were multifocal. French Federation of Cancer Centers Sarcoma Group tumor grades were intermediate in 53% of patients and high in 28% (unknown 19%). Resections were complete (R0/R1) in 80% of patients and incomplete (R2) in 11% (unknown 9%). Tumors were removed intact in 72% of patients and fragmented in 16% (unknown 12%). Median follow-up was 74.1 months. One hundred patients (84%) experienced recurrence or progression, with 92% occurring in the retroperitoneum. Median PFS, LRFS, DRFS, and OS were 21.1, 21.5, 45.8, and 59.0 months, respectively, and were significantly worse with R2 resection. On multivariate analysis, tumor integrity (intact vs fragmented) was predictive of PFS, multifocality predicted LRFS, and extent of resection (R0/R1 vs R2), grade, and tumor integrity predicted OS. In this cohort of primary RP DDLPS, factors under surgeon control (tumor integrity, extent of resection) and reflective of tumor biology (grade, multifocality) impact patient outcomes. Copyright © 2014 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Apparent Disk-mass Reduction and Planetisimal Formation in Gravitationally Unstable Disks in Class 0/I Young Stellar Objects

NASA Astrophysics Data System (ADS)

Tsukamoto, Y.; Okuzumi, S.; Kataoka, A.

2017-04-01

We investigate the dust structure of gravitationally unstable disks undergoing mass accretion from the envelope, envisioning its application to Class 0/I young stellar objects (YSOs). We find that the dust disk quickly settles into a steady state and that, compared to a disk with interstellar medium (ISM) dust-to-gas mass ratio and micron-sized dust, the dust mass in the steady state decreases by a factor of 1/2 to 1/3, and the dust thermal emission decreases by a factor of 1/3 to 1/5. The latter decrease is caused by dust depletion and opacity decrease owing to dust growth. Our results suggest that the masses of gravitationally unstable disks in Class 0/I YSOs are underestimated by a factor of 1/3 to 1/5 when calculated from the dust thermal emission assuming an ISM dust-to-gas mass ratio and micron-sized dust opacity, and that a larger fraction of disks in Class 0/I YSOs is gravitationally unstable than was previously believed. We also investigate the orbital radius {r}{{P}} within which planetesimals form via coagulation of porous dust aggregates and show that {r}{{P}} becomes ˜20 au for a gravitationally unstable disk around a solar mass star. Because {r}{{P}} increases as the gas surface density increases and a gravitationally unstable disk has maximum gas surface density, {r}{{P}}˜ 20 {au} is the theoretical maximum radius for planetesimal formation. We suggest that planetesimal formation in the Class 0/I phase is preferable to that in the Class II phase because a large amount of dust is supplied by envelope-to-disk accretion.

Topically applied NO-releasing nanoparticles can increase intracorporal pressure and elicit spontaneous erections in a rat model of radical prostatectomy

PubMed Central

Tar, Moses; Cabrales, Pedro; Mahantesh, Navarti; Adler, Brandon; Nacharaju, Parimala; Friedman, Adam; Friedman, Joel; Davies, Kelvin P.

2014-01-01

Introduction Patients undergoing radical prostatectomy (RP) suffer from erectile dysfunction (ED) refractory to PDE5 inhibitors, which act downstream of CN-mediated release of nitric oxide (NO). Direct delivery of NO to the penis could potentially circumvent this limitation. Aim To determine if topically applied NO-releasing nanoparticles (NO-np) can elicit erections in a rat model of RP and demonstrate that the mechanism is through increased blood flow. Methods 26 Sprague–Dawley rats underwent bilateral transection of the CN. One week later NO-np were applied topically to the penile shaft in DMSO-gel (10 animals) or coconut oil (6 animals). Control animals were treated with empty-np. Erectile function was determined through the intracorporal pressure/blood pressure ratio (ICP/BP). The effect of the NO-np on blood flow was determined using a hamster dorsal window chamber. Main Outcome Measures Animals were investigated for spontaneous erections, onset and duration of erectile response and basal ICP/BP ratio. Microcirculatory blood-flow was determined through arteriolar and venular diameter and blood flow. Results Eight of ten animals treated with NO-np suspended in DMSO-gel had significant increases in basal ICP/BP, and six out of these ten animals demonstrated spontaneous erections of approximately one minute duration. Onset of spontaneous erections ranged from 5–37 minutes and occurred for at least 45 minutes. Similar results were observed with NO-np applied in coconut oil. No erectile response was observed in control animal models treated with empty-np. The hamster dorsal window chamber demonstrated NO-np applied as a suspension in coconut oil caused a significant increase in the microcirculatory blood flow, sustained over 90 minutes. Conclusions Topically applied NO-np induced spontaneous erections and increased basal ICP in an animal model of RP. These effects are most likely due to increased microcirculatory blood flow. These characteristics suggest that the NO-np would be useful in penile rehabilitation of patients following RP. PMID:25302850

Topically applied NO-releasing nanoparticles can increase intracorporal pressure and elicit spontaneous erections in a rat model of radical prostatectomy.

PubMed

Tar, Moses; Cabrales, Pedro; Navati, Mahantesh; Adler, Brandon; Nacharaju, Parimala; Friedman, Adam J; Friedman, Joel; Davies, Kelvin P

2014-12-01

Patients undergoing radical prostatectomy (RP) suffer from erectile dysfunction (ED) refractory to phosphodiesterase 5 inhibitors, which act downstream of cavernous nerve (CN)-mediated release of nitric oxide (NO). Direct delivery of NO to the penis could potentially circumvent this limitation. This study aimed to determine if topically applied NO-releasing nanoparticles (NO-NPs) could elicit erections in a rat model of RP through increased blood flow. Twenty-six Sprague Dawley rats underwent bilateral transection of the CN. One week later, NO-NPs were applied topically to the penile shaft in dimethylsulfoxide (DMSO) gel (10 animals) or coconut oil (6 animals). Control animals were treated with empty NPs. Erectile function was determined through the intracorporal pressure/blood pressure ratio (ICP/BP). The effect of the NO-NPs on blood flow was determined using a hamster dorsal window chamber. Animals were investigated for spontaneous erections, onset and duration of erectile response, and basal ICP/BP ratio. Microcirculatory blood flow was determined through measurements of arteriolar and venular diameter and red blood cell velocity. Eight of 10 animals treated with NO-NPs suspended in DMSO gel had significant increases in basal ICP/BP, and 6 out of these 10 animals demonstrated spontaneous erections of approximately 1 minute in duration. Time to onset of spontaneous erections ranged from 5 to 37 minutes, and they occurred for at least 45 minutes. Similar results were observed with NO-NPs applied in coconut oil. No erectile response was observed in control animal models treated with empty NPs. The hamster dorsal window chamber experiment demonstrated that NO-NPs applied as a suspension in coconut oil caused a significant increase in the microcirculatory blood flow, sustained over 90 minutes. Topically applied NO-NPs induced spontaneous erections and increased basal ICP in an animal model of RP. These effects are most likely due to increased microcirculatory blood flow. These characteristics suggest that NO-NPs would be useful in penile rehabilitation of patients following RP. © 2014 International Society for Sexual Medicine.

Is the adjustable transobturator system ATOMS® useful for the treatment of male urinary incontinence in low to medium volume urological centers?

PubMed

Manso, M; Alexandre, B; Antunes-Lopes, T; Martins-da-Silva, C; Cruz, F

2018-05-01

Urinary incontinence (UI) is a complication of radical prostatectomy (RP) and transurethral resection of the prostate (TURP). The gold-standard treatment is the artificial urinary sphincter, however, new treatments have been investigated. To examine the outcome of an adjustable transobturator male system (ATOMS ® ) in men with UI after prostatic surgery in a low to medium volume continence center. Twenty-five men with UI were implanted with ATOMS ® system between 2012 and 2014. The most common indication was UI after RP (92%), followed by UI after TURP (8%). Eleven patients (44%) had received adjuvant external beam radiotherapy (RT). Patients were considered to be 'dry' if they stopped wearing pads or needed just one protective pad per day; and improved if the daily number of pads used decreased by at least half. The Incontinence Quality of Life questionnaire (ICIQ-SF) was used, adding a verbal question about the satisfaction of the patient considering the outcome. After a mean follow-up of 21.56 months, 64% were dry and 8% revealed a significant improvement. The success of the procedure was negatively correlated with the severity of the previous UI and with previous treatment with RT. Concerning patients satisfaction, 84% of the patients would repeat the procedure. ATOMS ® offers good rates of cure and improvement of UI after prostatic surgery with a reasonable rate of minor complications. The results of this study, performed in a low to medium volume continence center, are comparable to the results achieved in high volume continence centers. Copyright © 2017 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

Biological properties of prolactin-releasing peptide analogs with a modified aromatic ring of a C-terminal phenylalanine amide.

PubMed

Maletínská, Lenka; Spolcová, Andrea; Maixnerová, Jana; Blechová, Miroslava; Zelezná, Blanka

2011-09-01

Prolactin-releasing peptide (PrRP)-induced secretion of prolactin is not currently considered a primary function of PrRP, but the development of late-onset obesity in both PrRP and PrRP receptor knock-out mice indicates the unique anorexigenic properties of PrRP. In our recent study, we showed comparable potencies of peptides PrRP31 and PrRP20 in binding, intracellular signaling and prolactin release in pituitary RC-4B/C cells, and anorexigenic effect after central administration in fasted mice. In the present study, eight analogs of PrRP20 with C-terminal Phe amide modified with a bulky side chain or a halogenated aromatic ring revealed high binding potency, activation of mitogen-activated protein kinase/extracellular-regulated kinase (MAPK/ERK1/2) and cAMP response element-binding protein (CREB) and prolactin release in RC-4B/C cells. In particular, [PheNO(2)(31)]PrRP20, [1-Nal(31)]PrRP20, [2-Nal(31)]PrRP20 and [Tyr(31)]PrRP20 showed not only in vitro effects comparable or higher than those of PrRP20, but also a very significant and long-lasting anorexigenic effect after central administration in fasted mice. The design of potent and long-lasting PrRP analogs with selective anorexigenic properties promises to contribute to the study of food intake disorders. Copyright © 2011 Elsevier Inc. All rights reserved.

Inflatable penile prosthesis implant length with baseline characteristic correlations: preliminary analysis of the PROPPER study

PubMed Central

Henry, Gerard; Karpman, Edward; Brant, William; Jones, LeRoy; Khera, Mohit; Kohler, Tobias; Christine, Brian; Rhee, Eugene; Kansas, Bryan; Bella, Anthony J.

2017-01-01

Background “Prospective Registry of Outcomes with Penile Prosthesis for Erectile Restoration” (PROPPER) is a large, multi-institutional, prospective clinical study to collect, analyze, and report real-world outcomes for men implanted with penile prosthetic devices. We prospectively correlated co-morbid conditions and demographic data with implanted penile prosthesis size to enable clinicians to better predict implanted penis size following penile implantation. We present many new data points for the first time in the literature and postulate that radical prostatectomy (RP) is negatively correlated with penile corporal length. Methods Patient demographics, medical history, baseline characteristics and surgical details were compiled prospectively. Pearson correlation coefficient was generated for the correlation between demographic, etiology of ED, duration of ED, co-morbid conditions, pre-operative penile length (flaccid and stretched) and length of implanted penile prosthesis. Multivariate analysis was performed to define predictors of implanted prosthesis length. Results From June 2011 to June 2017, 1,135 men underwent primary implantation of penile prosthesis at a total of 11 study sites. Malleable (Spectra), 2-piece Ambicor, and 3-piece AMS 700 CX/LGX were included in the analysis. The most common patient comorbidities were CV disease (26.1%), DM (11.1%), and PD (12.4%). Primary etiology of ED: RP (27.4%), DM (20.3%), CVD (18.0%), PD (10.3%), and Priapism (1.4%), others (22.6%). Mean duration of ED is 6.2¡À4.1 years. Implant length was weakly negatively correlated with White/Caucasian (r=−0.18; P<0.01), history of RP (r=−0.13; P<0.01), PD as comorbidity (r=−0.16; P<0.01), venous leak (r=−0.08; P<0.01), and presence of stress incontinence (r=−0.13; P<0.01). Analyses showed weak positive correlations with Black/AA (r=0.32; P<0.01), CV disease as primary ED etiology (r=0.08; P<0.01) and pre-operative stretched penile length (r=0.18; P<0.01). There is a moderate correlation with pre-operative flaccid penile length (r=0.30; P<0.01). Conclusions Implanted penile prosthesis length is negatively correlated with some ethnic groups, prostatectomy, and incontinence. Positive correlates include CV disease, preoperative stretched penile length, and flaccid penile length. PMID:29354506

Effect of a 1-month vs. a 12-month reference period on responses to the 14-item Oral Health Impact Profile.

PubMed

Sutinen, Saila; Lahti, Satu; Nuttall, Nigel M; Sanders, Anne E; Steele, Jimmy G; Allen, P Finbarr; Slade, Gary D

2007-06-01

The length of the reference period used in surveys of subjective oral health may have a marked influence on the responses obtained. We aimed to evaluate the effect of a 1-month (RP-1) vs. a 12-month (RP-12) reference period in the Oral Health Impact Profile (OHIP-14) questionnaire. Using a randomized cross-over design, RP-1 and RP-12 OHIP-14 questionnaires were administered, 1 month apart, to two samples of Finnish adults, namely people awaiting orthognathic surgery (n = 104) and non-patient workers (n = 111). The effect of the reference period was computed by subtracting RP-1 OHIP-14 severity scores from RP-12 OHIP-14 severity scores (DeltaRP). Potential order effects were assessed by comparing DeltaRP between groups completing the RP-1 vs. the RP-12 questionnaire first. Mean OHIP-14 severity scores were slightly higher when the RP-12 questionnaire was administered first, but mean DeltaRP values were below the value of 2.5 considered clinically meaningful, and all 95% confidence intervals for DeltaRP included zero. No order effects in the OHIP-14 severity scores were observed. Therefore, although a standardized reference period of 12 months is recommended, in population surveys the use of a shorter reference period does not appear to influence responses.

Rapid versus delayed stimulation of feeding by the endogenously released AgRP neuron mediators, GABA, NPY and AgRP

PubMed Central

Krashes, Michael J.; Shah, Bhavik P.; Koda, Shuichi; Lowell, Bradford B.

2013-01-01

Summary Agouti-related peptide (AgRP) neurons of the hypothalamus release a fast transmitter (GABA) in addition to neuropeptides (NPY and AgRP). This raises questions as to their respective functions. Acute activation of AgRP neurons robustly promotes food intake, while central injections of AgRP, NPY or GABA agonist results in marked escalation of food consumption with temporal variance. Given the orexigenic capability of all three of these neuroactive substances in conjunction with their coexpression in AgRP neurons, we looked to unravel their relative temporal role in driving food intake. Following acute stimulation of AgRP neurons using DREADD technology, we found that either GABA or NPY is required for rapid stimulation of feeding, and the neuropeptide AgRP, through action on MC4 receptors, is sufficient to induce feeding over a delayed, yet prolonged period. These studies help to elucidate the neurochemical mechanisms of AgRP neurons in controlling temporally distinct phases of eating. PMID:24093681

Clinical differences between men and women undergoing surgery for acute Type A aortic dissection.

PubMed

Suzuki, Tomoaki; Asai, Tohru; Kinoshita, Takeshi

2018-06-01

The differences in clinical features, surgical outcome and long-term prognosis between men and women who undergo surgery for Type A aortic dissection are not well known. From January 2004 to December 2016, 303 patients, consisting of 147 women and 156 men, underwent surgery for acute Type A aortic dissection at our institution. We compared clinical outcomes between the 2 cohorts. Women were older than men (72.6 vs 63.0; P < 0.001). Operative mortality was similar between the groups (8.2% vs 8.9%; P = 0.80). The duration of intensive care unit stay (54 vs 64 h median; P = 0.03) and mechanical ventilator support (34 vs 43 h; P = 0.02) was significantly shorter in women. Multivariate logistic regression analysis revealed that preoperative cardiopulmonary resuscitation, cardiac tamponade, chronic obstructive pulmonary disease, haemodialysis and longer cardiopulmonary bypass time were independent risk factors for early death. Among the hospital survivors, the actuarial survival rate was 59.0% in women and 65.7% in men at 10 years (P = 0.81). During the follow-up period, there were 9 female and 27 male patients who underwent reoperation related to the aortic dissection. The rate of 10-year actuarial freedom from reoperation was 80.7% in women and 53.1% in men (log-rank P = 0.018). No differences were observed in both early and long-term mortality between women and men. Male patients had a significantly higher rate of reoperation. UMIN000029179.

Genetic and molecular characterization of the maize rp3 rust resistance locus.

PubMed Central

Webb, Craig A; Richter, Todd E; Collins, Nicholas C; Nicolas, Marie; Trick, Harold N; Pryor, Tony; Hulbert, Scot H

2002-01-01

In maize, the Rp3 gene confers resistance to common rust caused by Puccinia sorghi. Flanking marker analysis of rust-susceptible rp3 variants suggested that most of them arose via unequal crossing over, indicating that rp3 is a complex locus like rp1. The PIC13 probe identifies a nucleotide binding site-leucine-rich repeat (NBS-LRR) gene family that maps to the complex. Rp3 variants show losses of PIC13 family members relative to the resistant parents when probed with PIC13, indicating that the Rp3 gene is a member of this family. Gel blots and sequence analysis suggest that at least 9 family members are at the locus in most Rp3-carrying lines and that at least 5 of these are transcribed in the Rp3-A haplotype. The coding regions of 14 family members, isolated from three different Rp3-carrying haplotypes, had DNA sequence identities from 93 to 99%. Partial sequencing of clones of a BAC contig spanning the rp3 locus in the maize inbred line B73 identified five different PIC13 paralogues in a region of approximately 140 kb. PMID:12242248

Sperm DNA damage has a negative association with live-birth rates after IVF.

PubMed

Simon, L; Proutski, I; Stevenson, M; Jennings, D; McManus, J; Lutton, D; Lewis, S E M

2013-01-01

Sperm DNA damage has a negative impact on pregnancy rates following assisted reproduction treatment (ART). The aim of the present study was to examine the relationship between sperm DNA fragmentation and live-birth rates after IVF and intracytoplasmic sperm injection (ICSI). The alkaline Comet assay was employed to measure sperm DNA fragmentation in native semen and in spermatozoa following density-gradient centrifugation in semen samples from 203 couples undergoing IVF and 136 couples undergoing ICSI. Men were divided into groups according to sperm DNA damage. Following IVF, couples with <25% sperm DNA fragmentation had a live-birth rate of 33%; in contrast, couples with >50% sperm DNA fragmentation had a much lower live-birth rate of 13%. Following ICSI, no significant differences in sperm DNA damage were found between any groups of patients. Sperm DNA damage was also associated with low live-birth rates following IVF in both men and couples with idiopathic infertility: 39% of couples and 41% of men with idiopathic infertility have high sperm DNA damage. Sperm DNA damage assessed by the Comet assay has a close inverse relationship with live-birth rates after IVF. Sperm DNA damage has a negative impact on assisted reproduction treatment outcome, in particular, on pregnancy rates. The aim of the present study was to examine the relationship between sperm DNA fragmentation and live-birth rates after IVF and intracytoplasmic sperm injection (ICSI). The alkaline Comet assay was employed to measure sperm DNA fragmentation in native semen and in spermatozoa following density-gradient centrifugation in semen samples from 203 couples undergoing IVF and 136 couples undergoing ICSI. Men were divided into groups according to sperm DNA damage and treatment outcome. Following IVF, couples with <25% sperm DNA fragmentation had a live birth rate of 33%. In contrast, couples with >50% sperm DNA fragmentation had a much lower live-birth rate of 13% following IVF. Following ICSI, there were no significant differences in levels of sperm DNA damage between any groups of patients. Sperm DNA damage was also associated with the very low live-birth rates following IVF in both men and couples with idiopathic infertility: 39% of couples and 41% of men have high level of sperm DNA damage. Sperm DNA damage assessed by the Comet assay has a close inverse relationship with live-birth rates after IVF. Copyright © 2012 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Rapid versus delayed stimulation of feeding by the endogenously released AgRP neuron mediators GABA, NPY, and AgRP.

PubMed

Krashes, Michael J; Shah, Bhavik P; Koda, Shuichi; Lowell, Bradford B

2013-10-01

Agouti-related peptide (AgRP) neurons of the hypothalamus release a fast transmitter (GABA) in addition to neuropeptides (neuropeptide Y [NPY] and Agouti-related peptide [AgRP]). This raises questions as to their respective functions. The acute activation of AgRP neurons robustly promotes food intake, while central injections of AgRP, NPY, or GABA agonist results in the marked escalation of food consumption with temporal variance. Given the orexigenic capability of all three of these neuroactive substances in conjunction with their coexpression in AgRP neurons, we looked to unravel their relative temporal role in driving food intake. After the acute stimulation of AgRP neurons with DREADD technology, we found that either GABA or NPY is required for the rapid stimulation of feeding, and the neuropeptide AgRP, through action on MC4 receptors, is sufficient to induce feeding over a delayed yet prolonged period. These studies help to elucidate the neurochemical mechanisms of AgRP neurons in controlling temporally distinct phases of eating. Copyright © 2013 Elsevier Inc. All rights reserved.

Oncologic control obtained after radical prostatectomy in men with a pathological Gleason score ≥ 8: a single-center experience.

PubMed

Audenet, François; Comperat, Eva; Seringe, Elise; Drouin, Sarah J; Richard, François; Cussenot, Olivier; Bitker, Marc-Olivier; Rouprêt, Morgan

2011-01-01

To assess the oncologic control afforded by radical prostatectomy (RP) in high-risk prostate cancers with a Gleason score ≥ 8. We performed a retrospective review of prostate cancer patients who underwent RP between 1995 and 2005 for prostate cancer and who had a pathologic Gleason score ≥ 8. Biochemical recurrence was defined as a single rise in PSA levels over 0.2 ng/ml after surgery. Overall, 64 patients were included and followed for a median time of 84.3 months. The mean age was 63 ± 5.2 years. The mean preoperative PSA was 11.9 ± 7.3 ng/ml (1.9-31), and 29 patients (46%) had a PSA > 10 ng/ml. The biopsy Gleason score was ≤ 7 for 49 patients (76.6%). After pathologic analysis, there were 25 (39%) stage pT2, 37 (58%) stage pT3, and 2 (3%) stage pT4 patients. Nine patients had lymph node involvement (14%). The surgical margins were positive in 25 patients (39%). In 51 patients, (80%) the Gleason score was underestimated by biopsies: 40 patients with a definitive score of Gleason 8 had a Gleason score of 6 or 7 on biopsies, while 11 patients with a Gleason score of 9 initially, had a Gleason score of 7 or 8. Twenty-seven patients underwent adjuvant treatment: external radiation therapy (n = 19), HRT (n = 3), or both (n = 5). During follow-up, 41 patients (64%) presented with a biochemical recurrence, and 11 (17%) died. The PSA-free survival rate at five year was 44%. RP remains a possible therapeutic option in certain cases of the high-risk cohort of patients with a Gleason score ≥ 8. However, patients should be warned that surgery might only be the first step of a multi-modal treatment approach. The modalities of adjuvant treatments and the right schedule to deliver it following RP still need to be defined. Copyright © 2011 Elsevier Inc. All rights reserved.

Genomic Prostate Cancer Classifier Predicts Biochemical Failure and Metastases in Patients After Postoperative Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Den, Robert B., E-mail: Robert.Den@jeffersonhospital.org; Feng, Felix Y.; Showalter, Timothy N.

2014-08-01

Purpose: To test the hypothesis that a genomic classifier (GC) would predict biochemical failure (BF) and distant metastasis (DM) in men receiving radiation therapy (RT) after radical prostatectomy (RP). Methods and Materials: Among patients who underwent post-RP RT, 139 were identified for pT3 or positive margin, who did not receive neoadjuvant hormones and had paraffin-embedded specimens. Ribonucleic acid was extracted from the highest Gleason grade focus and applied to a high-density-oligonucleotide microarray. Receiver operating characteristic, calibration, cumulative incidence, and Cox regression analyses were performed to assess GC performance for predicting BF and DM after post-RP RT in comparison with clinical nomograms.more » Results: The area under the receiver operating characteristic curve of the Stephenson model was 0.70 for both BF and DM, with addition of GC significantly improving area under the receiver operating characteristic curve to 0.78 and 0.80, respectively. Stratified by GC risk groups, 8-year cumulative incidence was 21%, 48%, and 81% for BF (P<.0001) and for DM was 0, 12%, and 17% (P=.032) for low, intermediate, and high GC, respectively. In multivariable analysis, patients with high GC had a hazard ratio of 8.1 and 14.3 for BF and DM. In patients with intermediate or high GC, those irradiated with undetectable prostate-specific antigen (PSA ≤0.2 ng/mL) had median BF survival of >8 years, compared with <4 years for patients with detectable PSA (>0.2 ng/mL) before initiation of RT. At 8 years, the DM cumulative incidence for patients with high GC and RT with undetectable PSA was 3%, compared with 23% with detectable PSA (P=.03). No outcome differences were observed for low GC between the treatment groups. Conclusion: The GC predicted BF and metastasis after post-RP irradiation. Patients with lower GC risk may benefit from delayed RT, as opposed to those with higher GC; however, this needs prospective validation. Genomic-based models may be useful for improved decision-making for treatment of high-risk prostate cancer.« less

Aircraft Alerting Systems Standardization Study. Volume I. Candidate System Validation and Time-Critical Display Evaluation.

DTIC Science & Technology

1981-01-01

SELCAL FLT ALT ATNI AUO ALT BRK CANSELCAL OVSO CALL CONTRL ALRT _ I7CT be SPLR b 0 11CALL Figure 5.4.4-1 Pilot’s Response Panel Figure 5.4.4-2 Flight...Galley bus off 27 GLY BUS OFF A RP ELEC CYCLE SWITCH Utility bus off 28 UTIL BUS OFF A RP ELEC CYCLE SWITCH Right engine 29 R ENG HYD PUMP A RP HYD...CYCLE SWITCH hydraulic pump Left engine 30 L ENG FIRE DET A RP FIRE RP FIRE fire detector Left brake overheat 31 L BRAKE OVHT A RP BRK RP BRK Right

RP105 deficiency attenuates early atherosclerosis via decreased monocyte influx in a CCR2 dependent manner.

PubMed

Wezel, Anouk; van der Velden, Daniël; Maassen, Johanna M; Lagraauw, H Maxime; de Vries, Margreet R; Karper, Jacco C; Kuiper, Johan; Bot, Ilze; Quax, Paul H A

2015-01-01

Toll like receptor 4 (TLR4) plays a key role in inflammation and previously it was established that TLR4 deficiency attenuates atherosclerosis. RadioProtective 105 (RP105) is a structural homolog of TLR4 and an important regulator of TLR4 signaling, suggesting that RP105 may also be an important effector in atherosclerosis. We thus aimed to determine the role of RP105 in atherosclerotic lesion development using RP105 deficient mice on an atherosclerotic background. Atherosclerosis was induced in Western-type diet fed low density lipoprotein receptor deficient (LDLr(-/-)) and LDLr/RP105 double knockout (LDLr(-/-)/RP105(-/-)) mice by means of perivascular carotid artery collar placement. Lesion size was significantly reduced by 58% in LDLr(-/-)/RP105(-/-) mice, and moreover, plaque macrophage content was markedly reduced by 40%. In a model of acute peritonitis, monocyte influx was almost 3-fold reduced in LDLr(-/-)/RP105(-/-) mice (P = 0.001), while neutrophil influx remained unaltered, suggestive of an altered migratory capacity of monocytes upon deletion of RP105. Interestingly, in vitro stimulation of monocytes with LPS induced a downregulation of CCR2, a chemokine receptor crucially involved in monocyte influx to atherosclerotic lesions, which was more pronounced in LDLr(-/-)/RP105(-/-) monocytes as compared to LDLr(-/-) monocytes. We here show that RP105 deficiency results in reduced early atherosclerotic plaque development with a marked decrease in lesional macrophage content, which may be due to disturbed migration of RP105 deficient monocytes resulting from CCR2 downregulation. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Prevalence of fibromyalgia and chronic widespread pain in community-dwelling elderly subjects living in São Paulo, Brazil.

PubMed

Santos, Adriana M Barsante; Burti, Juliana Schulze; Lopes, Jaqueline B; Scazufca, Márcia; Marques, Amélia Pasqual; Pereira, Rosa Maria R

2010-11-01

To estimate the prevalence of fibromyalgia (FM) and chronic widespread pain (CWP) in community-dwelling elderly individuals living in São Paulo, to assess the spectrum of problems related to these diseases using the Fibromyalgia Impact Questionnaire (FIQ) and to correlate the FIQ with the number of tender points and with pain threshold. Our sample consisted of 361 individuals (64% women, 36% men, mean age of 73.3±5.7 years). Individuals were classified into four groups: FM (according to American College of Rheumatology criteria), CWP, regional pain (RP) and no pain (NP). Pain characteristics and dolorimetry for 18 tender points and the FIQ were assessed. The prevalence of FM was 5.5% [95% confidence interval (CI)=5.4-5.7], and the prevalence of CWP was 14.1% (95% CI: 10.5-17.7%). The frequency of RP was 52.6% and the prevalence of NP was 27.7%. FIQ scores were higher in people with FM (44.5), followed by CWP (31.4), RP (18.1) and NP (5.5) (p<0.001). There was a positive correlation between the domains of the FIQ and the number of tender points (p<0.05), and a negative correlation between FIQ score and pain threshold (p<0.05). In our elderly subjects, the prevalence of FM was slightly higher compared to previously reported studies, and CWP was around 14%. The spectrum of problems related to chronic pain was more severe in FM followed by CWP, strongly suggesting that these conditions should be diagnosed and adequately treated in older individuals. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Preparing Patients and Partners for Recovery From the Side Effects of Prostate Cancer Surgery: A Group Approach.

PubMed

Paich, Kellie; Dunn, Rodney; Skolarus, Ted; Montie, James; Hollenbeck, Brent; Palapattu, Ganesh; Wood, David; Mitchell, Staci; Hola, Victor; Erickson, Kim; Shifferd, Jennifer; Wittmann, Daniela

2016-02-01

To evaluate the acceptance and knowledge attained in a preoperative psychoeducational group seminar for patients and partners. Education before radical prostatectomy (RP) helps patients set appropriate expectations for functional recovery. We hypothesized that the seminar would be acceptable and would facilitate learning. Men scheduled for RP from March 1, 2012, to July 31, 2013, were eligible, and partners were invited. The 2.5-hour interactive seminar included multidisciplinary presentations about surgery-related urinary and sexual outcomes, rehabilitation, and couples' work toward recovering sexual intimacy. A satisfaction and knowledge survey was administered immediately afterward. We analyzed demographic and satisfaction data with descriptive statistics and evaluated congruence of patients' and partners' knowledge responses using nonparametric statistics. Of 618 patients scheduled, 426 patients and 342 partners attended; 323 couples provided complete data. Over 90% of participants found the seminar informative and 74% found a group setting comfortable; 84% found travel to the seminar burdensome. Most patients and partners (84% and 90%, respectively) expected some urinary incontinence and understood rehabilitation strategies to regain bladder control; 84% of patients and 78% of partners expected postsurgery sexual activity to be different and 73% of patients and 65% of partners expected surgery to make erections worse. Couples were incongruent regarding frequency of incontinence, likelihood of erectile dysfunction, and sex being different after surgery: patients were more realistic. A preoperative psychoeducational group seminar on the recovery from RP side effects promotes realistic expectations and is acceptable to patients and partners. Incongruent couples may need further instruction after surgery. Web-based methodology could improve access and should be studied in future research. Copyright © 2016 Elsevier Inc. All rights reserved.

Unravelling the genetic basis of simplex Retinitis Pigmentosa cases

PubMed Central

Bravo-Gil, Nereida; González-del Pozo, María; Martín-Sánchez, Marta; Méndez-Vidal, Cristina; Rodríguez-de la Rúa, Enrique; Borrego, Salud; Antiñolo, Guillermo

2017-01-01

Retinitis Pigmentosa (RP) is the most common form of inherited retinal dystrophy (IRD) characterized ultimately by photoreceptors degeneration. Exhibiting great clinical and genetic heterogeneity, RP can be inherited as an autosomal dominant (ad), autosomal recessive (ar) and X-linked (xl) disorder. Although the relative prevalence of each form varies somewhat between populations, a major proportion (41% in Spain) of patients represent simplex cases (sRP) in which the mode of inheritance is unknown. Molecular genetic diagnostic is crucial, but also challenging, for sRP patients because any of the 81 RP genes identified to date may be causative. Herein, we report the use of a customized targeted gene panel consisting of 68 IRD genes for the molecular characterization of 106 sRP cases. The diagnostic rate was 62.26% (66 of 106) with a proportion of clinical refinements of 30.3%, demonstrating the high efficiency of this genomic approach even for clinically ambiguous cases. The high number of patients diagnosed here has allowed us to study in detail the genetic basis of the sRP. The solved sRP cohort is composed of 62.1% of arRP cases, 24.2% of adRP and 13.6% of xlRP, which implies consequences for counselling of patients and families. PMID:28157192

Opioid receptor involvement in the effect of AgRP- (83-132) on food intake and food selection.

PubMed

Hagan, M M; Rushing, P A; Benoit, S C; Woods, S C; Seeley, R J

2001-03-01

Agouti-related peptide (AgRP) is a receptor antagonist of central nervous system (CNS) melanocortin receptors and appears to have an important role in the control of food intake since exogenous CNS administration in rats and overexpression in mice result in profound hyperphagia and weight gain. Given that AgRP is heavily colocalized with neuropeptide Y (NPY) and that orexigenic effects of NPY depend on activity at opioid receptors, we hypothesized that AgRP's food-intake effects are also mediated by opioid receptors. Subthreshold doses of the opioid receptor antagonist naloxone blocked AgRP-induced intake when given simultaneously but not 24 h after AgRP injection. Opioids not only influence food intake but food selection as well. Hence, we tested AgRP's effect to alter food choice between matched diets with differing dietary fat content. AgRP selectively enhanced intake of the high-fat but not the low-fat diet. Additionally, AgRP selectively increased chow intake in rats given ad libitum access to a 20% sucrose solution and standard rat chow. The current results indicate that AgRP influences not only caloric intake but food selection as well and that the early effects of AgRP depend critically on an interaction with opioid receptors.

Alternative splicing at exon 2 results in the loss of the catalytic activity of mouse DNA polymerase iota in vitro.

PubMed

Kazachenko, Konstantin Y; Miropolskaya, Nataliya A; Gening, Leonid V; Tarantul, Vyacheslav Z; Makarova, Alena V

2017-02-01

Y-family DNA polymerase iota (Pol ι) possesses both DNA polymerase and dRP lyase activities and was suggested to be involved in DNA translesion synthesis and base excision repair in mammals. The 129 strain of mice and its derivatives have a natural nonsense codon mutation in the second exon of the Pol ι gene resulting in truncation of the Pol ι protein. These mice were widely used as a Pol ι-null model for in vivo studies of the Pol ι function. However whether 129-derived strains of mice are fully deficient in the Pol ι functions was a subject of discussion since Pol ι mRNA undergoes alternative splicing at exon 2. Here we report purification of mouse Pol ι lacking the region encoded by exon 2, which includes several conserved residues involved in catalysis. We show that the deletion abrogates both the DNA polymerase and dRP lyase activities of Pol ι in the presence of either Mg 2+ or Mn 2+ ions. Thus, 129-derived strains of mice express catalytically inactive alternatively spliced Pol ι variant, whose cellular functions, if any exist, remain to be established. Copyright © 2017 Elsevier B.V. All rights reserved.

Quality of Life in Patients with Bladder Cancer Undergoing Ileal Conduit: A Comparison of Women Versus Men

PubMed Central

SIRACUSANO, SALVATORE; D’ELIA, CAROLINA; CERRUTO, MARIA ANGELA; SALEH, OMAR; SERNI, SERGIO; GACCI, MAURO; CICILIATO, STEFANO; SIMONATO, ALCHIEDE; PORCARO, ANTONIO; DE MARCO, VINCENZO; TALAMINI, RENATO; TOFFOLI, LAURA; VISALLI, FRANCESCO; NIERO, MAURO; LONARDI, CRISTINA; IMBIMBO, CIRO; VERZE, PAOLO; MIRONE, VINCENZO; RACIOPPI, MARCO; IAFRATE, MASSIMO; CACCIAMANI, GIOVANNI; DE MARCHI, DAVIDE; BASSI, PIERFRANCESCO; ARTIBANI, WALTER

2018-01-01

Background/Aim: Studies comparing health-related quality of life (HR-QoL) between patients who underwent radical cystectomy (RC) and those who underwent a different form of urinary diversion has not reached yet univocal and reliable conclusions. The aim of our study was to evaluate bladder-specific long-term HR-QoL after radical cystectomy and ileal conduit. Patients and Methods: A multicenter study was carried out on 145 consecutive patients (112 males and 33 females) undergoing RC and ileal conduit (IC). HR-QoL assessment was conducted using Italian versions of European Organisation for Research and Treatment of Cancer QLQ-C30 and EORTC BLM-30 questionnaires. Results: Our data showed that women who underwent IC presented greater problems than men in cognitive functioning (mean score±SD: 77.3±27.9 vs. 87.8±18.6) as well in future perspective (score: 42.4±34.4 vs. 21.9±24.6). Nevertheless, men undergoing IC had more problems in sexual functioning than women (score: 23.3±24.5 vs. 7.0±20.3) (all p<0.05). Conclusion: In our series, female patients presented a greater burden than male patients in cognitive functioning as well in future perspective, but lower concerns with regard to sexual function. PMID:29275311

Quality of Life in Patients with Bladder Cancer Undergoing Ileal Conduit: A Comparison of Women Versus Men.

PubMed

Siracusano, Salvatore; D'Elia, Carolina; Cerruto, Maria Angela; Saleh, Omar; Serni, Sergio; Gacci, Mauro; Ciciliato, Stefano; Simonato, Alchiede; Porcaro, Antonio; DE Marco, Vincenzo; Talamini, Renato; Toffoli, Laura; Visalli, Francesco; Niero, Mauro; Lonardi, Cristina; Imbimbo, Ciro; Verze, Paolo; Mirone, Vincenzo; Racioppi, Marco; Iafrate, Massimo; Cacciamani, Giovanni; DE Marchi, Davide; Bassi, Pierfrancesco; Artibani, Walter

2018-01-01

Studies comparing health-related quality of life (HR-QoL) between patients who underwent radical cystectomy (RC) and those who underwent a different form of urinary diversion has not reached yet univocal and reliable conclusions. The aim of our study was to evaluate bladder-specific long-term HR-QoL after radical cystectomy and ileal conduit. A multicenter study was carried out on 145 consecutive patients (112 males and 33 females) undergoing RC and ileal conduit (IC). HR-QoL assessment was conducted using Italian versions of European Organisation for Research and Treatment of Cancer QLQ-C30 and EORTC BLM-30 questionnaires. Our data showed that women who underwent IC presented greater problems than men in cognitive functioning (mean score±SD: 77.3±27.9 vs. 87.8±18.6) as well in future perspective (score: 42.4±34.4 vs. 21.9±24.6). Nevertheless, men undergoing IC had more problems in sexual functioning than women (score: 23.3±24.5 vs. 7.0±20.3) (all p<0.05). In our series, female patients presented a greater burden than male patients in cognitive functioning as well in future perspective, but lower concerns with regard to sexual function. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Arcuate AgRP neurons mediate orexigenic and glucoregulatory actions of ghrelin★

PubMed Central

Wang, Qian; Liu, Chen; Uchida, Aki; Chuang, Jen-Chieh; Walker, Angela; Liu, Tiemin; Osborne-Lawrence, Sherri; Mason, Brittany L.; Mosher, Christina; Berglund, Eric D.; Elmquist, Joel K.; Zigman, Jeffrey M.

2013-01-01

The hormone ghrelin stimulates eating and helps maintain blood glucose upon caloric restriction. While previous studies have demonstrated that hypothalamic arcuate AgRP neurons are targets of ghrelin, the overall relevance of ghrelin signaling within intact AgRP neurons is unclear. Here, we tested the functional significance of ghrelin action on AgRP neurons using a new, tamoxifen-inducible AgRP-CreERT2 transgenic mouse model that allows spatiotemporally-controlled re-expression of physiological levels of ghrelin receptors (GHSRs) specifically in AgRP neurons of adult GHSR-null mice that otherwise lack GHSR expression. AgRP neuron-selective GHSR re-expression partially restored the orexigenic response to administered ghrelin and fully restored the lowered blood glucose levels observed upon caloric restriction. The normalizing glucoregulatory effect of AgRP neuron-selective GHSR expression was linked to glucagon rises and hepatic gluconeogenesis induction. Thus, our data indicate that GHSR-containing AgRP neurons are not solely responsible for ghrelin's orexigenic effects but are sufficient to mediate ghrelin's effects on glycemia. PMID:24567905

Arcuate AgRP neurons mediate orexigenic and glucoregulatory actions of ghrelin.

PubMed

Wang, Qian; Liu, Chen; Uchida, Aki; Chuang, Jen-Chieh; Walker, Angela; Liu, Tiemin; Osborne-Lawrence, Sherri; Mason, Brittany L; Mosher, Christina; Berglund, Eric D; Elmquist, Joel K; Zigman, Jeffrey M

2014-02-01

The hormone ghrelin stimulates eating and helps maintain blood glucose upon caloric restriction. While previous studies have demonstrated that hypothalamic arcuate AgRP neurons are targets of ghrelin, the overall relevance of ghrelin signaling within intact AgRP neurons is unclear. Here, we tested the functional significance of ghrelin action on AgRP neurons using a new, tamoxifen-inducible AgRP-CreER(T2) transgenic mouse model that allows spatiotemporally-controlled re-expression of physiological levels of ghrelin receptors (GHSRs) specifically in AgRP neurons of adult GHSR-null mice that otherwise lack GHSR expression. AgRP neuron-selective GHSR re-expression partially restored the orexigenic response to administered ghrelin and fully restored the lowered blood glucose levels observed upon caloric restriction. The normalizing glucoregulatory effect of AgRP neuron-selective GHSR expression was linked to glucagon rises and hepatic gluconeogenesis induction. Thus, our data indicate that GHSR-containing AgRP neurons are not solely responsible for ghrelin's orexigenic effects but are sufficient to mediate ghrelin's effects on glycemia.

Effectiveness of interventions to increase the participation rate of gastric cancer screening in the Republic of Korea: a pilot study.

PubMed

Lee, Myung Ha; Lee, Yoon Young; Jung, Da Won; Park, Boyoung; Yun, E Hwa; Lee, Hoo-Yeon; Jun, Jae Kwan; Choi, Kui Son

2012-01-01

This study assessed the effectiveness of three intervention strategies to improve the participation rate of gastric cancer screening among people who had never undergone such screening, and those who had been screened for the disease, but not recently. It was conducted in the Ilsandong-gu District of Goyang City, Korea. The population for the current study was restricted to male residents, aged 40-65 years, who received an invitation letter to undergo gastric cancer screening from the National Health Insurance (NHI) Corporation at the beginning of 2010. The subjects were divided into two categories according to their screening history: never-screened, and ever-screened. A total of 2,065 men were eligible: 803 never-screened and 1,262 ever-screened. In each screening category they were randomly assigned to one of three intervention groups: 1) tailored telephone counseling; 2) tailored postcard reminder after tailored telephone counseling;and 3) tailored telephone counseling after tailored postcard reminder. At 3 months post-intervention, never- screened men with any intervention were more likely to undergo gastric cancer screening (OR=2.75, 95% CI: 1.22-6.18) compared to those in the reference group (no intervention). However, there was no statistically significant intervention effect in ever-screened men (OR=1.21, 95% CI: 0.65-2.27). Examination of the intervention effects by intervention group among never-screened men showed that those in the postcard reminder after telephone counseling group to be statistically significantly more likely to undergo gastric cancer screening (OR=4.49, 95% CI: 1.79-11.29) than the reference group (no intervention). Our results highlight that use of tailored postcard reminders after tailored telephone counseling is an effective method to increase participation in gastric cancer screening among men who had never been screened.

Metallized Gelled Propellants: Oxygen/RP-1/Aluminum Rocket Heat Transfer and Combustion Measurements

NASA Technical Reports Server (NTRS)

Palaszewski, Bryan; Zakany, James S.

1996-01-01

A series of rocket engine heat transfer experiments using metallized gelled liquid propellants was conducted. These experiments used a small 20- to 40-lb/f thrust engine composed of a modular injector, igniter, chamber and nozzle. The fuels used were traditional liquid RP-1 and gelled RP-1 with 0-, 5-, and 55-percentage by weight loadings of aluminum particles. Gaseous oxygen was used as the oxidizer. Three different injectors were used during the testing: one for the baseline O(2)/RP-1 tests and two for the gelled and metallized gelled fuel firings. Heat transfer measurements were made with a rocket engine calorimeter chamber and nozzle with a total of 31 cooling channels. Each chamber used a water flow to carry heat away from the chamber and the attached thermocouples and flow meters allowed heat flux estimates at each of the 31 stations. The rocket engine Cstar efficiency for the RP-1 fuel was in the 65-69 percent range, while the gelled 0 percent by weight RP-1 and the 5-percent by weight RP-1 exhibited a Cstar efficiency range of 60 to 62% and 65 to 67%, respectively. The 55-percent by weight RP-1 fuel delivered a 42-47% Cstar efficiency. Comparisons of the heat flux and temperature profiles of the RP-1 and the metallized gelled RP-1/A1 fuels show that the peak nozzle heat fluxes with the metallized gelled O2/RP-1/A1 propellants are substantially higher than the baseline O2/RP-1: up to double the flux for the 55 percent by weight RP-1/A1 over the RP-1 fuel. Analyses showed that the heat transfer to the wall was significantly different for the RP-1/A1 at 55-percent by weight versus the RP-1 fuel. Also, a gellant and an aluminum combustion delay was inferred in the 0 percent and 5-percent by weight RP-1/A1 cases from the decrease in heat flux in the first part of the chamber. A large decrease in heat flux in the last half of the chamber was caused by fuel deposition in the chamber and nozzle. The engine combustion occurred well downstream of the injector face based on the heat flux estimates from the temperature measurements.

Examining the Potential for Gender Bias in the Prediction of Symptom Validity Test Failure by MMPI-2 Symptom Validity Scale Scores

ERIC Educational Resources Information Center

Lee, Tayla T. C.; Graham, John R.; Sellbom, Martin; Gervais, Roger O.

2012-01-01

Using a sample of individuals undergoing medico-legal evaluations (690 men, 519 women), the present study extended past research on potential gender biases for scores of the Symptom Validity (FBS) scale of the Minnesota Multiphasic Personality Inventory-2 by examining score- and item-level differences between men and women and determining the…

RP1 Is a Phosphorylation Target of CK2 and Is Involved in Cell Adhesion

PubMed Central

Göttig, Stephan; Henschler, Reinhard; Markuly, Norbert; Kleber, Sascha; Faust, Michael; Mischo, Axel; Bauer, Stefan; Zweifel, Martin; Knuth, Alexander; Renner, Christoph; Wadle, Andreas

2013-01-01

RP1 (synonym: MAPRE2, EB2) is a member of the microtubule binding EB1 protein family, which interacts with APC, a key regulatory molecule in the Wnt signalling pathway. While the other EB1 proteins are well characterized the cellular function and regulation of RP1 remain speculative to date. However, recently RP1 has been implicated in pancreatic cancerogenesis. CK2 is a pleiotropic kinase involved in adhesion, proliferation and anti-apoptosis. Overexpression of protein kinase CK2 is a hallmark of many cancers and supports the malignant phenotype of tumor cells. In this study we investigate the interaction of protein kinase CK2 with RP1 and demonstrate that CK2 phosphorylates RP1 at Ser236 in vitro. Stable RP1 expression in cell lines leads to a significant cleavage and down-regulation of N-cadherin and impaired adhesion. Cells expressing a Phospho-mimicking point mutant RP1-ASP236 show a marked decrease of adhesion to endothelial cells under shear stress. Inversely, we found that the cells under shear stress downregulate endogenous RP1, most likely to improve cellular adhesion. Accordingly, when RP1 expression is suppressed by shRNA, cells lacking RP1 display significantly increased cell adherence to surfaces. In summary, RP1 phosphorylation at Ser236 by CK2 seems to play a significant role in cell adhesion and might initiate new insights in the CK2 and EB1 family protein association. PMID:23844040

RP1 is a phosphorylation target of CK2 and is involved in cell adhesion.

PubMed

Stenner, Frank; Liewen, Heike; Göttig, Stephan; Henschler, Reinhard; Markuly, Norbert; Kleber, Sascha; Faust, Michael; Mischo, Axel; Bauer, Stefan; Zweifel, Martin; Knuth, Alexander; Renner, Christoph; Wadle, Andreas

2013-01-01

RP1 (synonym: MAPRE2, EB2) is a member of the microtubule binding EB1 protein family, which interacts with APC, a key regulatory molecule in the Wnt signalling pathway. While the other EB1 proteins are well characterized the cellular function and regulation of RP1 remain speculative to date. However, recently RP1 has been implicated in pancreatic cancerogenesis. CK2 is a pleiotropic kinase involved in adhesion, proliferation and anti-apoptosis. Overexpression of protein kinase CK2 is a hallmark of many cancers and supports the malignant phenotype of tumor cells. In this study we investigate the interaction of protein kinase CK2 with RP1 and demonstrate that CK2 phosphorylates RP1 at Ser(236) in vitro. Stable RP1 expression in cell lines leads to a significant cleavage and down-regulation of N-cadherin and impaired adhesion. Cells expressing a Phospho-mimicking point mutant RP1-ASP(236) show a marked decrease of adhesion to endothelial cells under shear stress. Inversely, we found that the cells under shear stress downregulate endogenous RP1, most likely to improve cellular adhesion. Accordingly, when RP1 expression is suppressed by shRNA, cells lacking RP1 display significantly increased cell adherence to surfaces. In summary, RP1 phosphorylation at Ser(236) by CK2 seems to play a significant role in cell adhesion and might initiate new insights in the CK2 and EB1 family protein association.

Developments in the invasive diagnostic–therapeutic cascade of women and men with acute coronary syndromes from 2005 to 2011: a nationwide cohort study

PubMed Central

Hansen, Kim Wadt; Soerensen, R; Madsen, M; Madsen, J K; Jensen, J S; von Kappelgaard, L M; Mortensen, P E; Galatius, S

2015-01-01

Objectives To investigate for trends in sex-related differences in the invasive diagnostic–therapeutic cascade in a population of patients with acute coronary syndromes (ACS). Design A nationwide cohort study. Setting Administrative and clinical registries covering all hospitalisations, invasive cardiac procedures and deaths in the Danish population of 5.6 million inhabitants. Participants We included 52 565 patients aged 30–90 years who were hospitalised with a first ACS from January 2005 to November 2011. Follow-up was 60 days from the day of index admission. Main outcome measures Diagnostic coronary angiography, percutaneous coronary intervention or coronary artery bypass within 60 days of index admission. Results Women constituted 36%, were older, had more comorbidity and were less likely to be admitted to a hospital with cardiac catheterisation facilities than men. Mortality rates were similar for both sexes. Diagnostic coronary angiography was performed less frequently on women compared with men, both within 1 day (31% vs 42%; p<0.001) and within 60 days (67% vs 80%; p<0.001), yielding adjusted female–male HRs of 0.83 (0.79–0.87) and 0.86 (0.84–0.89), respectively.Among the 39 677 patients undergoing coronary angiography, non-obstructive coronary artery disease was more frequent among women than men (22% vs 9%; p<0.001). Women were less likely to undergo percutaneous coronary intervention (58% vs 72%; p<0.001) and coronary artery bypass (6% vs 11%, p<0.001) within 60 days than men, yielding adjusted HRs of 0.96 (0.92–0.99) and 0.81 (0.74–0.89), respectively. The sex-related differences were not attenuated over time for any of the invasive cardiac procedures (p values for trend >0.05). Conclusions In this nationwide study, men were more likely to undergo an invasive approach than women when hospitalised with a first ACS—a difference persisting from 2005 to 2011. Future studies should focus on the potential mechanisms behind this differential treatment. PMID:26063568

Multiparametric Magnetic Resonance Imaging (MRI) and MRI-Transrectal Ultrasound Fusion Biopsy for Index Tumor Detection: Correlation with Radical Prostatectomy Specimen.

PubMed

Radtke, Jan P; Schwab, Constantin; Wolf, Maya B; Freitag, Martin T; Alt, Celine D; Kesch, Claudia; Popeneciu, Ionel V; Huettenbrink, Clemens; Gasch, Claudia; Klein, Tilman; Bonekamp, David; Duensing, Stefan; Roth, Wilfried; Schueler, Svenja; Stock, Christian; Schlemmer, Heinz-Peter; Roethke, Matthias; Hohenfellner, Markus; Hadaschik, Boris A

2016-11-01

Multiparametric magnetic resonance imaging (mpMRI) and MRI fusion targeted biopsy (FTB) detect significant prostate cancer (sPCa) more accurately than conventional biopsies alone. To evaluate the detection accuracy of mpMRI and FTB on radical prostatectomy (RP) specimen. From a cohort of 755 men who underwent transperineal MRI and transrectal ultrasound fusion biopsy under general anesthesia between 2012 and 2014, we retrospectively analyzed 120 consecutive patients who had subsequent RP. All received saturation biopsy (SB) in addition to FTB of lesions with Prostate Imaging Reporting and Data System (PI-RADS) score ≥2. The index lesion was defined as the lesion with extraprostatic extension, the highest Gleason score (GS), or the largest tumor volume (TV) if GS were the same, in order of priority. GS 3+3 and TV ≥1.3ml or GS ≥3+4 and TV ≥0.55ml were considered sPCa. We assessed the detection accuracy by mpMRI and different biopsy approaches and analyzed lesion agreement between mpMRI and RP specimen. Overall, 120 index and 71 nonindex lesions were detected. Overall, 107 (89%) index and 51 (72%) nonindex lesions harbored sPCa. MpMRI detected 110 of 120 (92%) index lesions, FTB (two cores per lesion) alone diagnosed 96 of 120 (80%) index lesions, and SB alone diagnosed 110 of 120 (92%) index lesions. Combined SB and FTB detected 115 of 120 (96%) index foci. FTB performed significantly less accurately compared with mpMRI (p=0.02) and the combination for index lesion detection (p=0.002). Combined FTB and SB detected 97% of all sPCa lesions and was superior to mpMRI (85%), FTB (79%), and SB (88%) alone (p<0.001 each). Spearman's rank correlation coefficient for index lesion agreement between mpMRI and RP was 0.87 (p<0.001). Limitations included the retrospective design, multiple operators, and nonblinding of radiologists. MpMRI identified 92% of index lesions compared with RP histopathology. The combination of FTB and SB was superior to both approaches alone, reliably detecting 97% of sPCa lesions. Multiparametric magnetic resonance imaging detects the index lesion accurately in 9 of 10 patients; however, the combined biopsy approach, while missing less significant cancer, comes at the cost of detecting more insignificant cancer. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

AgRP Neurons Control Systemic Insulin Sensitivity via Myostatin Expression in Brown Adipose Tissue.

PubMed

Steculorum, Sophie M; Ruud, Johan; Karakasilioti, Ismene; Backes, Heiko; Engström Ruud, Linda; Timper, Katharina; Hess, Martin E; Tsaousidou, Eva; Mauer, Jan; Vogt, Merly C; Paeger, Lars; Bremser, Stephan; Klein, Andreas C; Morgan, Donald A; Frommolt, Peter; Brinkkötter, Paul T; Hammerschmidt, Philipp; Benzing, Thomas; Rahmouni, Kamal; Wunderlich, F Thomas; Kloppenburg, Peter; Brüning, Jens C

2016-03-24

Activation of Agouti-related peptide (AgRP) neurons potently promotes feeding, and chronically altering their activity also affects peripheral glucose homeostasis. We demonstrate that acute activation of AgRP neurons causes insulin resistance through impairment of insulin-stimulated glucose uptake into brown adipose tissue (BAT). AgRP neuron activation acutely reprograms gene expression in BAT toward a myogenic signature, including increased expression of myostatin. Interference with myostatin activity improves insulin sensitivity that was impaired by AgRP neurons activation. Optogenetic circuitry mapping reveals that feeding and insulin sensitivity are controlled by both distinct and overlapping projections. Stimulation of AgRP → LHA projections impairs insulin sensitivity and promotes feeding while activation of AgRP → anterior bed nucleus of the stria terminalis (aBNST)vl projections, distinct from AgRP → aBNSTdm projections controlling feeding, mediate the effect of AgRP neuron activation on BAT-myostatin expression and insulin sensitivity. Collectively, our results suggest that AgRP neurons in mice induce not only eating, but also insulin resistance by stimulating expression of muscle-related genes in BAT, revealing a mechanism by which these neurons rapidly coordinate hunger states with glucose homeostasis. Copyright © 2016 Elsevier Inc. All rights reserved.

X-Linked Retinitis Pigmentosa 2 Is a Novel Maternal-Effect Gene Required for Left-Right Asymmetry in Zebrafish.

PubMed

Desvignes, Thomas; Nguyen, Thaovi; Chesnel, Franck; Bouleau, Aurélien; Fauvel, Christian; Bobe, Julien

2015-08-01

Retinitis pigmentosa 2 (RP2) gene is responsible for up to 20% of X-linked retinitis pigmentosa, a severe heterogeneous genetic disorder resulting in progressive retinal degeneration in humans. In vertebrates, several bodies of evidence have clearly established the role of Rp2 protein in cilia genesis and/or function. Unexpectedly, some observations in zebrafish have suggested the oocyte-predominant expression of the rp2 gene, a typical feature of maternal-effect genes. In the present study, we investigate the maternal inheritance of rp2 gene products in zebrafish eggs in order to address whether rp2 could be a novel maternal-effect gene required for normal development. Although both rp2 mRNA and corresponding protein are expressed during oogenesis, rp2 mRNA is maternally inherited, in contrast to Rp2 protein. A knockdown of the protein transcribed from both rp2 maternal and zygotic mRNA results in delayed epiboly and severe developmental defects, including eye malformations, that were not observed when only the protein from zygotic origin was knocked down. Moreover, the knockdown of maternal and zygotic Rp2 revealed a high incidence of left-right asymmetry establishment defects compared to only zygotic knockdown. Here we show that rp2 is a novel maternal-effect gene exclusively expressed in oocytes within the zebrafish ovary and demonstrate that maternal rp2 mRNA is essential for successful embryonic development and thus contributes to egg developmental competence. Our observations also reveal that Rp2 protein translated from maternal mRNA is important to allow normal heart loop formation, thus providing evidence of a direct maternal contribution to left-right asymmetry establishment. © 2015 by the Society for the Study of Reproduction, Inc.

An assessment of the feasibility and effectiveness of an e-learning module in delivering a curriculum in radiation protection to undergraduate medical students.

PubMed

Leong, Sum; Mc Laughlin, Patrick; O'Connor, Owen J; O'Flynn, Siun; Maher, Michael M

2012-03-01

Integrating radiation protection (RP) education in the undergraduate medical curriculum is gaining importance and is mandatory in certain jurisdictions. An e-learning module for RP was developed at the authors' medical school and was integrated into year 4 of the 5-year undergraduate medical program. The aim of this study was to investigate its impact on RP knowledge, student preferences for various teaching methods, self-assessment of RP knowledge, and perceptions of career prospects in radiology. Likert-type 5-point scale evaluations and general comments about the RP module and various methods of teaching were also obtained. An e-learning module in RP was designed and presented to year 4 medical undergraduates. All students were required to complete premodule and postmodule questionnaires. Eighty-nine percent (n = 113) and 99% (n = 126) of the 127 medical students successfully completed and returned the premodule and postmodule questionnaires, respectively. After the e-learning module, students' postmodule RP knowledge had improved significantly. Analysis of postmodule RP knowledge suggested that a favorable self-assessment of knowledge of RP, perception of career prospects in radiology, and completion of the e-learning module with an increased number of sessions were factors predictive of improved RP knowledge. Students expressed a preference for didactic lectures and clinical attachment for instruction in RP over e-learning. The development of an e-learning module in RP is feasible and results in improved knowledge of RP among medical undergraduates. Combining e-learning and more traditional educational programs such as a clinical radiology rotation is likely to improve student experience. Copyright © 2012 American College of Radiology. Published by Elsevier Inc. All rights reserved.

Risk Factors for Acute and Early HIV Infection Among Men Who Have Sex With Men (MSM) in San Diego, 2008 to 2014: A Cohort Study.

PubMed

Hoenigl, Martin; Green, Nella; Mehta, Sanjay R; Little, Susan J

2015-07-01

The objectives of this study were to identify risk factors associated with acute and early HIV infection (AEH) among men who have sex with men (MSM) undergoing community HIV testing and to compare demographics in those diagnosed with AEH with those diagnosed at chronic stage of HIV infection.In this retrospective cohort study, we analyzed risk factors associated with AEH among 8925 unique MSM (including 200 with AEH [2.2%] and 219 [2.5%] with newly diagnosed chronic HIV infection) undergoing community-based, confidential AEH screening in San Diego, California.The combination of condomless receptive anal intercourse (CRAI) plus ≥5 male partners, CRAI with an HIV-positive male, CRAI with a person who injects drugs, and prior syphilis diagnosis were significant predictors of AEH in the multivariable Cox regression model. Individuals reporting ≥1 of these 4 risk factors had a hazard ratio of 4.6 for AEH. MSM diagnosed with AEH differed in race (P = 0.005; more reported white race [P = 0.001], less black race [P = 0.030], trend toward less Native American race [P = 0.061]), when compared to those diagnosed with chronic HIV infection, while there was no difference observed regarding age.We established a multivariate model for the predicting risk of AEH infection in a cohort of MSM undergoing community HIV screening, which could be potentially used to discern those in need of further HIV nucleic acid amplification testing for community screening programs that do not test routinely for AEH. In addition, we found that race differed between those diagnosed with AEH and those diagnosed at chronic stage of HIV infection underlining the need for interventions that reduce stigma and promote the uptake of HIV testing for black MSM.

Does Patient Preference Measurement in Decision Aids Improve Decisional Conflict? A Randomized Trial in Men with Prostate Cancer.

PubMed

Shirk, Joseph D; Crespi, Catherine M; Saucedo, Josemanuel D; Lambrechts, Sylvia; Dahan, Ely; Kaplan, Robert; Saigal, Christopher

2017-12-01

Shared decision making (SDM) has been advocated as an approach to medical decision making that can improve decisional quality. Decision aids are tools that facilitate SDM in the context of limited physician time; however, many decision aids do not incorporate preference measurement. We aim to understand whether adding preference measurement to a standard patient educational intervention improves decisional quality and is feasible in a busy clinical setting. Men with incident localized prostate cancer (n = 122) were recruited from the Greater Los Angeles Veterans Affairs (VA) Medical Center urology clinic, Olive View UCLA Medical Center, and Harbor UCLA Medical Center from January 2011 to May 2015 and randomized to education with a brochure about prostate cancer treatment or software-based preference assessment in addition to the brochure. Men undergoing preference assessment received a report detailing the relative strength of their preferences for treatment outcomes used in review with their doctor. Participants completed instruments measuring decisional conflict, knowledge, SDM, and patient satisfaction with care before and/or after their cancer consultation. Baseline knowledge scores were low (mean 62%). The baseline mean total score on the Decisional Conflict Scale was 2.3 (±0.9), signifying moderate decisional conflict. Men undergoing preference assessment had a significantly larger decrease in decisional conflict total score (p = 0.023) and the Perceived Effective Decision Making subscale (p = 0.003) post consult compared with those receiving education only. Improvements in satisfaction with care, SDM, and knowledge were similar between groups. Individual-level preference assessment is feasible in the clinic setting. Patients with prostate cancer who undergo preference assessment are more certain about their treatment decisions and report decreased levels of decisional conflict when making these decisions.

The British Association of Urological Surgeons (BAUS) radical prostatectomy audit 2014/2015 - an update on current practice and outcomes by centre and surgeon case-volume.

PubMed

Khadhouri, Sinan; Miller, Catherine; Fowler, Sarah; Hounsome, Luke; McNeill, Alan; Adshead, Jim; McGrath, John S

2018-02-01

To describe contemporary radical prostatectomy (RP) practice using the British Association of Urological Surgeons (BAUS) data and audit project and to observe differences in practice in relation to surgeon or centre case-volume. Data on 13 920 RP procedures performed by 179 surgeons across 86 centres were recorded on the BAUS data and audit platform between 1 January 2014 and 31 December 2015. This equates to ~95% of total RPs performed over this period when compared to Hospital Episode Statistics (HES) data. Centre case-volumes were categorised as 'high' (>200), 'medium' (100-200) and 'low' (<100); surgeon case-volumes were categorised as 'high' (>100) and 'low' (<100). Differences in surgical practice and selected outcome measures were observed between groups. All data and volume categories were for the combined 2-year period. The median number of RPs performed over the 2-year period was 63.5 per surgeon and 164 per centre. Overall, surgical approach was robot-assisted laparoscopic RP (RALP) in 65%, laparoscopic RP (LRP) in 23%, and open RP (ORP) in 12%. The dominant approach in high-case-volume centres and by high-case-volume surgeons was RALP (74.3% and 69.2%, respectively). There was a greater percentage of ORPs reported by low-volume surgeons and centres when compared to higher volume equivalents. In all, 51.6% of all patients in this series underwent RP in high-case-volume centres using robot-assisted surgery (RAS). High-case-volume surgeons performed nerve-sparing (NS) procedures on 57.3% of their cases; low-volume surgeons performing NS on 48.2%. Overall, lymph node dissection (LND) rates were very similar across the groups. An 'extended' LND was more commonly performed in high-volume centres (22.1%). The median length of stay (LOS) was lowest in patients undergoing RALP at high-volume centres (1 day) and highest in ORP across all volume categories (3-4 days). Reported pT2 positive surgical margin (PSM) rate varied by technique, centre volume, and surgeon volume. In general, observed PSM rates were lower when RALP was the surgical approach (14.4%) and when high-volume surgeons were compared to low-volume surgeons (13.6% vs 17.7%). Transfusion rates were highest in ORP across all centres and surgeons (2.96-4.49%) compared to techniques using a minimally-invasive approach (0.25-2.41%). Training cases ranged from 0.5% in low-volume centres to 6.0% in high-volume centres. Compliance with data registration for centres and surgeons performing RP is high in the present series. Most RPs were performed in high-case-volume centres and by high-case-volume surgeons, with the most common approaches being minimally invasive and specifically RAS. High-case-volume centres and surgeons reported higher rates of extended LND and training cases. Higher-case-volume surgeons reported lower pT2 PSM rates, whilst the most marked differences in transfusion rates and LOS were seen when ORP was compared to minimally invasive approaches. Caution must be applied when interpreting these differences on the basis of this being registry data - causality cannot be assumed. © 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.

A recombination outside the BB deletion refines the location of the X-linked retinitis pigmentosa locus RP3

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fujita, R.; Bingham, E.; Forsythe, P.

1996-07-01

Genetic loci for X-linked retinitis pigmentosa (XLRP) have been mapped between Xp11.22 and Xp22.13 (RP2, RP3, RP6, and RP15). The RP3 gene, which is responsible for the predominant form of XLRP in most Caucasian populations, has been localized to Xp21.1 by linkage analysis and the map positions of chromosomal deletions associated with the disease. Previous linkage studies have suggested that RP3 is flanked by the markers DXS1110 (distal) and OTC (proximal). Patient BB was though to have RP because of a lesion at the RP3 locus, in addition to chronic granulomatous disease, Duchenne muscular dystrophy (DMD), mild mental retardation, andmore » the McLeod phenotype. This patient carried a deletion extending {approximately}3 Mb from DMD in Xp21.3 to Xp21.1, with the proximal breakpoint located {approximately}40 kb centromeric to DXS1110. The RP3 gene, therefore, is believed to reside between DXS1110 and the proximal breakpoint of the BB deletion. In order to refine the location of RP3 and to ascertain patients with RP3, we have been analyzing several XLRP families for linkage to Xp markers. Linkage analysis in an American family of 27 individuals demonstrates segregation of XLRP with markers in Xp21.1, consistent with the RP3 subtype. One affected male shows a recombination event proximal to DXS1110. Additional markers within the DXS1110-OTC interval show that the crossover is between two novel polymorphic markers, DXS8349 and M6, both of which are present in BB DNA and lie centromeric to the proximal breakpoint. This recombination places the XLRP mutation in this family outside the BB deletion and redefines the location of RP3. 22 refs., 3 figs., 2 tabs.« less

Assessing the Clinical Role of Genetic Markers of Early-Onset Prostate Cancer Among High-Risk Men Enrolled in Prostate Cancer Early Detection

PubMed Central

Hughes, Lucinda; Zhu, Fang; Ross, Eric; Gross, Laura; Uzzo, Robert G.; Chen, David Y. T.; Viterbo, Rosalia; Rebbeck, Timothy R.; Giri, Veda N.

2011-01-01

Background Men with familial prostate cancer (PCA) and African American men are at risk for developing PCA at younger ages. Genetic markers predicting early-onset PCA may provide clinically useful information to guide screening strategies for high-risk men. We evaluated clinical information from six polymorphisms associated with early-onset PCA in a longitudinal cohort of high-risk men enrolled in PCA early detection with significant African American participation. Methods Eligibility criteria include ages 35–69 with a family history of PCA or African American race. Participants undergo screening and biopsy per study criteria. Six markers associated with early-onset PCA (rs2171492 (7q32), rs6983561 (8q24), rs10993994 (10q11), rs4430796 (17q12), rs1799950 (17q21), and rs266849 (19q13)) were genotyped. Cox models were used to evaluate time to PCA diagnosis and PSA prediction for PCA by genotype. Harrell’s concordance index was used to evaluate predictive accuracy for PCA by PSA and genetic markers. Results 460 participants with complete data and ≥1 follow-up visit were included. 56% were African American. Among African American men, rs6983561 genotype was significantly associated with earlier time to PCA diagnosis (p=0.005) and influenced prediction for PCA by the PSA (p<0.001). When combined with PSA, rs6983561 improved predictive accuracy for PCA compared to PSA alone among African American men (PSA= 0.57 vs. PSA+rs6983561=0.75, p=0.03). Conclusions Early-onset marker rs6983561 adds potentially useful clinical information for African American men undergoing PCA risk assessment. Further study is warranted to validate these findings. Impact Genetic markers of early-onset PCA have potential to refine and personalize PCA early detection for high-risk men. PMID:22144497

Association between exercise and primary incidence of prostate cancer: does race matter?

PubMed

Singh, Abhay A; Jones, Lee W; Antonelli, Jodi A; Gerber, Leah; Calloway, Elizabeth E; Shuler, Kathleen H; Freedland, Stephen J; Grant, Delores J; Hoyo, Cathrine; Bañez, Lionel L

2013-04-01

Exercise is a modifiable lifestyle risk factor associated with prostate cancer risk reduction. However, whether this association is different as a function of race is unclear. In the current study, the authors attempted to characterize the link between exercise and prostate cancer (CaP) in white and black American men. Using a prospective design, 307 men (164 of whom were white and 143 of whom were black) who were undergoing prostate biopsy completed a self-reported survey that assessed exercise behavior (metabolic equivalent [MET] hours per week). Crude and adjusted logistic regression analyses were used to estimate the risk of prostate cancer controlling for age, body mass index, digital rectal examination findings, previous biopsy, Charlson comorbidity score, and family history of CaP stratified by self-reported race. There was no significant difference noted with regard to the amount of exercise between racial groups (P = .12). Higher amounts of MET hours per week were associated with a decreased risk of CaP for white men in both crude (P = .02) and adjusted (P = .04) regression models. Among whites, men who exercised ≥ 9 MET hours per week were less likely to have a positive biopsy result compared with men exercising < 9 MET hours per week (odds ratio, 0.47; 95% confidence interval, 0.22-0.99 [P = .047]). There was no association noted between MET hours per week and risk of CaP among black men in both crude (P = .79) and adjusted (P = .76) regression models. In a prospective cohort of men undergoing biopsy, increased exercise, measured as MET hours per week, was found to be associated with CaP risk reduction among white but not black men. Investigating race-specific mechanisms by which exercise modifies CaP risk and why these mechanisms disfavor black men in particular are warranted. Copyright © 2013 American Cancer Society.

Does a similar procedure result in similar survival for women and men undergoing isolated coronary artery bypass grafting?

PubMed

Attia, Tamer; Koch, Colleen G; Houghtaling, Penny L; Blackstone, Eugene H; Sabik, Ellen Mayer; Sabik, Joseph F

2017-03-01

To (1) identify sex-related differences in risk factors and revascularization strategies for patients undergoing coronary artery bypass grafting (CABG), (2) assess whether these differences influenced early and late survival, and (3) determine whether clinical effectiveness of the same revascularization strategy was influenced by sex. From January 1972 to January 2011, 57,943 adults-11,009 (19%) women-underwent primary isolated CABG. Separate models for long-term mortality were developed for men and women, followed by assessing sex-related differences in strength of risk factors (interaction terms). Incomplete revascularization was more common in men than women (26% vs 22%, P < .0001), but women received fewer bilateral internal thoracic artery (ITA) grafts (4.8% vs 12%; P < .0001) and fewer arterial grafts (68% vs 70%; P < .0001). Overall, women had lower survival than men after CABG (65% and 31% at 10 and 20 years, respectively, vs 74% and 41%; P ≤ .0001), even after risk adjustment. Incomplete revascularization was associated equally (P > .9) with lower survival in both sexes. Single ITA grafting was associated with equally (P = .3) better survival in women and men. Although bilateral ITA grafting was associated with better survival than single ITA grafting, it was less effective in women-11% lower late mortality (hazard ratio, 0.89 [0.77-1.022]) versus 27% lower in men (hazard ratio, 0.73 [0.69-0.77]; P = .01). Women on average have longer life expectancies than men but not after CABG. Every attempt should be made to use arterial grafting and complete revascularization, but for unexplained reasons, sex-related differences in effectiveness of bilateral arterial grafting were identified. Copyright © 2016. Published by Elsevier Inc.

Emotional Distress Increases the Likelihood of Undergoing Surgery among Men with Localized Prostate Cancer.

PubMed

Orom, Heather; Underwood, Willie; Biddle, Caitlin

2017-02-01

We determined whether among men with clinically localized prostate cancer, particularly men with low risk disease, greater emotional distress increases the likelihood of undergoing surgery vs radiation or active surveillance. Participants were 1,531 patients recruited from 2 academic and 3 community facilities (nonHispanic white 83%, nonHispanic black 11% and Hispanic 6%; low risk 36%, intermediate risk 49% and high risk 15%; choice of active surveillance 24%, radiation 27% and surgery 48%). Emotional distress was assessed shortly after diagnosis and after men made a treatment decision with the Distress Thermometer. We used multinomial logistic regression with robust standard errors to test if emotional distress at either point predicted treatment choice in the sample as a whole and after stratifying by D'Amico risk score. In the sample as a whole the participants who were more emotionally distressed at diagnosis were more likely to choose surgery over active surveillance (RRR 1.07; 95% CI 1.01, 1.14; p=0.02). Men who were more distressed close to the time they made a treatment choice were more likely to have chosen surgery over active surveillance (RRR 1.16; 95% CI 1.09, 1.24; p <0.001) or surgery over radiation (RRR 1.12; 95% CI 1.05, 1.19; p=0.001). This pattern was also found in men with low risk disease. Emotional distress may motivate men with low risk prostate cancer to choose more aggressive treatment. Addressing emotional distress before and during treatment decision making may reduce a barrier to the uptake of active surveillance. Copyright © 2017 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Improving the prediction of pathologic outcomes in patients undergoing radical prostatectomy: the value of prostate cancer antigen 3 (PCA3), prostate health index (phi) and sarcosine.

PubMed

Ferro, Matteo; Lucarelli, Giuseppe; Bruzzese, Dario; Perdonà, Sisto; Mazzarella, Claudia; Perruolo, Giuseppe; Marino, Ada; Cosimato, Vincenzo; Giorgio, Emilia; Tagliamonte, Virginia; Bottero, Danilo; De Cobelli, Ottavio; Terracciano, Daniela

2015-02-01

Several efforts have been made to find biomarkers that could help clinicians to preoperatively determine prostate cancer (PCa) pathological characteristics and choose the best therapeutic approach, avoiding over-treatment. On this effort, prostate cancer antigen 3 (PCA3), prostate health index (phi) and sarcosine have been presented as promising tools. We evaluated the ability of these biomarkers to predict the pathologic PCa characteristics within a prospectively collected contemporary cohort of patients who underwent radical prostatectomy (RP) for clinically localized PCa at a single high-volume Institution. The prognostic performance of PCA3, phi and sarcosine were evaluated in 78 patients undergoing RP for biopsy-proven PCa. Receiver operating characteristic (ROC) curve analyses tested the accuracy (area under the curve (AUC)) in predicting PCa pathological characteristics. Decision curve analyses (DCA) were used to assess the clinical benefit of the three biomarkers. We found that PCA3, phi and sarcosine levels were significantly higher in patients with tumor volume (TV)≥0.5 ml, pathologic Gleason sum (GS)≥7 and pT3 disease (all p-values≤0.01). ROC curve analysis showed that phi is an accurate predictor of high-stage (AUC 0.85 [0.77-0.93]), high-grade (AUC 0.83 [0.73-0.93]) and high-volume disease (AUC 0.94 [0.88-0.99]). Sarcosine showed a comparable AUC (0.85 [0.76-0.94]) only for T3 stage prediction, whereas PCA3 score showed lower AUCs, ranging from 0.74 (for GS) to 0.86 (for TV). PCA3, phi and sarcosine are predictors of PCa characteristics at final pathology. Successful clinical translation of these findings would reduce the frequency of surveillance biopsies and may enhance acceptance of active surveillance (AS). Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Mutant MiRP1 subunits modulate HERG K+ channel gating: a mechanism for pro-arrhythmia in long QT syndrome type 6

PubMed Central

Lu, Yu; Mahaut-Smith, Martyn P; Huang, Christopher L-H; Vandenberg, Jamie I

2003-01-01

Mutations in KCNE2, which encodes the minK-related protein 1 (MiRP1), are associated with an increased risk of arrhythmias; however, the underlying mechanisms are unknown. MiRP1 is thought to associate with many K+ channel α-subunits, including HERG K+ channels, which have a major role in suppressing arrhythmias initiated by premature beats. In this study we have investigated in chinese hamster ovary (CHO) cells at 37 °C the effects of co-expressing HERG K+ channels with either wild-type (WT) MiRP1 or one of three mutant MiRP1 subunits, T8A, Q9E and M54T. The most significant effects of MiRP1 subunits on HERG channels were a more negative steady-state activation for HERG + T8A MiRP1 and a more positive steady-state activation for HERG + M54T MiRP1 compared to either HERG + WT MiRP1 or HERG alone. All three mutants caused a significant slowing of deactivation at depolarised potentials. T8A MiRP1 also caused an acceleration of inactivation and recovery from inactivation compared to HERG + WT MiRP1. During ventricular action potential clamp experiments there was a significant decrease in current in the early phases of the action potential for HERG + WT MiRP1 channels compared to HERG alone. This effect was not as prominent for the mutant MiRP1 subunits. During premature action potential clamp protocols, the T8A and Q9E mutants, but not the M54T mutant, resulted in significantly larger current spikes during closely coupled premature beats, compared to HERG + WT MiRP1. At longer coupling intervals, all three mutants resulted in larger current spikes than HERG alone or HERG + WT MiRP1 channels. It is therefore possible that augmentation of HERG currents in the early diastolic period may be pro-arrhythmic. PMID:12923204

Outcomes of men with an elevated prostate-specific antigen (PSA) level as their sole preoperative intermediate- or high-risk feature.

PubMed

Faisal, Farzana A; Sundi, Debasish; Pierorazio, Phillip M; Ball, Mark W; Humphreys, Elizabeth B; Han, Misop; Epstein, Jonathan I; Partin, Alan W; Carter, H Ballentine; Bivalacqua, Trinity J; Schaeffer, Edward M; Ross, Ashley E

2014-12-01

To investigate the post-prostatectomy and long-term outcomes of men presenting with an elevated pretreatment prostate-specific antigen (PSA) level (>10 ng/mL), but otherwise low-risk features (biopsy Gleason score ≤6 and clinical stage ≤T2a). PSA-incongruent intermediate-risk (PII) cases were defined as those patients with preoperative PSA >10 and ≤20 ng/mL but otherwise low-risk features, and PSA-incongruent high-risk (PIH) cases were defined as men with PSA >20 ng/mL but otherwise low-risk features. Our institutional radical prostatectomy database (1992-2012) was queried and the results were stratified into D'Amico low-, intermediate- and high risk, PSA-incongruent intermediate-risk and PSA-incongruent high-risk cases. Prostate cancer (PCa) features and outcomes were evaluated using appropriate comparative tests. Multivariable analyses were adjusted for age, race and year of surgery. Of the total cohort of 17 608 men, 1132 (6.4%) had PII-risk disease and 183 (1.0%) had PIH-risk disease. Compared with the low-risk group, the odds of upgrading at radical prostatectomy (RP) were 2.20 (95% CI 1.93-2.52; P < 0.001) for the PII group and 3.58 (95% CI 2.64-4.85; P < 0.001) for the PIH group, the odds of extraprostatic disease at RP were 2.35 (95% CI 2.05-2.68; P < 0.001) for the PII group and 6.68 (95% CI 4.89-9.15; P < 0.001) for the PIH group, and the odds of positive surgical margins were 1.97 (95% CI 1.67-2.33; P < 0.001) for the PII group and 3.54 (95% CI 2.50-4.95, P < 0.001) for the PIH group. Compared with low-risk disease, PII-risk disease was associated with a 2.85-, 2.99- and 3.32-fold greater risk of biochemical recurrence (BCR), metastasis and PCa-specific mortality, respectively, and PIH-risk disease was associated with a 5.32-, 6.14- and 7.07-fold greater risk of BCR, metastasis and PCa-specific mortality, respectively (P ≤ 0.001 for all comparisons). For the PII group, the higher risks of positive surgical margins, upgrading, upstaging and BCR were dependent on PSA density (PSAD): men in the PII group who had a PSAD <0.15 ng/mL/g were not at higher risk compared with those in the low-risk group. Men in the PII group with a PSAD ≥0.15 ng/mL/g and men in the PIH group were more likely to have an anterior component of the dominant tumour (59 and 64%, respectively) compared with those in the low- (35%) and intermediate-risk group (39%) and those in the PII-risk group with PSAD <0.15 ng/mL/g (29%). Men with PSA >20 ng/mL or men with PSA >10 and ≤20 ng/mL with a PSAD ≥0.15 ng/mL/g, but otherwise low-risk PCa, are at greater risk of adverse pathological and oncological outcomes and may be inappropriate candidates for active surveillance. These men are at greater risk of having anterior tumours that are undersampled at biopsy, so if treatment is deferred, ancillary testing such as anterior zone sampling or magnetic resonance imaging should be strongly encouraged. Men with elevated PSA levels >10 and ≤20 ng/mL but low PSAD have outcomes similar to those in the low-risk group, and consideration of surveillance is appropriate in these cases. © 2014 The Authors. BJU International © 2014 BJU International.

Next-generation sequencing-based molecular diagnosis of a Chinese patient cohort with autosomal recessive retinitis pigmentosa.

PubMed

Fu, Qing; Wang, Feng; Wang, Hui; Xu, Fei; Zaneveld, Jacques E; Ren, Huanan; Keser, Vafa; Lopez, Irma; Tuan, Han-Fang; Salvo, Jason S; Wang, Xia; Zhao, Li; Wang, Keqing; Li, Yumei; Koenekoop, Robert K; Chen, Rui; Sui, Ruifang

2013-06-14

Retinitis pigmentosa (RP) is a highly heterogeneous genetic disease; therefore, an accurate molecular diagnosis is essential for appropriate disease treatment and family planning. The prevalence of RP in China had been reported at 1 in 3800, resulting in an estimated total of 340,000 Chinese RP patients. However, genetic studies of Chinese RP patients have been very limited. To date, no comprehensive molecular diagnosis has been done for Chinese RP patients. With the emergence of next-generation sequencing (NGS), comprehensive molecular diagnosis of RP is now within reach. The purpose of this study was to perform the first NGS-based comprehensive molecular diagnosis for Chinese RP patients. Thirty-one well-characterized autosomal recessive RP (arRP) families were recruited. For each family, the DNA sample from one affected member was sequenced using our custom capture panel, which includes 163 retinal disease genes. Variants were called, filtered, and annotated by our in-house automatic pipeline. Twelve arRP families were successfully molecular diagnosed, achieving a diagnostic rate of approximately 40%. Interestingly, approximately 63% of the pathogenic mutations we identified are novel, which is higher than that observed in a similar study on European descent (45%). Moreover, the clinical diagnoses of two families were refined based on the pathogenic mutations identified in the patients. We conclude that comprehensive molecular diagnosis can be vital for an accurate clinical diagnosis of RP. Applying this tool on patients from different ethnic groups is essential for enhancing our knowledge of the global spectrum of RP disease-causing mutations.

Correlations between trans-membrane pressure (TMP) and sludge properties in submerged membrane electro-bioreactor (SMEBR) and conventional membrane bioreactor (MBR).

PubMed

Hasan, Shadi W; Elektorowicz, Maria; Oleszkiewicz, Jan A

2012-09-01

The influence of sludge properties in SMEBR and conventional MBR pilot systems on membrane fouling was investigated. Generated data were analyzed using statistical analysis Pearson's product momentum correlation coefficient (r(p)). Analysis showed that TMP had strong direct (r(p)=0.9182) and inverse (r(p)=-0.9205) correlations to mean particle size diameter in MBR and SMEBR, respectively. TMP in SMEBR had a strong direct correlation to the sludge mixed liquor suspended solids concentration (MLSS) (r(p)=0.7757) while a weak direct correlation (r(p)=0.1940) was observed in MBR. SMEBR showed a moderate inverse correlation (r(p)=-0.6118) between TMP and soluble carbohydrates (EPS(c)) and a very weak direct correlation (r(p)=0.3448) to soluble proteins (EPS(p)). Conversely, EPS(p) in MBR had more significant impact (r(p)=0.4856) on membrane fouling than EPS(c) (r(p)=0.3051). The results provide insight into optimization of operational conditions in SMEBR system to overcome membrane fouling. Copyright © 2012 Elsevier Ltd. All rights reserved.

The Relevance of AgRP Neuron-Derived GABA Inputs to POMC Neurons Differs for Spontaneous and Evoked Release

PubMed Central

2017-01-01

Hypothalamic agouti-related peptide (AgRP) neurons potently stimulate food intake, whereas proopiomelanocortin (POMC) neurons inhibit feeding. Whether AgRP neurons exert their orexigenic actions, at least in part, by inhibiting anorexigenic POMC neurons remains unclear. Here, the connectivity between GABA-releasing AgRP neurons and POMC neurons was examined in brain slices from male and female mice. GABA-mediated spontaneous IPSCs (sIPSCs) in POMC neurons were unaffected by disturbing GABA release from AgRP neurons either by cell type-specific deletion of the vesicular GABA transporter or by expression of botulinum toxin in AgRP neurons to prevent vesicle-associated membrane protein 2-dependent vesicle fusion. Additionally, there was no difference in the ability of μ-opioid receptor (MOR) agonists to inhibit sIPSCs in POMC neurons when MORs were deleted from AgRP neurons, and activation of the inhibitory designer receptor hM4Di on AgRP neurons did not affect sIPSCs recorded from POMC neurons. These approaches collectively indicate that AgRP neurons do not significantly contribute to the strong spontaneous GABA input to POMC neurons. Despite these observations, optogenetic stimulation of AgRP neurons reliably produced evoked IPSCs in POMC neurons, leading to the inhibition of POMC neuron firing. Thus, AgRP neurons can potently affect POMC neuron function without contributing a significant source of spontaneous GABA input to POMC neurons. Together, these results indicate that the relevance of GABAergic inputs from AgRP to POMC neurons is state dependent and highlight the need to consider different types of transmitter release in circuit mapping and physiologic regulation. SIGNIFICANCE STATEMENT Agouti-related peptide (AgRP) neurons play an important role in driving food intake, while proopiomelanocortin (POMC) neurons inhibit feeding. Despite the importance of these two well characterized neuron types in maintaining metabolic homeostasis, communication between these cells remains poorly understood. To provide clarity to this circuit, we made electrophysiological recordings from mouse brain slices and found that AgRP neurons do not contribute spontaneously released GABA onto POMC neurons, although when activated with channelrhodopsin AgRP neurons inhibit POMC neurons through GABA-mediated transmission. These findings indicate that the relevance of AgRP to POMC neuron GABA connectivity depends on the state of AgRP neuron activity and suggest that different types of transmitter release should be considered when circuit mapping. PMID:28667175

The Relevance of AgRP Neuron-Derived GABA Inputs to POMC Neurons Differs for Spontaneous and Evoked Release.

PubMed

Rau, Andrew R; Hentges, Shane T

2017-08-02

Hypothalamic agouti-related peptide (AgRP) neurons potently stimulate food intake, whereas proopiomelanocortin (POMC) neurons inhibit feeding. Whether AgRP neurons exert their orexigenic actions, at least in part, by inhibiting anorexigenic POMC neurons remains unclear. Here, the connectivity between GABA-releasing AgRP neurons and POMC neurons was examined in brain slices from male and female mice. GABA-mediated spontaneous IPSCs (sIPSCs) in POMC neurons were unaffected by disturbing GABA release from AgRP neurons either by cell type-specific deletion of the vesicular GABA transporter or by expression of botulinum toxin in AgRP neurons to prevent vesicle-associated membrane protein 2-dependent vesicle fusion. Additionally, there was no difference in the ability of μ-opioid receptor (MOR) agonists to inhibit sIPSCs in POMC neurons when MORs were deleted from AgRP neurons, and activation of the inhibitory designer receptor hM4Di on AgRP neurons did not affect sIPSCs recorded from POMC neurons. These approaches collectively indicate that AgRP neurons do not significantly contribute to the strong spontaneous GABA input to POMC neurons. Despite these observations, optogenetic stimulation of AgRP neurons reliably produced evoked IPSCs in POMC neurons, leading to the inhibition of POMC neuron firing. Thus, AgRP neurons can potently affect POMC neuron function without contributing a significant source of spontaneous GABA input to POMC neurons. Together, these results indicate that the relevance of GABAergic inputs from AgRP to POMC neurons is state dependent and highlight the need to consider different types of transmitter release in circuit mapping and physiologic regulation. SIGNIFICANCE STATEMENT Agouti-related peptide (AgRP) neurons play an important role in driving food intake, while proopiomelanocortin (POMC) neurons inhibit feeding. Despite the importance of these two well characterized neuron types in maintaining metabolic homeostasis, communication between these cells remains poorly understood. To provide clarity to this circuit, we made electrophysiological recordings from mouse brain slices and found that AgRP neurons do not contribute spontaneously released GABA onto POMC neurons, although when activated with channelrhodopsin AgRP neurons inhibit POMC neurons through GABA-mediated transmission. These findings indicate that the relevance of AgRP to POMC neuron GABA connectivity depends on the state of AgRP neuron activity and suggest that different types of transmitter release should be considered when circuit mapping. Copyright © 2017 the authors 0270-6474/17/377362-11$15.00/0.

MRI-Targeted or Standard Biopsy for Prostate-Cancer Diagnosis.

PubMed

Kasivisvanathan, Veeru; Rannikko, Antti S; Borghi, Marcelo; Panebianco, Valeria; Mynderse, Lance A; Vaarala, Markku H; Briganti, Alberto; Budäus, Lars; Hellawell, Giles; Hindley, Richard G; Roobol, Monique J; Eggener, Scott; Ghei, Maneesh; Villers, Arnauld; Bladou, Franck; Villeirs, Geert M; Virdi, Jaspal; Boxler, Silvan; Robert, Grégoire; Singh, Paras B; Venderink, Wulphert; Hadaschik, Boris A; Ruffion, Alain; Hu, Jim C; Margolis, Daniel; Crouzet, Sébastien; Klotz, Laurence; Taneja, Samir S; Pinto, Peter; Gill, Inderbir; Allen, Clare; Giganti, Francesco; Freeman, Alex; Morris, Stephen; Punwani, Shonit; Williams, Norman R; Brew-Graves, Chris; Deeks, Jonathan; Takwoingi, Yemisi; Emberton, Mark; Moore, Caroline M

2018-05-10

Multiparametric magnetic resonance imaging (MRI), with or without targeted biopsy, is an alternative to standard transrectal ultrasonography-guided biopsy for prostate-cancer detection in men with a raised prostate-specific antigen level who have not undergone biopsy. However, comparative evidence is limited. In a multicenter, randomized, noninferiority trial, we assigned men with a clinical suspicion of prostate cancer who had not undergone biopsy previously to undergo MRI, with or without targeted biopsy, or standard transrectal ultrasonography-guided biopsy. Men in the MRI-targeted biopsy group underwent a targeted biopsy (without standard biopsy cores) if the MRI was suggestive of prostate cancer; men whose MRI results were not suggestive of prostate cancer were not offered biopsy. Standard biopsy was a 10-to-12-core, transrectal ultrasonography-guided biopsy. The primary outcome was the proportion of men who received a diagnosis of clinically significant cancer. Secondary outcomes included the proportion of men who received a diagnosis of clinically insignificant cancer. A total of 500 men underwent randomization. In the MRI-targeted biopsy group, 71 of 252 men (28%) had MRI results that were not suggestive of prostate cancer, so they did not undergo biopsy. Clinically significant cancer was detected in 95 men (38%) in the MRI-targeted biopsy group, as compared with 64 of 248 (26%) in the standard-biopsy group (adjusted difference, 12 percentage points; 95% confidence interval [CI], 4 to 20; P=0.005). MRI, with or without targeted biopsy, was noninferior to standard biopsy, and the 95% confidence interval indicated the superiority of this strategy over standard biopsy. Fewer men in the MRI-targeted biopsy group than in the standard-biopsy group received a diagnosis of clinically insignificant cancer (adjusted difference, -13 percentage points; 95% CI, -19 to -7; P<0.001). The use of risk assessment with MRI before biopsy and MRI-targeted biopsy was superior to standard transrectal ultrasonography-guided biopsy in men at clinical risk for prostate cancer who had not undergone biopsy previously. (Funded by the National Institute for Health Research and the European Association of Urology Research Foundation; PRECISION ClinicalTrials.gov number, NCT02380027 .).

In vitro activity of RP 74501-RP 74502, a novel streptogramin antimicrobial mixture, against clinical isolates of Legionella species.

PubMed Central

Edelstein, P H; Edelstein, M A

1993-01-01

Agar and broth microdilution MICs of RP 74501-RP 74502, a mixture of streptogramin antimicrobial agents that inhibited 90% of 22 Legionella strains tested, were 0.64 and 0.08 microgram/ml, respectively; respective erythromycin values were 1.0 and 0.12 microgram/ml. RP 74501-RP 74502 at 1 microgram/ml was more active than the same erythromycin concentration in a macrophage system for both L. pneumophila strains studied but at a lower concentration (0.25 microgram/ml) was much less active than erythromycin. PMID:8494390

Arcuate hypothalamic AgRP and putative POMC neurons show opposite changes in spiking across multiple timescales

PubMed Central

Mandelblat-Cerf, Yael; Ramesh, Rohan N; Burgess, Christian R; Patella, Paola; Yang, Zongfang; Lowell, Bradford B; Andermann, Mark L

2015-01-01

Agouti-related-peptide (AgRP) neurons—interoceptive neurons in the arcuate nucleus of the hypothalamus (ARC)—are both necessary and sufficient for driving feeding behavior. To better understand the functional roles of AgRP neurons, we performed optetrode electrophysiological recordings from AgRP neurons in awake, behaving AgRP-IRES-Cre mice. In free-feeding mice, we observed a fivefold increase in AgRP neuron firing with mounting caloric deficit in afternoon vs morning recordings. In food-restricted mice, as food became available, AgRP neuron firing dropped, yet remained elevated as compared to firing in sated mice. The rapid drop in spiking activity of AgRP neurons at meal onset may reflect a termination of the drive to find food, while residual, persistent spiking may reflect a sustained drive to consume food. Moreover, nearby neurons inhibited by AgRP neuron photostimulation, likely including satiety-promoting pro-opiomelanocortin (POMC) neurons, demonstrated opposite changes in spiking. Finally, firing of ARC neurons was also rapidly modulated within seconds of individual licks for liquid food. These findings suggest novel roles for antagonistic AgRP and POMC neurons in the regulation of feeding behaviors across multiple timescales. DOI: http://dx.doi.org/10.7554/eLife.07122.001 PMID:26159614

Evidence for a major retinitis pigmentosa locus on 19q13.4 (RP11), and association with a unique bimodal expressivity phenotype

DOE Office of Scientific and Technical Information (OSTI.GOV)

Al-Maghtheh, M.; Vithana, E.; Tarttelin, E.

Retinitis pigmentosa (RP) is the name given to a heterogeneous group of retinal degenerations mapping to at least 16 loci. The autosomal dominant form (adRP), accounting for {approximately}25% of cases, can be caused by mutations in two genes, rhodopsin and peripherin/RDS, and by at least six other loci identified by linkage analysis. The RP11 locus for adRP has previously been mapped to chromosome 19q13.4 in a large English family. This linkage has been independently confirmed in a Japanese family, and we now report three additional unrelated linked U.K. families, suggesting that this is a major locus for RP. Linkage analysismore » in the U.K. families refines the RP11 interval to 5 cM between markers D19S180 and AFMc001yb1. All linked families exhibit incomplete penetrance; some obligate gene carriers remain asymptomatic throughout their lives, whereas symptomatic individuals experience night blindness and visual field loss in their teens and are generally registered as blind by their 30s. This {open_quotes}bimodal expressivity{close_quotes} contrasts with the variable-expressivity RP mapping to chromosome 7p (RP9) in another family, which has implications for diagnosis and counseling of RP11 families. These results may also imply that a proportion of sporadic RP, previously assumed to be recessive, might result from mutations at this locus. 27 refs., 3 figs., 1 tab.« less

Investigating the mechanism underlying urinary continence recovery after radical prostatectomy: effectiveness of a longer urethral stump to prevent urinary incontinence.

PubMed

Kadono, Yoshifumi; Nohara, Takahiro; Kawaguchi, Shohei; Naito, Renato; Urata, Satoko; Nakashima, Kazufumi; Iijima, Masashi; Shigehara, Kazuyoshi; Izumi, Kouji; Gabata, Toshifumi; Mizokami, Atsushi

2018-02-28

To assess the chronological changes in urinary incontinence and urethral function before and after radical prostatectomy (RP), and to compare the findings of pelvic magnetic resonance imaging (MRI) before and after RP to evaluate the anatomical changes. In total, 185 patients were evaluated with regard to the position of the distal end of the membranous urethra (DMU) on a mid-sagittal MRI slice and urethral sphincter function using the urethral pressure profilometry. The patients also underwent an abdominal leak point pressure test before RP and at 10 days and 12 months after RP. The results were then compared with the chronological changes in urinary incontinence. The MRI results showed that the DMU shifted proximally to an average distance of 4 mm at 10 days after RP and returned to the preoperative position at 12 months after RP. Urethral sphincter function also worsened 10 days after RP, with recovery after 12 months. The residual length of the urethral stump and urinary incontinence were significantly associated with the migration length of the DMU at 10 days after RP. The residual length of the urethral stump was a significant predictor of urinary incontinence after RP. This is the first study to elucidate that the slight vertical repositioning of the membranous urethra after RP causes chronological changes in urinary incontinence. A long urethral residual stump reduces urinary incontinence after RP. © 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.

Planned nerve preservation to reduce positive surgical margins during robot-assisted laparoscopic radical prostatectomy.

PubMed

Zorn, Kevin C; Gofrit, Ofer N; Steinberg, Gary P; Taxy, Jerome B; Zagaja, Gregory P; Shalhav, Arieh L

2008-06-01

The main objective of radical prostatectomy (RP) is optimal oncologic resection with preservation of sexual function (SF). During our initial experience with robot-assisted laparoscopic radical prostatectomy (RLRP), we noted a high rate of posterolateral location of positive surgical margins (PSM) with nerve preservation (NP). With its magnified view of the surgical field and improved instrument precision, one potential advantage of RLRP is the ability to tailor the degree of NP. We evaluated the effect of a protocol for side-specific NP based on preoperative variables on PSM rates and SF outcomes. Between June and November 2006, 150 consecutive RLRPs were performed using a surgical protocol to select side-specific NP techniques (interfascial [IF], partial extrafascial [pEF], and wide extrafascial resection [WEFR]) based on preoperative risk factors (clinical stage, biopsy Gleason score, percentage of positive cores and maximal core cancer percentage, and preoperative PSA). Pathologic and SF outcomes in these patients were compared with those of a control group of 245 consecutive RLRPs in whom non-selective IF dissection was performed. All data were prospectively collected. Mean patient age, PSA, clinical stage, biopsy Gleason score and positive core involvement, pathologic Gleason score, and stage were comparable among the two groups. The overall PSM rate (12.6% nu 20.4%; P = 0.04) and posterolateral location of PSMs (37% nu 70%; P = 0.04) were significantly lower in the study group. At 12 months, potency was reported in 80%, 67%, and 11% of men undergoing bilateral IFNP, partial extrafascial nerve preservation (pEFNP), and WEFR, respectively (P = 0.27). Planning side-specific NP during RLRP, according to selected preoperative variables, can significantly reduce overall and posterolateral PSM rates. Furthermore, partial nerve sparing (pEFNP) also appears to confer favorable early SF outcomes.

Preparation and mechanical properties of edible rapeseed protein films.

PubMed

Jang, Sung-Ae; Lim, Geum-Ok; Song, Kyung Bin

2011-03-01

Edible films were manufactured from rapeseed oil extraction residues. To prepare rapeseed protein (RP) films, various concentrations of plasticizers and emulsifiers were incorporated into the preparation of a film-forming solution. The optimal conditions for the preparation of the RP film were 2% sorbitol/0.5% sucrose as plasticizer and 1.5% polysorbate 20 as an emulsifier. In addition, RP blend films were prepared. Gelidium corneum or gelatin was added to improve the physical properties of the RP film, and the highest tensile strength value of the films was 53.45 MPa for the 3% RP/4% gelatin film. Our results suggest that the RP-gelatin blend film is suitable for applications in food packaging. Edible RP films prepared in the present investigation can be applied in food packaging.

Recombinant Rp1 genes confer necrotic or nonspecific resistance phenotypes.

PubMed

Smith, Shavannor M; Steinau, Martin; Trick, Harold N; Hulbert, Scot H

2010-06-01

Genes at the Rp1 rust resistance locus of maize confer race-specific resistance to the common rust fungus Puccinia sorghi. Three variant genes with nonspecific effects (HRp1 -Kr1N, -D*21 and -MD*19) were found to be generated by intragenic crossing over within the LRR region. The LRR region of most NBS-LRR encoding genes is quite variable and codes for one of the regions in resistance gene proteins that controls specificity. Sequence comparisons demonstrated that the Rp1-Kr1N recombinant gene was identical to the N-terminus of the rp1-kp2 gene and C-terminus of another gene from its HRp1-K grandparent. The Rp1-D*21 recombinant gene consists of the N-terminus of the rp1-dp2 gene and C-terminus of the Rp1-D gene from the parental haplotype. Similarly, a recombinant gene from the Rp1-MD*19 haplotype has the N-terminus of an rp1 gene from the HRp1-M parent and C-terminus of the rp1-D19 gene from the HRp1-D parent. The recombinant Rp1 -Kr1N, -D*21 and -MD*19 genes activated defense responses in the absence of their AVR proteins triggering HR (hypersensitive response) in the absence of the pathogen. The results indicate that the frequent intragenic recombination events that occur in the Rp1 gene cluster not only recombine the genes into novel haplotypes, but also create genes with nonspecific effects. Some of these may contribute to nonspecific quantitative resistance but others have severe consequences for the fitness of the plant.

Running-specific prostheses permit energy cost similar to nonamputees.

PubMed

Brown, Mary Beth; Millard-Stafford, Mindy L; Allison, Andrew R

2009-05-01

Improvements in prosthesis design have facilitated participation in competitive running for persons with lower limb loss (AMP). The purpose of this study was to examine the physiological responses of AMP using a run-specific prosthesis (RP) versus a traditional prosthesis (P) and cross-referenced with nonamputee controls (C) matched by training status, age, gender, and body composition during level treadmill running (TM). Twelve trained runners completed a multistage submaximal TM exercise during which HR and oxygen uptake (VO(2)) were obtained. Steady state measures at 134 m x min(-1) were compared between RP and P in AMP. AMP using RP (AMP-RP) and C also performed a continuous speed-incremented maximal TM test until volitional fatigue. RP elicited lower HR and VO(2) compared with P in AMP. Using RP, AMP achieved similar VO(2max) and peak TM speed compared with C but with higher HR(max). Relative HR (%HR(max)) and oxygen uptake (%VO(2max)), the regression intercept, slope, SEE, and Pearson's r correlation were not different between AMP-RP and C. %HR(max) calculated with the published equation, %HR(max) = 0.73(%VO(2max)) + 30, was not significantly different from actual %HR(max) for AMP-RP or C in any stage. RP permits AMP to attain peak TM speed and aerobic capacity similar to trained nonamputees and significantly attenuates HR and energy cost of submaximal running compared with a P. Use of RP confers no physiological advantage compared with nonamputee runners because energy cost at the set speed was not significantly different for AMP-RP. Current equations on the basis of the relative HR-VO(2) relationship seem appropriate to prescribe exercise intensity for persons with transtibial amputations using RP.

Molecular genetic analysis of retinitis pigmentosa in Indonesia using genome-wide homozygosity mapping

PubMed Central

Siemiatkowska, Anna M.; Arimadyo, Kentar; Moruz, Luminita M.; Astuti, Galuh D.N.; de Castro-Miro, Marta; Zonneveld, Marijke N.; Strom, Tim M.; de Wijs, Ilse J.; Hoefsloot, Lies H.; Faradz, Sultana M.H.; Cremers, Frans P.M.; den Hollander, Anneke I.

2011-01-01

Purpose Retinitis pigmentosa (RP) is a clinically and genetically heterogeneous retinal disorder. Despite tremendous knowledge about the genes involved in RP, little is known about the genetic causes of RP in Indonesia. Here, we aim to identify the molecular genetic causes underlying RP in a small cohort of Indonesian patients, using genome-wide homozygosity mapping. Methods DNA samples from affected and healthy individuals from 14 Indonesian families segregating autosomal recessive, X-linked, or isolated RP were collected. Homozygosity mapping was conducted using Illumina 6k or Affymetrix 5.0 single nucleotide polymorphism (SNP) arrays. Known autosomal recessive RP (arRP) genes residing in homozygous regions and X-linked RP genes were sequenced for mutations. Results In ten out of the 14 families, homozygous regions were identified that contained genes known to be involved in the pathogenesis of RP. Sequence analysis of these genes revealed seven novel homozygous mutations in ATP-binding cassette, sub-family A, member 4 (ABCA4), crumbs homolog 1 (CRB1), eyes shut homolog (Drosophila) (EYS), c-mer proto-oncogene tyrosine kinase (MERTK), nuclear receptor subfamily 2, group E, member 3 (NR2E3) and phosphodiesterase 6A, cGMP-specific, rod, alpha (PDE6A), all segregating in the respective families. No mutations were identified in the X-linked genes retinitis pigmentosa GTPase regulator (RPGR) and retinitis pigmentosa 2 (X-linked recessive; RP2). Conclusions Homozygosity mapping is a powerful tool to identify the genetic defects underlying RP in the Indonesian population. Compared to studies involving patients from other populations, the same genes appear to be implicated in the etiology of recessive RP in Indonesia, although all mutations that were discovered are novel and as such may be unique for this population. PMID:22128245

Genes and Mutations Causing Autosomal Dominant Retinitis Pigmentosa

PubMed Central

Daiger, Stephen P.; Bowne, Sara J.; Sullivan, Lori S.

2015-01-01

Retinitis pigmentosa (RP) has a prevalence of approximately one in 4000; 25%–30% of these cases are autosomal dominant retinitis pigmentosa (adRP). Like other forms of inherited retinal disease, adRP is exceptionally heterogeneous. Mutations in more than 25 genes are known to cause adRP, more than 1000 mutations have been reported in these genes, clinical findings are highly variable, and there is considerable overlap with other types of inherited disease. Currently, it is possible to detect disease-causing mutations in 50%–75% of adRP families in select populations. Genetic diagnosis of adRP has advantages over other forms of RP because segregation of disease in families is a useful tool for identifying and confirming potentially pathogenic variants, but there are disadvantages too. In addition to identifying the cause of disease in the remaining 25% of adRP families, a central challenge is reconciling clinical diagnosis, family history, and molecular findings in patients and families. PMID:25304133

Fasting Activation of AgRP Neurons Requires NMDA Receptors and Involves Spinogenesis and Increased Excitatory Tone

PubMed Central

Liu, Tiemin; Kong, Dong; Shah, Bhavik P.; Ye, Chianping; Koda, Shuichi; Saunders, Arpiar; Ding, Jun B.; Yang, Zongfang; Sabatini, Bernardo L.; Lowell, Bradford B.

2012-01-01

SUMMARY AgRP neuron activity drives feeding and weight gain while that of nearby POMC neurons does the opposite. However, the role of excitatory glutamatergic input in controlling these neurons is unknown. To address this question, we generated mice lacking NMDA receptors (NMDARs) on either AgRP or POMC neurons. Deletion of NMDARs from AgRP neurons markedly reduced weight, body fat and food intake whereas deletion from POMC neurons had no effect. Activation of AgRP neurons by fasting, as assessed by c-Fos, Agrp and Npy mRNA expression, AMPA receptor-mediated EPSCs, depolarization and firing rates, required NMDARs. Furthermore, AgRP but not POMC neurons have dendritic spines and increased glutamatergic input onto AgRP neurons caused by fasting was paralleled by an increase in spines, suggesting fasting induced synaptogenesis and spinogenesis. Thus glutamatergic synaptic transmission and its modulation by NMDARs play key roles in controlling AgRP neurons and determining the cellular and behavioral response to fasting. PMID:22325203

Genetic high throughput screening in Retinitis Pigmentosa based on high resolution melting (HRM) analysis.

PubMed

Anasagasti, Ander; Barandika, Olatz; Irigoyen, Cristina; Benitez, Bruno A; Cooper, Breanna; Cruchaga, Carlos; López de Munain, Adolfo; Ruiz-Ederra, Javier

2013-11-01

Retinitis Pigmentosa (RP) involves a group of genetically determined retinal diseases caused by a large number of mutations that result in rod photoreceptor cell death followed by gradual death of cone cells. Most cases of RP are monogenic, with more than 80 associated genes identified so far. The high number of genes and variants involved in RP, among other factors, is making the molecular characterization of RP a real challenge for many patients. Although HRM has been used for the analysis of isolated variants or single RP genes, as far as we are concerned, this is the first study that uses HRM analysis for a high-throughput screening of several RP genes. Our main goal was to test the suitability of HRM analysis as a genetic screening technique in RP, and to compare its performance with two of the most widely used NGS platforms, Illumina and PGM-Ion Torrent technologies. RP patients (n = 96) were clinically diagnosed at the Ophthalmology Department of Donostia University Hospital, Spain. We analyzed a total of 16 RP genes that meet the following inclusion criteria: 1) size: genes with transcripts of less than 4 kb; 2) number of exons: genes with up to 22 exons; and 3) prevalence: genes reported to account for, at least, 0.4% of total RP cases worldwide. For comparison purposes, RHO gene was also sequenced with Illumina (GAII; Illumina), Ion semiconductor technologies (PGM; Life Technologies) and Sanger sequencing (ABI 3130xl platform; Applied Biosystems). Detected variants were confirmed in all cases by Sanger sequencing and tested for co-segregation in the family of affected probands. We identified a total of 65 genetic variants, 15 of which (23%) were novel, in 49 out of 96 patients. Among them, 14 (4 novel) are probable disease-causing genetic variants in 7 RP genes, affecting 15 patients. Our HRM analysis-based study, proved to be a cost-effective and rapid method that provides an accurate identification of genetic RP variants. This approach is effective for medium sized (<4 kb transcript) RP genes, which constitute over 80% of the total of known RP genes.

Genetic highthroughput screening in retinitis pigmentosa based on high resolution melting (HRM) analysis.

PubMed

Anasagasti, Ander; Barandika, Olatz; Irigoyen, Cristina; Benitez, Bruno A; Cooper, Breanna; Cruchaga, Carlos; López de Munain, Adolfo; Ruiz-Ederra, Javier

2013-10-24

Retinitis Pigmentosa (RP) involves a group of genetically determined retinal diseases caused by a large number of mutations that result in rod photoreceptor cell death followed by gradual death of cone cells. Most cases of RP are monogenic, with more than 80 associated genes identified so far. The high number of genes and variants involved in RP, among other factors, is making the molecular characterization of RP a real challenge for many patients. Although HRM has been used for the analysis of isolated variants or single RP genes, as far as we are concerned, this is the first study that uses HRM analysis for a high-throughput screening of several RP genes. Our main goal was to test the suitability of HRM analysis as a genetic screening technique in RP, and to compare its performance with two of the most widely used NGS platforms, Illumina and PGM-Ion Torrent technologies. RP patients (n=96) were clinically diagnosed at the Ophthalmology Department of Donostia University Hospital, Spain. We analyzed a total of 16 RP genes that meet the following inclusion criteria: 1) size: genes with transcripts of less than 4 kb; 2) number of exons: genes with up to 22 exons; and 3) prevalence: genes reported to account for, at least, 0.4 % of total RP cases worldwide. For comparison purposes, RHO gene was also sequenced with Illumina (GAII; Illumina), Ion semiconductor technologies (PGM; Life Technologies) and Sanger sequencing (ABI 3130xl platform; Applied Biosystems). Detected variants were confirmed in all cases by Sanger sequencing and tested for co-segregation in the family of affected probands. We identified a total of 65 genetic variants, 15 of which (23%) were novel, in 49 out of 96 patients. Among them, 14 (4 novel) are probable disease-causing genetic variants in 7 RP genes, affecting 15 patients. Our HRM analysis-based study, proved to be a cost-effective and rapid method that provides an accurate identification of genetic RP variants. This approach is effective for medium sized (<4 kb transcript) RP genes, which constitute over 80% of the total of known RP genes. © 2013 Published by Elsevier Ltd.

RP-1776, a novel cyclic peptide produced by Streptomyces sp., inhibits the binding of PDGF to the extracellular domain of its receptor.

PubMed

Toki, S; Agatsuma, T; Ochiai, K; Saitoh, Y; Ando, K; Nakanishi, S; Lokker, N A; Giese, N A; Matsuda, Y

2001-05-01

RP-1776, a novel cyclic peptide, was isolated from the culture broth of Streptomyces sp. KY11784. RP-1776 selectively inhibited the binding of PDGF BB to the extracellular domain of the PDGF beta-receptor with an IC50 value of 11 +/- 6 microM. Detailed binding experiments suggested that RP-1776 directly interacts with PDGF BB. RP-1776 inhibited the phosphorylation of the PDGF beta-receptor induced by PDGF BB. These results suggested that RP-1776 antagonizes the signaling of PDGF BB probably through the inhibition of PDGF BB binding to the PDGF beta-receptor.

Symportin 1 chaperones 5S RNP assembly during ribosome biogenesis by occupying an essential rRNA-binding site

PubMed Central

Calviño, Fabiola R.; Kharde, Satyavati; Ori, Alessandro; Hendricks, Astrid; Wild, Klemens; Kressler, Dieter; Bange, Gert; Hurt, Ed; Beck, Martin; Sinning, Irmgard

2015-01-01

During 60S biogenesis, mature 5S RNP consisting of 5S RNA, RpL5 and RpL11, assembles into a pre-60S particle, where docking relies on RpL11 interacting with helix 84 (H84) of the 25S RNA. How 5S RNP is assembled for recruitment into the pre-60S is not known. Here we report the crystal structure of a ternary symportin Syo1–RpL5-N–RpL11 complex and provide biochemical and structural insights into 5S RNP assembly. Syo1 guards the 25S RNA-binding surface on RpL11 and competes with H84 for binding. Pull-down experiments show that H84 releases RpL11 from the ternary complex, but not in the presence of 5S RNA. Crosslinking mass spectrometry visualizes structural rearrangements on incorporation of 5S RNA into the Syo1–RpL5–RpL11 complex supporting the formation of a pre-5S RNP. Our data underline the dual role of Syo1 in ribosomal protein transport and as an assembly platform for 5S RNP. PMID:25849277

Symportin 1 chaperones 5S RNP assembly during ribosome biogenesis by occupying an essential rRNA-binding site.

PubMed

Calviño, Fabiola R; Kharde, Satyavati; Ori, Alessandro; Hendricks, Astrid; Wild, Klemens; Kressler, Dieter; Bange, Gert; Hurt, Ed; Beck, Martin; Sinning, Irmgard

2015-04-07

During 60S biogenesis, mature 5S RNP consisting of 5S RNA, RpL5 and RpL11, assembles into a pre-60S particle, where docking relies on RpL11 interacting with helix 84 (H84) of the 25S RNA. How 5S RNP is assembled for recruitment into the pre-60S is not known. Here we report the crystal structure of a ternary symportin Syo1-RpL5-N-RpL11 complex and provide biochemical and structural insights into 5S RNP assembly. Syo1 guards the 25S RNA-binding surface on RpL11 and competes with H84 for binding. Pull-down experiments show that H84 releases RpL11 from the ternary complex, but not in the presence of 5S RNA. Crosslinking mass spectrometry visualizes structural rearrangements on incorporation of 5S RNA into the Syo1-RpL5-RpL11 complex supporting the formation of a pre-5S RNP. Our data underline the dual role of Syo1 in ribosomal protein transport and as an assembly platform for 5S RNP.

Parallel studies of His-DTrp-Ala-Trp-DPhe-Lys-NH2 and human pancreatic growth hormone-releasing factor-44-NH2 in rat primary pituitary cell monolayer culture.

PubMed

Sartor, O; Bowers, C Y; Chang, D

1985-03-01

His-DTrp-Ala-Trp-DPhe-Lys-NH2 (GH-RP-6) is a synthetic hexapeptide that specifically releases GH both in vivo and in vitro in pituitary incubates. In this study, for the first time, GH-RP-6 was studied in primary pituitary cell monolayer culture. Parallel studies were performed with human pancreatic GH-releasing factor-44 (hpGRF-44). Culture conditions optimal for GH-RP-6 were not optimal for hpGRF-44. Both peptides released GH in a dose- and time-dependent manner. In this assay system, the ED50 for GH-RP-6 was 9 nM, and the ED50 for hp-GRF-44 was 1.6 nM. Calcium-blocking agents inhibited the GH responses of both peptides as well as basal GH release. Pretreatment with GH-RP-6 decreased the subsequent response to both GH-RP-6 and hpGRF-44. hpGRF-44 down regulated itself but not GH-RP-6. Rat sera potentiated the GH response of hpGRF-44 but not that of GH-RP-6. GH-RP-6 and hpGRF-44 GH responses were additive. These results suggest that GH-RP-6 and hpGRF-44 stimulate GH release via different somatotroph receptors.

Effects of Presurgical Treatment for Prostate Cancer

Cancer.gov

In this study, men diagnosed with androgen-sensitive prostate cancer with intermediate- or high-risk features will be examined with mpMRI, undergo targeted biopsies, and be treated with neoadjuvant androgen deprivation therapy.

Glycosylations in the globular head of the hemagglutinin protein modulate the virulence and antigenic properties of the H1N1 influenza viruses

PubMed Central

Medina, Rafael A.; Stertz, Silke; Manicassamy, Balaji; Zimmermann, Petra; Sun, Xiangjie; Albrecht, Randy A.; Uusi-Kerttula, Hanni; Zagordi, Osvaldo; Belshe, Robert B.; Frey, Sharon E.; Eggink, Dirk; Tumpey, Terrence M.; García-Sastre, Adolfo

2014-01-01

The global spread of the 2009 pandemic H1N1 (pH1N1) virus in humans increases the likelihood that this influenza virus strain could undergo antigenic drift in the coming years. Previous seasonal H1N1 and H3N2 influenza strains acquired additional glycosylations in the globular head of their hemagglutinin (HA) proteins as they evolved over time; these are believed to shield antigenically relevant regions. We used influenza A/Netherlands/602/2009 recombinant (rpH1N1) viruses to which we added additional HA glycosylation sites reflecting their temporal appearance in previous seasonal H1N1 viruses. Additional glycosylations resulted in substantial attenuation in mice and ferrets, while deleting HA glycosylation sites from a pre-pandemic 1991 seasonal H1N1 influenza virus resulted in increased pathogenicity in mice. Sera from mice infected with wild type (WT) rpH1N1 virus showed a considerable loss of HA inhibitory (HI) activity against rpH1N1 viruses glycosylated at sites 144 or 144-172, indicating that the polyclonal antibody response elicited by WT rpH1N1 HA seems to be directed against an immunodominant region, likely site Sa, shielded by glycosylation at 144. Sera from humans vaccinated with the pH1N1 inactivated vaccine also showed reduced activity against the 144 and 144-172 mutant viruses. Remarkably, the HI activity of sera from virus-infected mice demonstrated that glycosylation at position 144 resulted in the induction of a broader polyclonal response able to cross-neutralize all WT and glycosylation mutant pH1N1 viruses. Mice infected with a recent seasonal virus in which glycosylation sites 71, 142 and 177 were removed, elicited antibodies that protected against challenge with the antigenically distant pH1N1 virus. Thus, acquisition of glycosylation sites in the HA of H1N1 human influenza viruses not only affects their pathogenicity and ability to escape from polyclonal antibodies elicited by previous influenza virus strains, but also their ability to induce cross-reactive antibodies against drifted antigenic variants. These findings provide the basis for designing improved vaccines and immunization strategies capable of protecting against a broader range of influenza virus strains. PMID:23720581

Mortality Among Men with Advanced Prostate Cancer Excluded from the ProtecT Trial.

PubMed

Johnston, Thomas J; Shaw, Greg L; Lamb, Alastair D; Parashar, Deepak; Greenberg, David; Xiong, Tengbin; Edwards, Alison L; Gnanapragasam, Vincent; Holding, Peter; Herbert, Phillipa; Davis, Michael; Mizielinsk, Elizabeth; Lane, J Athene; Oxley, Jon; Robinson, Mary; Mason, Malcolm; Staffurth, John; Bollina, Prasad; Catto, James; Doble, Andrew; Doherty, Alan; Gillatt, David; Kockelbergh, Roger; Kynaston, Howard; Prescott, Steve; Paul, Alan; Powell, Philip; Rosario, Derek; Rowe, Edward; Donovan, Jenny L; Hamdy, Freddie C; Neal, David E

2017-03-01

Early detection and treatment of asymptomatic men with advanced and high-risk prostate cancer (PCa) may improve survival rates. To determine outcomes for men diagnosed with advanced PCa following prostate-specific antigen (PSA) testing who were excluded from the ProtecT randomised trial. Mortality was compared for 492 men followed up for a median of 7.4 yr to a contemporaneous cohort of men from the UK Anglia Cancer Network (ACN) and with a matched subset from the ACN. PCa-specific and all-cause mortality were compared using Kaplan-Meier analysis and Cox's proportional hazards regression. Of the 492 men excluded from the ProtecT cohort, 37 (8%) had metastases (N1, M0=5, M1=32) and 305 had locally advanced disease (62%). The median PSA was 17μg/l. Treatments included radical prostatectomy (RP; n=54; 11%), radiotherapy (RT; n=245; 50%), androgen deprivation therapy (ADT; n=122; 25%), other treatments (n=11; 2%), and unknown (n=60; 12%). There were 49 PCa-specific deaths (10%), of whom 14 men had received radical treatment (5%); and 129 all-cause deaths (26%). In matched ProtecT and ACN cohorts, 37 (9%) and 64 (16%), respectively, died of PCa, while 89 (22%) and 103 (26%) died of all causes. ProtecT men had a 45% lower risk of death from PCa compared to matched cases (hazard ratio 0.55, 95% confidence interval 0.38-0.83; p=0.0037), but mortality was similar in those treated radically. The nonrandomised design is a limitation. Men with PSA-detected advanced PCa excluded from ProtecT and treated radically had low rates of PCa death at 7.4-yr follow-up. Among men who underwent nonradical treatment, the ProtecT group had a lower rate of PCa death. Early detection through PSA testing, leadtime bias, and group heterogeneity are possible factors in this finding. Prostate cancer that has spread outside the prostate gland without causing symptoms can be detected via prostate-specific antigen testing and treated, leading to low rates of death from this disease. Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Gs-coupled GPCR signalling in AgRP neurons triggers sustained increase in food intake.

PubMed

Nakajima, Ken-ichiro; Cui, Zhenzhong; Li, Chia; Meister, Jaroslawna; Cui, Yinghong; Fu, Ou; Smith, Adam S; Jain, Shalini; Lowell, Bradford B; Krashes, Michael J; Wess, Jürgen

2016-01-08

Agouti-related peptide (AgRP) neurons of the hypothalamus play a key role in regulating food intake and body weight, by releasing three different orexigenic molecules: AgRP; GABA; and neuropeptide Y. AgRP neurons express various G protein-coupled receptors (GPCRs) with different coupling properties, including Gs-linked GPCRs. At present, the potential role of Gs-coupled GPCRs in regulating the activity of AgRP neurons remains unknown. Here we show that the activation of Gs-coupled receptors expressed by AgRP neurons leads to a robust and sustained increase in food intake. We also provide detailed mechanistic data linking the stimulation of this class of receptors to the observed feeding phenotype. Moreover, we show that this pathway is clearly distinct from other GPCR signalling cascades that are operative in AgRP neurons. Our data suggest that drugs able to inhibit this signalling pathway may become useful for the treatment of obesity.

Characterization of aluminum/RP-1 gel propellant properties

NASA Technical Reports Server (NTRS)

Rapp, Douglas C.; Zurawski, Robert L.

1988-01-01

Research efforts are being conducted by the NASA Lewis Research Center to formulate and characterize the properties of Al/RP-1 and RP-1 gelled propellants for rocket propulsion systems. Twenty four different compositions of gelled fuels were formulated with 5 and 16 micron, atomized aluminum powder in RP-1. The total solids concentration in the propellant varied from 5 to 60 wt percent. Tests were conducted to evaluate the stability and rheological characteristics of the fuels. Physical separation of the solids occurred in fuels with less than 50 wt percent solids concentration. The rheological characteristics of the Al/RP-1 fuels varied with solids concentration. Both thixotropic and rheopectic gel behavior were observed. The unmetallized RP-1 gels, which were formulated by a different technique than the Al/RP-1 gels, were highly viscoelastic. A history of research efforts which were conducted to formulate and characterize the properties of metallized propellants for various applications is also given.

Severe manifestations in carrier females in X linked retinitis pigmentosa.

PubMed Central

Souied, E; Segues, B; Ghazi, I; Rozet, J M; Chatelin, S; Gerber, S; Perrault, I; Michel-Awad, A; Briard, M L; Plessis, G; Dufier, J L; Munnich, A; Kaplan, J

1997-01-01

Retinitis pigmentosa (RP) is a group of progressive hereditary disorders of the retina in which various modes of inheritance have been described. Here, we report on X linked RP in nine families with constant and severe expression in carrier females. In our series, however, the phenotype was milder and delayed in carrier females compared to hemizygous males. This form of X linked RP could be regarded therefore as partially dominant. The disease gene maps to chromosome Xp2.1 in the genetic interval encompassing the RP3 locus (Zmax=13.71 at the DXS1100 locus). Single strand conformation polymorphism and direct sequence analysis of the retinitis pigmentosa GTPase regulator (RPGR) gene, which accounts for RP3, failed to detect any mutation in our families. Future advances in the identification of X linked RP genes will hopefully help to elucidate the molecular basis of this X linked dominant RP. Images PMID:9350809

75 FR 67165 - Proposed Collection; Comment Request for Revenue Procedure2007-XX (RP-155430-05)

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-01

... Revenue Procedure 2007- XX (RP-155430-05) AGENCY: Internal Revenue Service (IRS), Treasury. ACTION: Notice... soliciting comments concerning Revenue Procedure 2007-XX (RP-155430-05), Section 6707/6707A Accelerated... Procedure 2007-XX (RP-155430-05). Abstract: The collection of information this revenue procedure requires is...

Connecting Research on Retinitis Pigmentosa to the Practice of Orientation and Mobility.

ERIC Educational Resources Information Center

Geruschat, Duane R.; Turano, Kathleen A.

2002-01-01

Retinitis pigmentosa (RP) causes restriction of the visual field, progressive vision loss, and night blindness. This article presents an overview of the most common problems in orientation and mobility (O&M) for individuals with RP, appropriate interventions, vision science discoveries related to RP, and the impact of RP on functional visual…

Relapse prevention for addictive behaviors

PubMed Central

2011-01-01

The Relapse Prevention (RP) model has been a mainstay of addictions theory and treatment since its introduction three decades ago. This paper provides an overview and update of RP for addictive behaviors with a focus on developments over the last decade (2000-2010). Major treatment outcome studies and meta-analyses are summarized, as are selected empirical findings relevant to the tenets of the RP model. Notable advances in RP in the last decade include the introduction of a reformulated cognitive-behavioral model of relapse, the application of advanced statistical methods to model relapse in large randomized trials, and the development of mindfulness-based relapse prevention. We also review the emergent literature on genetic correlates of relapse following pharmacological and behavioral treatments. The continued influence of RP is evidenced by its integration in most cognitive-behavioral substance use interventions. However, the tendency to subsume RP within other treatment modalities has posed a barrier to systematic evaluation of the RP model. Overall, RP remains an influential cognitive-behavioral framework that can inform both theoretical and clinical approaches to understanding and facilitating behavior change. PMID:21771314

Panel-based NGS Reveals Novel Pathogenic Mutations in Autosomal Recessive Retinitis Pigmentosa

PubMed Central

Perez-Carro, Raquel; Corton, Marta; Sánchez-Navarro, Iker; Zurita, Olga; Sanchez-Bolivar, Noelia; Sánchez-Alcudia, Rocío; Lelieveld, Stefan H.; Aller, Elena; Lopez-Martinez, Miguel Angel; López-Molina, Mª Isabel; Fernandez-San Jose, Patricia; Blanco-Kelly, Fiona; Riveiro-Alvarez, Rosa; Gilissen, Christian; Millan, Jose M; Avila-Fernandez, Almudena; Ayuso, Carmen

2016-01-01

Retinitis pigmentosa (RP) is a group of inherited progressive retinal dystrophies (RD) characterized by photoreceptor degeneration. RP is highly heterogeneous both clinically and genetically, which complicates the identification of causative genes and mutations. Targeted next-generation sequencing (NGS) has been demonstrated to be an effective strategy for the detection of mutations in RP. In our study, an in-house gene panel comprising 75 known RP genes was used to analyze a cohort of 47 unrelated Spanish families pre-classified as autosomal recessive or isolated RP. Disease-causing mutations were found in 27 out of 47 cases achieving a mutation detection rate of 57.4%. In total, 33 pathogenic mutations were identified, 20 of which were novel mutations (60.6%). Furthermore, not only single nucleotide variations but also copy-number variations, including three large deletions in the USH2A and EYS genes, were identified. Finally seven out of 27 families, displaying mutations in the ABCA4, RP1, RP2 and USH2A genes, could be genetically or clinically reclassified. These results demonstrate the potential of our panel-based NGS strategy in RP diagnosis. PMID:26806561

Mutation analysis of 272 Spanish families affected by autosomal recessive retinitis pigmentosa using a genotyping microarray.

PubMed

Ávila-Fernández, Almudena; Cantalapiedra, Diego; Aller, Elena; Vallespín, Elena; Aguirre-Lambán, Jana; Blanco-Kelly, Fiona; Corton, M; Riveiro-Álvarez, Rosa; Allikmets, Rando; Trujillo-Tiebas, María José; Millán, José M; Cremers, Frans P M; Ayuso, Carmen

2010-12-03

Retinitis pigmentosa (RP) is a genetically heterogeneous disorder characterized by progressive loss of vision. The aim of this study was to identify the causative mutations in 272 Spanish families using a genotyping microarray. 272 unrelated Spanish families, 107 with autosomal recessive RP (arRP) and 165 with sporadic RP (sRP), were studied using the APEX genotyping microarray. The families were also classified by clinical criteria: 86 juveniles and 186 typical RP families. Haplotype and sequence analysis were performed to identify the second mutated allele. At least one-gene variant was found in 14% and 16% of the juvenile and typical RP groups respectively. Further study identified four new mutations, providing both causative changes in 11% of the families. Retinol Dehydrogenase 12 (RDH12) was the most frequently mutated gene in the juvenile RP group, and Usher Syndrome 2A (USH2A) and Ceramide Kinase-Like (CERKL) were the most frequently mutated genes in the typical RP group. The only variant found in CERKL was p.Arg257Stop, the most frequent mutation. The genotyping microarray combined with segregation and sequence analysis allowed us to identify the causative mutations in 11% of the families. Due to the low number of characterized families, this approach should be used in tandem with other techniques.

Mutation analysis of Leber congenital amaurosis‑associated genes in patients with retinitis pigmentosa.

PubMed

Shen, Tao; Guan, Liping; Li, Shiqiang; Zhang, Jianguo; Xiao, Xueshan; Jiang, Hui; Yang, Jianhua; Guo, Xiangming; Wang, Jun; Zhang, Qingjiong

2015-03-01

The genetic defects underlying approximately half of all retinitis pigmentosa (RP) cases are unknown. A number of genes responsible for Leber congenital amaurosis (LCA) may also cause RP when they are mutated. Our previous study revealed that variants in the most frequently mutated nine exons accounted for approximately half of the mutations detected in a cohort of patients with LCA. The aim of the present study was to detect mutations in LCA-associated genes in patients with RP using two different strategies. Sanger sequencing was used to screen mutations in the nine exons in 293 patients with RP and exome sequencing was used to detect variants in 12 LCA-associated genes in 157 of the 293 patients with RP and then to validate the variants by Sanger sequencing. Potential pathogenic mutations were identified in four patients with early onset RP, including homozygous CRB1 mutations in two patients, compound heterozygous CRB1 mutations in one patient and compound heterozygous CEP290 mutations in one patient. The present study indicated that mutations in CEP290 may also be associated with RP but not with LCA. With the exception of CEP290, the remaining 11 genes known to be associated with LCA but not with RP are unlikely to be a common cause of RP.

The Genetic Basis of Pericentral Retinitis Pigmentosa—A Form of Mild Retinitis Pigmentosa

PubMed Central

Comander, Jason; Weigel-DiFranco, Carol; Maher, Matthew; Place, Emily; Wan, Aliete; Harper, Shyana; Sandberg, Michael A.; Navarro-Gomez, Daniel; Pierce, Eric A.

2017-01-01

Pericentral retinitis pigmentosa (RP) is an atypical form of RP that affects the near-peripheral retina first and tends to spare the far periphery. This study was performed to further define the genetic basis of this phenotype. We identified a cohort of 43 probands with pericentral RP based on a comprehensive analysis of their retinal phenotype. Genetic analyses of DNA samples from these patients were performed using panel-based next-generation sequencing, copy number variations, and whole exome sequencing (WES). Mutations provisionally responsible for disease were found in 19 of the 43 families (44%) analyzed. These include mutations in RHO (five patients), USH2A (four patients), and PDE6B (two patients). Of 28 putatively pathogenic alleles, 15 (54%) have been previously identified in patients with more common forms of typical RP, while the remaining 13 mutations (46%) were novel. Burden testing of WES data successfully identified HGSNAT as a cause of pericentral RP in at least two patients, suggesting it is also a relatively common cause of pericentral RP. While additional sequencing might uncover new genes specifically associated with pericentral RP, the current results suggest that genetically pericentral RP is not a separate clinical entity, but rather is part of the spectrum of mild RP phenotypes. PMID:28981474

Heterosexual Partnerships and the Need for HIV Prevention and Testing for Men Who Have Sex With Men and Women in China: A Qualitative Study.

PubMed

Wang, Sijia; Song, Dandan; Huang, Wen; He, Huan; Wang, Min; Manning, David; Zaller, Nickolas; Zhang, Hongbo; Operario, Don

2015-04-01

Previous studies have reported that approximately 30% of men who have sex with men (MSM) in China have concurrent female partners. Men who have sex with men and women (MSMW) might "bridge" HIV transmission to their female sex partners. This study aimed to explore (a) motivations for why MSMW in China engage in relationships and sexual behaviors with female partners; (b) patterns of sexual behaviors and condom use between MSMW and their female partners; and (c) barriers to and strategies for encouraging MSMW and their female partners to undergo HIV testing. The authors conducted in-depth interviews with 30 MSMW in two urban cities in China, Guangzhou and Chengdu, and used thematic analysis methods to code and interpret the data. MSMW described family, social, and workplace pressures to have a female partner, and expressed futility about their ability to form stable same-sex relationships. Although participants reported concern about the risk of personally acquiring and transmitting HIV or other sexually transmitted infections (STIs) to their female partners, they described the challenges to using condoms with female partners. HIV-positive participants described how stigma restricted their ability to disclose their HIV status to female partners, and HIV-negative participants displayed less immediate concern about the need for female partners to undergo HIV testing. Participants described a range of possible strategies to encourage HIV testing among female partners. These findings highlight the urgent need for HIV risk reduction and testing interventions for Chinese MSMW in the context of heterosexual partnerships, and they also underscore the additional need for privacy and cultural sensitivity when designing future studies.

An exploration of men's experiences of undergoing active surveillance for favourable-risk prostate cancer: A mixed methods study protocol.

PubMed

Ruane-McAteer, Eimear; O'Sullivan, Joe; Porter, Sam; Venderbos, Lionne; Prue, Gillian

2016-08-02

Prostate cancer is one of the most common male cancers worldwide. Active Surveillance (AS) has been developed to allow men with lower risk disease to postpone or avoid the adverse side effects associated with curative treatments until the disease progresses. Despite the medical benefits of AS, it is reported that living with untreated cancer can create a significant emotional burden for patients. The aim of this study is to gain insight into the experiences of men eligible to undergo AS for favourable-risk PCa. This study has a mixed-methods sequential explanatory design consisting of two phases: quantitative followed by qualitative. Phase 1 has a multiple point, prospective, longitudinal exploratory design. Ninety men diagnosed with favourable-risk prostate cancer will be assessed immediately post-diagnosis (baseline) and followed over a period of 12 months, in intervals of 3 month. Ninety age-matched men with no cancer diagnosis will also be recruited using peer nomination and followed up in the same 3 month intervals. Following completion of Phase 1, 10-15 AS participants who have reported both the best and worst psychological functioning will be invited to participate in semi-structured qualitative interviews. Phase 2 will facilitate further exploration of the quantitative results and obtain a richer understanding of participants' personal interpretations of their illness and psychological wellbeing. To our knowledge, this is the first study to utilise early baseline measures; include a healthy comparison group; calculate sample size through power calculations; and use a mixed methods approach to gain a deeper more holistic insight into the experiences of men diagnosed with favourable-risk prostate cancer.

Validation study of the SCREENIVF: an instrument to screen women or men on risk for emotional maladjustment before the start of a fertility treatment.

PubMed

Ockhuijsen, Henrietta D L; van Smeden, Maarten; van den Hoogen, Agnes; Boivin, Jacky

2017-06-01

To examine construct and criterion validity of the Dutch SCREENIVF among women and men undergoing a fertility treatment. A prospective longitudinal study nested in a randomized controlled trial. University hospital. Couples, 468 women and 383 men, undergoing an IVF/intracytoplasmic sperm injection (ICSI) treatment in a fertility clinic, completed the SCREENIVF. Construct and criteria validity of the SCREENIVF. The comparative fit index and root mean square error of approximation for women and men show a good fit of the factor model. Across time, the sensitivity for Hospital Anxiety and Depression Scale subscale in women ranged from 61%-98%, specificity 53%-65%, predictive value of a positive test (PVP) 13%-56%, predictive value of a negative test (PVN) 70%-99%. The sensitivity scores for men ranged from 38%-100%, specificity 71%-75%, PVP 9%-27%, PVN 92%-100%. A prediction model revealed that for women 68.7% of the variance in the Hospital Anxiety and Depression Scale on time 1 and 42.5% at time 2 and 38.9% at time 3 was explained by the predictors, the sum score scales of the SCREENIVF. For men, 58.1% of the variance in the Hospital Anxiety and Depression Scale on time 1 and 46.5% at time 2 and 37.3% at time 3 was explained by the predictors, the sum score scales of the SCREENIVF. The SCREENIVF has good construct validity but the concurrent validity is better than the predictive validity. SCREENIVF will be most effectively used in fertility clinics at the start of treatment and should not be used as a predictive tool. Copyright © 2017 American Society for Reproductive Medicine. All rights reserved.

Pharmacodynamic and pharmacokinetic neoadjuvant study of hedgehog pathway inhibitor Sonidegib (LDE-225) in men with high-risk localized prostate cancer undergoing prostatectomy.

PubMed

Ross, Ashley E; Hughes, Robert M; Glavaris, Stephanie; Ghabili, Kamyar; He, Ping; Anders, Nicole M; Harb, Rana; Tosoian, Jeffrey J; Marchionni, Luigi; Schaeffer, Edward M; Partin, Alan W; Allaf, Mohamad E; Bivalacqua, Trinity J; Chapman, Carolyn; O'Neal, Tanya; DeMarzo, Angelo M; Hurley, Paula J; Rudek, Michelle A; Antonarakis, Emmanuel S

2017-11-28

To determine the pharmacodynamic effects of Sonidegib (LDE-225) in prostate tumor tissue from men with high-risk localized prostate cancer, by comparing pre-surgical core-biopsy specimens to tumor tissue harvested post-treatment at prostatectomy. We conducted a prospective randomized (Sonidegib vs. observation) open-label translational clinical trial in men with high-risk localized prostate cancer undergoing radical prostatectomy. The primary endpoint was the proportion of patients in each arm who achieved at least a two-fold reduction in GLI1 mRNA expression in post-treatment versus pre-treatment tumor tissue. Secondary endpoints included the effect of pre-surgical treatment with Sonidegib on disease progression following radical prostatectomy, and safety. Fourteen men were equally randomized (7 per arm) to either neoadjuvant Sonidegib or observation for 4 weeks prior to prostatectomy. Six of seven men (86%) in the Sonidegib arm (and none in the control group) achieved a GLI1 suppression of at least two-fold. In the Sonidegib arm, drug was detectable in plasma and in prostatic tissue; and median intra-patient GLI1 expression decreased by 63-fold, indicating potent suppression of Hedgehog signaling. Sonidegib was well tolerated, without any Grade 3-4 adverse events observed. Disease-free survival was comparable among the two arms (HR = 1.50, 95% CI 0.26-8.69, P = 0.65). Hedgehog pathway activity (as measured by GLI1 expression) was detectable at baseline in men with localized high-risk prostate cancer. Sonidegib penetrated into prostatic tissue and induced a >60-fold suppression of the Hedgehog pathway. The oncological benefit of Hedgehog pathway inhibition in prostate cancer remains unclear.

Long term cancer-specific anxiety in men undergoing active surveillance for prostate cancer: findings from a large prospective cohort.

PubMed

Marzouk, Karim; Assel, Melissa; Ehdaie, Behfar; Vickers, Andrew

2018-06-07

Active surveillance is the preferred management of men with low-risk prostate cancer. Cancer-specific anxiety during active surveillance remains understudied. We sought to report long-term anxiety for men on active surveillance to determine if interventions need to be tailored to improve adherence. Four hundred and thirteen men enrolled in active surveillance at a single tertiary care center completed quality of life surveys as part of routine care. A modified version of the Memorial Anxiety Scale for Prostate Cancer was used to determine cancer-specific anxiety. Generalized estimating equations evaluated the association between anxiety and length of time on surveillance. Additionally, we examined associations between anxiety and patient age, marital status, Gleason score, number of positive cores, family history, and overall health. The median age of men was 61 years with a median PSA at diagnosis 4.4 ng/ml; 95% of patients had Gleason 6 disease. The median time from initiation of active surveillance to last survey was 3.7 years. There was a 29% risk of reporting cancer-specific anxiety within the first year. Anxiety significantly decreased over time (OR=0.87; 95% CI: 0.79, 0.95; p=0.003). Pathologic and demographic characteristics were not associated with anxiety after adjusting for time on surveillance. In men undergoing active surveillance, we observed a moderate risk of cancer-specific anxiety that significantly decreases over time. Those considering conservative management can be informed that, although it is common experience some anxiety initially, most patients rapidly adjust and report low levels of anxiety within 2 years. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Robotic radical prostatectomy in overweight and obese patients: oncological and validated-functional outcomes.

PubMed

Wiltz, Aimee L; Shikanov, Sergey; Eggener, Scott E; Katz, Mark H; Thong, Alan E; Steinberg, Gary D; Shalhav, Arieh L; Zagaja, Gregory P; Zorn, Kevin C

2009-02-01

To determine the impact of body mass index (BMI) on perioperative functional and oncological outcomes in patients undergoing robotic laparoscopic radical prostatectomy (RLRP) when stratified by BMI. Data were collected prospectively for 945 consecutive patients undergoing RLRP. Patients were evaluated with the UCLA-PCI-SF36v2 validated-quality-of-life questionnaire preoperatively and postoperatively to 24 months. Patients were stratified by BMI as normal weight (BMI < 25 kg/m(2)), overweight (BMI = 25 to < 30 kg/m(2)) and obese (BMI > or = 30 kg/m(2)) for outcomes analysis. Preoperatively, obese men had a significantly greater percentage of medical comorbidities (P < .01) as well as a baseline erectile dysfunction (lower mean baseline Sexual Health Inventory for Men score [P = .01] and UCLA-PCI-SF36v2 sexual function domain scores [P = .01]). Mean operative time was significantly longer in obese patients when compared with normal and overweight men (234 minutes vs 217 minutes vs 214 minutes; P = .0003). Although overall complication rates were comparable between groups, a greater incidence of case abortion caused by pneumoperitoneal pressure with excessive airway pressures was noted in obese men. Urinary continence and potency outcomes were significantly lower for obese men at both 12 and 24 months (all P < .05). In this series, obese men experienced a longer operative time, particularly during the initial robotic experience. As such, surgeons early in their RLRP learning curve should proceed cautiously with surgery in these technically more difficult patients or reserve such cases until the learning curve has been surmounted. These details, including inferior urinary and sexual outcomes, should be discussed with obese patients during preoperative counseling.

Does sex matter? A matched pairs analysis of neuromodulation outcomes in women and men.

PubMed

Nguyen, Laura N; Bartley, Jamie; Killinger, Kim A; Gupta, Priyanka; Lavin, John; Khourdaji, Ayad; Gilleran, Jason; Gaines, Natalie; Boura, Judith A; Peters, Kenneth M

2018-05-01

To evaluate whether baseline symptoms and outcomes are influenced by gender in a matched cohort undergoing neuromodulation. Patients in our prospective neuromodulation database that had a tined lead placed were reviewed. Those that had implantable pulse generator (IPG) placed were matched on age and urologic diagnosis. History, voiding diaries, satisfaction, Interstitial Cystitis Symptom/Problem Index (ICSIPI), and overactive bladder symptom severity (OABq ss)/health-related quality of life (HRQOL) preimplant and over 3 years were evaluated using descriptive statistics, repeated measures, and matched pair GEE or mixed analyses. Of 590 patients in the database, more women than men received an IPG (450/488; 92.2 vs. 84/102; 82.4%; p = 0.0011). Eighty matched pairs (n = 160; 81% ≥ 50 years old; 56.25% had urgency/frequency with urge incontinence-UI) were identified and evaluated. On voiding diaries, volume/void was greater in women only at baseline (p = 0.040); both groups improved over time (p < 0.0001). Urinary frequency improved in both women and men (p = 0.0010; p = 0.0025). Over 3 years, UI episodes/day improved only in men (p = 0.017) and UI severity improved only in women (p < 0.0001). ICSIPI, OABq ss, and HRQOL scores improved similarly in both groups (p < 0.0001 for all measures in both groups), and although more women were satisfied at 3 months (p = 0.027), groups did not differ at other time points. More women undergo neuromodulation and have initial success and subsequent IPG implantation. UI episodes improved only in men, and UI severity improved only in women. Both women and men experienced similar levels of symptom improvement on other measures.

Do Men Receive Information Required for Shared Decision Making About PSA Testing? Results from a National Survey.

PubMed

Leyva, Bryan; Persoskie, Alexander; Ottenbacher, Allison; Hamilton, Jada G; Allen, Jennifer D; Kobrin, Sarah C; Taplin, Stephen H

2016-12-01

Most professional organizations, including the American College of Physicians and U.S. Preventive Services Task Force, emphasize that screening for prostate cancer with the prostate-specific antigen (PSA) test should only occur after a detailed discussion between the health-care provider and patient about the known risks and potential benefits of the test. In fact, guidelines strongly advise health-care providers to involve patients, particularly those at elevated risk of prostate cancer, in a "shared decision making" (SDM) process about PSA testing. We analyzed data from the National Cancer Institute's Health Information National Trends Survey 2011-2012-a nationally representative, cross-sectional survey-to examine the extent to which health professionals provided men with information critical to SDM prior to PSA testing, including (1) that patients had a choice about whether or not to undergo PSA testing, (2) that not all doctors recommend PSA testing, and (3) that no one is sure if PSA testing saves lives. Over half (55 %) of men between the ages of 50 and 74 reported ever having had a PSA test. However, only 10 % of men, regardless of screening status, reported receiving all three pieces of information: 55 % reported being informed that they could choose whether or not to undergo testing, 22 % reported being informed that some doctors recommend PSA testing and others do not, and 14 % reported being informed that no one is sure if PSA testing actually saves lives. Black men and men with lower levels of education were less likely to be provided this information. There is a need to improve patient-provider communication about the uncertainties associated with the PSA test. Interventions directed at patients, providers, and practice settings should be considered.

FOXP3+ regulatory T cells in normal prostate tissue, postatrophic hyperplasia, prostatic intraepithelial neoplasia, and tumor histological lesions in men with and without prostate cancer

PubMed Central

Andren, Ove; Ohlson, Anna‐Lena; Carlsson, Jessica; Andersson, Swen‐Olof; Giunchi, Francesca; Rider, Jennifer R.; Fiorentino, Michelangelo

2017-01-01

Background The tumor promoting or counteracting effects of the immune response to cancer development are thought to be mediated to some extent by the infiltration of regulatory T cells (Tregs). In the present study we evaluated the prevalence of Treg populations in stromal and epithelial compartments of normal, post atrophic hyperplasia (PAH), prostatic intraepithelial neoplasia (PIN), and tumor lesions in men with and without prostate cancer. Methods Study subjects were 102 men consecutively diagnosed with localized prostate cancer undergoing radical prostatectomy and 38 men diagnosed with bladder cancer undergoing cystoprostatectomy without prostate cancer at the pathological examination. Whole mount sections from all patients were evaluated for the epithelial and stromal expression of CD4+ Tregs and CD8+ Tregs in normal, PAH, PIN, and tumor lesions. A Friedmańs test was used to investigate differences in the mean number of Tregs across histological lesions. Logistic regression was used to estimate crude and adjusted odds ratios (OR) for prostate cancer for each histological area. Results In men with prostate cancer, similarly high numbers of stromal CD4+ Tregs were identified in PAH and tumor, but CD4+ Tregs were less common in PIN. Greater numbers of epithelial CD4+ Tregs in normal prostatic tissue were positively associated with both Gleason score and pT‐stage. We observed a fourfold increased risk of prostate cancer in men with epithelial CD4+ Tregs in the normal prostatic tissue counterpart. Conclusions Our results may suggest a possible pathway through which PAH develops directly into prostate cancer in the presence of CD4+ Tregs and indicate that transformation of the anti‐tumor immune response may be initiated even before the primary tumor is established. PMID:29105795

Promoting calcium and vitamin D intake to reduce the risk of osteoporosis in men on androgen deprivation therapy for recurrent prostate cancer.

PubMed

Davison, B Joyce; Wiens, Kristin; Cushing, Meredith

2012-10-01

The aim of this study was to measure the impact of a patient education intervention aimed at increasing dietary intake of calcium and vitamin D in patients currently on androgen deprivation therapy (ADT) for the treatment of prostate cancer. Sixty-one participants attended a one-time dietitian-delivered group education session focusing on diet and lifestyle strategies to reduce the risk of bone loss while on ADT. Dietary intake was assessed using the diet history questionnaire at baseline and again at approximately 1 year post-intervention. Demographics, medical history (including comorbidities), awareness of developing bone loss while on ADT, and information resources utilized were recorded at baseline. Fifty-one participants completed both time points. Over one third of men did not meet minimum current clinical guidelines for calcium or vitamin D intake at baseline. Sixty-three percent of men reported they were aware that osteoporosis was a known side effect of ADT therapy. Only supplemental calcium intake was significantly increased after the intervention. Men aware of their risk of developing bone loss while on ADT reported higher baseline calcium intake (p ≤ 0.05). Men undergoing ADT for less than 1 year at the time of intervention had significantly higher total calcium intake at follow-up compared to men on ADT for longer than 1 year (p = 0.038). Nonsignificant trends indicated that calcium and vitamin D intakes changed to a greater degree in those undergoing ADT for less than 1 year as well. Total calcium and vitamin D did not change significantly as a result of the intervention. Results suggest that promotion of dietary changes may be more effective if delivered closer to the initiation of therapy.

HETEROSEXUAL PARTNERSHIPS AND THE NEED FOR HIV PREVENTION AND TESTING FOR MEN WHO HAVE SEX WITH MEN AND WOMEN IN CHINA: A QUALITATIVE STUDY

PubMed Central

Wang, Sijia; Song, Dandan; Huang, Wen; He, Huan; Wang, Min; Manning, David; Zaller, Nickolas; Zhang, Hongbo; Operario, Don

2016-01-01

Previous studies have reported that approximately 30% of men who have sex with men (MSM) in China have concurrent female partners. Men who have sex with men and women (MSMW) might “bridge” HIV transmission to their female sex partners. This study aimed to explore (a) motivations for why MSMW in China engage in relationships and sexual behaviors with female partners; (b) patterns of sexual behaviors and condom use between MSMW and their female partners; and (c) barriers to and strategies for encouraging MSMW and their female partners to undergo HIV testing. The authors conducted in-depth interviews with 30 MSMW in two urban cities in China, Guangzhou and Chengdu, and used thematic analysis methods to code and interpret the data. MSMW described family, social, and workplace pressures to have a female partner, and expressed futility about their ability to form stable same-sex relationships. Although participants reported concern about the risk of personally acquiring and transmitting HIV or other sexually transmitted infections (STIs) to their female partners, they described the challenges to using condoms with female partners. HIV-positive participants described how stigma restricted their ability to disclose their HIV status to female partners, and HIV-negative participants displayed less immediate concern about the need for female partners to undergo HIV testing. Participants described a range of possible strategies to encourage HIV testing among female partners. These findings highlight the urgent need for HIV risk reduction and testing interventions for Chinese MSMW in the context of heterosexual partnerships, and they also under-score the additional need for privacy and cultural sensitivity when designing future studies. PMID:25915698

Effect of gonadectomy on AgRP-induced weight gain in rats.

PubMed

Goodin, Sean Z; Kiechler, Alicia R; Keichler, Alicia R; Smith, Marissa; Wendt, Donna; Strader, April D

2008-12-01

Agouti-related peptide (AgRP), the endogenous antagonist to the melanocortin 3 and 4 receptors, elicits robust hyperphagia and weight gain in rodents when administered directly into the central nervous system. The relative influence of AgRP to cause weight gain in rodents partially depends on the activity level of the melanocortin agonist-producing proopiomelanocortin neurons. Both proopiomelanocortin and AgRP neurons within the arcuate nucleus receive energy storage information from circulating peripheral signals such as leptin and insulin. Another modulator of AgRP activity includes the cell surface molecule syndecan-3. Because leptin and insulin affect food intake in a sexually dimorphic way in rodents and syndecan-3-deficient mice regulate adiposity levels through distinct physiological mechanisms, we hypothesized that AgRP-induced weight gain would also be sexually dimorphic in rats. In the present study, the behavioral and physiological effects of centrally-administered AgRP in male and female were investigated. In male rats, AgRP (1 nmol) induced 5 days (P < 0.0001) of significantly elevated feeding compared with vehicle-treated controls, while females displayed 3 days of hyperphagia (P < 0.05). However, 1 wk after the injection, both male and female rats gained the same percent body weight (6%). Interestingly, female rats exhibited a greater reduction in energy expenditure (Vo2) following AgRP compared with male rats (P < 0.05). Removal of the gonads did not alter cumulative food intake in male or female rats but did attenuate the dramatic reduction in Vo2 exhibited by females. Both intact and gonadectomized rats demonstrated significantly increased respiratory quotient supporting the anabolic action of AgRP (P < 0.01). These findings are novel in that they reveal sex-specific underlying physiology used to achieve weight gain following central AgRP in rats.

Dynamic behaviour of the soft palate during nasal positive pressure ventilation under anaesthesia and paralysis: comparison between patients with and without obstructive sleep-disordered breathing.

PubMed

Okuyama, M; Kato, S; Sato, S; Okazaki, J; Kitamura, Y; Ishikawa, T; Sato, Y; Isono, S

2018-01-01

Difficult mask ventilation is common and is known to be associated with sleep-disordered breathing (SDB). It is our hypothesis that the incidence of expiratory retropalatal (RP) airway closure (primary outcome) during nasal positive pressure ventilation (PPV) is more frequent in patients with SDB (apnea hypopnea index ≥5 h -1 ) than non-SDB subjects. The severity of SDB was assessed before surgery using a portable sleep monitor. In anaesthetized and paralysed patients with (n=11) and without SDB (n=9), we observed the behaviour of the RP airway endoscopically during nasal PPV with the mouth closed and determined the dynamic RP closing pressure, which was defined as the highest airway pressure above which the RP airway closure was reversed. The static RP closing pressure was obtained during cessation of mechanical ventilation in patients with dynamic RP closure during nasal PPV. The expiratory RP airway closure accompanied by expiratory flow limitation occurred more frequently in SDB patients (9/11, 82%) than in non-SDB subjects (2/9, 22%; exact logistic regression analysis: P=0.022, odds ratio 3.6, 95% confidence interval 1.1-15.4). Receiver operating characteristic curve analyses indicated AHI >10h -1 and presence of habitual snoring as clinically useful predictors for the occurrence of RP closure during PPV. Dynamic RP closing pressure was greater than the static RP closing pressure by approximately 4-5 cm H 2 O. Valve-like dynamic RP closure that limits expiratory flow during nasal PPV occurs more frequently in SDB patients. Copyright © 2017. Published by Elsevier Ltd.

Are severe depressive symptoms associated with infertility-related distress in individuals and their partners?

PubMed

Peterson, Brennan D; Sejbaek, Camilla S; Pirritano, Matthew; Schmidt, Lone

2014-01-01

Are severe depressive symptoms in women and men associated with individual and dyadic infertility-related stress in couples undergoing infertility treatment? Severe depressive symptoms were significantly associated with increased infertility-related distress at both the individual and partner level. WHAT IS KNOWN ALREADY?: An infertility diagnosis, the stress of medical treatments and a prior history of depression are risk factors for future depression in those undergoing fertility treatments. Studies examining the impact of severe depressive symptoms on infertility-related distress in couples are lacking. This cross-sectional study included 1406 couples who were consecutively referred patients undergoing fertility treatments in Denmark in the year 2000. A total of 1049 men and 1131 women were included in the study. Participants were consecutively referred patients undergoing a cycle of medically assisted reproduction treatment at five Danish public and private clinics specializing in treating fertility patients. Severe depressive symptoms were measured by the Mental Health Inventory 5 from the Short Form Health Survey 36. Infertility distress was measured by the COMPI Fertility Problem Stress Scales. Multilevel modelling using the actor-partner interdependence model was used to study the couple as the unit of analysis. Severe depressive symptoms were reported in 11.6% of women and 4.3% of men, and were significantly associated with increased infertility-related distress at the individual and partner level. There was no significant interaction for gender indicating that men and women did not differ in how severe depressive symptoms were associated with infertility distress. Because of the cross-sectional study design, the study findings only show an association between severe depressive symptoms to individual and partner distress at a single point in time; however, nothing is known about causality. This study adds to the growing body of literature using the couple as the unit of analysis to study the relationship between depression and infertility distress. Recommendations for medical and mental health professionals that underscore the potential risk factors for depressed men and women who are pursuing infertility treatments are provided. Additional studies using a longitudinal study design to track the impact of depression on distress over the course of the infertility treatment cycle would be valuable for increasing our understanding of the complex relationship that exists between these psychosocial factors. Authors Brennan Peterson and Matthew Pirritano have no financial disclosures for this study. Camilla Sandal Sejbaek and Lone Schmidt have received research grants from the Danish Health Insurance Foundation (J. nr. 2008B105) and Merck Sharp & Dohme. The funders had no influence on the data collection, analyses or conclusions of the study.

The impact of reference pricing of nonsteroidal anti-inflammatory agents on the use and costs of analgesic drugs.

PubMed

Grootendorst, Paul V; Marshall, John K; Holbrook, Anne M; Dolovich, Lisa R; O'Brien, Bernie J; Levy, Adrian R

2005-10-01

To estimate the effect of reference pricing (RP) of nonsteroidal anti-inflammatory drugs (NSAIDs) on drug subsidy program and beneficiary expenditures on analgesic drugs. Monthly claims data from Pharmacare, the public drug subsidy program for seniors in British Columbia, Canada, over the period of February 1993 to June 2001. RP limits drug plan reimbursement of interchangeable medicines to a reference price, which is typically equal to the price of the lowest cost interchangeable drug; any cost above that is borne by the patient. Pharmacare introduced two different forms of RP to the NSAIDs, Type 1 in April 1994 and Type 2 in November 1995. Under Type 1 RP, generic and brand versions of the same NSAID are considered interchangeable, whereas under Type 2 RP different NSAIDs are considered interchangeable. We extrapolated average reimbursement per day of NSAID therapy over the months before RP to estimate what expenditures would have been without the policies. These counterfactual predictions were compared with actual values to estimate the impact of the policies; the estimated impacts on reimbursement rates were multiplied by the postpolicy volume of NSAIDS dispensed, which appeared unaffected by the policies, to estimate expenditure changes. After Type 2 RP, program expenditures declined by $22.7 million (CAN), or $4 million (CAN), annually cutting expenditure by about half. Most savings accrued from the substitution of low-cost NSAIDs for more costly alternatives. About 20 percent of savings represented expenditures by seniors who elected to pay for partially reimbursed drugs. Type 1 RP produced one-quarter the savings of type 2 RP. Type 2 RP of NSAIDs achieved its goal of reducing drug expenditures and was more effective than Type 1 RP. The effects of RP on patient health and associated health care costs remain to be investigated.

Metallized Gelled Propellants: Oxygen/RP-1/aluminum Rocket Combustion Experiments

NASA Technical Reports Server (NTRS)

Palaszewski, Bryan; Zakany, James S.

1995-01-01

A series of combustion experiments were conducted to measure the specific impulse, Cstar-, and specific-impulse efficiencies of a rocket engine using metallized gelled liquid propellants. These experiments used a small 20- to 40-1bf (89- to 178-N) thrust, modular engine consisting of an injector, igniter, chamber and nozzle. The fuels used were traditional liquid RP-1 and gelled RP-1 with 0-, 5-, and 55-wt% loadings of aluminum and gaseous oxygen was the oxidizer. Ten different injectors were used during the testing: 6 for the baseline 02/RP-1 tests and 4 for the gelled fuel tests which covered a wide range of mixture ratios. At the peak of the Isp versus oxidizer-to-fuel ratio (O/F) data, a range of 93 to 99% Cstar efficiency was reached with ungelled 02/RP-1. A Cstar efficiency range of 75 to 99% was obtained with gelled RP-l (0-wt% RP-1/Al) while the metallized 5-wt% RP-1/Al delivered a Cstar efficiency of 94 to 99% at the peak Isp in the O/F range tested. An 88 to 99% Cstar efficiency was obtained at the peak Isp of the gelled RP1/Al with 55-wt% Al. Specific impulse efficiencies for the 55-wt% RP-1/Al of 67%-83% were obtained at a 2.4:1 expansion ratio. Injector erosion was evident with the 55-wt% testing, while there was little or no erosion seen with the gelled RP-1 with 0- and 5-wt% Al. A protective layer of gelled fuel formed in the firings that minimized the damage to the rocket injector face. This effect may provide a useful technique for engine cooling. These experiments represent a first step in characterizing the performance of and operational issues with gelled RP-1 fuels.

High-sensitivity serum C-reactive protein levels in subjects with or without myocardial infarction or periodontitis.

PubMed

Persson, G Rutger; Pettersson, Thomas; Ohlsson, Ola; Renvert, Stefan

2005-03-01

Serum high-sensitivity C-reactive protein (hsC-rp) is a non-specific marker of inflammation. Elevated hsC-rp levels are found in subjects with cardiovascular diseases (CVDs). Periodontitis may influence hsC-rp levels. To assess periodontal status and hsC-rp serum levels in consecutive subjects hospitalized and diagnosed with acute myocardial infarction (AMI) (n=85) and in a group of carefully matched subjects (gender, age social, ethnic, and smoking habits) without clinical evidence of CVD (n=63). hsC-rp levels, other routine serum values, and clinical periodontal conditions were studied. Subjects with AMI had higher hsC-rp levels than control subjects (p<0.001, Mann-Whitney U-test). The odds that subjects in the control group with periodontitis (30% or more sites with>4.0 mm loss of alveolar bone) had serum hsC-rp>1.8 mg/l was 1.5 (95% CI: 1.1-7.3, p<0.05). Stepwise linear regression analysis failed to include periodontal parameters in an explanatory model to hsC-rp values. Only the serum leucocyte (white blood cell (WBC)) counts were explanatory to hsC-rp values (beta standard coefficient=0.45, t=3.2, p<0.001). Serum WBC counts were significantly higher in control subjects with periodontitis (p<0.03) but not in subjects in the AMI group (p<0.57). (1) As expected, elevated serum hsC-rp concentration and serum WBC counts are associated with acute coronary heart disease. (2) Elevated serum hsC-rp values are associated with radiographically defined periodontitis in subjects with no evidence of CVD. (3) Periodontal parameters are not explanatory to elevated serum hsC-rp values if serum WBC and low-density lipoprotein counts are included in the regression model. Copyright 2005 Blackwell Munksgaard.

Good Epidemiologic Practice in Retinitis Pigmentosa: From Phenotyping to Biobanking

PubMed Central

Chizzolini, Marzio; Galan, Alessandro; Milan, Elisabeth; Sebastiani, Adolfo; Costagliola, Ciro; Parmeggiani, Francesco

2011-01-01

Inherited retinal dystrophies, such as retinitis pigmentosa (RP), include a group of relatively rare hereditary diseases caused by mutations in genes that code for proteins involved in the maintenance and function of the photoreceptor cells (cones and rods). The different forms of RP consist of progressive neurodegenerative disorders which are generally related to various and severe limitations of visual performances. In the course of typical RP (rod-cone dystrophy), the affected individuals first experience night-blindness and/or visual field constriction (secondary to rod dysfunctions), followed by variable alterations of the central vision (due to cone damages). On the other hand, during the atypical form of RP (cone-rod dystrophy), the cone’s functionalities are prevalently disrupted in comparison with the rod’s ones. The basic diagnosis of RP relies upon the documentation of unremitting loss in photoreceptor activity by electroretinogram and/or visual field testing. The prevalence of all RP typologies is variably reported in about one case for each 3000-5000 individuals, with a total of about two millions of affected persons worldwide. The inherited retinal dystrophies are sometimes the epiphenomenon of a complex framework (syndromic RP), but more often they represent an isolated disorder (about 85-90 % of cases). Although 200 causative RP mutations have been hitherto detected in more than 100 different genes, the molecular defect is identifiable in just about the 50% of the analyzed patients with RP. Not only the RP genotypes are very heterogeneous, but also the patients with the same mutation can be affected by different phenotypic manifestations. RP can be inherited as autosomal dominant, autosomal recessive or X-linked trait, and many sporadic forms are diagnosed in patients with no affected relatives. Dissecting the clinico-genetic complexity of RP has become an attainable objective by means of large-scale research projects, in which the collaboration between ophthalmologists, geneticists, and epidemiologists becomes a crucial aspect. In the present review, the main issues regarding clinical phenotyping and epidemiologic criticisms of RP are focused, especially highlighting the importance of both standardization of the diagnostic protocols and appropriateness of the disease’s registration systems. PMID:22131871

The role of GluN2A and GluN2B NMDA receptor subunits in AgRP and POMC neurons on body weight and glucose homeostasis.

PubMed

Üner, Aykut; Gonçalves, Gabriel H M; Li, Wenjing; Porceban, Matheus; Caron, Nicole; Schönke, Milena; Delpire, Eric; Sakimura, Kenji; Bjørbæk, Christian

2015-10-01

Hypothalamic agouti-related peptide (AgRP) and pro-opiomelanocortin (POMC) expressing neurons play critical roles in control of energy balance. Glutamatergic input via n-methyl-d-aspartate receptors (NMDARs) is pivotal for regulation of neuronal activity and is required in AgRP neurons for normal body weight homeostasis. NMDARs typically consist of the obligatory GluN1 subunit and different GluN2 subunits, the latter exerting crucial differential effects on channel activity and neuronal function. Currently, the role of specific GluN2 subunits in AgRP and POMC neurons on whole body energy and glucose balance is unknown. We used the cre-lox system to genetically delete GluN2A or GluN2B only from AgRP or POMC neurons in mice. Mice were then subjected to metabolic analyses and assessment of AgRP and POMC neuronal function through morphological studies. We show that loss of GluN2B from AgRP neurons reduces body weight, fat mass, and food intake, whereas GluN2B in POMC neurons is not required for normal energy balance control. GluN2A subunits in either AgRP or POMC neurons are not required for regulation of body weight. Deletion of GluN2B reduces the number of AgRP neurons and decreases their dendritic length. In addition, loss of GluN2B in AgRP neurons of the morbidly obese and severely diabetic leptin-deficient Lep (ob/ob) mice does not affect body weight and food intake but, remarkably, leads to full correction of hyperglycemia. Lep (ob/ob) mice lacking GluN2B in AgRP neurons are also more sensitive to leptin's anti-obesity actions. GluN2B-containing NMDA receptors in AgRP neurons play a critical role in central control of body weight homeostasis and blood glucose balance via mechanisms that likely involve regulation of AgRP neuronal survival and structure, and modulation of hypothalamic leptin action.

Upgrading and Downgrading of Prostate Cancer from Biopsy to Radical Prostatectomy: Incidence and Predictive Factors Using the Modified Gleason Grading System and Factoring in Tertiary Grades

PubMed Central

Epstein, Jonathan I.; Feng, Zhaoyong; Trock, Bruce J.; Pierorazio, Phillip M.

2015-01-01

Background Prior studies assessing the correlation of Gleason score (GS) at needle biopsy and corresponding radical prostatectomy (RP) predated the use of the modified Gleason scoring system and did not factor in tertiary grade patterns. Objective To assess the relation of biopsy and RP grade in the largest study to date. Design, setting, and participants A total of 7643 totally embedded RP and corresponding needle biopsies (2004–2010) were analyzed according to the updated Gleason system. Interventions All patients underwent prostate biopsy prior to RP. Measurements The relation of upgrading or downgrading to patient and cancer characteristics was compared using the chi-square test, Student t test, and multivariable logistic regression. Results and limitations A total of 36.3% of cases were upgraded from a needle biopsy GS 5–6 to a higher grade at RP (11.2% with GS 6 plus tertiary). Half of the cases had matching GS 3 + 4 = 7 at biopsy and RP with an approximately equal number of cases downgraded and upgraded at RP. With biopsy GS 4 + 3 = 7, RP GS was almost equally 3 + 4 = 7 and 4 + 3 = 7. Biopsy GS 8 led to an almost equal distribution between RP GS 4 + 3 = 7, 8, and 9–10. A total of 58% of the cases had matching GS 9–10 at biopsy and RP. In multivariable analysis, increasing age (p < 0.0001), increasing serum prostate-specific antigen level (p < 0.0001), decreasing RP weight (p < 0.0001), and increasing maximum percentage cancer/core (p < 0.0001) predicted the upgrade from biopsy GS 5–6 to higher at RP. Despite factoring in multiple variables including the number of positive cores and the maximum percentage of cancer per core, the concordance indexes were not sufficiently high to justify the use of nomograms for predicting upgrading and downgrading for the individual patient. Conclusions Almost 20% of RP cases have tertiary patterns. A needle biopsy can sample a tertiary higher Gleason pattern in the RP, which is then not recorded in the standard GS reporting, resulting in an apparent overgrading on the needle biopsy. PMID:22336380

Upgrading and downgrading of prostate cancer from biopsy to radical prostatectomy: incidence and predictive factors using the modified Gleason grading system and factoring in tertiary grades.

PubMed

Epstein, Jonathan I; Feng, Zhaoyong; Trock, Bruce J; Pierorazio, Phillip M

2012-05-01

Prior studies assessing the correlation of Gleason score (GS) at needle biopsy and corresponding radical prostatectomy (RP) predated the use of the modified Gleason scoring system and did not factor in tertiary grade patterns. To assess the relation of biopsy and RP grade in the largest study to date. A total of 7643 totally embedded RP and corresponding needle biopsies (2004-2010) were analyzed according to the updated Gleason system. All patients underwent prostate biopsy prior to RP. The relation of upgrading or downgrading to patient and cancer characteristics was compared using the chi-square test, Student t test, and multivariable logistic regression. A total of 36.3% of cases were upgraded from a needle biopsy GS 5-6 to a higher grade at RP (11.2% with GS 6 plus tertiary). Half of the cases had matching GS 3+4=7 at biopsy and RP with an approximately equal number of cases downgraded and upgraded at RP. With biopsy GS 4+3=7, RP GS was almost equally 3+4=7 and 4+3=7. Biopsy GS 8 led to an almost equal distribution between RP GS 4+3=7, 8, and 9-10. A total of 58% of the cases had matching GS 9-10 at biopsy and RP. In multivariable analysis, increasing age (p<0.0001), increasing serum prostate-specific antigen level (p<0.0001), decreasing RP weight (p<0.0001), and increasing maximum percentage cancer/core (p<0.0001) predicted the upgrade from biopsy GS 5-6 to higher at RP. Despite factoring in multiple variables including the number of positive cores and the maximum percentage of cancer per core, the concordance indexes were not sufficiently high to justify the use of nomograms for predicting upgrading and downgrading for the individual patient. Almost 20% of RP cases have tertiary patterns. A needle biopsy can sample a tertiary higher Gleason pattern in the RP, which is then not recorded in the standard GS reporting, resulting in an apparent overgrading on the needle biopsy. Copyright © 2012 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Development of a definition for Rapid Progression (RP) of renal function in HIV-positive persons: the D:A:D study

PubMed Central

2014-01-01

Background No consensus exists on how to define abnormally rapid deterioration in renal function (Rapid Progression, RP). We developed an operational definition of RP in HIV-positive persons with baseline estimated glomerular filtration rate (eGFR) >90 ml/min/1.73 m2 (using Cockcroft Gault) in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study from 2004 to 2011. Methods Two definitions were evaluated; RP definition A: An average eGFR decline (slope) ≥5 ml/min/1.73 m2/year over four years of follow-up with ≥3 eGFR measurements/year, last eGFR <90 ml/min/1.73 m2 and an absolute decline ≥5 ml/min/1.73 m2/year in two consecutive years. RP definition B: An absolute annual decline ≥5 ml/min/1.73 m2/year in each year and last eGFR <90 ml/min/1.73 m2. Sensitivity analyses were performed considering two and three years’ follow-up. The percentage with and without RP who went on to subsequently develop incident chronic kidney disease (CKD; 2 consecutive eGFRs <60 ml/min/1.73 m2 and 3 months apart) was calculated. Results 22,603 individuals had baseline eGFR ≥90 ml/min/1.73 m2. 108/3655 (3.0%) individuals with ≥4 years’ follow-up and ≥3 measurements/year experienced RP under definition A; similar proportions were observed when considering follow-up periods of three (n=195/6375; 3.1%) and two years (n=355/10756; 3.3%). In contrast under RP definition B, greater proportions experienced RP when considering two years (n=476/10756; 4.4%) instead of three (n=48/6375; 0.8%) or four (n=15/3655; 0.4%) years’ follow-up. For RP definition A, 13 (12%) individuals who experienced RP progressed to CKD, and only (21) 0.6% of those without RP progressed to CKD (sensitivity 38.2% and specificity 97.4%); whereas for RP definition B, fewer RP individuals progressed to CKD. Conclusions Our results suggest using three years’ follow-up and at least two eGFR measurements per year is most appropriate for a RP definition, as it allows inclusion of a reasonable number of individuals and is associated with the known risk factors. The definition does not necessarily identify all those that progress to incident CKD, however, it can be used alongside other renal measurements to early identify and assess those at risk of developing CKD. Future analyses will use this definition to identify other risk factors for RP, including the role of antiretrovirals. PMID:24666792

Development of a definition for Rapid Progression (RP) of renal function in HIV-positive persons: the D:A:D study.

PubMed

Kamara, David A; Ryom, Lene; Ross, Michael; Kirk, Ole; Reiss, Peter; Morlat, Philippe; Moranne, Olivier; Fux, Christoph A; Mocroft, Amanda; Sabin, Caroline; Lundgren, Jens D; Smith, Colette J

2014-03-25

No consensus exists on how to define abnormally rapid deterioration in renal function (Rapid Progression, RP). We developed an operational definition of RP in HIV-positive persons with baseline estimated glomerular filtration rate (eGFR) >90 ml/min/1.73 m2 (using Cockcroft Gault) in the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study from 2004 to 2011. Two definitions were evaluated; RP definition A: An average eGFR decline (slope) ≥5 ml/min/1.73 m2/year over four years of follow-up with ≥3 eGFR measurements/year, last eGFR <90 ml/min/1.73 m2 and an absolute decline ≥5 ml/min/1.73 m2/year in two consecutive years. RP definition B: An absolute annual decline ≥5 ml/min/1.73 m2/year in each year and last eGFR <90 ml/min/1.73 m2. Sensitivity analyses were performed considering two and three years' follow-up. The percentage with and without RP who went on to subsequently develop incident chronic kidney disease (CKD; 2 consecutive eGFRs <60 ml/min/1.73 m2 and 3 months apart) was calculated. 22,603 individuals had baseline eGFR ≥90 ml/min/1.73 m2. 108/3655 (3.0%) individuals with ≥4 years' follow-up and ≥3 measurements/year experienced RP under definition A; similar proportions were observed when considering follow-up periods of three (n=195/6375; 3.1%) and two years (n=355/10756; 3.3%). In contrast under RP definition B, greater proportions experienced RP when considering two years (n=476/10756; 4.4%) instead of three (n=48/6375; 0.8%) or four (n=15/3655; 0.4%) years' follow-up. For RP definition A, 13 (12%) individuals who experienced RP progressed to CKD, and only (21) 0.6% of those without RP progressed to CKD (sensitivity 38.2% and specificity 97.4%); whereas for RP definition B, fewer RP individuals progressed to CKD. Our results suggest using three years' follow-up and at least two eGFR measurements per year is most appropriate for a RP definition, as it allows inclusion of a reasonable number of individuals and is associated with the known risk factors. The definition does not necessarily identify all those that progress to incident CKD, however, it can be used alongside other renal measurements to early identify and assess those at risk of developing CKD. Future analyses will use this definition to identify other risk factors for RP, including the role of antiretrovirals.

Mineralization of soluble P fertilizers and insoluble rock phosphate in response to phosphate-solubilizing bacteria and poultry manure and their effect on the growth and P utilization efficiency of chilli (Capsicum annuum L.)

NASA Astrophysics Data System (ADS)

Abbasi, M. K.; Musa, N.; Manzoor, M.

2015-08-01

The ability of soil microorganisms and organic manure to convert insoluble phosphorus (P) to an accessible form offers a biological rescue system for improving P utilization efficiency in soil-plant systems. Our objective was to examine the P mineralization potential of two soluble P fertilizers (SPF), i.e., single superphosphate (SSP) and diammonium phosphate (DAP), and of insoluble rock phosphate (RP) with and without phosphate-solubilizing bacteria (PSB) and poultry manure (PM) and their subsequent effect on the growth, yield and P utilization efficiency (PUE) of chilli (Capsicum annuum L.). An incubation study was carried out on a loam (slightly alkaline) soil with 12 treatments: T0 - control; T1 - RP; T2 - SSP; T3 - DAP; T4 - PM; T5 - 1/2 RP+1/2 SSP; T6 - 1/2 RP+1/2 DAP; T7 - 1/2 RP+1/2 PM; T8 - RP+PSB; T9 - 1/2 RP+1/2 SSP+PSB; T10 - 1/2 RP+1/2 DAP+PSB; and T11 - 1/2 RP+1/2 PM+PSB. Phosphorus mineralization was measured by analyzing extractable P from the amended soil incubated under controlled conditions at 25 °C for periods of 0, 5, 15, 25, 35 and 60 days. A complementary greenhouse experiment was conducted in pots with chilli (Capsicum annuum L.) as a test crop. Growth, yield, P uptake and PUE of the chilli was determined during the study. Results indicated that P mineralization in soil amended with RP was 6.0-11.5 mg kg-1, while both soluble P fertilizers resulted in 68-73 mg P kg-1 at day 0, which decreased by 79-82 % at the end of incubation. The integrated use of PSB and PM with RP in T11 stimulated P mineralization by releasing a maximum of 25 mg P kg-1 that was maintained at high levels without any loss. Use of PSB decreased soil pH. In the greenhouse experiment, RP alone or RP+PSB did not have a significant impact on plant growth. However, the combined use of RP, PM and PSB in T11 resulted in similar growth, yield and P uptake of chilli as DAP. The PUE of applied P varied from 4 to 29 % and was higher in the treatments that included PSB. We conclude that the use of PSB and PM with insoluble RP or with soluble P fertilizers could be a promising approach to enhance P availability from both low-grade RP and SPF for crop production in intensive cropping systems.

A Structural Overview of RNA-Dependent RNA Polymerases from the Flaviviridae Family

PubMed Central

Wu, Jiqin; Liu, Weichi; Gong, Peng

2015-01-01

RNA-dependent RNA polymerases (RdRPs) from the Flaviviridae family are representatives of viral polymerases that carry out RNA synthesis through a de novo initiation mechanism. They share a ≈ 600-residue polymerase core that displays a canonical viral RdRP architecture resembling an encircled right hand with palm, fingers, and thumb domains surrounding the active site. Polymerase catalytic motifs A–E in the palm and motifs F/G in the fingers are shared by all viral RdRPs with sequence and/or structural conservations regardless of the mechanism of initiation. Different from RdRPs carrying out primer-dependent initiation, Flaviviridae and other de novo RdRPs utilize a priming element often integrated in the thumb domain to facilitate primer-independent initiation. Upon the transition to the elongation phase, this priming element needs to undergo currently unresolved conformational rearrangements to accommodate the growth of the template-product RNA duplex. In the genera of Flavivirus and Pestivirus, the polymerase module in the C-terminal part of the RdRP protein may be regulated in cis by the N-terminal region of the same polypeptide. Either being a methyltransferase in Flavivirus or a functionally unclarified module in Pestivirus, this region could play auxiliary roles for the canonical folding and/or the catalysis of the polymerase, through defined intra-molecular interactions. PMID:26062131

Rapid prototyping and stereolithography in dentistry

PubMed Central

Nayar, Sanjna; Bhuminathan, S.; Bhat, Wasim Manzoor

2015-01-01

The word rapid prototyping (RP) was first used in mechanical engineering field in the early 1980s to describe the act of producing a prototype, a unique product, the first product, or a reference model. In the past, prototypes were handmade by sculpting or casting, and their fabrication demanded a long time. Any and every prototype should undergo evaluation, correction of defects, and approval before the beginning of its mass or large scale production. Prototypes may also be used for specific or restricted purposes, in which case they are usually called a preseries model. With the development of information technology, three-dimensional models can be devised and built based on virtual prototypes. Computers can now be used to create accurately detailed projects that can be assessed from different perspectives in a process known as computer aided design (CAD). To materialize virtual objects using CAD, a computer aided manufacture (CAM) process has been developed. To transform a virtual file into a real object, CAM operates using a machine connected to a computer, similar to a printer or peripheral device. In 1987, Brix and Lambrecht used, for the first time, a prototype in health care. It was a three-dimensional model manufactured using a computer numerical control device, a type of machine that was the predecessor of RP. In 1991, human anatomy models produced with a technology called stereolithography were first used in a maxillofacial surgery clinic in Viena. PMID:26015715

Multimodal Imaging of Disease-Associated Pigmentary Changes in Retinitis Pigmentosa

PubMed Central

Schuerch, Kaspar; Marsiglia, Marcela; Lee, Winston; Tsang, Stephen H.; Sparrow, Janet R.

2016-01-01

Purpose Using multiple imaging modalities we evaluated the changes in photoreceptor cells and RPE that are associated with bone spicule-shaped melanin pigmentation in retinitis pigmentosa (RP). Methods In a cohort of 60 RP patients, short-wavelength autofluorescence (SW-AF), near-infrared (NIR)-AF, NIR-reflectance (NIR-R), spectral domain optical coherence tomography (SD-OCT) and color fundus images were studied. Results Central AF rings were visible in both SW-AF and NIR-AF images. Bone spicule pigmentation was non-reflective in NIR-R, hypoautofluorescent with SW-AF and NIR-AF imaging and presented as intraretinal hyperreflective foci in SD-OCT images. In areas beyond the AF ring outer border, the photoreceptor ellipsoid zone (EZ) band was absent in SD-OCT scans and the visibility of choroidal vessels in SW-AF, NIR-AF and NIR-R images was indicative of reduced RPE pigmentation. Choroidal visibility was most pronounced in the zone approaching peripheral areas of bone spicule pigmentation; here RPE/Bruch’s membrane thinning became apparent in SD-OCT scans. Conclusions These findings are consistent with a process by which RPE cells vacate their monolayer and migrate into inner retina in response to photoreceptor cell degeneration. The remaining RPE spread, undergo thinning and consequently become less pigmented. An explanation for the absence of NIR-AF melanin signal in relation to bone spicule pigmentation is not forthcoming. PMID:28005673

Rapid prototyping and stereolithography in dentistry.

PubMed

Nayar, Sanjna; Bhuminathan, S; Bhat, Wasim Manzoor

2015-04-01

The word rapid prototyping (RP) was first used in mechanical engineering field in the early 1980s to describe the act of producing a prototype, a unique product, the first product, or a reference model. In the past, prototypes were handmade by sculpting or casting, and their fabrication demanded a long time. Any and every prototype should undergo evaluation, correction of defects, and approval before the beginning of its mass or large scale production. Prototypes may also be used for specific or restricted purposes, in which case they are usually called a preseries model. With the development of information technology, three-dimensional models can be devised and built based on virtual prototypes. Computers can now be used to create accurately detailed projects that can be assessed from different perspectives in a process known as computer aided design (CAD). To materialize virtual objects using CAD, a computer aided manufacture (CAM) process has been developed. To transform a virtual file into a real object, CAM operates using a machine connected to a computer, similar to a printer or peripheral device. In 1987, Brix and Lambrecht used, for the first time, a prototype in health care. It was a three-dimensional model manufactured using a computer numerical control device, a type of machine that was the predecessor of RP. In 1991, human anatomy models produced with a technology called stereolithography were first used in a maxillofacial surgery clinic in Viena.

Remission of relapsing polychondritis after successful treatment of myelodysplastic syndrome with azacitidine: a case and review of the literature.

PubMed

Erden, Abdulsamet; Bilgin, Emre; Kılıç, Levent; Sarı, Alper; Armağan, Berkan; Büyükaşık, Yahya; Kalyoncu, Umut

2018-05-01

Relapsing polychondritis (RP) is a rare autoimmune disorder, and myelodysplastic syndrome (MDS) is accompanied by RP at variable rates. Herein, we report a case with RP and MDS who responded dramatically to 5-azacitidine for MDS. With conventional immunosuppressive treatment, our patient had several episodes of different side effects, including infections. With the diagnosis of MDS and initiation of azacitidine treatment, all the manifestations of RP disappeared, and remission was achieved for MDS. Although he had relapses of either RP or MDS after several years of azacitidine treatment, all relapses were controlled well with the initiation of azacitidine treatment every time. Azacitidine should be kept in mind as a treatment option for RP patients with MDS.

A review of rapid prototyping (RP) techniques in the medical and biomedical sector.

PubMed

Webb, P A

2000-01-01

The evolution of rapid prototyping (RP) technology is briefly discussed, and the application of RP technologies to the medical sector is reviewed. Although the use of RP technology has been slow arriving in the medical arena, the potential of the technique is seen to be widespread. Various uses of the technology within surgical planning, prosthesis development and bioengineering are discussed. Some possible drawbacks are noted in some applications, owing to the poor resolution of CT slice data in comparison with that available on RP machines, but overall, the methods are seen to be beneficial in all areas, with one early report suggesting large improvements in measurement and diagnostic accuracy as a result of using RP models.

The role of BPH, lower urinary tract symptoms, and PSA levels on erectile function of Brazilian men who undergo prostate cancer screening.

PubMed

Antunes, Alberto A; Srougi, Miguel; Dall'oglio, Marcos F; Vicentini, Fabio; Paranhos, Mario; Freire, Geraldo C

2008-07-01

Lower urinary tract symptoms (LUTS) and erectile dysfunction (ED) are common problems in middle-aged and older men. Recently, epidemiologic studies have shown significant associations between severity of LUTS and male sexual dysfunction. We analyzed the role of prostate enlargement, LUTS, and prostate specific antigen (PSA) levels in the erectile function of Brazilian men who underwent prostate cancer (PCa) screening. We analyzed data from 1,008 consecutive patients enrolled in a PCa screening program. Benign prostatic hyperplasia (BPH) was defined as a prostate weight greater than 30 g as defined by digital rectal examination. For statistical analysis, we used the chi-squared and analysis of variance tests. The odds ratios (OR) for correlation of ED with prostate volume LUTS and PSA were estimated using logistic regression models. The American Urological Association (AUA) symptom score for LUTS and the International Index of Erectile Function. Mean patient age was 61.2 years (45-87) and median PSA value was 1.9 ng/mL. BPH was identified in 48.5% of patients. Mild, moderate, and severe LUTS were found in 52.3%, 30.9%, and 16.8% of cases, respectively. ED was classified as absent, mild, mild to moderate, moderate, and severe in 18.6%, 23.1%, 18.6%, 15.2%, and 24.5%, respectively. While only 5.4% of the patients with no ED presented severe LUTS, this finding was observed in 27.1% of patients with severe ED (P < 0.001). Univariate logistic regression analysis demonstrated that age, prostate volume, AUA symptom score, and PSA levels were significant predictors of ED. However, when controlled for patient age, only LUTS remained as an independent predictor of ED. Controlling for patient age, LUTS are independent risk factors for the development of ED among Brazilian men who undergo PCa screening. Antunes AA, Srougi M, Dall'Oglio MF, Vicentini F, Paranhos M, and Freire GC. The role of BPH, lower urinary tract symptoms, and PSA levels on erectile function of Brazilian men who undergo prostate cancer screening.

Sperm retrieval rate and pregnancy rate in infertile couples undergoing in-vitro fertilisation and testicular sperm extraction for non-obstructive azoospermia in Hong Kong.

PubMed

Ko, J Ky; Chai, J; Lee, V Cy; Li, R Hw; Lau, E; Ho, K L; Tam, P C; Yeung, W Sb; Ho, P C; Ng, E Hy

2016-12-01

There are currently no local data on the sperm retrieval and pregnancy rates in in-vitro fertilisation and testicular sperm extraction cycles, especially with regard to the presence of genetic abnormalities. This study aimed to determine the sperm retrieval and pregnancy rates in infertile couples who underwent in-vitro fertilisation and testicular sperm extraction for non-obstructive azoospermia. This retrospective case series was conducted at a tertiary assisted reproduction unit in Hong Kong. Men with non-obstructive azoospermia who underwent in-vitro fertilisation and testicular sperm extraction between January 2001 and December 2013 were included. The main outcome measures were sperm retrieval and pregnancy rates. During the study period, 89 men with non-obstructive azoospermia underwent in-vitro fertilisation and testicular sperm extraction. Sperm was successfully retrieved in 40 (44.9%) men. There was no statistically significant difference in the sperm retrieval rate of those with karyotypic abnormalities (2/5, 40.0% vs 28/61, 45.9%; P=1.000) and AZFc microdeletion (3/6, 50.0% vs 28/61, 45.9%; P=1.000) compared with those without. Sperms were successfully retrieved in patients who had mosaic Klinefelter syndrome (2/3, 66.7%) but not in the patient with non-mosaic Klinefelter syndrome. No sperms were found in men with AZFa or AZFb microdeletions. Pregnancy test was positive in 15 (16.9%) patients and the clinical pregnancy rate was 13.5% (12/89) per cycle. The clinical pregnancy rate per transfer was 34.3% (12/35). The sperm retrieval rate and clinical pregnancy rate per initiated cycle in men undergoing in-vitro fertilisation and testicular sperm extraction in our unit were 44.9% and 13.5%, respectively. No sperms could be retrieved in the presence of AZFa and AZFb microdeletions, but karyotype and AZFc microdeletion abnormalities otherwise did not predict the success of sperm retrieval in couples undergoing in-vitro fertilisation and testicular sperm extraction. Genetic tests are important prior to testicular sperm extraction for patient selection and genetic counselling.

Psychological aspects of male fertility treatment.

PubMed

Mikkelsen, Alice Toft; Madsen, Svend Aage; Humaidan, Peter

2013-09-01

To explore and to identify the possible need for psychological communicative support in men undergoing fertility treatment. Male infertility affects many aspects of a man's life and may cause a life crisis. Although infertility treatment is now commonplace in men, they often feel remote and disconnected from the treatment process. A descriptive survey. A questionnaire with structured and open-ended questions was completed by 210 Danish men undergoing fertility treatment. The questionnaire covered three issues: individual perception of male infertility, gender equality issues, and communication with health professionals in the clinic. Data were collected during 2008. Of the participants, 28% believed that their reduced sperm quality affected their perception of masculinity. 46% stated that equal involvement between partners was a very important element of the treatment; however, 63% said that the health professionals communicated primarily with their female partner. Finally, 62% found that there was a need for a deeper dialogue with the nurses concerning male infertility and 72% lacked information about the psychological consequences of male infertility. In general, participants wanted a more open and balanced dialogue about infertility treatment and the role of the male partner during this process. Infertile men want health professionals to view them on equal terms with their partner. When treating the infertile man, there is a further need to develop more inclusive communication skills. © 2012 Blackwell Publishing Ltd.

Rationale, Design and Methods of the Ecological Study of Sexual Behaviors and HIV/STI among African American Men Who Have Sex with Men in the Southeastern United States (The MARI Study)

PubMed Central

Hickson, DeMarc A.; Truong, Nhan L.; Smith-Bankhead, Neena; Sturdevant, Nikendrick; Duncan, Dustin T.; Schnorr, Jordan; Gipson, June A.; Mena, Leandro A.

2015-01-01

Background This paper describes the rationale, design, and methodology of the Ecological Study of Sexual Behaviors and HIV/STI among African American Men Who Have Sex with Men (MSM) in the Southeastern United States (U.S.; known locally simply as the MARI Study). Methods Participants are African American MSM aged 18 years and older residing in the deep South. Results Between 2013 and 2015, 800 African American MSM recruited from two study sites (Jackson, MS and Atlanta, GA) will undergo a 1.5-hour examination to obtain anthropometric and blood pressure measures as well as to undergo testing for sexually transmitted infections (STI), including HIV. Intrapersonal, interpersonal, and environmental factors are assessed by audio computer-assisted self-interview survey. Primary outcomes include sexual risk behaviors (e.g., condomless anal sex) and prevalent STIs (HIV, syphilis, gonorrhea, and Chlamydia). Conclusion The MARI Study will typify the HIV environmental 'riskscape' and provide empirical evidence into novel ecological correlates of HIV risk among African American MSM in the deep South, a population most heavily impacted by HIV. The study's anticipated findings will be of interest to a broad audience and lead to more informed prevention efforts, including effective policies and interventions, that achieve the goals of the updated 2020 U.S. National HIV/AIDS Strategy. PMID:26700018

α1A-Adrenergic Receptor Antagonism Improves Erectile and Cavernosal Responses in Rats With Cavernous Nerve Injury and Enhances Neurogenic Responses in Human Corpus Cavernosum From Patients With Erectile Dysfunction Secondary to Radical Prostatectomy.

PubMed

Martínez-Salamanca, Juan I; La Fuente, José M; Martínez-Salamanca, Eduardo; Fernández, Argentina; Pepe-Cardoso, Augusto J; Louro, Nuno; Carballido, Joaquín; Angulo, Javier

2016-12-01

Cavernous nerve injury (CNI) in rats and radical prostatectomy (RP) in men result in loss of nitrergic function and increased adrenergic-neurogenic contractions of cavernosal tissue. To evaluate the modulation of the α-adrenergic system as a strategy to relieve erectile dysfunction (ED) and functional cavernosal alterations induced by CNI. A non-selective α-blocker (phentolamine 1 mg/kg daily), a selective α 1A -blocker (silodosin [SILOD] 0.1 mg/kg daily), or vehicle was orally administered for 4 weeks after bilateral crush CNI (BCNI). Erectile and neurogenic responses of the corpus cavernosum (CC) were evaluated. The acute effects of SILOD also were evaluated in vivo (0.03 mg/kg intravenously) and ex vivo (10 nmol/L). The effects of SILOD and tadalafil (TAD) on nitrergic relaxations were determined in human CC from patients with ED with a vascular etiology or ED secondary to RP. Erectile responses in vivo in rats and neurogenic contractions and relaxations of rat and human CC. Long-term treatment with SILOD significantly improved erectile responses and allowed for the potentiation of erectile responses by acute treatment with TAD (0.3 mg/kg intravenously) in rats with BCNI. SILOD partly recovered nitrergic relaxations and normalized neurogenic contractions in CC from rats with BCNI. Long-term treatment with SILOD partly prevented BCNI-induced decreases in neuronal nitric oxide synthase expression. Acute administration of SILOD (0.03 mg/kg intravenously) improved erectile responses in vivo and potentiated nitrergic relaxation and decreased neurogenic contractions ex vivo in CC from rats with BCNI. In human CC from patients with ED with a vascular etiology, TAD (30 nmol/L), SILOD (10 nmol/L), or their combination increased nitrergic relaxations. Potentiation by TAD was lost in human CC from patients with ED after RP but was recovered after co-treatment with SILOD. α-Adrenergic modulation, especially selective α 1A -blockade, improves erectile and cavernosal functions after BCNI. Modulation of the adrenergic system, mainly in combination strategies, could have a role in the management of ED after RP. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Offline pentafluorophenyl (PFP)-RP prefractionation as an alternative to high-pH RP for comprehensive LC-MS/MS proteomics and phosphoproteomics.

PubMed

Grassetti, Andrew V; Hards, Rufus; Gerber, Scott A

2017-07-01

Technological advances in liquid chromatography and tandem mass spectrometry (LC-MS/MS) have enabled comprehensive analyses of proteins and their post-translational modifications from cell culture and tissue samples. However, sample complexity necessitates offline prefractionation via a chromatographic method that is orthogonal to online reversed-phase high-performance liquid chromatography (RP-HPLC). This additional fractionation step improves target identification rates by reducing the complexity of the sample as it is introduced to the instrument. A commonly employed offline prefractionation method is high pH reversed-phase (Hi-pH RP) chromatography. Though highly orthogonal to online RP-HPLC, Hi-pH RP relies on buffers that interfere with electrospray ionization. Thus, samples that are prefractionated using Hi-pH RP are typically desalted prior to LC-MS/MS. In the present work, we evaluate an alternative offline prefractionation method, pentafluorophenyl (PFP)-based reversed-phase chromatography. Importantly, PFP prefractionation results in samples that are dried prior to analysis by LC-MS/MS. This reduction in sample handling relative to Hi-pH RP results in time savings and could facilitate higher target identification rates. Here, we have compared the performances of PFP and Hi-pH RP in offline prefractionation of peptides and phosphopeptides that have been isolated from human cervical carcinoma (HeLa) cells. Given the prevalence of isobaric mass tags for peptide quantification, we evaluated PFP chromatography of peptides labeled with tandem mass tags. Our results suggest that PFP is a viable alternative to Hi-pH RP for both peptide and phosphopeptide offline prefractionation.

Lipopolysaccharide (LPS) and tumor necrosis factor alpha (TNFα) blunt the response of Neuropeptide Y/Agouti-related peptide (NPY/AgRP) glucose inhibited (GI) neurons to decreased glucose

PubMed Central

Hao, Lihong; Sheng, Zhenyu; Potian, Joseph; Deak, Adam; Rohowsky-Kochan, Christine; Routh, Vanessa H.

2016-01-01

A population of Neuropeptide Y (NPY) neurons which co-express Agouti-related peptide (AgRP) in the arcuate nucleus of the hypothalamus (ARC) are inhibited at physiological levels of brain glucose and activated when glucose levels decline (e.g. glucose-inhibited or GI neurons). Fasting enhances the activation of NPY/AgRP-GI neurons by low glucose. In the present study we tested the hypothesis that lipopolysaccharide (LPS) inhibits the enhanced activation of NPY/AgRP-GI neurons by low glucose following a fast. Mice which express green fluorescent protein (GFP) on their NPY promoter were used to identify NPY/AgRP neurons. Fasting for 24 hours and LPS injection decreased blood glucose levels. As we have found previously, fasting increased c-fos expression in NPY/AgRP neurons and increased the activation of NPY/AgRP-GI neurons by decreased glucose. As we predicted, LPS blunted these effects of fasting at the 24 hour time point. Moreover, the inflammatory cytokine tumor necrosis factor alpha (TNFα) blocked the activation of NPY/AgRP-GI neurons by decreased glucose. These data suggest that LPS and TNFα may alter glucose and energy homeostasis, in part, due to changes in the glucose sensitivity of NPY/AgRP neurons. Interestingly, our findings also suggest that NPY/AgRP-GI neurons use a distinct mechanism to sense changes in extracellular glucose as compared to our previous studies of GI neurons in the adjacent ventromedial hypothalamic nucleus. PMID:27473896

The effect of autoimmune retinopathy on retinal vessel oxygen saturation.

PubMed

Waizel, Maria; Türksever, Cengiz; Todorova, Margarita G

2018-05-22

To study the retinal vessel oxygen saturation alterations in patients with autoimmune retinopathy (AIR) and patients with autoimmune retinopathy associated with retinitis pigmentosa (AIR-RP) in comparison with healthy controls and patients with isolated retinitis pigmentosa (RP). Prospective, cross-sectional, and non-interventional study. Retinal vessel oximetry (RO) was performed on a total of 139 eyes: six eyes suffering from AIR and four eyes with AIR-RP were compared to 59 healthy control eyes and to 70 eyes with RP. A computer-based program of the retinal vessel analyser unit (IMEDOS Systems UG, Jena, Germany) was used to evaluate retinal vessel oxygen saturation. The mean oxygen saturation in the first and second branch retinal arterioles (A-SO 2 ) and venules (V-SO 2 ) were measured and their difference (A-V SO 2 ) was calculated. In addition, we measured the diameter of the retinal arterioles (D-A) and venules (D-V). Oxygen metabolism is altered in patients with isolated AIR and AIR-RP. Both, AIR and AIR-RP groups, differed from healthy controls showing significantly higher V-SO 2 values and significantly lower A-V SO 2 values (p < 0.025). In addition, the AIR-RP group could be differentiated from eyes suffering from isolated RP by means of significantly higher V-SO 2 values. Comparing retinal vessel diameters, both, the AIR and AIR-RP groups, presented with significant arterial (p = 0.05) and venular (p < 0.03) vessel attenuation than the healthy control group. Based on our results, in analogy to patients suffering from RP, oxygen metabolism seems to be altered in AIR patients.

[Neurological disorders in preterm children with neuropathy].

PubMed

Nikolaeva, G V; Sidorenko, E I; Guseva, M R; Akbasheva, N G

2017-01-01

To establish the correlation between the frequency and severity of hypoxic CNS lesions in preterm children with neuropathy and improve the early diagnosis of lesions of the brain structures based on clinical ophthalmologic results. The authors examined 712 premature infants with body mass <1500 g born before 30 weeks of gestation during 2006-2016. Ophthalmological monitoring of retinopathy (RP), an analysis of medical history, neurological examination and neurosonography were performed. RP was found in 367 (51.5%) children. In 255 children, the disease regressed naturally. One hundred and twelve (15.7%) children, underwent laser coagulation of the avascular retina due to the severity of RP. Signs of intraventricular hemorrhages (IVH) were noted in 434 (61%) children in the neonatal period. IVH were found in 285 (77.6%) children with RP. RP with the regression after laser coagulation was combined with IVH in 98% of cases, with the higher frequency (55.3%) of IVH, 3 rd degree. Periventricular leucomalation (PVL) was found in 10% of children without RP, in 22.3% of children with RP with naturally regression and in 51,7% of children with RP with laser coagulation of the retina. In 70 children, neurosonographic signs of ischemia of the head of caudate nucleus were identified on the 14-15 th days of life. In this group, RP developed in 54 (77%) children, 27 (38.5%) children needed laser coagulation of the retina. The correlation found between the severity of RP and hypoxic CNS lesions in highly preterm infants might allow the prognosis of visual and neurosomatic disturbances in the early age and timely effective rehabilitation.

Lipopolysaccharide (LPS) and tumor necrosis factor alpha (TNFα) blunt the response of Neuropeptide Y/Agouti-related peptide (NPY/AgRP) glucose inhibited (GI) neurons to decreased glucose.

PubMed

Hao, Lihong; Sheng, Zhenyu; Potian, Joseph; Deak, Adam; Rohowsky-Kochan, Christine; Routh, Vanessa H

2016-10-01

A population of Neuropeptide Y (NPY) neurons which co-express Agouti-related peptide (AgRP) in the arcuate nucleus of the hypothalamus (ARC) are inhibited at physiological levels of brain glucose and activated when glucose levels decline (e.g. glucose-inhibited or GI neurons). Fasting enhances the activation of NPY/AgRP-GI neurons by low glucose. In the present study we tested the hypothesis that lipopolysaccharide (LPS) inhibits the enhanced activation of NPY/AgRP-GI neurons by low glucose following a fast. Mice which express green fluorescent protein (GFP) on their NPY promoter were used to identify NPY/AgRP neurons. Fasting for 24h and LPS injection decreased blood glucose levels. As we have found previously, fasting increased c-fos expression in NPY/AgRP neurons and increased the activation of NPY/AgRP-GI neurons by decreased glucose. As we predicted, LPS blunted these effects of fasting at the 24h time point. Moreover, the inflammatory cytokine tumor necrosis factor alpha (TNFα) blocked the activation of NPY/AgRP-GI neurons by decreased glucose. These data suggest that LPS and TNFα may alter glucose and energy homeostasis, in part, due to changes in the glucose sensitivity of NPY/AgRP neurons. Interestingly, our findings also suggest that NPY/AgRP-GI neurons use a distinct mechanism to sense changes in extracellular glucose as compared to our previous studies of GI neurons in the adjacent ventromedial hypothalamic nucleus. Copyright © 2016 Elsevier B.V. All rights reserved.

Operative simulation of anterior clinoidectomy using a rapid prototyping model molded by a three-dimensional printer.

PubMed

Okonogi, Shinichi; Kondo, Kosuke; Harada, Naoyuki; Masuda, Hiroyuki; Nemoto, Masaaki; Sugo, Nobuo

2017-09-01

As the anatomical three-dimensional (3D) positional relationship around the anterior clinoid process (ACP) is complex, experience of many surgeries is necessary to understand anterior clinoidectomy (AC). We prepared a 3D synthetic image from computed tomographic angiography (CTA) and magnetic resonance imaging (MRI) data and a rapid prototyping (RP) model from the imaging data using a 3D printer. The objective of this study was to evaluate anatomical reproduction of the 3D synthetic image and intraosseous region after AC in the RP model. In addition, the usefulness of the RP model for operative simulation was investigated. The subjects were 51 patients who were examined by CTA and MRI before surgery. The size of the ACP, thickness and length of the optic nerve and artery, and intraosseous length after AC were measured in the 3D synthetic image and RP model, and reproducibility in the RP model was evaluated. In addition, 10 neurosurgeons performed AC in the completed RP models to investigate their usefulness for operative simulation. The RP model reproduced the region in the vicinity of the ACP in the 3D synthetic image, including the intraosseous region, at a high accuracy. In addition, drilling of the RP model was a useful operative simulation method of AC. The RP model of the vicinity of ACP, prepared using a 3D printer, showed favorable anatomical reproducibility, including reproduction of the intraosseous region. In addition, it was concluded that this RP model is useful as a surgical education tool for drilling.

Involvement of Prolactin-Releasing Peptide in the Activation of Oxytocin Neurones in Response to Food Intake

PubMed Central

Yamashita, M; Takayanagi, Y; Yoshida, M; Nishimori, K; Kusama, M; Onaka, T

2013-01-01

Food intake activates neurones expressing prolactin-releasing peptide (PrRP) in the medulla oblongata and oxytocin neurones in the hypothalamus. Both PrRP and oxytocin have been shown to have an anorexic action. In the present study, we investigated whether the activation of oxytocin neurones following food intake is mediated by PrRP. We first examined the expression of PrRP receptors (also known as GPR10) in rats. Immunoreactivity of PrRP receptors was observed in oxytocin neurones and in vasopressin neurones in the paraventricular and supraoptic nuclei of the hypothalamus and in the bed nucleus of the stria terminalis. Application of PrRP to isolated supraoptic nuclei facilitated the release of oxytocin and vasopressin. In mice, re-feeding increased the expression of Fos protein in oxytocin neurones of the hypothalamus and bed nucleus of the stria terminalis. The increased expression of Fos protein in oxytocin neurones following re-feeding or i.p. administration of cholecystokinin octapeptide (CCK), a peripheral satiety factor, was impaired in PrRP-deficient mice. CCK-induced oxytocin increase in plasma was also impaired in PrRP-deficient mice. Furthermore, oxytocin receptor-deficient mice showed an increased meal size, as reported in PrRP-deficient mice and in CCKA receptor-deficient mice. These findings suggest that PrRP mediates, at least in part, the activation of oxytocin neurones in response to food intake, and that the CCK–PrRP–oxytocin pathway plays an important role in the control of the termination of each meal. PMID:23363338

The first USH2A mutation analysis of Japanese autosomal recessive retinitis pigmentosa patients: a totally different mutation profile with the lack of frequent mutations found in Caucasian patients.

PubMed

Zhao, Yang; Hosono, Katsuhiro; Suto, Kimiko; Ishigami, Chie; Arai, Yuuki; Hikoya, Akiko; Hirami, Yasuhiko; Ohtsubo, Masafumi; Ueno, Shinji; Terasaki, Hiroko; Sato, Miho; Nakanishi, Hiroshi; Endo, Shiori; Mizuta, Kunihiro; Mineta, Hiroyuki; Kondo, Mineo; Takahashi, Masayo; Minoshima, Shinsei; Hotta, Yoshihiro

2014-09-01

Retinitis pigmentosa (RP) is a highly heterogeneous genetic disease. The USH2A gene, which accounts for approximately 74-90% of Usher syndrome type 2 (USH2) cases, is also one of the major autosomal recessive RP (arRP) causative genes among Caucasian populations. To identify disease-causing USH2A gene mutations in Japanese RP patients, all 73 exons were screened for mutations by direct sequencing. In total, 100 unrelated Japanese RP patients with no systemic manifestations were identified, excluding families with obvious autosomal dominant inheritance. Of these 100 patients, 82 were included in this present study after 18 RP patients with very likely pathogenic EYS (eyes shut homolog) mutations were excluded. The mutation analysis of the USH2A revealed five very likely pathogenic mutations in four patients. A patient had only one very likely pathogenic mutation and the others had two of them. Caucasian frequent mutations p.C759F in arRP and p.E767fs in USH2 were not found. All the four patients exhibited typical clinical features of RP. The observed prevalence of USH2A gene mutations was approximately 4% among Japanese arRP patients, and the profile of the USH2A gene mutations differed largely between Japanese patients and previously reported Caucasian populations.

RpA, an extracellular protease similar to the metalloprotease of serralysin family, is required for pathogenicity of Ralstonia pickettii.

PubMed

Chen, C-M; Liu, J-J; Chou, C-W; Lai, C-H; Wu, L-T

2015-10-01

To investigate the biochemical and functional properties of an extracellular protease, RpA, in Ralstonia pickettii WP1 isolated from water supply systems. An extracellular protease was identified and characterized from R. pickettii WP1. A mutant strain WP1M2 was created from strain WP1 by mini-Tn5 transposition. The culture filtrates from WP1M2 had a lower cytotoxic effect than the parental WP1 on several mammalian cell lines. Cloning and sequence analysis revealed the Tn5 transposon inserted at a protease gene (rpA) which is 81% homologous to prtA and aprX genes of Pseudomonas fluorescens. The rpA gene encodes a 482-residue protein showing sequence similarity to metalloproteases of the serralysin family. The RpA protein was expressed in Escherichia coli using a pET expression vector and purified as a 55 kDa molecular weight protein. Furthermore, the protease activity of RpA was inhibited by protease inhibitor and heat treatment. The in vitro cytotoxic activity of R. pickettii culture filtrates was attributed to RpA protease. An extracellular protease, RpA, was identified from R. pickettii WP1 isolated from water supply system. The RpA metalloproteases is required for the pathogenicity of R. pickettii to mammalian cell lines. © 2015 The Society for Applied Microbiology.

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2010-11-15

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Clinical and Rehabilitative Management of Retinitis Pigmentosa: Up-to-Date

PubMed Central

Parmeggiani, Francesco; Sato, Giovanni; De Nadai, Katia; Romano, Mario R; Binotto, Andrea; Costagliola, Ciro

2011-01-01

The term retinitis pigmentosa (RP) indicates a heterogeneous group of genetic rare ocular diseases in which either rods or cones are prevalently damaged. RP represents the most common hereditary cause of blindness in people from 20 to 60 years old. In general, the different RP forms consist of progressive photo-receptorial neuro-degenerations, which are characterized by variable visual disabilities and considerable socio-sanitary burden. Sometimes, RP patients do not become visually impaired or legally blind until their 40-50 years of age and/or maintain a quite acceptable sight for all their life. Other individuals with RP become completely blind very early or in middle childhood. Although there is no treatment that can effectively cure RP, in some case-series the disease’s progression seems to be reducible by specific preventive approaches. In the most part of RP patients, the quality of vision can be considerably increased by means of nanometer-controlled filters. In the present review, the main aspects of the routine clinical and rehabilitative managements for RP patients are described, particularly focusing on the importance of specific referral Centers to practice a real multidisciplinary governance of these dramatic diseases. PMID:22131870

Ribosomal Protein S6 Phosphorylation Is Involved in Novelty-Induced Locomotion, Synaptic Plasticity and mRNA Translation

PubMed Central

Puighermanal, Emma; Biever, Anne; Pascoli, Vincent; Melser, Su; Pratlong, Marine; Cutando, Laura; Rialle, Stephanie; Severac, Dany; Boubaker-Vitre, Jihane; Meyuhas, Oded; Marsicano, Giovanni; Lüscher, Christian; Valjent, Emmanuel

2017-01-01

The phosphorylation of the ribosomal protein S6 (rpS6) is widely used to track neuronal activity. Although it is generally assumed that rpS6 phosphorylation has a stimulatory effect on global protein synthesis in neurons, its exact biological function remains unknown. By using a phospho-deficient rpS6 knockin mouse model, we directly tested the role of phospho-rpS6 in mRNA translation, plasticity and behavior. The analysis of multiple brain areas shows for the first time that, in neurons, phospho-rpS6 is dispensable for overall protein synthesis. Instead, we found that phospho-rpS6 controls the translation of a subset of mRNAs in a specific brain region, the nucleus accumbens (Acb), but not in the dorsal striatum. We further show that rpS6 phospho-mutant mice display altered long-term potentiation (LTP) in the Acb and enhanced novelty-induced locomotion. Collectively, our findings suggest a previously unappreciated role of phospho-rpS6 in the physiology of the Acb, through the translation of a selective subclass of mRNAs, rather than the regulation of general protein synthesis. PMID:29311811

Heterogeneity analysis in 40 X-linked retinitis pigmentosa families

DOE Office of Scientific and Technical Information (OSTI.GOV)

Teague, P.W.; Aldred, M.A.; Dempster, M.

1994-07-01

Analysis of genetic heterogeneity in 40 kindreds with X-linked retinitis pigmentosa (XLRP), with 20 polymorphic markers, showed that significant heterogeneity is present (P=.001) and that 56% of kindreds are of RP3 type and that 26% are of RP2 type. The location of the RP3 locus was found to be 0.4 cM distal to OTC in the Xp21.1 region, and that of the RP2 locus was 6.5 cM proximal to DXS7 in Xp11.2-p11.3. Bayesian probabilities of linkage to RP2, RP3, or to neither locus were calculated. This showed that 20 of 40 kindreds could be assigned to one or the othermore » locus, with a probability >.70 (14 kindreds with RP3 and 6 kindreds with RP2 disease). A further three kindreds were found to be unlinked to either locus, with a probability >.8. The remaining 17 kindreds could not be classified unambiguously. This highlights the difficulty of classifying families in the presence of genetic heterogeneity, where two loci are separated by an estimated 16 cM. 34 refs., 1 fig., 4 tabs.« less

A Small Potassium Current in AgRP/NPY Neurons Regulates Feeding Behavior and Energy Metabolism.

PubMed

He, Yanlin; Shu, Gang; Yang, Yongjie; Xu, Pingwen; Xia, Yan; Wang, Chunmei; Saito, Kenji; Hinton, Antentor; Yan, Xiaofeng; Liu, Chen; Wu, Qi; Tong, Qingchun; Xu, Yong

2016-11-08

Neurons that co-express agouti-related peptide (AgRP) and neuropeptide Y (NPY) are indispensable for normal feeding behavior. Firing activities of AgRP/NPY neurons are dynamically regulated by energy status and coordinate appropriate feeding behavior to meet nutritional demands. However, intrinsic mechanisms that regulate AgRP/NPY neural activities during the fed-to-fasted transition are not fully understood. We found that AgRP/NPY neurons in satiated mice express high levels of the small-conductance calcium-activated potassium channel 3 (SK3) and are inhibited by SK3-mediated potassium currents; on the other hand, food deprivation suppresses SK3 expression in AgRP/NPY neurons, and the decreased SK3-mediated currents contribute to fasting-induced activation of these neurons. Genetic mutation of SK3 specifically in AgRP/NPY neurons leads to increased sensitivity to diet-induced obesity, associated with chronic hyperphagia and decreased energy expenditure. Our results identify SK3 as a key intrinsic mediator that coordinates nutritional status with AgRP/NPY neural activities and animals' feeding behavior and energy metabolism. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Mutation of the key residue for extraribosomal function of ribosomal protein S19 cause increased grooming behaviors in mice.

PubMed

Chen, Jun; Kaitsuka, Taku; Fujino, Rika; Araki, Kimi; Tomizawa, Kazuhito; Yamamoto, Tetsuro

2016-08-26

Ribosomal protein S19 (RP S19) possesses ribosomal function as RP S19 monomer and extraribosomal function as cross-linked RP S19 oligomers which function as a ligand of the complement 5a (C5a) receptor (CD88). We have generated a Gln137Glu-RP S19 knock-in (KI) mouse, which is shown to possess the weakened extraribosomal function of RP S19. Because whether the extraribosomal function of RP S19 has a role in brain function had been unclear, we performed behavioral analysis on these mice and demonstrated that KI mice displayed an increased grooming behavior during open-field test and elevated plus maze test and an enhanced freezing behavior in contextual fear conditioning test. These results suggest an involvement of RP S19 oligomers in some anxiety-like behavior, especially grooming behavior. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Gs-coupled GPCR signalling in AgRP neurons triggers sustained increase in food intake

PubMed Central

Nakajima, Ken-ichiro; Cui, Zhenzhong; Li, Chia; Meister, Jaroslawna; Cui, Yinghong; Fu, Ou; Smith, Adam S.; Jain, Shalini; Lowell, Bradford B.; Krashes, Michael J.; Wess, Jürgen

2016-01-01

Agouti-related peptide (AgRP) neurons of the hypothalamus play a key role in regulating food intake and body weight, by releasing three different orexigenic molecules: AgRP; GABA; and neuropeptide Y. AgRP neurons express various G protein-coupled receptors (GPCRs) with different coupling properties, including Gs-linked GPCRs. At present, the potential role of Gs-coupled GPCRs in regulating the activity of AgRP neurons remains unknown. Here we show that the activation of Gs-coupled receptors expressed by AgRP neurons leads to a robust and sustained increase in food intake. We also provide detailed mechanistic data linking the stimulation of this class of receptors to the observed feeding phenotype. Moreover, we show that this pathway is clearly distinct from other GPCR signalling cascades that are operative in AgRP neurons. Our data suggest that drugs able to inhibit this signalling pathway may become useful for the treatment of obesity. PMID:26743492

Multiple assembly chaperones govern biogenesis of the proteasome regulatory particle base.

PubMed

Funakoshi, Minoru; Tomko, Robert J; Kobayashi, Hideki; Hochstrasser, Mark

2009-05-29

The central protease of eukaryotes, the 26S proteasome, has a 20S proteolytic core particle (CP) and an attached 19S regulatory particle (RP). The RP is further subdivided into lid and base subcomplexes. Little is known about RP assembly. Here, we show that four conserved assembly factors govern biogenesis of the yeast RP base. Nas2 forms a complex with the Rpt4 and Rpt5 ATPases and enhances 26S proteasome formation in vivo and in vitro. Other RP subcomplexes contain Hsm3, which is related to mammalian proteasome subunit S5b. Hsm3 also contributes to base assembly. Larger Hsm3-containing complexes include two additional proteins, Nas6 and Rpn14, which function as assembly chaperones as well. Specific deletion combinations affecting these four factors cause severe perturbations to RP assembly. Our results demonstrate that proteasomal RP biogenesis requires multiple, functionally overlapping chaperones and suggest a model in which subunits form specific subcomplexes that then assemble into the base.

Interest in nonsurgical female permanent contraception among men in Portland, Oregon and eastern Maharashtra, India.

PubMed

Harrington, Elizabeth K; Gordon, Diana; Bahulekar, Pramod; Garg, B S; Osgood-Roach, Isabel; Jensen, Jeffrey T; Aengst, Jennifer

2015-08-01

We examined the men's attitudes and perceptions toward the concept of female nonsurgical permanent contraception (NSPC) or novel approaches to permanent contraception (PC) that do not require incisions or surgical equipment/hysteroscope. Cross-sectional survey of married/partnered men in Portland, OR, and rural eastern Maharashtra, India. Descriptive analysis was performed. In India (N=150), most men (80%) anticipated that their partners would undergo PC in the future, compared to 30% in Portland (N=170). About a third (39.6% in India, 82% in Portland) reported being uncomfortable with PC for partners due to the need for surgery. Most men (85% in India, 82% in Portland) expressed a preference for a hypothetical new method of female NSPC over surgery, if safe and effective. Most men sampled in two diverse settings expressed interest in NSPC for women. Men's perceptions of new female contraceptive methods are important to the contraceptive development process. Men may find a safe and effective nonsurgical method of permanent female contraception more acceptable than surgical PC. Copyright © 2015 Elsevier Inc. All rights reserved.

Broadband 0.25-um Gallium Nitride (GaN) Power Amplifier Designs

DTIC Science & Technology

2017-08-14

CP pF RES ID=R1 R=RP Ohm PORT P=1 Z=50 Ohm RP=87.5ohm/mm... CP =-0.31pF/mm For 1.75mm, RP=50ohms, CP =0.54pf CP = 0.31 * size size=1.75 RP = 87.5 / size CAP ID=C1 C=CP1 pF RES ID=R1 R=RP Ohm IND ID=L1 L=LP1 nH CAP...ID=C2 C=Cser2 pF IND ID=L2 L=Lser2 nH IND ID=L3 L=LP1 nH CAP ID=C3 C=CP1 pF PORT P=1 Z=50 Ohm PORT P=2 Z=50 Ohm size=1.75 RP = 87.5 / size CP =

Phosphorus release capacity of soluble P fertilizers and insoluble rock phosphate in response to phosphate solubilizing bacteria and poultry manure and their effect on plant growth promotion and P utilization efficiency of chilli (Capsicum annuum L.)

NASA Astrophysics Data System (ADS)

Abbasi, M. K.; Musa, N.; Manzoor, M.

2015-01-01

The ability of soil microorganisms and organic manures to convert insoluble phosphorus (P) to an accessible form offers a biological rescue system for improving P solubilization and utilization in soil-plant systems. Our objective was to examine the P supplying capacity of soluble P fertilizers (SPF) i.e. single super phosphate (SSP) and di-ammonium phosphate (DAP) and insoluble rock phosphate (RP) after adding phosphate solubilizing bacteria (PSB) and poultry manure (PM) and their subsequent effect on the growth, yield and P-utilization efficiency (PUE) of chill (Capsicum annuum L.). An incubation study was carried-out on a sandy loam neutral soil with twelve treatments including T0: control; T1: RP; T2: SSP; T3: DAP; T4: PM; T5: 1/2 RP + 1/2 SSP; T6: 1/2 RP + 1/2 DAP; T7: 1/2 RP + 1/2 PM; T8: RP + PSB; T9: 1/2 RP + 1/2 SSP + PSB; T10: 1/2 RP + 1/2 DAP + PSB; T11: 1/2 RP + 1/2 PM + PSB. Phosphorus release capacity of added amendments was measured by analyzing extractable P from the amended soil incubated under controlled condition at 25 °C for 0, 5, 15, 25, 35, 60 days period. To complement the incubation study, a greenhouse experiment was conducted in pots with chilli (Capsicum annuum L.) used as a test crop. Growth, yield, P-uptake and PUE of the chilli was determined during the study. Results indicated that P release capacity of soil amended with RP varied between 6.0 and 11.5 mg kg-1 while the soluble P fertilizers i.e. SSP and DAP displayed a maximum of 73 and 68 mg P kg-1 at the start of the experiment (day 0). However, the P released tendency from SSP and DAP declined during incubation and at the end 82 and 79% of P initially present had been lost from the mineral pool. Integrated use of PSB and PM with RP in 1/2 RP + 1/2 PM + PSB treatment stimulated P mineralization by releasing a maximum of 25 mg P kg-1 that was maintained at high levels without any loss. Application of PSB tended to decrease pH showing an acidifying effect on soil. In the greenhouse experiment, RP alone or RP + PSB was not able to generate any significant impact on plant while DAP displayed the superiority over the remaining treatments. Combined use of RP, PM and PSB in 1/2 RP + 1/2 PM + PSB resulted in the growth, yield and P-uptake of chilli comparative/equivalent to that recorded under DAP. The PUE of applied P varied between 4-29% and higher in the treatments supplemented with PSB compared to those without PSB. These results suggest that use of PSB and PM with insoluble RP or with soluble P fertilizers could be a promising management strategy and viable technology to utilize both low-grade RP and SPF or PM efficiently for crop production and nutrient improvement in our cropping systems.

Cardiovascular disease risk factors and socioeconomic variables in a nation undergoing epidemiologic transition.

PubMed

Rasiah, Rajah; Yusoff, Khalid; Mohammadreza, Amiri; Manikam, Rishya; Tumin, Makmor; Chandrasekaran, Sankara Kumar; Khademi, Shabnam; Bakar, Najmin Abu

2013-09-25

Cardiovascular disease (CVD) related deaths is not only the prime cause of mortality in the world, it has also continued to increase in the low and middle income countries. Hence, this study examines the relationship between CVD risk factors and socioeconomic variables in Malaysia, which is a rapidly growing middle income nation undergoing epidemiologic transition. Using data from 11,959 adults aged 30 years and above, and living in urban and rural areas between 2007 and 2010, this study attempts to examine the prevalence of CVD risk factors, and the association between these factors, and socioeconomic and demographic variables in Malaysia. The socioeconomic and demographic, and anthropometric data was obtained with blood pressure and fasting venous blood for glucose and lipids through a community-based survey. The association between CVD risk factors, and education and income was mixed. There was a negative association between smoking and hypertension, and education and income. The association between diabetes, hypercholesterolemia and being overweight with education and income was not clear. More men than women smoked in all education and income groups. The remaining consistent results show that the relationship between smoking, and education and income was obvious and inverse among Malays, others, rural women, Western Peninsular Malaysia (WPM) and Eastern Peninsular Malaysia (EPM). Urban men showed higher prevalence of being overweight than rural men in all education and income categories. Except for those with no education more rural men smoked than urban men. Also, Malay men in all education and income categories showed the highest prevalence of smoking among the ethnic groups. The association between CVD risk factors and socioeconomic variables should be considered when formulating programmes to reduce morbidity and mortality rates in low and middle income countries. While general awareness programmes should be targeted at all, specific ones should be focused on vulnerable groups, such as, men and rural inhabitants for smoking, Malays for hypertension and hypercholesterolemia, and Indians and Malays, and respondents from EPM for diabetes.

Sex-related differences in coronary revascularization practices: the perspective from a Canadian queue management project.

PubMed

Naylor, C D; Levinton, C M

1993-10-01

To assess sex-related differences in coronary revascularization practices in a Canadian setting. Prospective analytic cohort study. Regional referral office in Toronto. A selected but consecutive group of 131 women and 440 men referred by cardiologists for revascularization procedures between Jan. 3, 1989, and June 30, 1991. Coronary artery bypass grafting (CABG) or percutaneous transluminal coronary angioplasty (PTCA). Nurse-coordinators placed the referral with a surgeon or interventional cardiologist at one of three hospitals, who then communicated directly with the referring cardiologist. Symptom status at referral, procedures requested and performed, and time from referral to procedure. Although the women were more likely than the men to have unstable angina at the time of referral (odds ratio [OR] 2.28, 95% confidence interval [CI] 1.38 to 3.79, p = 0.0006), more women than men (16.8% v. 12.1%) were turned down for a procedure. Significant sex-related differences in practice patterns (p < 0.001) persisted after controlling for age or for the referring cardiologists' perception of expected procedural risk. A stepwise multivariate model showed that anatomy was the main determinant of case management; sex was the only other significant variable (p = 0.016). The referring physicians requested CABG more often for men than for women (p = 0.009), and the men accepted for a procedure were much more likely to undergo CABG than the women (OR 2.40, CI 1.47 to 3.93, p = 0.0002). Although the women undergoing CABG waited shorter periods than the men (p = 0.0035), this difference was attributable to their more severe symptoms. In this selected group women had more serious symptoms before referral but were turned down for revascularization more often than men. Reduced use of CABG rather than PTCA largely accounted for the sex-related differences in revascularization. Once accepted for a procedure women had shorter waiting times, which was appropriate given their more severe symptoms.

Psychosocial impact of undergoing prostate cancer screening for men with BRCA1 or BRCA2 mutations.

PubMed

Bancroft, Elizabeth K; Saya, Sibel; Page, Elizabeth C; Myhill, Kathryn; Thomas, Sarah; Pope, Jennifer; Chamberlain, Anthony; Hart, Rachel; Glover, Wayne; Cook, Jackie; Rosario, Derek J; Helfand, Brian T; Hutten Selkirk, Christina; Davidson, Rosemarie; Longmuir, Mark; Eccles, Diana M; Gadea, Neus; Brewer, Carole; Barwell, Julian; Salinas, Monica; Greenhalgh, Lynn; Tischkowitz, Marc; Henderson, Alex; Evans, David Gareth; Buys, Saundra S; Eeles, Rosalind A; Aaronson, Neil K

2018-05-26

To report the baseline results of a longitudinal psychosocial study that forms part of the IMPACT study, a multi-national investigation of targeted prostate cancer (PCa) screening among men with a known pathogenic germline mutation in the BRCA1 or BRCA2 genes. Men enrolled in the IMPACT study were invited to complete a questionnaire at collaborating sites prior to each annual screening visit. The questionnaire included sociodemographic characteristics and the following measures: the Hospital Anxiety and Depression Scale (HADS), Impact of Event Scale (IES), 36-item short-form health survey (SF-36), Memorial Anxiety Scale for Prostate Cancer, Cancer Worry Scale-Revised, risk perception and knowledge. The results of the baseline questionnaire are presented. A total of 432 men completed questionnaires: 98 and 160 had mutations in BRCA1 and BRCA2 genes, respectively, and 174 were controls (familial mutation negative). Participants' perception of PCa risk was influenced by genetic status. Knowledge levels were high and unrelated to genetic status. Mean scores for the HADS and SF-36 were within reported general population norms and mean IES scores were within normal range. IES mean intrusion and avoidance scores were significantly higher in BRCA1/BRCA2 carriers than in controls and were higher in men with increased PCa risk perception. At the multivariate level, risk perception contributed more significantly to variance in IES scores than genetic status. This is the first study to report the psychosocial profile of men with BRCA1/BRCA2 mutations undergoing PCa screening. No clinically concerning levels of general or cancer-specific distress or poor quality of life were detected in the cohort as a whole. A small subset of participants reported higher levels of distress, suggesting the need for healthcare professionals offering PCa screening to identify these risk factors and offer additional information and support to men seeking PCa screening. © 2018 The Authors BJU International published by John Wiley & Sons Ltd on behalf of BJU International.

Gender, TIMI risk score and in-hospital mortality in STEMI patients undergoing primary PCI: results from the Belgian STEMI registry.

PubMed

Gevaert, Sofie A; De Bacquer, Dirk; Evrard, Patrick; Convens, Carl; Dubois, Philippe; Boland, Jean; Renard, Marc; Beauloye, Christophe; Coussement, Patrick; De Raedt, Herbert; de Meester, Antoine; Vandecasteele, Els; Vranckx, Pascal; Sinnaeve, Peter R; Claeys, Marc J

2014-01-22

The relationship between the predictive performance of the TIMI risk score for STEMI and gender has not been evaluated in the setting of primary PCI (pPCI). Here, we compared in-hospital mortality and predictive performance of the TIMI risk score between Belgian women and men undergoing pPCI. In-hospital mortality was analysed in 8,073 (1,920 [23.8%] female and 6,153 [76.2%] male patients) consecutive pPCI-treated STEMI patients, included in the prospective, observational Belgian STEMI registry (January 2007 to February 2011). A multivariable logistic regression model, including TIMI risk score variables and gender, evaluated differences in in-hospital mortality between men and women. The predictive performance of the TIMI risk score according to gender was evaluated in terms of discrimination and calibration. Mortality rates for TIMI scores in women and men were compared. Female patients were older, had more comorbidities and longer ischaemic times. Crude in-hospital mortality was 10.1% in women vs. 4.9% in men (OR 2.2; 95% CI: 1.82-2.66, p<0.001). When adjusting for TIMI risk score variables, mortality remained higher in women (OR 1.47, 95% CI: 1.15-1.87, p=0.002). The TIMI risk score provided a good predictive discrimination and calibration in women as well as in men (c-statistic=0.84 [95% CI: 0.809-0.866], goodness-of-fit p=0.53 and c-statistic=0.89 [95% CI: 0.873-0.907], goodness-of-fit p=0.13, respectively), but mortality prediction for TIMI scores was better in men (p=0.02 for TIMI score x gender interaction). In the Belgian STEMI registry, pPCI-treated women had a higher in-hospital mortality rate even after correcting for TIMI risk score variables. The TIMI risk score was effective in predicting in-hospital mortality but performed slightly better in men. The database was registered with clinicaltrials.gov (NCT00727623).

Prostate-specific antigen (PSA) testing of men in UK general practice: a 10-year longitudinal cohort study

PubMed Central

Young, Grace J; Harrison, Sean; Turner, Emma L; Walsh, Eleanor I; Oliver, Steven E; Ben-Shlomo, Yoav; Evans, Simon; Lane, J Athene; Neal, David E; Hamdy, Freddie C; Donovan, Jenny L; Martin, Richard M; Metcalfe, Chris

2017-01-01

Objectives Cross-sectional studies suggest that around 6% of men undergo prostate-specific antigen (PSA) testing each year in UK general practice (GP). This longitudinal study aims to determine the cumulative testing pattern of men over a 10-year period and whether this testing can be considered equivalent to screening for prostate cancer (PCa). Setting, participants and outcome measures Patient-level data on PSA tests, biopsies and PCa diagnoses were obtained from the UK Clinical Practice Research Datalink (CPRD) for the years 2002 to 2011. The cumulative risks of PSA testing and of being diagnosed with PCa were estimated for the 10-year study period. Associations of a man’s age, region and index of multiple deprivation with the cumulative risk of PSA testing and PCa diagnosis were investigated. Rates of biopsy and diagnosis, following a high test result, were compared with those from the programme of PSA testing in the Prostate Testing for Cancer and Treatment (ProtecT) study. Results The 10-year risk of exposure to at least one PSA test in men aged 45 to 69 years in UK GP was 39.2% (95% CI 39.0 to 39.4%). The age-specific risks ranged from 25.2% for men aged 45–49 years to 53.0% for men aged 65–69 years (p for trend <0.001). For those with a PSA level ≥3, a test in UK GP was less likely to result in a biopsy (6%) and/or diagnosis of PCa (15%) compared with ProtecT study participants (85% and 34%, respectively). Conclusion A high proportion of men aged 45–69 years undergo PSA tests in UK GP: 39% over a 10-year period. A high proportion of these tests appear to be for the investigation of lower urinary tract symptoms and not screening for PCa. Trial registration number ISRCTN20141297, NCT02044172. PMID:29084797

Early weight loss predicts the reduction of obesity in men with erectile dysfunction and hypogonadism undergoing long-term testosterone replacement therapy.

PubMed

Salman, Mahmoud; Yassin, Dany-Jan; Shoukfeh, Huda; Nettleship, Joanne Elisabeth; Yassin, Aksam

2017-03-01

We and others have previously shown that testosterone replacement therapy (TRT) results in sustained weight loss in the majority of middle-aged hypogonadal men. Previously, however, a small proportion failed to lose at least 5% of their baseline weight. The reason for this is not yet understood. In the present study, we sought to identify early indicators that may predict successful long-term weight loss, defined as a reduction of at least 5% of total body weight relative to baseline weight (T0), in men with hypogonadism undergoing TRT. Eight parameters measured were assessed as potential predictors of sustained weight loss: loss of 3% or more of baseline weight after 1 year of TU treatment, severe hypogonadism, BMI, waist circumference, International Prostate Symptom Score (IPSS), glycated hemoglobin (HbA 1C ), age and use of vardenafil. Among the eight measured parameters, three factors were significantly associated with sustained weight loss over the entire period of TU treatment: (1) a loss of 3% of the baseline body weight after 1 year of TRT; (2) baseline BMI over 30; and (3) a waist circumference >102 cm. Age was not a predictor of weight loss.

Modification of the SHABERTH bearing code to incorporate RP-1 and a discussion of the traction model

NASA Technical Reports Server (NTRS)

Woods, Claudia M.

1990-01-01

Recently developed traction data for Rocket Propellant 1 (RP-1), a hydrocarbon fuel of the kerosene family, was used to develop the parameters needed by the bearing code SHABERTH in order to include RP-1 as a lubricant choice. The procedure for inputting data for a new lubricant choice is reviewed, and the theoretical fluid traction model is discussed. Comparisons are made between experimental traction data and those predicted by SHABERTH for RP-1. All data needed to modify SHABERTH for use with RP-1 as a lubricant are specified.

The effect of reproductive performance on the dairy cattle herd value assessed by integrating a daily dynamic programming model with a daily Markov chain model.

PubMed

Kalantari, A S; Cabrera, V E

2012-10-01

The objective of this study was to determine the effect of reproductive performance on dairy cattle herd value. Herd value was defined as the herd's average retention payoff (RPO). Individual cow RPO is the expected profit from keeping the cow compared with immediate replacement. First, a daily dynamic programming model was developed to calculate the RPO of all cow states in a herd. Second, a daily Markov chain model was applied to estimate the herd demographics. Finally, the herd value was calculated by aggregating the RPO of all cows in the herd. Cow states were described by 5 milk yield classes (76, 88, 100, 112, and 124% with respect to the average), 9 lactations, 750 d in milk, and 282 d in pregnancy. Five different reproductive programs were studied (RP1 to RP5). Reproductive program 1 used 100% timed artificial insemination (TAI; 42% conception rate for first TAI and 30% for second and later services) and the other programs combined TAI with estrus detection. The proportion of cows receiving artificial insemination after estrus detection ranged from 30 to 80%, and conception rate ranged from 25 to 35%. These 5 reproductive programs were categorized according to their 21-d pregnancy rate (21-d PR), which is an indication of the rate that eligible cows become pregnant every 21 d. The 21-d PR was 17% for RP1, 14% for RP2, 16% for RP3, 18% for RP4, and 20% for RP5. Results showed a positive relationship between 21-d PR and herd value. The most extreme herd value difference between 2 reproductive programs was $77/cow per yr for average milk yield (RP5 - RP2), $13/cow per yr for lowest milk yield (RP5 - RP1), and $160/cow per yr for highest milk yield (RP5 - RP2). Reproductive programs were ranked based on their calculated herd value. With the exception of the best reproductive program (RP5), all other programs showed some level of ranking change according to milk yield. The most dramatic ranking change was observed in RP1, which moved from being the worst ranked for lowest milk yield to the second ranked for highest milk yield. Within a reproductive program, RPO changed based on the stage of lactation at pregnancy. Cows getting pregnant in the early stage of a lactation had higher RPO compared with getting pregnant later in the lactation. However, the RPO at calving was similar for early and late lactation pregnancies. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Effects of recreational soccer in men with prostate cancer undergoing androgen deprivation therapy: study protocol for the ‘FC Prostate’ randomized controlled trial

PubMed Central

2013-01-01

Background Androgen deprivation therapy (ADT) is a cornerstone in the treatment of advanced prostate cancer. Adverse musculoskeletal and cardiovascular effects of ADT are widely reported and investigations into the potential of exercise to ameliorate the effects of treatment are warranted. The ‘Football Club (FC) Prostate’ study is a randomized trial comparing the effects of soccer training with standard treatment approaches on body composition, cardiovascular function, physical function parameters, glucose tolerance, bone health, and patient-reported outcomes in men undergoing ADT for prostate cancer. Methods/Design Using a single-center randomized controlled design, 80 men with histologically confirmed locally advanced or disseminated prostate cancer undergoing ADT for 6 months or more at The Copenhagen University Hospital will be enrolled on this trial. After baseline assessments eligible participants will be randomly assigned to a soccer training group or a control group receiving usual care. The soccer intervention will consist of 12 weeks of training 2–3 times/week for 45–60 min after which the assessment protocol will be repeated. Soccer training will then continue bi-weekly for an additional 20 weeks at the end of which all measures will be repeated to allow for additional analyses of long-term effects. The primary endpoint is changes in lean body mass from baseline to 12 weeks assessed by dual X-ray absorptiometry scan. Secondary endpoints include changes of cardiovascular, metabolic, and physical function parameters, as well as markers of bone metabolism and patient-reported outcomes. Discussion The FC Prostate trial will assess the safety and efficacy of a novel soccer-training approach to cancer rehabilitation on a number of clinically important health outcomes in men with advanced prostate cancer during ADT. The results may pave the way for innovative, community-based interventions in the approach to treating prostate cancer. Trial registration ClinicalTrials.gov: NCT01711892 PMID:24330570

Effect of sex difference in clinical presentation (stable coronary artery disease vs unstable angina pectoris or non-ST-elevation myocardial infarction vs ST-elevation myocardial infarction) on 2-year outcomes in patients undergoing percutaneous coronary intervention.

PubMed

Tang, Xiao-Fang; Song, Ying; Xu, Jing-Jing; Ma, Yuan-Liang; Zhang, Jia-Hui; Yao, Yi; He, Chen; Wang, Huan-Huan; Jiang, Ping; Jiang, Lin; Liu, Ru; Gao, Zhan; Zhao, Xue-Yan; Qiao, Shu-Bin; Xu, Bo; Yang, Yue-Jin; Gao, Run-Lin; Yuan, Jin-Qing

2018-02-01

To determine whether there is a difference in 2-year prognosis among patients across the spectrum of coronary artery disease undergoing percutaneous coronary intervention (PCI). We analyzed all consecutive patients undergoing PCI at a single center from 1/1-12/31/2013. Clinical presentations were compared between sexes according to baseline clinical, angiographic, and procedural characteristics and 2-year (mean 730 ± 30-day) outcomes. We grouped 10 724 consecutive patients based on sex and clinical presentation. Among patients with ST-elevation myocardial infarction (STEMI), rates of all-cause death (6.7% vs 1.4%) and cardiac death (3.8% vs 1.1%) were significantly higher in women than in men (P < 0.05), but these rates did not differ between men and women with stable coronary artery disease (SCAD) and non-ST-elevation acute coronary syndrome ((NSTE-ACS). Incidence of major bleeding was greater than in men only in those women presenting with ACS. After multivariable adjustment, female sex was not an independent predictor of outcomes in STEMI (hazard ratio [HR] for all-cause death: 1.33, 95% confidence interval [CI]:0.52-3.38; P = 0.55; HR for cardiac death: 0.69, 95%CI: 0.23-2.09, P = 0.51], but was still an independent predictor of bleeding in STEMI (HR: 3.53, 95%CI: 1.26-9.91, P = 0.017). Among STEMI patients, women had worse 2-year mortality after PCI therapy, but female sex was not an independent predictor of mortality after adjustment for baseline characteristics. In STEMI patients, women were at higher bleeding risk than men after PCI, even after multivariable adjustment. © 2017, Wiley Periodicals, Inc.

Smoking and primary total hip or knee replacement due to osteoarthritis in 54,288 elderly men and women.

PubMed

Mnatzaganian, George; Ryan, Philip; Reid, Christopher M; Davidson, David C; Hiller, Janet E

2013-09-05

The reported association of smoking with risk of undergoing a total joint replacement (TJR) due to osteoarthritis (OA) is not consistent. We evaluated the independent association between smoking and primary TJR in a large cohort. The electronic records of 54,288 men and women, who were initially recruited for the Second Australian National Blood Pressure study, were linked to the Australian Orthopaedic Association National Joint Replacement Registry to detect total hip replacement (THR) or total knee replacement (TKR) due to osteoarthritis. Competing risk regressions that accounted for the competing risk of death estimated the subhazard ratios for TJR. One-way and probabilistic sensitivity analyses were undertaken to represent uncertainty in the classification of smoking exposure and socioeconomic disadvantage scores. An independent inverse association was found between smoking and risk of THR and TKR observed in both men and women. Compared to non-smokers, male and female smokers were respectively 40% and 30% less likely to undergo a TJR. This significant association persisted after controlling for age, co-morbidities, body mass index (BMI), physical exercise, and socioeconomic disadvantage. The overweight and obese were significantly more likely to undergo TJR compared to those with normal weight. A dose-response relationship between BMI and TJR was observed (P < 0.001). Socioeconomic status was not independently associated with risk of either THR or TKR. The strengths of the inverse association between smoking and TJR, the temporal relationship of the association, together with the consistency in the findings warrant further investigation about the role of smoking in the pathogenesis of osteoarthritis causing TJR.

Inter-ethnic marriages and severity of coronary artery disease: A multicenter study of Arabian Gulf States

PubMed Central

Daoulah, Amin; Al-kaabi, Salem; Lotfi, Amir; Al-Murayeh, Mushabab; Nasseri, S Ali; Ahmed, Waleed; Al-Otaibi, Salah N; Alama, Mohamed N; Elkhateeb, Osama E; Plotkin, Amy J; Malak, Majed M; Alshali, Khalid; Hamzi, Mohamed; Al Khunein, Saleh; Abufayyah, Mohammed; Alsheikh-Ali, Alawi A

2017-01-01

AIM To assess the association of inter-ethnic vs intra-ethnic marriage with severity of coronary artery disease (CAD) in men undergoing angiography. METHODS We conducted a prospective multicenter, multi-ethnic, cross sectional observational study at five hospitals in Saudi Arabia and the United Arab Emirates, in which we used logistic regression analysis with and without adjustment for baseline differences. RESULTS Data were collected for 1068 enrolled patients undergoing coronary angiography for clinical indications during the period of April 1st, 2013 to March 30th, 2014. Ethnicities of spouses were available only for male patients. Of those enrolled, 687 were married men and constituted the cohort for the present analysis. Intra-ethnic marriages were reported in 70% and inter-ethnic marriages in 30%. After adjusting for baseline differences, inter-ethnic marriage was associated with lower odds of having significant CAD [adjusted odds ratio 0.52 (95%CI: 0.33, 0.81)] or multi-vessel disease (MVD) [adjusted odds ratio 0.57 (95%CI: 0.37, 0.86)]. The adjusted association with left main disease showed a similar trend, but was not statistically significant [adjusted odds ratio 0.74 (95%CI: 0.41, 1.32)]. The association between inter-ethnic marriage and the presence of significant CAD and MVD was not modified by number of concurrent wives (P interaction > 0.05 for both). CONCLUSION Among married men undergoing coronary angiography, inter-ethnic, as compared to intra-ethnic, marriage is associated with lower odds of significant CAD and MVD. PMID:28515856

New COL6A6 variant detected by whole-exome sequencing is linked to break points in intron 4 and 3′-UTR, deleting exon 5 of RHO, and causing adRP

PubMed Central

de Sousa Dias, Miguel; Hernan, Imma; Delás, Barbara; Pascual, Beatriz; Borràs, Emma; Gamundi, Maria José; Mañé, Begoña; Fernández-San José, Patricia; Ayuso, Carmen

2015-01-01

Purpose This study aimed to test a newly devised cost-effective multiplex PCR assay for the molecular diagnosis of autosomal dominant retinitis pigmentosa (adRP), as well as the use of whole-exome sequencing (WES) to detect disease-causing mutations in adRP. Methods Genomic DNA was extracted from peripheral blood lymphocytes of index patients with adRP and their affected and unaffected family members. We used a newly devised multiplex PCR assay capable of amplifying the genetic loci of RHO, PRPH2, RP1, PRPF3, PRPF8, PRPF31, IMPDH1, NRL, CRX, KLHL7, and NR2E3 to molecularly diagnose 18 index patients with adRP. We also performed WES in affected and unaffected members of four families with adRP in whom a disease-causing mutation was previously not found. Results We identified five previously reported mutations (p.Arg677X in the RP1 gene, p.Asp133Val and p.Arg195Leu in the PRPH2 gene, and p.Pro171Leu and p.Pro215Leu in the RHO gene) and one novel mutation (p.Val345Gly in the RHO gene) representing 33% detection of causative mutations in our adRP cohort. Comparative WES analysis showed a new variant (p.Gly103Arg in the COL6A6 gene) that segregated with the disease in one family with adRP. As this variant was linked with the RHO locus, we sequenced the complete RHO gene, which revealed a deletion in intron 4 that encompassed all of exon 5 and 28 bp of the 3′-untranslated region (UTR). Conclusions The novel multiplex PCR assay with next-generation sequencing (NGS) proved effective for detecting most of the adRP-causing mutations. A WES approach led to identification of a deletion in RHO through detection of a new linked variant in COL6A6. No pathogenic variants were identified in the remaining three families. Moreover, NGS and WES were inefficient for detecting the complete deletion of exon 5 in the RHO gene in one family with adRP. Carriers of this deletion showed variable clinical status, and two of these carriers had not previously been diagnosed with RP. PMID:26321861

Synaptic Activation of Ribosomal Protein S6 Phosphorylation Occurs Locally in Activated Dendritic Domains

ERIC Educational Resources Information Center

Pirbhoy, Patricia Salgado; Farris, Shannon; Steward, Oswald

2016-01-01

Previous studies have shown that induction of long-term potentiation (LTP) induces phosphorylation of ribosomal protein S6 (rpS6) in postsynaptic neurons, but the functional significance of rpS6 phosphorylation is poorly understood. Here, we show that synaptic stimulation that induces perforant path LTP triggers phosphorylation of rpS6 (p-rpS6)…

Updating the reference population to achieve constant genomic prediction reliability across generations.

PubMed

Pszczola, M; Calus, M P L

2016-06-01

The reliability of genomic breeding values (DGV) decays over generations. To keep the DGV reliability at a constant level, the reference population (RP) has to be continuously updated with animals from new generations. Updating RP may be challenging due to economic reasons, especially for novel traits involving expensive phenotyping. Therefore, the goal of this study was to investigate a minimal RP update size to keep the reliability at a constant level across generations. We used a simulated dataset resembling a dairy cattle population. The trait of interest was not included itself in the selection index, but it was affected by selection pressure by being correlated with an index trait that represented the overall breeding goal. The heritability of the index trait was assumed to be 0.25 and for the novel trait the heritability equalled 0.2. The genetic correlation between the two traits was 0.25. The initial RP (n=2000) was composed of cows only with a single observation per animal. Reliability of DGV using the initial RP was computed by evaluating contemporary animals. Thereafter, the RP was used to evaluate animals which were one generation younger from the reference individuals. The drop in the reliability when evaluating younger animals was then assessed and the RP was updated to re-gain the initial reliability. The update animals were contemporaries of evaluated animals (EVA). The RP was updated in batches of 100 animals/update. First, the animals most closely related to the EVA were chosen to update RP. The results showed that, approximately, 600 animals were needed every generation to maintain the DGV reliability at a constant level across generations. The sum of squared relationships between RP and EVA and the sum of off-diagonal coefficients of the inverse of the genomic relationship matrix for RP, separately explained 31% and 34%, respectively, of the variation in the reliability across generations. Combined, these parameters explained 53% of the variation in the reliability across generations. Thus, for an optimal RP update an algorithm considering both relationships between reference and evaluated animals, as well as relationships among reference animals, is required.

Effects of AgRP Inhibition on Energy Balance and Metabolism in Rodent Models

PubMed Central

Dutia, Roxanne; Kim, Andrea J.; Modes, Matthew; Rothlein, Robert; Shen, Jane M.; Tian, Ye Edward; Ihbais, Jumana; Victory, Sam F.; Valcarce, Carmen; Wardlaw, Sharon L.

2013-01-01

Activation of brain melanocortin-4 receptors (MC4-R) by α-melanocyte-stimulating hormone (MSH) or inhibition by agouti-related protein (AgRP) regulates food intake and energy expenditure and can modulate neuroendocrine responses to changes in energy balance. To examine the effects of AgRP inhibition on energy balance, a small molecule, non-peptide compound, TTP2515, developed by TransTech Pharma, Inc., was studied in vitro and in rodent models in vivo. TTP2515 prevented AgRP from antagonizing α-MSH-induced increases in cAMP in HEK 293 cells overexpressing the human MC4-R. When administered to rats by oral gavage TTP2515 blocked icv AgRP-induced increases in food intake, weight gain and adiposity and suppression of T4 levels. In both diet-induced obese (DIO) and leptin-deficient mice, TTP2515 decreased food intake, weight gain, adiposity and respiratory quotient. TTP2515 potently suppressed food intake and weight gain in lean mice immediately after initiation of a high fat diet (HFD) but had no effect on these parameters in lean chow-fed mice. However, when tested in AgRP KO mice, TTP2515 also suppressed food intake and weight gain during HFD feeding. In several studies TTP2515 increased T4 but not T3 levels, however this was also observed in AgRP KO mice. TTP2515 also attenuated refeeding and weight gain after fasting, an effect not evident in AgRP KO mice when administered at moderate doses. This study shows that TTP2515 exerts many effects consistent with AgRP inhibition however experiments in AgRP KO mice indicate some off-target effects of this drug. TTP2515 was particularly effective during fasting and in mice with leptin deficiency, conditions in which AgRP is elevated, as well as during acute and chronic HFD feeding. Thus the usefulness of this drug in treating obesity deserves further exploration, to define the AgRP dependent and independent mechanisms by which TTP2515 exerts its effects on energy balance. PMID:23762342

RP5063, an atypical antipsychotic drug with a unique pharmacologic profile, improves declarative memory and psychosis in mouse models of schizophrenia.

PubMed

Rajagopal, Lakshmi; Kwon, Sunoh; Huang, Mei; Michael, Eric; Bhat, Laxminarayan; Cantillon, Marc; Meltzer, Herbert Y

2017-08-14

Various types of atypical antipsychotic drugs (AAPDs) modestly improve the cognitive impairment associated with schizophrenia (CIAS). RP5063 is an AAPD with a diverse and unique pharmacology, including partial agonism at dopamine (DA) D 2 , D 3 , D 4 , serotonin (5-HT) 1A , and 5-HT 2A receptors (Rs), full agonism at α 4 β 2 nicotinic acetylcholine (ACh)R (nAChR), and antagonism at 5-HT 2B , 5-HT 6 , and 5-HT 7 Rs. Most atypical APDs are 5-HT 2A inverse agonists. The efficacy of RP5063 in mouse models of psychosis and episodic memory were studied. RP5063 blocked acute phencyclidine (PCP)-as well as amphetamine-induced hyperactivity, indicating antipsychotic activity. Acute administration of RP5063 significantly reversed subchronic (sc)PCP-induced impairment in novel object recognition (NOR), a measure of episodic memory, but not reversal learning, a measure of executive function. Co-administration of a sub-effective dose (SED) of RP5063 with SEDs of a 5-HT 7 R antagonist, a 5-HT 1B R antagonist, a 5-HT 2A R inverse agonist, or an α 4 β 2 nAChR agonist, restored the ability of RP5063 to ameliorate the NOR deficit in scPCP mice. Pre-treatment with a 5-HT 1A R, a D 4 R, antagonist, but not an α 4 β 2 nAChR antagonist, blocked the ameliorating effect of RP5063. Further, co-administration of scRP5063 prior to each dose of PCP prevented the effect of PCP to produce a deficit in NOR for one week. RP5063, given to scPCP-treated mice for one week restored NOR for one week only. Acute administration of RP5063 significantly increased cortical DA efflux, which may be critical to some of its cognitive enhancing properties. These results indicate that RP5063, by itself, or as an adjunctive treatment has a multifaceted basis for improving some cognitive deficits associated with schizophrenia. Copyright © 2017. Published by Elsevier B.V.

Molecular cloning and sequence analysis of heat shock proteins 70 (HSP70) and 90 (HSP90) and their expression analysis when exposed to benzo(a)pyrene in the clam Ruditapes philippinarum.

PubMed

Liu, Tong; Pan, Luqing; Cai, Yuefeng; Miao, Jingjing

2015-01-25

HSP70 and HSP90 are the most important heat shock proteins (HSPs), which play the key roles in the cell as molecular chaperones and may involve in metabolic detoxification. The present research has obtained full-length cDNAs of genes HSP70 and HSP90 from the clam Ruditapes philippinarum and studied the transcriptional responses of the two genes when exposed to benzo(a)pyrene (BaP). The full-length RpHSP70 cDNA was 2336bp containing a 5' untranslated region (UTR) of 51bp, a 3' UTR of 335bp and an open reading frame (ORF) of 1950bp encoding 650 amino acid residues. The full-length RpHSP90 cDNA was 2839bp containing a 107-bp 5' UTR, a 554-bp 3' UTR and a 2178-bp ORF encoding 726 amino acid residues. The deduced amino acid sequences of RpHSP70 and RpHSP90 shared the highest identity with the sequences of Paphia undulata, and the phylogenetic trees showed that the evolutions of RpHSP70 and RpHSP90 were almost in accord with the evolution of species. The RpHSP70 and RpHSP90 mRNA expressions were detected in all tested tissues in the adult clams (digestive gland, gill, adductor muscle and mantle) and the highest mRNA expression level was observed in the digestive gland compared to other tissues. Quantitative real-time RT-PCR analysis revealed that mRNA expression levels of the clam RpHSP70, RpHSP90 and other xenobiotic metabolizing enzymes (XMEs) (AhR, DD, GST, GPx) in the digestive gland of R. philippinarum were induced by benzo(a)pyrene (BaP) and the absolute expression levels of these genes showed a temporal and dose-dependent response. The results suggested that RpHSP70 and RpHSP90 were involved in the metabolic detoxification of BaP in the clam R. philippinarum. Copyright © 2014 Elsevier B.V. All rights reserved.

Mutation analysis of pre-mRNA splicing genes in Chinese families with retinitis pigmentosa

PubMed Central

Pan, Xinyuan; Chen, Xue; Liu, Xiaoxing; Gao, Xiang; Kang, Xiaoli; Xu, Qihua; Chen, Xuejuan; Zhao, Kanxing; Zhang, Xiumei; Chu, Qiaomei; Wang, Xiuying

2014-01-01

Purpose Seven genes involved in precursor mRNA (pre-mRNA) splicing have been implicated in autosomal dominant retinitis pigmentosa (adRP). We sought to detect mutations in all seven genes in Chinese families with RP, to characterize the relevant phenotypes, and to evaluate the prevalence of mutations in splicing genes in patients with adRP. Methods Six unrelated families from our adRP cohort (42 families) and two additional families with RP with uncertain inheritance mode were clinically characterized in the present study. Targeted sequence capture with next-generation massively parallel sequencing (NGS) was performed to screen mutations in 189 genes including all seven pre-mRNA splicing genes associated with adRP. Variants detected with NGS were filtered with bioinformatics analyses, validated with Sanger sequencing, and prioritized with pathogenicity analysis. Results Mutations in pre-mRNA splicing genes were identified in three individual families including one novel frameshift mutation in PRPF31 (p.Leu366fs*1) and two known mutations in SNRNP200 (p.Arg681His and p.Ser1087Leu). The patients carrying SNRNP200 p.R681H showed rapid disease progression, and the family carrying p.S1087L presented earlier onset ages and more severe phenotypes compared to another previously reported family with p.S1087L. In five other families, we identified mutations in other RP-related genes, including RP1 p. Ser781* (novel), RP2 p.Gln65* (novel) and p.Ile137del (novel), IMPDH1 p.Asp311Asn (recurrent), and RHO p.Pro347Leu (recurrent). Conclusions Mutations in splicing genes identified in the present and our previous study account for 9.5% in our adRP cohort, indicating the important role of pre-mRNA splicing deficiency in the etiology of adRP. Mutations in the same splicing gene, or even the same mutation, could correlate with different phenotypic severities, complicating the genotype–phenotype correlation and clinical prognosis. PMID:24940031

Feasibility and potential utility of multicomponent exhaled breath analysis for predicting development of radiation pneumonitis after stereotactic ablative radiotherapy.

PubMed

Moré, Jayaji M; Eclov, Neville C W; Chung, Melody P; Wynne, Jacob F; Shorter, Joanne H; Nelson, David D; Hanlon, Alexandra L; Burmeister, Robert; Banos, Peter; Maxim, Peter G; Loo, Billy W; Diehn, Maximilian

2014-07-01

In this prospective pilot study, we evaluated the feasibility and potential utility of measuring multiple exhaled gases as biomarkers of radiation pneumonitis (RP) in patients receiving stereotactic ablative radiotherapy (SABR) for lung tumors. Breath analysis was performed for 26 patients receiving SABR for lung tumors. Concentrations of exhaled nitric oxide (eNO), carbon monoxide (eCO), nitrous oxide (eN2O), and carbon dioxide (eCO2) were measured before and immediately after each fraction using real-time, infrared laser spectroscopy. RP development (CTCAE grade ≥2) was correlated with baseline gas concentrations, acute changes in gas concentrations after each SABR fraction, and dosimetric parameters. Exhaled breath analysis was successfully completed in 77% of patients. Five of 20 evaluable patients developed RP at a mean of 5.4 months after SABR. Acute changes in eNO and eCO concentrations, defined as percent changes between each pre-fraction and post-fraction measurement, were significantly smaller in RP versus non-RP cases (p = 0.022 and 0.015, respectively). In an exploratory analysis, a combined predictor of baseline eNO greater than 24 parts per billion and acute decrease in eCO less than 5.5% strongly correlated with RP incidence (p =0.0099). Neither eN2O nor eCO2 concentrations were significantly associated with RP development. Although generally higher in patients destined to develop RP, dosimetric parameters were not significantly associated with RP development. The majority of SABR patients in this pilot study were able to complete exhaled breath analysis. Baseline concentrations and acute changes in concentrations of exhaled breath components were associated with RP development after SABR. If our findings are validated, exhaled breath analysis may become a useful approach for noninvasive identification of patients at highest risk for developing RP after SABR.

A pipeline of spatio-temporal filtering for predicting the laterality of self-initiated fine movements from single trial readiness potentials.

PubMed

Zeid, Elias Abou; Sereshkeh, Alborz Rezazadeh; Chau, Tom

2016-12-01

In recent years, the readiness potential (RP), a type of pre-movement neural activity, has been investigated for asynchronous electroencephalogram (EEG)-based brain-computer interfaces (BCIs). Since the RP is attenuated for involuntary movements, a BCI driven by RP alone could facilitate intentional control amid a plethora of unintentional movements. Previous studies have attempted single trial classification of RP via spatial and temporal filtering methods, or by combining the RP with event-related desynchronization. However, RP feature extraction remains challenging due to the slow non-oscillatory nature of the potential, its variability among participants and the inherent noise in EEG signals. Here, we propose a participant-specific, individually optimized pipeline of spatio-temporal filtering (PSTF) to improve RP feature extraction for laterality prediction. PSTF applies band-pass filtering on RP signals, followed by Fisher criterion spatial filtering to maximize class separation, and finally temporal window averaging for feature dimension reduction. Optimal parameters are simultaneously found by cross-validation for each participant. Using EEG data from 14 participants performing self-initiated left or right key presses as well as two benchmark BCI datasets, we compared the performance of PSTF to two popular methods: common spatial subspace decomposition, and adaptive spatio-temporal filtering. On the BCI benchmark data sets, PSTF performed comparably to both existing methods. With the key press EEG data, PSTF extracted more discriminative features, thereby leading to more accurate (74.99% average accuracy) predictions of RP laterality than that achievable with existing methods. Naturalistic and volitional interaction with the world is an important capacity that is lost with traditional system-paced BCIs. We demonstrated a significant improvement in fine movement laterality prediction from RP features alone. Our work supports further study of RP-based BCI for intuitive asynchronous control of the environment, such as augmentative communication or wheelchair navigation.

A pipeline of spatio-temporal filtering for predicting the laterality of self-initiated fine movements from single trial readiness potentials

NASA Astrophysics Data System (ADS)

Abou Zeid, Elias; Rezazadeh Sereshkeh, Alborz; Chau, Tom

2016-12-01

Objective. In recent years, the readiness potential (RP), a type of pre-movement neural activity, has been investigated for asynchronous electroencephalogram (EEG)-based brain-computer interfaces (BCIs). Since the RP is attenuated for involuntary movements, a BCI driven by RP alone could facilitate intentional control amid a plethora of unintentional movements. Previous studies have attempted single trial classification of RP via spatial and temporal filtering methods, or by combining the RP with event-related desynchronization. However, RP feature extraction remains challenging due to the slow non-oscillatory nature of the potential, its variability among participants and the inherent noise in EEG signals. Here, we propose a participant-specific, individually optimized pipeline of spatio-temporal filtering (PSTF) to improve RP feature extraction for laterality prediction. Approach. PSTF applies band-pass filtering on RP signals, followed by Fisher criterion spatial filtering to maximize class separation, and finally temporal window averaging for feature dimension reduction. Optimal parameters are simultaneously found by cross-validation for each participant. Using EEG data from 14 participants performing self-initiated left or right key presses as well as two benchmark BCI datasets, we compared the performance of PSTF to two popular methods: common spatial subspace decomposition, and adaptive spatio-temporal filtering. Main results. On the BCI benchmark data sets, PSTF performed comparably to both existing methods. With the key press EEG data, PSTF extracted more discriminative features, thereby leading to more accurate (74.99% average accuracy) predictions of RP laterality than that achievable with existing methods. Significance. Naturalistic and volitional interaction with the world is an important capacity that is lost with traditional system-paced BCIs. We demonstrated a significant improvement in fine movement laterality prediction from RP features alone. Our work supports further study of RP-based BCI for intuitive asynchronous control of the environment, such as augmentative communication or wheelchair navigation.

The mitochondrial SIR2 related protein 2 (SIR2RP2) impacts Leishmania donovani growth and infectivity

PubMed Central

Mittal, Nimisha; Muthuswami, Rohini

2017-01-01

Background Leishmania donovani, a protozoan parasite is the major causative agent of visceral leishmaniasis. Increased toxicity and resistance to the existing repertoire of drugs has been reported. Hence, an urgent need exists for identifying newer drugs and drug targets. Previous reports have shown sirtuins (Silent Information Regulator) from kinetoplastids as promising drug targets. Leishmania species code for three SIR2 (Silent Information Regulator) related proteins. Here, we for the first time report the functional characterization of SIR2 related protein 2 (SIR2RP2) of L. donovani. Methodology Recombinant L. donovani SIR2RP2 was expressed in E. coli and purified. The enzymatic functions of SIR2RP2 were determined. The subcellular localization of LdSIR2RP2 was done by constructing C-terminal GFP-tagged full-length LdSIR2RP2. Deletion mutants of LdSIR2RP2 were generated in Leishmania by double targeted gene replacement methodology. These null mutants were tested for their proliferation, virulence, cell cycle defects, mitochondrial functioning and sensitivity to known SIR2 inhibitors. Conclusion Our data suggests that LdSIR2RP2 possesses NAD+-dependent ADP-ribosyltransferase activity. However, NAD+-dependent deacetylase and desuccinylase activities were not detected. The protein localises to the mitochondrion of the promastigotes. Gene deletion studies showed that ΔLdSIR2RP2 null mutants had restrictive growth phenotype associated with accumulation of cells in the G2/M phase and compromised mitochondrial functioning. The null mutants had attenuated infectivity. Deletion of LdSIR2RP2 resulted in increased sensitivity of the parasites to the known SIR2 inhibitors. The sirtuin inhibitors inhibited the ADP-ribosyltransferase activity of recombinant LdSIR2RP2. In conclusion, sirtuins could be used as potential new drug targets for visceral leishmaniasis. PMID:28493888

Transforming growth factor-beta-1 is a serum biomarker of radiation-induced pneumonitis in esophageal cancer patients treated with thoracic radiotherapy: preliminary results of a prospective study.

PubMed

Li, Jingxia; Mu, Shuangfeng; Mu, Lixiang; Zhang, Xiaohui; Pang, Ranran; Gao, Shegan

2015-01-01

To examine the relationship between cytokine levels of transforming growth factor-beta-1 (TGF-β1), interleukin-1 beta (IL-1β), and angiotensin-converting enzyme (ACE) in the plasma of esophageal carcinoma patients and radiation-induced pneumonitis (RP). Sixty-three patients with esophageal carcinoma were treated with three-dimensional conformal radiotherapy (RT) using the Elekta Precise treatment planning system with a prescribed dose of 50-70 Gy. Dose-volume histograms were collected from three-dimensional conformal RT to determine the volume percentage of the lung received V5, V10, V20, and the normal tissue complication probability. RP was diagnosed based on computed tomography imaging, respiratory symptoms, and signs. The severity of radiation-induced lung toxicity was determined using the Lent-Soma scale defined by the Radiation Therapy Oncology Group. Plasma samples obtained before RT, during RT (at 40 Gy), and at 1 day, 1 month, and 3 months after RT were assayed for TGF-β1, IL-1β, and ACE levels by enzyme-linked immunosorbent assay. From the 63 patients, 17 (27%) developed RP, and 13 (21%) had RP of grade I and four (6%) had grade II or higher. We found plasma TGF-β1 levels were elevated in the patients that had RP when compared with the other 46 patients who did not have RP. The plasma IL-1β levels were not changed. The ACE levels were significantly lower in the 17 patients with RP compared to the 46 patients without RP throughout the RT. As expected, RP is associated with a higher dose of irradiation (>60 Gy); no other factors, including dose-volume histogram, age, sex, smoking status, location of tumor, and methods of treatment, are associated with RP. Elevated plasma TGF-β1 levels can be used as a marker for RP.

Isolation, purification and characterisation of selenium-containing polysaccharides and proteins in selenium-enriched Radix puerariae.

PubMed

Zou, Ye; Zhao, Ting; Mao, Guanghua; Zhang, Min; Zheng, Daheng; Feng, Weiwei; Wang, Wei; Wu, Xiangyang; Yang, Liuqing

2014-01-30

Selenium (Se) is an essential dietary mineral and Radix puerariae (RP) (the dried root of Pueraria lobata Willd.) is a botanical supplement widely used as a nutraceutical. Food enriched with Se provides a feasible and economic approach for production of organic Se compounds. However, little is known about Se-enriched RP and the structure of Se-containing polysaccharides and proteins derived from Se-enriched RP. The organic form of Se accounted for 82.42% of total content. Purification by DEAE-52 and Sephadex G-100 column chromatography yielded three single fractions--RP-SeP-11, RP-SeP-22 and RP-SeP-33--with Se contents of 0.9562 × 10⁻³, 0.6113 × 10⁻³ and 0.3827 × 10⁻³ g kg⁻¹, respectively. RP-SeP-11 (3.5 kDa) was made of glucose, RP-SeP-22 (19.6 kDa) was composed of xylose and glucose, and RP-SeP-33 (97.9 kDa) was made up galactose, mannose and glucose. Two Se-containing proteins were obtained with Se content of 3.175 × 10⁻³ and 4.328 × 10⁻³ g kg⁻¹, respectively. One appeared as three subunits with molecular masses of 43.0, 29.0 and 17.8 kDa while the other appeared as two subunits with molecular masses of 43.0 and 26.3 kDa. The results provide a basis for promoting the utilisation of RP resources enriched with Se as a promising tool for the food industry and are significant for its contribution to Se biochemistry in plants. © 2013 Society of Chemical Industry.

The efficacy of microarray screening for autosomal recessive retinitis pigmentosa in routine clinical practice

PubMed Central

van Huet, Ramon A. C.; Pierrache, Laurence H.M.; Meester-Smoor, Magda A.; Klaver, Caroline C.W.; van den Born, L. Ingeborgh; Hoyng, Carel B.; de Wijs, Ilse J.; Collin, Rob W. J.; Hoefsloot, Lies H.

2015-01-01

Purpose To determine the efficacy of multiple versions of a commercially available arrayed primer extension (APEX) microarray chip for autosomal recessive retinitis pigmentosa (arRP). Methods We included 250 probands suspected of arRP who were genetically analyzed with the APEX microarray between January 2008 and November 2013. The mode of inheritance had to be autosomal recessive according to the pedigree (including isolated cases). If the microarray identified a heterozygous mutation, we performed Sanger sequencing of exons and exon–intron boundaries of that specific gene. The efficacy of this microarray chip with the additional Sanger sequencing approach was determined by the percentage of patients that received a molecular diagnosis. We also collected data from genetic tests other than the APEX analysis for arRP to provide a detailed description of the molecular diagnoses in our study cohort. Results The APEX microarray chip for arRP identified the molecular diagnosis in 21 (8.5%) of the patients in our cohort. Additional Sanger sequencing yielded a second mutation in 17 patients (6.8%), thereby establishing the molecular diagnosis. In total, 38 patients (15.2%) received a molecular diagnosis after analysis using the microarray and additional Sanger sequencing approach. Further genetic analyses after a negative result of the arRP microarray (n = 107) resulted in a molecular diagnosis of arRP (n = 23), autosomal dominant RP (n = 5), X-linked RP (n = 2), and choroideremia (n = 1). Conclusions The efficacy of the commercially available APEX microarray chips for arRP appears to be low, most likely caused by the limitations of this technique and the genetic and allelic heterogeneity of RP. Diagnostic yields up to 40% have been reported for next-generation sequencing (NGS) techniques that, as expected, thereby outperform targeted APEX analysis. PMID:25999674

Lipopolysacharide Rapidly and Completely Suppresses AgRP Neuron-Mediated Food Intake in Male Mice

PubMed Central

Liu, Yang; Huang, Ying; Liu, Tiemin; Wu, Hua; Cui, Huxing

2016-01-01

Although Agouti-related peptide (AgRP) neurons play a key role in the regulation of food intake, their contribution to the anorexia caused by proinflammatory insults has yet to be identified. Using a combination of neuroanatomical and pharmacogenetics experiments, this study sought to investigate the importance of AgRP neurons and downstream targets in the anorexia caused by the peripheral administration of a moderate dose of lipopolysaccharide (LPS) (100 μg/kg, ip). First, in the C57/Bl6 mouse, we demonstrated that LPS induced c-fos in select AgRP-innervated brain sites involved in feeding but not in any arcuate proopiomelanocortin neurons. Double immunohistochemistry further showed that LPS selectively induced c-Fos in a large subset of melanocortin 4 receptor-expressing neurons in the lateral parabrachial nucleus. Secondly, we used pharmacogenetics to stimulate the activity of AgRP neurons during the course of LPS-induced anorexia. In AgRP-Cre mice expressing the designer receptor hM3Dq-Gq only in AgRP neurons, the administration of the designer drug clozapine-N-oxide (CNO) induced robust food intake. Strikingly, CNO-mediated food intake was rapidly and completely blunted by the coadministration of LPS. Neuroanatomical experiments further indicated that LPS did not interfere with the ability of CNO to stimulate c-Fos in AgRP neurons. In summary, our findings combined together support the view that the stimulation of select AgRP-innervated brain sites and target neurons, rather than the inhibition of AgRP neurons themselves, is likely to contribute to the rapid suppression of food intake observed during acute bacterial endotoxemia. PMID:27111742

RP101 improves the efficacy of chemotherapy in pancreas carcinoma cell lines and pancreatic cancer patients.

PubMed

Fahrig, Rudolf; Quietzsch, Detlef; Heinrich, Jörg-Christian; Heinemann, Volker; Boeck, Stefan; Schmid, Roland M; Praha, Christian; Liebert, Andreas; Sonntag, Denise; Krupitza, Georg; Hänel, Mathias

2006-10-01

RP101 [(E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU)], which supports apoptosis and prevents the acquisition of chemoresistance, was tested in cultured human pancreatic tumor cells. RP101 downregulated uridine phosphorylase, a marker of poor prognosis, and APEX1, which is involved in DNA repair, and repressed Stat3 and its target vascular endothelial growth factor. Furthermore, RP101 activated antitumor immunity as demonstrated by enhanced cytolytic activity of NK-92 natural killer cells. This was concomitant with an enhanced expression of lymphotoxins alpha and beta, natural killer cell transcript 4, tumor necrosis factor LIGHT/TNFSF-14, and intercellular adhesion molecule-1 in pancreas carcinoma cells. These results encouraged us to investigate the effect of RP101 in pancreas cancer patients. Here, we present data from two RP101 combination therapy schemes. In a first pilot study, 13 patients in stage III and VI of the disease were treated with gemcitabine +cisplatin+RP101. RP101 co-treatment enhanced remissions, survival and time to progression. Seventy-seven percent of the patients lived or have lived longer than 1 year, and 23% have lived more than 2 years. Median survival was 447 days, time to progression 280 days and the response rate 33%. A second study with 21 patients in similar stages of disease, treated with RP101+gemcitabine alone, confirmed the results of the pilot study. Eighty-three percent of the presently evaluable patients live or lived 0.5 years or longer and 33% 1 year or longer. Considering both studies, the tumor control was 94%. The data indicate that acquisition of chemoresistance was prevented and the antitumor efficacy of standard chemotherapy was improved. To our knowledge, RP101 co-treatment is more efficient than any other regimen published.

Lipopolysacharide Rapidly and Completely Suppresses AgRP Neuron-Mediated Food Intake in Male Mice.

PubMed

Liu, Yang; Huang, Ying; Liu, Tiemin; Wu, Hua; Cui, Huxing; Gautron, Laurent

2016-06-01

Although Agouti-related peptide (AgRP) neurons play a key role in the regulation of food intake, their contribution to the anorexia caused by proinflammatory insults has yet to be identified. Using a combination of neuroanatomical and pharmacogenetics experiments, this study sought to investigate the importance of AgRP neurons and downstream targets in the anorexia caused by the peripheral administration of a moderate dose of lipopolysaccharide (LPS) (100 μg/kg, ip). First, in the C57/Bl6 mouse, we demonstrated that LPS induced c-fos in select AgRP-innervated brain sites involved in feeding but not in any arcuate proopiomelanocortin neurons. Double immunohistochemistry further showed that LPS selectively induced c-Fos in a large subset of melanocortin 4 receptor-expressing neurons in the lateral parabrachial nucleus. Secondly, we used pharmacogenetics to stimulate the activity of AgRP neurons during the course of LPS-induced anorexia. In AgRP-Cre mice expressing the designer receptor hM3Dq-Gq only in AgRP neurons, the administration of the designer drug clozapine-N-oxide (CNO) induced robust food intake. Strikingly, CNO-mediated food intake was rapidly and completely blunted by the coadministration of LPS. Neuroanatomical experiments further indicated that LPS did not interfere with the ability of CNO to stimulate c-Fos in AgRP neurons. In summary, our findings combined together support the view that the stimulation of select AgRP-innervated brain sites and target neurons, rather than the inhibition of AgRP neurons themselves, is likely to contribute to the rapid suppression of food intake observed during acute bacterial endotoxemia.

An Alternative Model for the Role of RP2 Protein in Flagellum Assembly in the African Trypanosome*

PubMed Central

Andre, Jane; Kerry, Louise; Qi, Xin; Hawkins, Erica; Drižytė, Kristina; Ginger, Michael L.; McKean, Paul G.

2014-01-01

The tubulin cofactor C domain-containing protein TbRP2 is a basal body (centriolar) protein essential for axoneme formation in the flagellate protist Trypanosoma brucei, the causal agent of African sleeping sickness. Here, we show how TbRP2 is targeted and tethered at mature basal bodies and provide novel insight into TbRP2 function. Regarding targeting, understanding how several hundred proteins combine to build a microtubule axoneme is a fundamental challenge in eukaryotic cell biology. We show that basal body localization of TbRP2 is mediated by twinned, N-terminal TOF (TON1, OFD1, and FOP) and LisH motifs, motifs that otherwise facilitate localization of only a few conserved proteins at microtubule-organizing centers in animals, plants, and flagellate protists. Regarding TbRP2 function, there is a debate as to whether the flagellar assembly function of specialized, centriolar tubulin cofactor C domain-containing proteins is processing tubulin, the major component of axonemes, or general vesicular trafficking in a flagellum assembly context. Here we report that TbRP2 is required for the recruitment of T. brucei orthologs of MKS1 and MKS6, proteins that, in animal cells, are part of a complex that assembles at the base of the flagellum to regulate protein composition and cilium function. We also identify that TbRP2 is detected by YL1/2, an antibody classically used to detect α-tubulin. Together, these data suggest a general processing role for TbRP2 in trypanosome flagellum assembly and challenge the notion that TbRP2 functions solely in assessing tubulin “quality” prior to tubulin incorporation into the elongating axoneme. PMID:24257747

TCPTP Regulates Insulin Signalling in AgRP Neurons to Coordinate Glucose Metabolism with Feeding.

PubMed

Dodd, Garron T; Lee-Young, Robert S; Brüning, Jens C; Tiganis, Tony

2018-04-30

Insulin regulates glucose metabolism by eliciting effects on peripheral tissues as well as the brain. Insulin receptor (IR) signalling inhibits AgRP-expressing neurons in the hypothalamus to contribute to the suppression of hepatic glucose production (HGP) by insulin, whereas AgRP neuronal activation attenuates brown adipose tissue (BAT) glucose uptake. The tyrosine phosphatase TCPTP suppresses IR signalling in AgRP neurons. Hypothalamic TCPTP is induced by fasting and degraded after feeding. Here we assessed the influence of TCPTP in AgRP neurons in the control of glucose metabolism. TCPTP deletion in AgRP neurons ( Agrp -Cre; Ptpn2 fl/fl ) enhanced insulin sensitivity as assessed by the increased glucose infusion rates and reduced HGP during hyperinsulinemic-euglycemic clamps, accompanied by increased [ 14 C]-2-deoxy-D-glucose uptake in BAT and browned white adipose tissue. TCPTP deficiency in AgRP neurons promoted the intracerebroventricular insulin-induced repression of hepatic gluconeogenesis in otherwise unresponsive food-restricted mice yet had no effect in fed/satiated mice where hypothalamic TCPTP levels are reduced. The improvement in glucose homeostasis in Agrp -Cre; Ptpn2 fl/fl mice was corrected by IR heterozygosity ( Agrp -Cre; Ptpn2 fl/fl ; Insr fl/+ ), causally linking the effects on glucose metabolism with the IR signalling in AgRP neurons. Our findings demonstrate that TCPTP controls IR signalling in AgRP neurons to coordinate HGP and brown/beige adipocyte glucose uptake in response to feeding/fasting. © 2018 by the American Diabetes Association.

Usher syndrome associated with Fuchs' heterochromic uveitis.

PubMed

Lichtinger, Alejandro; Chowers, Itay; Amer, Radgonde

2010-10-01

The purpose of this study is to report two new cases of Usher syndrome associated with Fuchs' heterochromic uveitis (FHU), to confirm our previous observation of the association between FHU and retinitis pigmentosa (RP), and to evaluate if FHU is particularly associated with Usher syndrome. Retrospective medical record review of all new RP cases at Hadassah Medical Center between the years 2000 and 2007, review of our previously published data, and a meta-analysis of published relevant articles in peer reviewed journals. During the time frame of the study we diagnosed 58 new cases of RP, of whom one male and one female had the typical findings of FHU, and both had Usher syndrome type II. The difference in the occurrence of FHU between the 616 controls and the patients with RP was significant (p = 0.0073, Fisher's exact test). In our combined data, FHU occurred only in two types of RP; RP simplex with an incidence of 0.57%, and Usher syndrome with an incidence of 13.5%. This difference between the incidence of FHU in patients with Usher syndrome and other types of RP was significant (p < 0.0001, Fisher's exact test). Adding up these two cases with what is already published in the literature makes up a total of 17 RP patients with coexisting FHU. This study confirms the association between FHU and RP; and a particularly stronger association with Usher syndrome type II. Although infectious agents seem to play a role, the cause for this significant correlation is still unclear.

Gleason pattern 5 is the strongest pathologic predictor of recurrence, metastasis, and prostate cancer-specific death in patients receiving salvage radiation therapy following radical prostatectomy.

PubMed

Jackson, William; Hamstra, Daniel A; Johnson, Skyler; Zhou, Jessica; Foster, Benjamin; Foster, Corey; Li, Darren; Song, Yeohan; Palapattu, Ganesh S; Kunju, Lakshmi P; Mehra, Rohit; Feng, Felix Y

2013-09-15

The presence of Gleason pattern 5 (GP5) at radical prostatectomy (RP) has been associated with worse clinical outcome; however, this pathologic variable has not been assessed in patients receiving salvage radiation therapy (SRT) after a rising prostate-specific antigen level. A total of 575 patients who underwent primary RP for localized prostate cancer and subsequently received SRT at a tertiary medical institution were reviewed retrospectively. Primary outcomes of interest were biochemical failure (BF), distant metastasis (DM), and prostate cancer-specific mortality (PCSM), which were assessed via univariate analysis and Fine and Grays competing risks multivariate models. On pathologic evaluation, 563 (98%) patients had a documented Gleason score (GS). The median follow-up post-SRT was 56.7 months. A total of 60 (10.7%) patients had primary, secondary, or tertiary GP5. On univariate analysis, the presence of GP5 was prognostic for BF (hazard ratio [HR] 3.3; P < .0001), DM (HR:11.1, P < .0001), and PCSM (HR:8.8, P < .0001). Restratification of the Gleason score to include GP5 as a distinct entity resulted in improved prognostic capability. Patients with GP5 had clinically worse outcomes than patients with GS8(4+4). On multivariate analysis, the presence of GP5 was the most adverse pathologic predictor of BF (HR 2.9; P < .0001), DM (HR 14.8; P < .0001), and PCSM (HR 5.7; P < .0001). In the setting of SRT for prostate cancer, the presence of GP5 is a critical pathologic predictor of BF, DM, and PCSM. Traditional GS risk stratification fails to fully utilize the prognostic capabilities of individual Gleason patterns among men receiving SRT post-RP. © 2013 American Cancer Society.

An audit of referral and treatment patterns of high-risk prostate cancer patients in Alberta.

PubMed

Alghamdi, Majed; Taggar, Amandeep; Tilley, Derek; Kerba, Marc; Kostaras, Xanthoula; Gotto, Geoffrey; Sia, Michael

2016-01-01

We aimed to determine the impact of clinical practice guidelines (CPG) on rates of radiation oncologist (RO) referral, androgen-deprivation therapy (ADT), radiation therapy (RT), and radical prostatectomy (RP) in patients with high-risk prostate cancer (HR-PCa). All men >18 years, diagnosed with PCa in 2005 and 2012 were identified from the Alberta Cancer Registry. Patient age, aggregated clinical risk group (ACRG) score, Gleason score (GS), pre-treatment prostate-specific antigen (PSA), RO referral, and treatment received were extracted from electronic medical records. Logistic regression modelling was used to examine associations between RO referral rates and relevant factors. HR-PCa was diagnosed in 261 of 1792 patients in 2005 and 435 of 2148 in 2012. Median age and ACRG scores were similar in both years (p>0.05). The rate of patients with PSA >20 were 67% and 57% in 2005 and 2012, respectively (p=0.004). GS ≤6 was found in 13% vs. 5% of patients, GS 7 in 27% vs. 24%, and GS ≥8 in 59% vs. 71% in 2005 and 2012, respectively (p<0.001). In 2005, RO referral rate was 68% compared to 56% in 2012 (p=0.001), use of RT + ADT was 53% compared to 32% (p<0.001), and RP rate was 9% vs. 17% (p=0.002). On regression analysis, older age, 2012 year of diagnosis and higher PSA were associated with decreased RO referral rates (odds ratios [OR] 0.49, 95% confidence interval [CI] 0.39-0.61; OR 0.51, 95% CI 0.34-0.76; and OR 0.64, 95% CI 0.39-0.61), respectively [p<0.001]). Since CPG creation in 2005, RO referral rates and ADT + RT use declined and RP rates increased, which demonstrates a need to improve adherence to CPG in the HR-PCa population.

A risk-adjusted definition of biochemical recurrence after radical prostatectomy.

PubMed

Morgan, T M; Meng, M V; Cooperberg, M R; Cowan, J E; Weinberg, V; Carroll, P R; Lin, D W

2014-06-01

To determine whether a variable definition of biochemical recurrence (BCR) based on clincopathologic features facilitates early identification of patients likely to suffer from disease progression. The definition of BCR after radical prostatectomy (RP) bears important implications for patient counseling and management; however, there remains a significant debate regarding the appropriate definition. The study cohort consisted of 3619 men who underwent RP for localized prostate cancer from 1989 to 2007, with data abstracted from the Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry. Patients were stratified into three risk groups according to Cancer of the Prostate Risk Assessment post-Surgical (CAPRA-S) score. Three single threshold PSA cut-points for BCR were evaluated (PSA > or =0.05, > or =0.2 and > or =0.4 ng ml(-1)) as well as a variable cut-point defined by risk group. After reaching the cut-points, patients were followed for further PSA progression. The proportion of patients with BCR differed by cut-point and risk group, ranging from 7 to 37% (low risk), 22 to 58% (intermediate risk) and 60 to 86% (high risk). The positive-predictive value (PPV) for predicting further PSA progression was 49% for the PSA > or =0.05 ng ml(-1), 62% for the PSA > or =0.2 ng ml(-1), 65% for the PSA > or =0.4 ng ml(-1) and 68% for the risk-adjusted definition. Five-year progression-free survival was 39% for the risk-adjusted definition compared with 45-52% for the other definitions of BCR. These data suggest that a variable definition of BCR determined by clinicopathologic risk may improve the identification of early recurrence after RP without increasing the overdiagnosis of BCR. By using a risk-adjusted BCR definition, clinicians can better predict future PSA progression and more appropriately counsel patients regarding salvage therapies.

Evaluation of syndromic patient management algorithm for urethral discharge.

PubMed

Djajakusumah, T; Sudigdoadi, S; Keersmaekers, K; Meheus, A

1998-06-01

To determine feasibility, validity, and cost effectiveness of the syndromic approach to male patients with urethral discharge in Bandung, Indonesia. The WHO algorithm on urethral discharge with no microscopy available was evaluated. Patients presented with a complaint of urethral discharge and if discharge was confirmed the algorithm was applied. Treatment covered gonococcal and chlamydial infection (ciprofloxacin 500 mg single oral dose plus doxycycline 100 mg, twice daily orally for 7 days). The gold standard for validation was gonococcal culture and chlamydia antigen detection. 140 male patients with a complaint of urethral discharge were enrolled; 119 had confirmed discharge and entered the decision tree: 107 were followed and 104 (97%) were clinically cured. Of the three patients with persistent discharge, one had a purulent urethral discharge, diagnosed as gonococcal urethritis and he was probably reinfected; two patients had a serous discharge and microbiological tests were negative. Overall, 106 out of 107 patients (99%) were microbiologically cured. Sensitivity of the algorithm is 100% and its positive predictive value (PPV) is 75% or 97% if validated against gold standard microbiological tests or Gram stain, respectively. Cost per patient is rupiah (Rp)5.894 ($US2.56) for the algorithm compared with Rp43.024 ($18.70) for full microbiological diagnosis. The cost estimate for an algorithm of urethral discharge with microscopy available is Rp6.432 ($2.80) The "symptom and sign" algorithm is fully adapted to the prevailing situation in primary healthcare settings, is acceptable to healthcare workers and patients (who are effectively treated at their first visit), is highly cost effective, is 100% sensitive (no false negatives, which is not the case with microbiological diagnosis), and has a high PPV, between 75% and 97%. It is an excellent patient management tool and a sound basis for partner notification so that it should have a major impact on STD/HIV control and prevention in both men and women.

Confirming psychogenic nonepileptic seizures with video-EEG: sex matters.

PubMed

Noe, Katherine H; Grade, Madeline; Stonnington, Cynthia M; Driver-Dunckley, Erika; Locke, Dona E C

2012-03-01

The influence of gender on psychogenic nonepileptic seizures (PNES) diagnosis was examined retrospectively in 439 subjects undergoing video-EEG (vEEG) for spell classification, of whom 142 women and 42 men had confirmed PNES. The epileptologist's predicted diagnosis was correct in 72% overall. Confirmed epilepsy was correctly predicted in 94% men and 88% women. In contrast, confirmed PNES was accurately predicted in 86% women versus 61% men (p=0.003). Sex-based differences in likelihood of an indeterminate admission were not observed for predicted epilepsy or physiologic events, but were for predicted PNES (39% men, 12% women, p=0.0002). More frequent failure to record spells in men than women with predicted PNES was not explained by spell frequency, duration of monitoring, age, medication use, or personality profile. PNES are not only less common in men, but also more challenging to recognize in the clinic, and even when suspected more difficult to confirm with vEEG. Copyright © 2012 Elsevier Inc. All rights reserved.

Men's role in women's antenatal health status: evidence from rural Rajshahi, Bangladesh.

PubMed

Rahman, Mosiur; Islam, Mohammad Touhidul; Mostofa, Md Golam; Reza, Md Shahin

2015-03-01

This study aimed to extend notions of men's role in women's antenatal care (ANC) status in rural Rajshahi, Bangladesh. The analyses were based on response of 480 men aged 15 to 54 years, living with at least 1 child younger than 3 years. Only 27% men accompanied their wives for ANC. Men's perception of actual roles for ANC services was low: 63% approved of women undergoing checkups; 33% discussed their wives' pregnancy with health professionals. Only 18% scored highly on the overall index of knowledge. From multivariate analysis, it was found that the number of men accompanying their wives for ANC was higher among those respondents who were married for the first time in the age-group 25 to 34 years and aged 35 years or more, had their last child at age-group 20 to 24 years or 25 to 34 years, had completed primary or secondary and higher education, and had mass media facilities. © 2012 APJPH.

Virtual Evidence Cart - RP (VEC-RP).

PubMed

Liu, Fang; Fontelo, Paul; Muin, Michael; Ackerman, Michael

2005-01-01

VEC-RP (Virtual Evident Cart) is an open, Web-based, searchable collection of clinical questions and relevant references from MEDLINE/PubMed for healthcare professionals. The architecture consists of four parts: clinical questions, relevant articles from MEDLINE/PubMed, "bottom-line" answers, and peer reviews of entries. Only registered users can add reviews but unregistered users can read them. Feedback from physicians, mostly in the Philippines (RP) who tested the system, is positive.

RHO Mutations (p.W126L and p.A346P) in Two Japanese Families with Autosomal Dominant Retinitis Pigmentosa

PubMed Central

Akahori, Masakazu; Itabashi, Takeshi; Nishino, Jo; Yoshitake, Kazutoshi; Ikeo, Kazuho; Tsuneoka, Hiroshi

2014-01-01

Purpose. To investigate genetic and clinical features of patients with rhodopsin (RHO) mutations in two Japanese families with autosomal dominant retinitis pigmentosa (adRP). Methods. Whole-exome sequence analysis was performed in ten adRP families. Identified RHO mutations for the cosegregation analysis were confirmed by Sanger sequencing. Ophthalmic examinations were performed to evaluate the RP phenotypes. The impact of the RHO mutation on the rhodopsin conformation was examined by molecular modeling analysis. Results. In two adRP families, we identified two RHO mutations (c.377G>T (p.W126L) and c.1036G>C (p.A346P)), one of which was novel. Complete cosegregation was confirmed for each mutation exhibiting the RP phenotype in both families. Molecular modeling predicted that the novel mutation (p.W126L) might impair rhodopsin function by affecting its conformational transition in the light-adapted form. Clinical phenotypes showed that patients with p.W126L exhibited sector RP, whereas patients with p.A346P exhibited classic RP. Conclusions. Our findings demonstrated that the novel mutation (p.W126L) may be associated with the phenotype of sector RP. Identification of RHO mutations is a very useful tool for predicting disease severity and providing precise genetic counseling. PMID:25485142

Novel USH2A mutations in Israeli patients with retinitis pigmentosa and Usher syndrome type 2.

PubMed

Kaiserman, Nadia; Obolensky, Alexey; Banin, Eyal; Sharon, Dror

2007-02-01

To identify USH2A mutations in Israeli patients with autosomal-recessive Usher syndrome type 2 (USH2) and retinitis pigmentosa (RP). Patients from 95 families with RP and 4 with USH2 were clinically evaluated. USH2A exons 2-72 were scanned for mutations using single-strand conformation and sequencing analyses. The frequency of novel missense changes was determined in patients and controls using restriction endonucleases. The analysis revealed 3 USH2A mutations, 2 of which are novel, in 2 families with USH2 and a large family (MOL0051) with both USH2 and RP. Compound heterozygotes for 2 null mutations (Thr80fs and Arg737stop) in MOL0051 suffered from USH2 while compound heterozygotes for 1 of the null mutations and a novel missense mutation (Gly4674Arg) had nonsyndromic RP. Our results support the involvement of USH2A in nonsyndromic RP and we report here of a second, novel, missense mutation in this gene causing autosomal-recessive RP. Possible involvement of USH2A should be considered in the molecular genetic evaluation of patients with autosomal-recessive RP. Understanding the mechanism by which different USH2A mutations cause either USH2 or RP may assist in the development of novel therapeutic approaches.

Action of Neurotransmitter: A Key to Unlock the AgRP Neuron Feeding Circuit

PubMed Central

Liu, Tiemin; Wang, Qian; Berglund, Eric D.; Tong, Qingchun

2013-01-01

The current obesity epidemic and lack of efficient therapeutics demand a clear understanding of the mechanism underlying body weight regulation. Despite intensive research focus on obesity pathogenesis, an effective therapeutic strategy to treat and cure obesity is still lacking. Exciting studies in last decades have established the importance of hypothalamic agouti-related protein-expressing neurons (AgRP neurons) in the regulation of body weight homeostasis. AgRP neurons are both required and sufficient for feeding regulation. The activity of AgRP neurons is intricately regulated by nutritional hormones as well as synaptic inputs from upstream neurons. Changes in AgRP neuron activity lead to alterations in the release of mediators, including neuropeptides Neuropeptide Y (NPY) and AgRP, and fast-acting neurotransmitter GABA. Recent studies based on mouse genetics, novel optogenetics, and designer receptor exclusively activated by designer drugs have identified a critical role for GABA release from AgRP neurons in the parabrachial nucleus and paraventricular hypothalamus in feeding control. This review will summarize recent findings about AgRP neuron-mediated control of feeding circuits with a focus on the role of neurotransmitters. Given the limited knowledge on feeding regulation, understanding the action of neurotransmitters may be a key to unlock neurocircuitry that governs feeding. PMID:23346045

Coping strategies to manage stress related to vision loss and fluctuations in retinitis pigmentosa

PubMed Central

Bittner, Ava K.; Edwards, Lori; George, Maureen

2010-01-01

Background Vision loss in retinitis pigmentosa (RP) is a slowly progressive and inexorable threat to patients’ independence. It is not surprising that RP patients, many of whom are young when diagnosed, are at high risk for stress related to their vision loss. To address these issues, eye care providers need to be aware of what coping strategies RP patients use to successfully manage their vision loss. Methods We held focus groups with eight legally blind RP patients to help us better understand how they cope with the stress that is generated from their progressive vision loss and fluctuations in vision. Focus group sessions were audiotaped and resulting notes were coded using conventional qualitative analytic techniques. Results Two themes were identified: 1) “kicking and screaming” captured the ways in which RP patients fight to maintain their independence in the face of worsening vision; and 2) “there are so many worse things” describes how RP patients keep their vision loss in perspective. These RP patients demonstrated high levels of resiliency. In particular, they often used humor as a coping mechanism. Conclusions Understanding the ways in which RP patients manage their gradual, impending vision loss may lead to improved quality of care for this patient population. PMID:20591747

Genotyping microarray: Mutation screening in Spanish families with autosomal dominant retinitis pigmentosa

PubMed Central

García-Hoyos, María; Cortón, Marta; Ávila-Fernández, Almudena; Riveiro-Álvarez, Rosa; Giménez, Ascensión; Hernan, Inma; Carballo, Miguel; Ayuso, Carmen

2012-01-01

Purpose Presently, 22 genes have been described in association with autosomal dominant retinitis pigmentosa (adRP); however, they explain only 50% of all cases, making genetic diagnosis of this disease difficult and costly. The aim of this study was to evaluate a specific genotyping microarray for its application to the molecular diagnosis of adRP in Spanish patients. Methods We analyzed 139 unrelated Spanish families with adRP. Samples were studied by using a genotyping microarray (adRP). All mutations found were further confirmed with automatic sequencing. Rhodopsin (RHO) sequencing was performed in all negative samples for the genotyping microarray. Results The adRP genotyping microarray detected the mutation associated with the disease in 20 of the 139 families with adRP. As in other populations, RHO was found to be the most frequently mutated gene in these families (7.9% of the microarray genotyped families). The rate of false positives (microarray results not confirmed with sequencing) and false negatives (mutations in RHO detected with sequencing but not with the genotyping microarray) were established, and high levels of analytical sensitivity (95%) and specificity (100%) were found. Diagnostic accuracy was 15.1%. Conclusions The adRP genotyping microarray is a quick, cost-efficient first step in the molecular diagnosis of Spanish patients with adRP. PMID:22736939

Debate: Open radical prostatectomy vs. laparoscopic vs. robotic.

PubMed

Nelson, Joel B

2007-01-01

Surgical removal of clinically localized prostate cancer remains the most definitive treatment for the disease. The emergence of laparoscopic and robotic radical prostatectomy (RP) as alternatives to open RP has generated considerable discussion about the real and relative merits of each approach. Such was the topic of a debate that took place during the 2006 Society of Urologic Oncology meeting. The participants were Dr. William Catalona, Northwestern University, advocating for open RP, Dr. Betrand Guillonneau, Memorial Sloan Kettering Cancer Center advocating for laparoscopic RP, and Dr. Mani Menon, Henry Ford Hospital, advocating for robotic RP. The debate was moderated by Dr. Joel Nelson, University of Pittsburgh. This paper summarizes that debate.

AgRP neurons regulate development of dopamine neuronal plasticity and nonfood-associated behaviors

PubMed Central

Dietrich, Marcelo O; Bober, Jeremy; Ferreira, Jozélia G; Tellez, Luis A; Mineur, Yann S; Souza, Diogo O; Gao, Xiao-Bing; Picciotto, Marina R; Araújo, Ivan; Liu, Zhong-Wu; Horvath, Tamas L

2012-01-01

It is not known whether behaviors unrelated to feeding are affected by hypothalamic regulators of hunger. We found that impairment of Agouti-related protein (AgRP) circuitry by either Sirt1 knockdown in AgRP-expressing neurons or early postnatal ablation of these neurons increased exploratory behavior and enhanced responses to cocaine. In AgRP circuit–impaired mice, ventral tegmental dopamine neurons exhibited enhanced spike timing–dependent long-term potentiation, altered amplitude of miniature postsynaptic currents and elevated dopamine in basal forebrain. Thus, AgRP neurons determine the set point of the reward circuitry and associated behaviors. PMID:22729177

A Postsynaptic AMPK→p21-Activated Kinase Pathway Drives Fasting-Induced Synaptic Plasticity in AgRP Neurons.

PubMed

Kong, Dong; Dagon, Yossi; Campbell, John N; Guo, Yikun; Yang, Zongfang; Yi, Xinchi; Aryal, Pratik; Wellenstein, Kerry; Kahn, Barbara B; Sabatini, Bernardo L; Lowell, Bradford B

2016-07-06

AMP-activated protein kinase (AMPK) plays an important role in regulating food intake. The downstream AMPK substrates and neurobiological mechanisms responsible for this, however, are ill defined. Agouti-related peptide (AgRP)-expressing neurons in the arcuate nucleus regulate hunger. Their firing increases with fasting, and once engaged they cause feeding. AgRP neuron activity is regulated by state-dependent synaptic plasticity: fasting increases dendritic spines and excitatory synaptic activity; feeding does the opposite. The signaling mechanisms underlying this, however, are also unknown. Using neuron-specific approaches to measure and manipulate kinase activity specifically within AgRP neurons, we establish that fasting increases AMPK activity in AgRP neurons, that increased AMPK activity in AgRP neurons is both necessary and sufficient for fasting-induced spinogenesis and excitatory synaptic activity, and that the AMPK phosphorylation target mediating this plasticity is p21-activated kinase. This provides a signaling and neurobiological basis for both AMPK regulation of energy balance and AgRP neuron state-dependent plasticity. Copyright © 2016 Elsevier Inc. All rights reserved.

Relapsing polychondritis associated with psoriasis vulgaris successfully treated with adalimumab: A case report with published work review.

PubMed

Matsuo, Haruka; Asahina, Akihiko; Fukuda, Takeshi; Umezawa, Yoshinori; Nakagawa, Hidemi

2017-07-01

Relapsing polychondritis (RP) is a rare autoimmune-mediated disease characterized by inflammation involving cartilaginous tissues. We report here a case of RP in a 38-year-old Japanese man with 13-year duration of psoriasis vulgaris treated with topical steroids and vitamin D 3 . The patient presented with tender swelling and erythema of both auricles, and the antibody to type II collagen was detected. The biopsy specimen revealed a dense mixed cell infiltration over the auricular cartilage. We reviewed eight cases with the association of RP and psoriasis, and in all cases the clinical course of psoriasis did not correlate with that of RP. The severity of RP was mild in the majority of cases, and our case was unique in that the patient had no joint symptoms. Adalimumab treatment was effective for both RP and psoriasis. Fat-suppressed contrast-enhanced magnetic resonance imaging was beneficial, not only to demonstrate subclinical inflammation in the nasal septum, but also to subjectively assess the improvement of RP. © 2017 Japanese Dermatological Association.

Lubrication of an 85-mm ball bearing with RP-1

NASA Technical Reports Server (NTRS)

Addy, Harold E., Jr.; Schuller, Frederick T.

1993-01-01

A parametric experimental investigation of an 85 millimeter bore angular contact ball bearing running in RP-1 fuel was performed at speeds of 10000 to 24000 RPM. Thrust loads were varied from 4450 to 17800 Newtons (1000 to 4000 lbs.). Radial loads were varied from 1335 to 13350 Newtons (300 to 3000 lbs.). RP-1 lubrication for the bearing was provided through a stationary jet ring located adjacent to the test bearing outer ring. Increases in both the thrust and radial loads resulted in increased bearing temperature, while increases in shaft speed resulted in much more dramatic increases in bearing temperature. These trends are typical for ball bearings operating under these types of conditions. Results are given for outer ring temperatures of the test bearing at the various test conditions employed. In addition, the heat energy removed from the bearing by the RP-1 was determined by measuring the increase in temperature as the RP-1 passed through the bearing. Results showed that the amount of heat energy removed by the RP-1 increased with both shaft speed and RP-1 flow rate to the bearing.

Photoirradiation of Retinyl Palmitate in Ethanol with Ultraviolet Light - Formation of Photodecomposition Products, Reactive Oxygen Species, and Lipid Peroxides

PubMed Central

Xia, Qingsu; Yin, Jun J.; Wamer, Wayne G.; Cherng, Shu-Hui; Boudreau, Mary D.; Howard, Paul C.; Yu, Hongtao; Fu, Peter P.

2006-01-01

We have previously reported that photoirradiation of retinyl palmitate (RP), a storage and ester form of vitamin A (retinol), with UVA light resulted in the formation of photodecomposition products, generation of reactive oxygen species, and induction of lipid peroxidation. In this paper, we report our results following the photoirradiation of RP in ethanol by an UV lamp with approximately equal UVA and UVB light. The photodecomposition products were separated by reversed-phase HPLC and characterized spectroscopically by comparison with authentic standards. The identified products include: 4-keto-RP, 11-ethoxy-12-hydroxy-RP, 13-ethoxy-14-hydroxy-RP, anhydroretinol (AR), and trans- and cis-15-ethoxy-AR. Photoirradiation of RP in the presence of a lipid, methyl linoleate, resulted in induction of lipid peroxidation. Lipid peroxidation was inhibited when sodium azide was present during photoirradiation which suggests free radicals were formed. Our results demonstrate that, similar to irradiation with UVA light, RP can act as a photosensitizer leading to free radical formation and induction of lipid peroxidation following irradiation with UVB light. PMID:16823091

[Analysis of phenylethanoid glycosides of Herba cistanchis by RP-HPLC].

PubMed

Tu, P F; Wang, B; Deyama, T; Zhang, Z G; Lou, Z C

1997-04-01

The Chinese drug "Rou Cong-rong" (Herba Cistanchis) is one of the commonly used drugs in Chinese traditional medicine. It is used to reinforce the vital function of kidney, especially that of the sexual organs and induce laxation, for the treatment of impotence, premature ejaculation in men, infertility, morbid leukorrhea, profuse metrorrhagia in women, and chronic constipation in the aged. This paper deals with the qualitative and quantitative analysis of phenylethanoid glycosides of four species and one variety of Genus Cistanche and 23 lots of commercial crude drugs of Herba Cistanchis by RP-HPLC. The results were as follows: the chemical constituents of Cistanche deserticola Ma, C. salsa (C. A. Mey) G. Beck, C. salsa var. albiflora P. F. Tu et Z. C. Lou and C. tubulosa were similar while those of C. sinensis were different from the others; the contents of echinacoside and acteoside of C. salsa, which were 2.13% and 1.51%, were the highest of the genus Cistanche. An ODS column (Alltima C18, 5 microns, 250 x 4.6 mm) was employed. Linear gradient elution of acetonitrile--1.5% acetic acid was used as mobile phase, and concentration of acetontrile was from 8% to 20% (0-60 min) in the qualitative analysis, and from 11.5 to 20% (0-35 min) in the quantitative analysis. The flow rate was 1.2 ml.min-1. The detection wavelength was set at 335 nm.

The effect of pioglitazone and resistance training on body composition in older men and women undergoing hypocaloric weight loss.

PubMed

Shea, M Kyla; Nicklas, Barbara J; Marsh, Anthony P; Houston, Denise K; Miller, Gary D; Isom, Scott; Miller, Michael E; Carr, J Jeffrey; Lyles, Mary F; Harris, Tamara B; Kritchevsky, Stephen B

2011-08-01

Age-related increases in ectopic fat accumulation are associated with greater risk for metabolic and cardiovascular diseases, and physical disability. Reducing skeletal muscle fat and preserving lean tissue are associated with improved physical function in older adults. PPARγ-agonist treatment decreases abdominal visceral adipose tissue (VAT) and resistance training preserves lean tissue, but their effect on ectopic fat depots in nondiabetic overweight adults is unclear. We examined the influence of pioglitazone and resistance training on body composition in older (65-79 years) nondiabetic overweight/obese men (n = 48, BMI = 32.3 ± 3.8 kg/m(2)) and women (n = 40, BMI = 33.3 ± 4.9 kg/m(2)) during weight loss. All participants underwent a 16-week hypocaloric weight-loss program and were randomized to receive pioglitazone (30 mg/day) or no pioglitazone with or without resistance training, following a 2 × 2 factorial design. Regional body composition was measured at baseline and follow-up using computed tomography (CT). Lean mass was measured using dual X-ray absorptiometry. Men lost 6.6% and women lost 6.5% of initial body mass. The percent of fat loss varied across individual compartments. Men who were given pioglitazone lost more visceral abdominal fat than men who were not given pioglitazone (-1,160 vs. -647 cm(3), P = 0.007). Women who were given pioglitazone lost less thigh subcutaneous fat (-104 vs. -298 cm(3), P = 0.002). Pioglitazone did not affect any other outcomes. Resistance training diminished thigh muscle loss in men and women (resistance training vs. no resistance training men: -43 vs. -88 cm(3), P = 0.005; women: -34 vs. -59 cm(3), P = 0.04). In overweight/obese older men undergoing weight loss, pioglitazone increased visceral fat loss and resistance training reduced skeletal muscle loss. Additional studies are needed to clarify the observed gender differences and evaluate how these changes in body composition influence functional status.

Differences in Presentation, Management and Outcomes in Women and Men Presenting to an Emergency Department With Possible Cardiac Chest Pain.

PubMed

Ruane, Lorcan; H Greenslade, Jaimi; Parsonage, William; Hawkins, Tracey; Hammett, Christopher; Lam, Carolyn Sp; Knowlman, Thomas; Doig, Shaela; Cullen, Louise

2017-12-01

Research suggests that female patients with acute coronary syndrome (ACS) experience delays in emergency department (ED) management and are less likely to receive guideline-based treatments and referrals for follow-up testing. Women are often found to have poorer clinical outcomes in comparison to men. This study aimed to assess current sex differences in the presentation, management and outcomes of patients with undifferentiated chest pain presenting to a tertiary ED. Data were analysed from two prospective studies conducted at a single Australian site between 2007 and 2014. Eligible patients were those of 18 years of age or older presenting with at least 5 minutes of chest pain or other symptoms for which the treating physician planned to investigate for possible ACS. Presenting symptoms, ED time measures, follow-up testing and outcomes, including 30-day ACS and mortality, were measured and compared between male and female patients. Of 2349 (60% men) patients presenting with chest pain, 153 men and 51 women were diagnosed with ACS within 30days . Presenting symptoms were similar in men and women with confirmed ACS. Time from symptom onset to ED presentation, time spent in the ED and total time in hospital were similar between the sexes. Male and female patients had similar rates of follow-up provocative testing. After adjustment for clinical factors, the odds of undergoing angiography were 1.8 (95% CI: 1.36-2.40) times higher for men than women. Of those undergoing coronary angiography within 30 days, a smaller proportion of women, compared to men, received revascularisation. Within 30 days, three (0.2%) male and one (0.1%) female patient died. Minimal sex differences were observed in the contemporary emergency management of patients presenting with suspected ACS. Thirty-day outcomes were similarly low in men and women despite lower rates of coronary angiography and revascularisation in women. Further research is required to replicate these results in different hospital systems and cultural settings. Copyright © 2017 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). All rights reserved.

77 FR 22772 - Sunshine Act Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-17

... Transmission. E-4 RM11-17-000 Enhancement of Electricity Market Surveillance and Analysis through Ongoing.... RP11-1566-009. RP11-1566-011. RP11-2066-001. Hydro H-1 P-12632-004 East Texas Electric Cooperative, Inc...

Diagnostic Challenges in Retinitis Pigmentosa: Genotypic Multiplicity and Phenotypic Variability

PubMed Central

Chang, Susie; Vaccarella, Leah; Olatunji, Sunday; Cebulla, Colleen; Christoforidis, John

2011-01-01

Retinitis pigmentosa (RP) is a heterogeneous group of inherited retinal disorders. Diagnosis can be challenging as more than 40 genes are known to cause non-syndromic RP and phenotypic expression can differ significantly resulting in variations in disease severity, age of onset, rate of progression, and clinical findings. We describe the clinical manifestations of RP, the more commonly known causative gene mutations, and the genotypic-phenotypic correlation of RP. PMID:22131872

Maize Homologs of Hydroxycinnamoyltransferase, a Key Enzyme in Lignin Biosynthesis, Bind the Nucleotide Binding Leucine-Rich Repeat Rp1 Proteins to Modulate the Defense Response.

PubMed

Wang, Guan-Feng; He, Yijian; Strauch, Renee; Olukolu, Bode A; Nielsen, Dahlia; Li, Xu; Balint-Kurti, Peter J

2015-11-01

In plants, most disease resistance genes encode nucleotide binding Leu-rich repeat (NLR) proteins that trigger a rapid localized cell death called a hypersensitive response (HR) upon pathogen recognition. The maize (Zea mays) NLR protein Rp1-D21 derives from an intragenic recombination between two NLRs, Rp1-D and Rp1-dp2, and confers an autoactive HR in the absence of pathogen infection. From a previous quantitative trait loci and genome-wide association study, we identified a single-nucleotide polymorphism locus highly associated with variation in the severity of Rp1-D21-induced HR. Two maize genes encoding hydroxycinnamoyltransferase (HCT; a key enzyme involved in lignin biosynthesis) homologs, termed HCT1806 and HCT4918, were adjacent to this single-nucleotide polymorphism. Here, we show that both HCT1806 and HCT4918 physically interact with and suppress the HR conferred by Rp1-D21 but not other autoactive NLRs when transiently coexpressed in Nicotiana benthamiana. Other maize HCT homologs are unable to confer the same level of suppression on Rp1-D21-induced HR. The metabolic activity of HCT1806 and HCT4918 is unlikely to be necessary for their role in suppressing HR. We show that the lignin pathway is activated by Rp1-D21 at both the transcriptional and metabolic levels. We derive a model to explain the roles of HCT1806 and HCT4918 in Rp1-mediated disease resistance. © 2015 American Society of Plant Biologists. All Rights Reserved.

Maize Homologs of Hydroxycinnamoyltransferase, a Key Enzyme in Lignin Biosynthesis, Bind the Nucleotide Binding Leucine-Rich Repeat Rp1 Proteins to Modulate the Defense Response1

PubMed Central

Wang, Guan-Feng; He, Yijian; Strauch, Renee; Olukolu, Bode A.; Nielsen, Dahlia; Li, Xu; Balint-Kurti, Peter J.

2015-01-01

In plants, most disease resistance genes encode nucleotide binding Leu-rich repeat (NLR) proteins that trigger a rapid localized cell death called a hypersensitive response (HR) upon pathogen recognition. The maize (Zea mays) NLR protein Rp1-D21 derives from an intragenic recombination between two NLRs, Rp1-D and Rp1-dp2, and confers an autoactive HR in the absence of pathogen infection. From a previous quantitative trait loci and genome-wide association study, we identified a single-nucleotide polymorphism locus highly associated with variation in the severity of Rp1-D21-induced HR. Two maize genes encoding hydroxycinnamoyltransferase (HCT; a key enzyme involved in lignin biosynthesis) homologs, termed HCT1806 and HCT4918, were adjacent to this single-nucleotide polymorphism. Here, we show that both HCT1806 and HCT4918 physically interact with and suppress the HR conferred by Rp1-D21 but not other autoactive NLRs when transiently coexpressed in Nicotiana benthamiana. Other maize HCT homologs are unable to confer the same level of suppression on Rp1-D21-induced HR. The metabolic activity of HCT1806 and HCT4918 is unlikely to be necessary for their role in suppressing HR. We show that the lignin pathway is activated by Rp1-D21 at both the transcriptional and metabolic levels. We derive a model to explain the roles of HCT1806 and HCT4918 in Rp1-mediated disease resistance. PMID:26373661

Family-based exposure and response prevention therapy for preschool-aged children with obsessive-compulsive disorder: a pilot randomized controlled trial.

PubMed

Lewin, Adam B; Park, Jennifer M; Jones, Anna M; Crawford, Erika A; De Nadai, Alessandro S; Menzel, Jessie; Arnold, Elysse B; Murphy, Tanya K; Storch, Eric A

2014-05-01

To examine the feasibility, acceptability and preliminary efficacy of family-based exposure/response prevention therapy (E/RP) versus treatment as usual (TAU) in a cohort of very young children with early onset obsessive-compulsive disorder (OCD). Thirty-one children ages 3-8 years (M = 5.8 years) with a primary diagnosis of OCD were randomized to E/RP or TAU. The E/RP condition received 12 sessions of family-based E/RP twice weekly over 6 weeks. Families were assessed at baseline, post-treatment, 1-month and 3-month follow up. The Children's Yale Brown Obsessive Compulsive Scale and Clinical Global Impression served as primary outcome measures. A large group effect emerged in favor of the E/RP group (d = 1.69). Sixty-five percent of the E/RP group was considered treatment responders as compared to 7% in the TAU group. Symptom remission was achieved in 35.2% of the E/RP group and 0% of the TAU group. There was no attrition and satisfaction was high; gains were maintained at 3 months. Even amongst children as young as 3 years, developmentally tailored E/RP is efficacious and well-tolerated in reducing OCD symptoms. Key adaptations for younger children include extensive parent involvement, targeting family accommodation, and frequent meetings while delivering a full course of E/RP. NCT01447966 http://clinicaltrials.gov/ct2/show/NCT01447966?term=ocd+and+st+petersburg&rank=1. Copyright © 2014 Elsevier Ltd. All rights reserved.

Molecular dynamics simulations of viral RNA polymerases link conserved and correlated motions of functional elements to fidelity

PubMed Central

Moustafa, Ibrahim M.; Shen, Hujun; Morton, Brandon; Colina, Coray M.; Cameron, Craig E.

2011-01-01

The viral RNA-dependent RNA polymerase (RdRp) is essential for multiplication of all RNA viruses. The sequence diversity of an RNA virus population contributes to its ability to infect the host. This diversity emanates from errors made by the RdRp during RNA synthesis. The physical basis for RdRp fidelity is unclear but is linked to conformational changes occurring during the nucleotide-addition cycle. To understand RdRp dynamics that might influence RdRp function, we have analyzed all-atom molecular dynamics (MD) simulations on the nanosecond timescale of four RdRps from the picornavirus family that exhibit 30–74% sequence identity. Principal component analysis showed that the major motions observed during the simulations derived from conserved structural motifs and regions of known function. Dynamics of residues participating in the same biochemical property, for example RNA binding, nucleotide binding or catalysis, were correlated even when spatially distant on the RdRp structure. The conserved and correlated dynamics of functional, structural elements suggest co-evolution of dynamics with structure and function of the RdRp. Crystal structures of all picornavirus RdRps exhibit a template-nascent RNA duplex channel too small to fully accommodate duplex RNA. Simulations revealed opening and closing motions of the RNA and NTP channels, which might be relevant to NTP entry, PPi exit and translocation. A role for nanosecond timescale dynamics in RdRp fidelity is supported by altered dynamics of the high-fidelity G64S derivative of PV RdRp relative to wild-type enzyme. PMID:21575642

National cohort study comparing severe medium-term urinary complications after robot-assisted vs laparoscopic vs retropubic open radical prostatectomy.

PubMed

Sujenthiran, Arunan; Nossiter, Julie; Parry, Matthew; Charman, Susan C; Aggarwal, Ajay; Payne, Heather; Dasgupta, Prokar; Clarke, Noel W; van der Meulen, Jan; Cathcart, Paul

2018-03-01

To evaluate the occurrence of severe urinary complications within 2 years of surgery in men undergoing either robot-assisted radical prostatectomy (RARP), laparoscopic radical prostatectomy (LRP) or retropubic open radical prostatectomy (ORP). We conducted a population-based cohort study in men who underwent RARP (n = 4 947), LRP (n = 5 479) or ORP (n = 6 873) between 2008 and 2012 in the English National Health Service (NHS) using national cancer registry records linked to Hospital Episodes Statistics, an administrative database of admissions to NHS hospitals. We identified the occurrence of any severe urinary or severe stricture-related complication within 2 years of surgery using a validated tool. Multi-level regression modelling was used to determine the association between the type of surgery and occurrence of complications, with adjustment for patient and surgical factors. Men undergoing RARP were least likely to experience any urinary complication (10.5%) or a stricture-related complication (3.3%) compared with those who had LRP (15.8% any or 5.7% stricture-related) or ORP (19.1% any or 6.9% stricture-related). The impact of the type of surgery on the occurrence of any urinary or stricture-related complications remained statistically significant after adjustment for patient and surgical factors (P < 0.01). Men who underwent RARP had the lowest risk of developing severe urinary complications within 2 years of surgery. © 2017 The Authors BJU International published by John Wiley & Sons Ltd on behalf of BJU International.

Stages of Change for Voluntary Medical Male Circumcision and Sexual Risk Behavior in Uncircumcised Zambian Men: The Spear and Shield Project.

PubMed

Redding, Colleen A; Jones, Deborah; Zulu, Robert; Chitalu, Ndashi; Cook, Ryan; Weiss, Stephen M

2015-12-01

Dissemination and scale up of voluntary medical male circumcision (VMMC) programs is well supported by evidence that VMMC reduces HIV risk in populations with high HIV prevalence and low rates of circumcision, as is the case in Zambia. At both individual and population levels, it is important to understand what stages of change for VMMC are associated with, especially across cultures. This study evaluated VMMC knowledge, misinformation, and stages of change for VMMC of uncircumcised men and boys (over 18 years), as well as the concurrent relationship between VMMC stages of change and sexual risk behaviors. Uncircumcised (N = 800) adult men and boys (over 18) were screened and recruited from urban community health centers in Lusaka, Zambia, where they then completed baseline surveys assessing knowledge, attitudes, HIV risk behaviors, and stages of change for VMMC. A series of analyses explored cross-sectional relationships among these variables. VMMC was culturally acceptable in half of the sample; younger, unmarried, and more educated men were more ready to undergo VMMC. Stage of change for VMMC was also related to knowledge, and those at greater HIV risk reported greater readiness to undergo VMMC. Efforts to increase VMMC uptake should address the role of perceived HIV risk, risk behaviors, readiness, accurate knowledge, cultural acceptance, and understanding of the significant degree of HIV protection conferred as part of the VMMC decision making process. These results support incorporating comprehensive HIV risk reduction in VMMC promotion programs.

Oncological Outcomes in Japanese Men Undergoing Orchiectomy for Stage I Testicular Germ Cell Tumor

PubMed Central

Harada, Ken-ichi; Miyake, Hideaki; Ogawa, Takayoshi; Inoue, Taka-aki; Fujisawa, Masato

2015-01-01

Background The objective of this study was to retrospectively review oncological outcomes in patients with stage I testicular germ cell tumor (GCT). Patients and Methods This study included 265 consecutive Japanese men undergoing orchiectomy for stage I testicular GCT, and a retrospective review of their records was performed. Results Of these 265 patients, 192 and 73 were pathologically classified with seminoma and nonseminoma, respectively. Prophylactic radiation and chemotherapy were performed in 62 patients with seminoma and 6 with nonseminoma, respectively. Disease recurrence occurred in 12 seminoma patients, of whom 11 had not received prophylactic radiation therapy; however, all 12 achieved a complete response to bleomycin, etoposide and cisplatin therapy. Of the nonseminoma patients, 19 experienced disease recurrence and were then treated with bleomycin, etoposide and cisplatin followed additionally by the surgical resection of residual tumors and salvage chemotherapy in 7 and 4, respectively. There was no cancer-specific death in the 265 patients, and 5-year recurrence-free survival rates in patients with seminoma and nonseminoma were 92.6 and 72.8%, respectively. Furthermore, following factors appeared to be significantly associated with recurrence-free survival in these patients: age, T classification, microvascular invasion and adjuvant therapy for those with seminoma, and microvascular invasion for those with nonseminoma. Conclusions Despite a generally favorable prognosis in Japanese men with stage I testicular GCT, intensive follow-up or prophylactic therapy should be considered for men with possible risk factors of disease recurrence. PMID:26889123

Transgender men's experiences of fertility preservation: a qualitative study.

PubMed

Armuand, G; Dhejne, C; Olofsson, J I; Rodriguez-Wallberg, K A

2017-02-01

How do transgender men experience fertility preservation (FP) by cryopreservation of oocytes? The procedures required prior to oocyte cryopreservation, such as hormonal ovarian stimulation and transvaginal ultrasound (TVS), have a negative impact on gender dysphoria as they are closely linked to the men's female assigned sex at birth, which is incompatible with their current status. Transgender persons often have high dissatisfaction with assigned sex-specific body features, such as the genital organs and androgen/oestrogen-responsive features. Thus, undergoing FP that requires genital-specific examinations, aimed at obtaining oocytes to cryopreserve, could be distressing. As no previous studies have investigated transgender men's experiences of FP involving cryopreservation of oocytes, little is known about their experience of the procedures. This is a prospective study among adult transgender men referred for FP between March 2014 and December 2015. Individual in-depth qualitative interviews were conducted shortly after FP treatment. The interviews lasted between 62 and 111 min (mean 81 min) and were digitally recorded and transcribed verbatim. Participants were recruited on their first visit to the assisted reproduction clinic for reproductive counseling. There were 15 men, scheduled for FP, who chose to participate in the study (age 19-35); none had given birth and eight had a partner. Data were analyzed by thematic content analysis. The analysis resulted in three main categories: the journey to FP, reactions to the FP proceedings and strategies for coping. The referral for FP was an important part of the assessment and diagnosis and sometimes lined with frustrating waits and doubts. The reaction to the FP proceedings revealed that the genital examinations and the physical changes associated with discontinuation of testosterone or hormonal stimulation treatment triggered gender incongruence and dysphoria. However, for some, the negative expectations were not met. The participants used several coping strategies in order to manage the procedure, such as focusing on their reasons for undergoing FP, reaching out to friends and family for support and the cognitive approaches of not hating their body or using non-gendered names for their body parts. The results demonstrate the importance of contextual sensitivity during FP procedures. The authors have strived to be reflective about their pre-understanding of the phenomenon. The majority of the participants resided in large urban areas; it is possible that transgender men living in rural areas have different experiences. As the results are based on qualitative data from 15 transgender men, the results cannot readily be generalized to larger populations. However, the results are suggested to be applicable to other transgender men who want to undergo FP by cryopreservation of oocytes. The results show that transgender men's experience of FP places may elicit gender incongruence and gender dysphoria. However, health care personnel can alleviate distress by using a gender-neutral language and the preferred pronoun. Also, reassuringly, the men also have coping strategies of how to handle the situation. This knowledge is important to ensure adequate professional support for patients with gender dysphoria during FP. Swedish Society of Medicine, Stockholm County Council and Karolinska Institutet (to K.A.R.-W.). N/A. © The Author 2016. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Targeted metabolomics: new insights into pathobiology of retained placenta in dairy cows and potential risk biomarkers.

PubMed

Dervishi, E; Zhang, G; Mandal, R; Wishart, D S; Ametaj, B N

2018-05-01

A targeted quantitative metabolomics approach was used to study temporal changes of serum metabolites in cows that normally released their fetal membranes and those that retained the placenta. We identified and measured serum concentrations of 128 metabolites including amino acids, acylcarnitines, biogenic amines, glycerophospholipids, sphingolipids and hexose at -8 and -4 weeks before parturition, during the week of retained placenta (RP) diagnosis, and at +4 and +8 weeks after parturition. In addition, we aimed at identifying metabolite signatures of pre-RP in the serum that might be used as predictive biomarkers for risk of developing RP in dairy cows. Results revealed major alterations in the metabolite fingerprints of pre-RP cows starting as early as -8 weeks before parturition and continuing as far as +8 weeks after calving. Biomarker candidates found in this study are mainly biomarkers of inflammation which might not be specific to RP. Therefore, the relevance of serum Lys, Orn, acetylornithine, lysophophatidylcholine LysoPC a C28:0, Asp, Leu and Ile as potential serum biomarkers for prediction of risk of RP in dairy cows will have to be tested in the future. In addition, lower concentrations of LysoPCs, Trp, and higher kynurenine in the serum during prepartum and the week of occurrence of RP suggest involvement of inflammation in the pathobiology of RP.

Roselle Polyphenols Exert Potent Negative Inotropic Effects via Modulation of Intracellular Calcium Regulatory Channels in Isolated Rat Heart.

PubMed

Lim, Yi-Cheng; Budin, Siti Balkis; Othman, Faizah; Latip, Jalifah; Zainalabidin, Satirah

2017-07-01

Roselle (Hibiscus sabdariffa Linn.) calyces have demonstrated propitious cardioprotective effects in animal and clinical studies; however, little is known about its action on cardiac mechanical function. This study was undertaken to investigate direct action of roselle polyphenols (RP) on cardiac function in Langendorff-perfused rat hearts. We utilized RP extract which consists of 12 flavonoids and seven phenolic acids (as shown by HPLC profiling) and has a safe concentration range between 125 and 500 μg/ml in this study. Direct perfusion of RP in concentration-dependent manner lowered systolic function of the heart as shown by lowered LVDP and dP/dt max , suggesting a negative inotropic effect. RP also reduced heart rate (negative chronotropic action) while simultaneously increasing maximal velocity of relaxation (positive lusitropic action). Conversely, RP perfusion increased coronary pressure, an indicator for improvement in coronary blood flow. Inotropic responses elicited by pharmacological agonists for L-type Ca 2+ channel [(±)-Bay K 8644], ryanodine receptor (4-chloro-m-cresol), β-adrenergic receptor (isoproterenol) and SERCA blocker (thapsigargin) were all abolished by RP. In conclusion, RP elicits negative inotropic, negative chronotropic and positive lusitropic responses by possibly modulating calcium entry, release and reuptake in the heart. Our findings have shown the potential use of RP as a therapeutic agent to treat conditions like arrhythmia.

A meta-analysis of robotic-assisted pancreatectomy versus laparoscopic and open pancreatectomy.

PubMed

Chen, Yigang; Yan, Jun; Yuan, Ziming; Yu, Song; Wang, Zhigang; Zheng, Qi

2013-12-01

To perform a meta-analysis of eligible studies from multiple medical centers to assess the safety, feasibility, and efficacy of robotic-assisted pancreatectomy (RP). We searched the electronic databases PubMed and EMBASE for studies comparing RP with laparoscopic pancreatectomy (LP) and open pancreatectomy (OP) for patients with pancreatic disease from June 2009 to June 2012. Continuous variables were pooled using the standardized mean difference (SMD) and odds ratio (OR), and dichotomous variables were pooled using the risk difference (RD) method. For all analyses, the 95% confidence interval (CI) was calculated. Three studies comparing RP and LP, and 4 studies comparing RP and OP were suitable for meta-analysis. Six published studies met the inclusion criteria. Our results showed that RP can reduce estimated blood loss and duration of hospitalization more than OP. For pancreatic fistula, there were no statistical differences between RP, OP, and LP, and no significant differences in intraoperative conversion rates between RP and LP. Robotic-assisted pancreatectomy may be able to increase microscopic negative margins of resection (R0) and spleen preserving rates. Robotic-assisted pancreatectomy was associated with increased R0 resection rates and spleen preserving rates than LP and OP. Moreover, RP can reduce estimated blood loss and duration of hospitalization more than OP. A robotic approach to pancreatectomy may be suited to patients with pancreatic disease.

Novel hypophysiotropic AgRP2 neurons and pineal cells revealed by BAC transgenesis in zebrafish.

PubMed

Shainer, Inbal; Buchshtab, Adi; Hawkins, Thomas A; Wilson, Stephen W; Cone, Roger D; Gothilf, Yoav

2017-03-20

The neuropeptide agouti-related protein (AgRP) is expressed in the arcuate nucleus of the mammalian hypothalamus and plays a key role in regulating food consumption and energy homeostasis. Fish express two agrp genes in the brain: agrp1, considered functionally homologous with the mammalian AgRP, and agrp2. The role of agrp2 and its relationship to agrp1 are not fully understood. Utilizing BAC transgenesis, we generated transgenic zebrafish in which agrp1- and agrp2-expressing cells can be visualized and manipulated. By characterizing these transgenic lines, we showed that agrp1-expressing neurons are located in the ventral periventricular hypothalamus (the equivalent of the mammalian arcuate nucleus), projecting throughout the hypothalamus and towards the preoptic area. The agrp2 gene was expressed in the pineal gland in a previously uncharacterized subgroup of cells. Additionally, agrp2 was expressed in a small group of neurons in the preoptic area that project directly towards the pituitary and form an interface with the pituitary vasculature, suggesting that preoptic AgRP2 neurons are hypophysiotropic. We showed that direct synaptic connection can exist between AgRP1 and AgRP2 neurons in the hypothalamus, suggesting communication and coordination between AgRP1 and AgRP2 neurons and, therefore, probably also between the processes they regulate.

Real-time monitoring of steady-state pulsed chemical beam epitaxy by p-polarized reflectance

NASA Astrophysics Data System (ADS)

Bachmann, K. J.; Sukidi, N.; Höpfner, C.; Harris, C.; Dietz, N.; Tran, H. T.; Beeler, S.; Ito, K.; Banks, H. T.

1998-01-01

The structure in the p-polarized reflectance (PR) intensity Rp4( t) - observed under conditions of pulsed chemical beam epitaxy (PCBE) - is modeled on the basis of the four-layer stack: ambient/surface reaction layer (SRL)/epilayer/substrate. Linearization of the PR intensity with regard to the phase factor associated with the SRL results in a good approximation that can be expressed as Rp4 = Rp3 + ΔRp. Rp3 is the reflectivity of the three-layer stack ambient-epilayer-substrate. ΔRp describes the properties of the SRL. An explicit relation is derived between ΔRp( t) and the time-dependent surface concentrations ch( t) ( h = 1, 2, …, N) of the constituents of the SRL, which holds for conditions of submonolayer coverage of the surface by source vapor molecules. Under conditions of low temperature PCBE at high flux, the SRL is expected to exhibit nonideal behavior, mandating replacement of the surface concentrations by activities. Also, in this case, the thickness of the SRL must be represented in terms of partial molar volumina Vh. Since the relation between ΔRp( t) and the activities of reactants, intermediates and products of the chemical reactions driving heteroepitaxial growth is non-linear, the extraction of kinetic parameters from the measured time dependence of the PR signal generally requires numerical modeling.

Identification of amino acid residues involved in the dRP-lyase activity of human Pol ι.

PubMed

Miropolskaya, Nataliya; Petushkov, Ivan; Kulbachinskiy, Andrey; Makarova, Alena V

2017-08-31

Besides X-family DNA polymerases (first of all, Pol β) several other human DNA polymerases from Y- and A- families were shown to possess the dRP-lyase activity and could serve as backup polymerases in base excision repair (Pol ι, Rev1, Pol γ and Pol θ). However the exact position of the active sites and the amino acid residues involved in the dRP-lyase activity in Y- and A- family DNA polymerases are not known. Here we carried out functional analysis of fifteen amino acid residues possibly involved in the dRP-lyase activity of human Pol ι. We show that substitutions of residues Q59, K60 and K207 impair the dRP-lyase activity of Pol ι while residues in the HhH motif of the thumb domain are dispensable for this activity. While both K60G and K207A substitutions decrease Schiff-base intermediate formation during dRP group cleavage, the latter substitution also strongly affects the DNA polymerase activity of Pol ι, suggesting that it may impair DNA binding. These data are consistent with an important role of the N-terminal region in the dRP-lyase activity of Pol ι, with possible involvement of residues from the finger domain in the dRP group cleavage.

Relative Bioavailability of Niacin Supplements for Dairy Cows: Effects of Rumen Protection and of Feed Processing.

PubMed

Tienken, Reka; Kersten, Susanne; Hüther, Liane; Frahm, Jana; Meyer, Ulrich; Dänicke, Sven

2015-12-16

The present study aimed to examine the effective systemic bioavailability of niacin- with particular focus on its galenic form-and feed processing. Experiment 1 was conducted with 35 dairy cows to investigate the effects of various doses of oral supplemented nicotinic acid (NA) either in differing galenic forms (non-rumen protected (nRP) vs. rumen protected form (RP)) on serum niacin concentrations. Experiment 2 was designed as a pharmacokinetic study examining the serum niacin kinetics over 24 h after giving a single oral bolus of 24 g nRP or RP NA admixed in either pelleted or ground concentrate. In both experiments, only the niacin vitamer nicotinamide (NAM) was detected. Results of experiment 1 showed that both galenic forms at a dose of 24 g/cow daily elevated NAM concentrations at the beginning of the experiment. Despite a daily supplementation, NAM concentrations decreased continuously towards the end of the experiment which was more steeply in nRP NA ( p = 0.03). On experimental day 21, NAM concentrations were higher when feeding RP NA ( p = 0.03) and the highest dose (24 g/day and cow) ( p < 0.01). Results of experiment 2 indicated that nRP and RP were characterized by similar pharmacokinetic profiles resulting in similar areas under the curves as a net result of the kinetic counterbalancing alterations. Pelleting seemed not to influence the relative bioavailability.

Down-regulation of long non-coding RNA RP11-708H21.4 is associated with poor prognosis for colorectal cancer and promotes tumorigenesis through regulating AKT/mTOR pathway.

PubMed

Sun, Longci; Jiang, Chunhui; Xu, Chunjie; Xue, Hanbing; Zhou, Hong; Gu, Lei; Liu, Ye; Xu, Qing

2017-04-25

Long non-coding RNAs (lncRNAs) serve critical roles in cancer development and progression. Herein, through next generation RNA sequencing and experimental validations, we determined the expression status of RP11-708H21.4 in colorectal cancer (CRC) and explored its clinical significance and biological functions in CRC. Differentially expressed lncRNAs from CRC samples and corresponding normal mucosa tissues was screened through RNA sequencing, and RP11-708H21.4 was selected for further experimental validation. The expression levels of RP11-708H21.4 in CRC tissues and cell lines were determined using qRT-PCR. Also, the relationship between the clinicopathological features and RP11-708H21.4 expression was analyzed. Cell viability was examined by CCK-8 and colony assays; cell migration and invasion were detected by transwell assays; cell cycle and cell apoptosis were analyzed by flow cytometry. The chemosensitivity of CRC cells to 5-Fluorouracil (5-FU) was also determined using CCK-8 assay. CRC xenograft tumor models were established to determine the biological functions of RP11-708H21.4 in vivo. Levels of cell cycle-related proteins and AKT/mTOR pathway-related proteins were detected by western blot assay. RP11-708H21.4 expression was aberrantly decreased in CRC, and its expression was closely associated with aggressive clinicopathologic features and unfavorable prognosis of CRC patients. Overexpressed RP11-708H21.4 suppresses CRC cell proliferation through inducing G1 arrest. Moreover, up-regulation of RP11-708H21.4 inhibits cell migration and invasion, causes cell apoptosis, and enhances 5-FU sensitivity of CRC cells. Finally, increased RP11-708H21.4 expression blocked AKT/mTOR pathway, and repressed in vivo CRC xenograft tumor growth. The results indicated that RP11-708H21.4 might have potential roles as a biomarker and a therapeutic target for CRC.

What is the role of retroperitoneal exploration in optimally debulked stage IIIC epithelial ovarian cancer? An NRG Oncology/Gynecologic Oncology Group ancillary data study.

PubMed

Rungruang, Bunja J; Miller, Austin; Krivak, Thomas C; Horowitz, Neil S; Rodriguez, Noah; Hamilton, Chad A; Backes, Floor J; Carson, Linda F; Friedlander, Michael; Mutch, David G; Goodheart, Michael J; Tewari, Krishnansu S; Wenham, Robert M; Bookman, Michael A; Maxwell, G Larry; Richard, Scott D

2017-05-15

The purpose of this study was to determine the effect of retroperitoneal (RP) exploration on progression-free survival (PFS) and overall survival (OS) in epithelial ovarian cancer (EOC) patients with stage IIIC disease who underwent optimal debulking surgery. Data were collected from records of the Gynecologic Oncology Group 182 (GOG-182) study of stage IIIC EOC patients cytoreduced to no gross residual disease (R0) or minimal gross residual (<1 cm) disease (MGRD) at primary surgery. Patients with stage IIIC disease by intraperitoneal (IP) tumor were included and divided into 3 groups: 1) > 2 cm IP tumor without lymph node involvement (IP/RP-), 2) > 2 cm IP tumor with lymph node involvement (IP/RP+), and 3) > 2 cm IP tumor with no RP exploration (IP/RP?). The effects of disease distribution and RP exploration on PFS and OS were assessed using Kaplan-Meier and proportional hazards methods. There were 1871 stage IIIC patients in GOG-182 who underwent optimal primary debulking surgery. Of these, 689 (36.8%) underwent RP exploration with removal of lymph nodes from at least 1 para-aortic site, and 1182 (63.2%) did not. There were 269 patients in the IP/RP- group, 420 patients in the IP/RP + group, and 1182 patients in the IP/RP? group. Improved PFS (18.5 vs 16.0 months; P < .0001) and OS (53.3 vs 42.8 months; P < .0001) were associated with RP exploration versus no exploration. Patients with MGRD had improved PFS (16.8 vs 15.1 months, P = 0.0108) and OS (44.9 vs 40.5 months, P = 0.0076) versus no exploration. RP exploration at the time of primary surgery in patients with optimally debulked stage IIIC EOC is associated with a survival benefit. Cancer 2017;123:985-93. © 2016 American Cancer Society. © 2016 American Cancer Society.

The Association between Socioeconomic Status and Adherence to Health Check-up in Korean Adults, Based on the 2010–2012 Korean National Health and Nutrition Examination Survey

PubMed Central

Shin, Hyun-Young; Lim, Hyoung-Ji

2018-01-01

Background We investigated the association between socioeconomic status and adherence to health check-ups in a Korean population aged 40 years or older. Methods This cross-sectional study included 12,311 participants who participated in the 2010–2012 Korean National Health and Nutrition Examination Survey. Self-reported questionnaires were used to assess each participant's socioeconomic status (household income, occupation, and education) and adherence to health check-ups. Results Men with a higher income (highest vs. lowest: odds ratio [OR], 1.799; 95% confidence interval [CI], 1.296–2.497) and men with a higher education level (≥12 vs. <6 years: OR, 1.488; 95% CI, 1.078–2.054) and office workers compared with manual workers (men: OR, 1.431; 95% CI, 1.077–1.902; women: OR, 1.783; 95% CI, 1.256–2.532) appeared to undergo more health check-ups. In particular, men and women with a higher income and education appeared more likely to undergo opportunistic health check-ups (men: highest vs. lowest income: OR, 2.380; 95% CI, 1.218–4.653; ≥12 vs. <6 years education: OR, 2.121; 95% CI, 1.142–3.936; women: highest vs. lowest income: OR, 4.042; 95% CI, 2.239–7.297; ≥12 vs. <6 years education: OR, 2.475; 95% CI, 1.283–4.775). Conclusion A higher socioeconomic status was associated with a higher rate of participation in health check-ups. More efforts are needed to identify the factors associated with disparity in adherence to health check-ups. PMID:29629044

Comparison between AMS 700™ CX and Coloplast™ Titan inflatable penile prosthesis for Peyronie's disease treatment and remodeling: clinical outcomes and patient satisfaction.

PubMed

Chung, Eric; Solomon, Matthew; DeYoung, Ling; Brock, Gerald B

2013-11-01

The implantation of inflatable penile prosthesis (IPP) with simultaneous manual penile remodeling allows for men to undergo a single procedure aimed at correcting both the penile deformity/curvature and erectile dysfunction (ED). To evaluate the clinical outcomes and patient satisfaction in men with Peyronie's disease (PD) and ED who underwent AMS 700™ CX and the newer Coloplast™ Titan inflatable penile prosthesis (IPP) implant. Patient demographics, type of IPP, clinical outcomes, post-implant sexual characteristics, and overall patient satisfaction. A single-center retrospective review of clinical database and prospective telephone survey were conducted in all men with PD who underwent IPP between January 2006 and November 2010. A total of 138 patients with an average age of 57.7 (32 to 80) underwent AMS 700 CX (88 patients) and Coloplast Titans (50 patients) IPP implantation during the 5-year period. The majority of patients (91%) had only one IPP implantation. The IPP clinical outcomes include eight (6%) revision surgery for device malfunction and three (2%) device explantation for prosthesis infection. While there was no statistically significance in device survival between the two devices, the trend favored AMS 700 CX over Titan (5-year Kaplan-Meier estimates of mechanical survival were 91% vs. 87%, P>0.05) and both IPPs provided similar penile straightening without the need for revision surgery. Most men (79%) reported great satisfaction following CX or Titan implants with greater than two thirds of men reported greater self-confidence and 82% of patients would undergo the same operation again. AMS 700™ CX and Coloplast™ Titan IPP implantation and penile remodeling appeared to provide permanent penile straightening and high patient satisfaction without an increase risk of revision surgery. © 2012 International Society for Sexual Medicine.

The effect of total knee arthroplasty on body weight.

PubMed

Lee, Gwo-Chin; Cushner, Fred D; Cannella, Laura Y; Scott, W Norman

2005-03-01

This prospective study quantified the weight change in 20 consecutive patients undergoing total knee arthroplasty. Resected bone, soft tissues, and bone reamings were collected during surgery and weighed using a digital scale at the end of the procedure. Results were compared to the cumulative weights of the prosthesis, bone cement, patellar component, and polyethylene liner. Average weight of the resected bone and soft tissues was 167.71 g for men and 130.13 g for women. Mean weight of the implanted prosthesis and cement used was 509.92 g for men and 422.56 g for women. Men tended to receive a larger-sized prosthesis than women. Overall, the average weight gain as a result of knee arthroplasty was 345.54 g for men and 292.44 g for women. This translates to an insignificant increase in body weight.

A community-based randomised controlled trial of three different educational resources for men about prostate cancer screening.

PubMed

Gattellari, Melina; Ward, Jeanette E

2005-05-01

Randomised evaluations of resources to facilitate informed decisions about prostate cancer screening are rarely conducted. In this study, 421 men recruited from the community were randomly allocated to receive a leaflet (n = 140) or one of two resources meeting criteria for a decision-aid: a video (n = 141) or an evidence-based booklet, developed by the authors (n = 140). Men in all three groups demonstrated significant increases in knowledge scores from pre to post-test. Scores were significantly higher at post-test amongst those who had received our evidence-based booklet compared with men who received the leaflet or video (P < 0.001). Scores were significantly modified by men's preferences for decisional control (P = 0.002). Decisional conflict was significantly lower amongst men receiving the evidence-based booklet (P = 0.038). Men receiving the evidence-based booklet also were less likely to accept a recommendation by a GP to undergo prostate-specific-antigen (PSA) screening (P = 0.003). Men require detailed information about the pros and cons of PSA screening in order to make an informed decision. Resources are not equivalent in achieving these outcomes.

All men with vasculogenic erectile dysfunction require a cardiovascular workup.

PubMed

Miner, Martin; Nehra, Ajay; Jackson, Graham; Bhasin, Shalender; Billups, Kevin; Burnett, Arthur L; Buvat, Jacques; Carson, Culley; Cunningham, Glenn; Ganz, Peter; Goldstein, Irwin; Guay, Andre; Hackett, Geoff; Kloner, Robert A; Kostis, John B; LaFlamme, K Elizabeth; Montorsi, Piero; Ramsey, Melinda; Rosen, Raymond; Sadovsky, Richard; Seftel, Allen; Shabsigh, Ridwan; Vlachopoulos, Charalambos; Wu, Frederick

2014-03-01

An association between erectile dysfunction and cardiovascular disease has long been recognized, and studies suggest that erectile dysfunction is an independent marker of cardiovascular disease risk. Therefore, assessment and management of erectile dysfunction may help identify and reduce the risk of future cardiovascular events, particularly in younger men. The initial erectile dysfunction evaluation should distinguish between predominantly vasculogenic erectile dysfunction and erectile dysfunction of other etiologies. For men believed to have predominantly vasculogenic erectile dysfunction, we recommend that initial cardiovascular risk stratification be based on the Framingham Risk Score. Management of men with erectile dysfunction who are at low risk for cardiovascular disease should focus on risk-factor control; men at high risk, including those with cardiovascular symptoms, should be referred to a cardiologist. Intermediate-risk men should undergo noninvasive evaluation for subclinical atherosclerosis. A growing body of evidence supports the use of emerging prognostic markers to further understand cardiovascular risk in men with erectile dysfunction, but few markers have been prospectively evaluated in this population. In conclusion, we support cardiovascular risk stratification and risk-factor management in all men with vasculogenic erectile dysfunction. Copyright © 2014 Elsevier Inc. All rights reserved.

Enhancing rock phosphate integration rate for fast bio-transformation of cow-dung waste-paper mixtures to organic fertilizer.

PubMed

Unuofin, F O; Siswana, M; Cishe, E N

2016-01-01

Rock phosphate (RP) addition in cow-dung waste-paper mixtures at rates above 2% P has been reported to increase the rate of bio-transformation and humification of organic waste mixtures during vermicomposting to produce organic fertilizer for organic farming. However, the optimization of RP for vermicomposting was not established. The objective of this study was to determine the optimal amount of RP integration rates for effective bio-transformation of cow-dung waste-paper mixtures. Arrays of RP integration degrees (0, 0.5, 1, 1.5, 2, and 4% P as RP) were thoroughly mixed with cow- dung waste-paper mixtures to achieve an optimized C:N ratio of 30 and allowed to vermidegrade following the introduction of earthworms at a stocking mass of 12.5 g-worms kg -1 . The bio-transformation of the waste mixtures was examined by measuring C:N ratios and humification index (HI) and per cent ash and volatile solids. Application of 1% P as RP resulted in fast bio-transformation and maturation of cow-dung waste-paper mixtures. A scanning electron microscopy (SEM) was used to evaluate the morphological properties of the different vermicomposts affected by rates of RP showing the degree of degradation of initial compacted aggregates of cellulose and protein fibres in the mixtures at maturity. A germination test was used to further determine phytotoxicity of the final composts and microbial biomass assessment. The final vermicompost (organic fertilizer) had a C:N ratio of 7, MBC of 900 mg kg -1 and HI of 27.1%. The RP incorporation rate of 1% P of RP investigated is therefore, recommended for efficient vermidegradation and humification of cow-dung waste-paper mixtures. However, higher rates of RP incorporation should be considered where greater P enrichment of the final vermicompost (organic fertilizer) is desired.

Peroxisome proliferator-activated receptor γ controls ingestive behavior, agouti-related protein, and neuropeptide Y mRNA in the arcuate hypothalamus.

PubMed

Garretson, John T; Teubner, Brett J W; Grove, Kevin L; Vazdarjanova, Almira; Ryu, Vitaly; Bartness, Timothy J

2015-03-18

Peroxisome proliferator-activated receptor γ (PPARγ) is clinically targeted for type II diabetes treatment; however, rosiglitazone (ROSI), a PPARγ agonist, increases food intake and body/fat mass as side-effects. Mechanisms for these effects and the role of PPARγ in feeding are not understood. Therefore, we tested this role in Siberian hamsters, a model of human energy balance, and C57BL/6 mice. We tested the following: (1) how ROSI and/or GW9662 (2-chloro-5-nitro-N-phenylbenzamide; PPARγ antagonist) injected intraperitoneally or into the third ventricle (3V) affected Siberian hamster feeding behaviors; (2) whether food deprivation (FD) co-increases agouti-related protein (AgRP) and PPARγ mRNA expression in Siberian hamsters and mice; (3) whether intraperitoneally administered ROSI increases AgRP and NPY in ad libitum-fed animals; (4) whether intraperitoneally administered PPARγ antagonism blocks FD-induced increases in AgRP and NPY; and finally, (5) whether intraperitoneally administered PPARγ modulation affects plasma ghrelin. Third ventricular and intraperitoneally administered ROSI increased food hoarding and intake for 7 d, an effect attenuated by 3V GW9662, and also prevented (intraperitoneal) FD-induced feeding. FD hamsters and mice increased AgRP within the arcuate hypothalamic nucleus with concomitant increases in PPARγ exclusively within AgRP/NPY neurons. ROSI increased AgRP and NPY similarly to FD, and GW9662 prevented FD-induced increases in AgRP and NPY in both species. Neither ROSI nor GW9662 affected plasma ghrelin. Thus, we demonstrated that PPARγ activation is sufficient to trigger food hoarding/intake, increase AgRP/NPY, and possibly is necessary for FD-induced increases in feeding and AgRP/NPY. These findings provide initial evidence that FD-induced increases in AgRP/NPY may be a direct PPARγ-dependent process that controls ingestive behaviors. Copyright © 2015 the authors 0270-6474/15/354571-11$15.00/0.

Peroxisome Proliferator-Activated Receptor γ Controls Ingestive Behavior, Agouti-Related Protein, and Neuropeptide Y mRNA in the Arcuate Hypothalamus

PubMed Central

Garretson, John T.; Teubner, Brett J.W.; Grove, Kevin L.; Vazdarjanova, Almira; Ryu, Vitaly

2015-01-01

Peroxisome proliferator-activated receptor γ (PPARγ) is clinically targeted for type II diabetes treatment; however, rosiglitazone (ROSI), a PPARγ agonist, increases food intake and body/fat mass as side-effects. Mechanisms for these effects and the role of PPARγ in feeding are not understood. Therefore, we tested this role in Siberian hamsters, a model of human energy balance, and C57BL/6 mice. We tested the following: (1) how ROSI and/or GW9662 (2-chloro-5-nitro-N-phenylbenzamide; PPARγ antagonist) injected intraperitoneally or into the third ventricle (3V) affected Siberian hamster feeding behaviors; (2) whether food deprivation (FD) co-increases agouti-related protein (AgRP) and PPARγ mRNA expression in Siberian hamsters and mice; (3) whether intraperitoneally administered ROSI increases AgRP and NPY in ad libitum-fed animals; (4) whether intraperitoneally administered PPARγ antagonism blocks FD-induced increases in AgRP and NPY; and finally, (5) whether intraperitoneally administered PPARγ modulation affects plasma ghrelin. Third ventricular and intraperitoneally administered ROSI increased food hoarding and intake for 7 d, an effect attenuated by 3V GW9662, and also prevented (intraperitoneal) FD-induced feeding. FD hamsters and mice increased AgRP within the arcuate hypothalamic nucleus with concomitant increases in PPARγ exclusively within AgRP/NPY neurons. ROSI increased AgRP and NPY similarly to FD, and GW9662 prevented FD-induced increases in AgRP and NPY in both species. Neither ROSI nor GW9662 affected plasma ghrelin. Thus, we demonstrated that PPARγ activation is sufficient to trigger food hoarding/intake, increase AgRP/NPY, and possibly is necessary for FD-induced increases in feeding and AgRP/NPY. These findings provide initial evidence that FD-induced increases in AgRP/NPY may be a direct PPARγ-dependent process that controls ingestive behaviors. PMID:25788674

Rp-cAMPS Prodrugs Reveal the cAMP Dependence of First-Phase Glucose-Stimulated Insulin Secretion

PubMed Central

Schwede, Frank; Chepurny, Oleg G.; Kaufholz, Melanie; Bertinetti, Daniela; Leech, Colin A.; Cabrera, Over; Zhu, Yingmin; Mei, Fang; Cheng, Xiaodong; Manning Fox, Jocelyn E.; MacDonald, Patrick E.; Genieser, Hans-G.; Herberg, Friedrich W.

2015-01-01

cAMP-elevating agents such as the incretin hormone glucagon-like peptide-1 potentiate glucose-stimulated insulin secretion (GSIS) from pancreatic β-cells. However, a debate has existed since the 1970s concerning whether or not cAMP signaling is essential for glucose alone to stimulate insulin secretion. Here, we report that the first-phase kinetic component of GSIS is cAMP-dependent, as revealed through the use of a novel highly membrane permeable para-acetoxybenzyl (pAB) ester prodrug that is a bioactivatable derivative of the cAMP antagonist adenosine-3′,5′-cyclic monophosphorothioate, Rp-isomer (Rp-cAMPS). In dynamic perifusion assays of human or rat islets, a step-wise increase of glucose concentration leads to biphasic insulin secretion, and under these conditions, 8-bromoadenosine-3′,5′-cyclic monophosphorothioate, Rp-isomer, 4-acetoxybenzyl ester (Rp-8-Br-cAMPS-pAB) inhibits first-phase GSIS by up to 80%. Surprisingly, second-phase GSIS is inhibited to a much smaller extent (≤20%). Using luciferase, fluorescence resonance energy transfer, and bioluminescence resonance energy transfer assays performed in living cells, we validate that Rp-8-Br-cAMPS-pAB does in fact block cAMP-dependent protein kinase activation. Novel effects of Rp-8-Br-cAMPS-pAB to block the activation of cAMP-regulated guanine nucleotide exchange factors (Epac1, Epac2) are also validated using genetically encoded Epac biosensors, and are independently confirmed in an in vitro Rap1 activation assay using Rp-cAMPS and Rp-8-Br-cAMPS. Thus, in addition to revealing the cAMP dependence of first-phase GSIS from human and rat islets, these findings establish a pAB-based chemistry for the synthesis of highly membrane permeable prodrug derivatives of Rp-cAMPS that act with micromolar or even nanomolar potency to inhibit cAMP signaling in living cells. PMID:26061564

Ginsenoside-Rp3 inhibits platelet activation and thrombus formation by regulating MAPK and cyclic nucleotide signaling.

PubMed

Irfan, Muhammad; Jeong, Da Hye; Kwon, Hyuk-Woo; Shin, Jung-Hae; Park, Sang-Joon; Kwak, Dongmi; Kim, Tae-Hwan; Lee, Dong-Ha; Park, Hwa-Jin; Rhee, Man Hee

2018-06-08

Ginseng (Panax ginseng C.A. Mayer) contains saponin fractions called ginsenosides, which are thought to be the main components responsible for its various pharmacological activities. Ginsenosides have cardioprotective and antiplatelet effects. In the present study, we evaluated the effects of ginsenoside Rp3 (G-Rp3) on platelet function. The in vitro effects of G-Rp3 were evaluated on agonist-induced human and rat platelet aggregation, while [Ca 2+ ] i mobilization, granule secretion, integrin α IIb β 3 activation, and clot retraction were assessed in rat platelets. Its effects on vasodilator-stimulated phosphoprotein (VASP) expression, phosphorylation of MAPK signaling molecules, and PI3K/Akt activation were also studied. Moreover, the tyrosine phosphorylation of components of the P 2 Y 12 receptor downstream signaling pathway was also examined. The in vivo effects of G-Rp3 were studied using an acute pulmonary thromboembolism model and lung histopathology. G-Rp3 significantly inhibited collagen, ADP, and thrombin-induced platelet aggregation. G-Rp3 elevated cAMP levels and VASP phosphorylation and suppressed agonist-induced [Ca 2+ ] i mobilization, ATP release, and P-selectin expression along with fibrinogen binding to integrin α IIb β 3 , fibronectin adhesion, and clot retraction. G-Rp3 also attenuated the phosphorylation of MAPK, Src, and PLCγ2 as well as PI3K/Akt activation. Furthermore, it inhibited tyrosine phosphorylation of the Src family kinases (Src, Fyn, and Lyn) and PLCγ2 and protected mice from thrombosis. G-Rp3 modulates agonist-induced platelet activation and thrombus formation by inhibiting granule secretion, integrin α IIb β 3 activation, MAPK signaling, and Src, PLCγ2, and PI3K/Akt activation, and VASP stimulation. Our data suggest that G-Rp3 has therapeutic potential as a treatment for platelet-related cardiovascular disorders. Copyright © 2017. Published by Elsevier Inc.

Genetic heterogeneity and consanguinity lead to a “double hit”: Homozygous mutations of MYO7A and PDE6B in a patient with retinitis pigmentosa

PubMed Central

Goldenberg-Cohen, Nitza; Banin, Eyal; Zalzstein, Yael; Cohen, Ben; Rotenstreich, Ygal; Rizel, Leah; Basel-Vanagaite, Lina

2013-01-01

Purpose Retinitis pigmentosa (RP), the most genetically heterogeneous disorder in humans, actually represents a group of pigmentary retinopathies characterized by night blindness followed by visual-field loss. RP can appear as either syndromic or nonsyndromic. One of the most common forms of syndromic RP is Usher syndrome, characterized by the combination of RP, hearing loss, and vestibular dysfunction. Methods The underlying cause of the appearance of syndromic and nonsyndromic RP in three siblings from a consanguineous Israeli Muslim Arab family was studied with whole-genome homozygosity mapping followed by whole exome sequencing. Results The family was found to segregate novel mutations of two different genes: myosin VIIA (MYO7A), which causes type 1 Usher syndrome, and phosphodiesterase 6B, cyclic guanosine monophosphate-specific, rod, beta (PDE6B), which causes nonsyndromic RP. One affected child was homozygous for both mutations. Since the retinal phenotype seen in this patient results from overlapping pathologies, one might expect to find severe retinal degeneration. Indeed, he was diagnosed with RP based on an abnormal electroretinogram (ERG) at a young age (9 months). However, this early diagnosis may be biased, as two of his older siblings had already been diagnosed, leading to increased awareness. At the age of 32 months, he had relatively good vision with normal visual fields. Further testing of visual function and structure at different ages in the three siblings is needed to determine whether the two RP-causing genes mutated in this youngest sibling confer increased disease severity. Conclusions This report further supports the genetic heterogeneity of RP, and demonstrates how consanguinity could increase intrafamilial clustering of multiple hereditary diseases. Moreover, this report provides a unique opportunity to study the clinical implications of the coexistence of pathogenic mutations in two RP-causative genes in a human patient. PMID:23882135

Genetic heterogeneity and consanguinity lead to a "double hit": homozygous mutations of MYO7A and PDE6B in a patient with retinitis pigmentosa.

PubMed

Goldenberg-Cohen, Nitza; Banin, Eyal; Zalzstein, Yael; Cohen, Ben; Rotenstreich, Ygal; Rizel, Leah; Basel-Vanagaite, Lina; Ben-Yosef, Tamar

2013-01-01

Retinitis pigmentosa (RP), the most genetically heterogeneous disorder in humans, actually represents a group of pigmentary retinopathies characterized by night blindness followed by visual-field loss. RP can appear as either syndromic or nonsyndromic. One of the most common forms of syndromic RP is Usher syndrome, characterized by the combination of RP, hearing loss, and vestibular dysfunction. The underlying cause of the appearance of syndromic and nonsyndromic RP in three siblings from a consanguineous Israeli Muslim Arab family was studied with whole-genome homozygosity mapping followed by whole exome sequencing. THE FAMILY WAS FOUND TO SEGREGATE NOVEL MUTATIONS OF TWO DIFFERENT GENES: myosin VIIA (MYO7A), which causes type 1 Usher syndrome, and phosphodiesterase 6B, cyclic guanosine monophosphate-specific, rod, beta (PDE6B), which causes nonsyndromic RP. One affected child was homozygous for both mutations. Since the retinal phenotype seen in this patient results from overlapping pathologies, one might expect to find severe retinal degeneration. Indeed, he was diagnosed with RP based on an abnormal electroretinogram (ERG) at a young age (9 months). However, this early diagnosis may be biased, as two of his older siblings had already been diagnosed, leading to increased awareness. At the age of 32 months, he had relatively good vision with normal visual fields. Further testing of visual function and structure at different ages in the three siblings is needed to determine whether the two RP-causing genes mutated in this youngest sibling confer increased disease severity. This report further supports the genetic heterogeneity of RP, and demonstrates how consanguinity could increase intrafamilial clustering of multiple hereditary diseases. Moreover, this report provides a unique opportunity to study the clinical implications of the coexistence of pathogenic mutations in two RP-causative genes in a human patient.

[Self-reported discrimination by adolescents in a Brazilian birth cohort: prevalence and associations].

PubMed

Gonçalves, Helen; Dumith, Samuel C; González, David Alejandro; Menezes, Ana M B; Araújo, Cora L P; Hallal, Pedro C; Bastos, João Luiz

2012-03-01

To evaluate the prevalence of and factors associated with discrimination self-reported by adolescents. Cross-sectional analysis of adolescents belonging to a cohort of live births in 1993 in the city of Pelotas, Brazil. From the 5 249 members of the cohort, information was collected from 4 452 adolescents in 2004 and 2005 regarding self-reported discrimination, sociodemographic variables, physical attributes, and nutritional status. A Poisson regression was utilized in the raw and adjusted analyses to estimate prevalence rates (RP). The global prevalence of self-reported discrimination was 16.4%. In the adjusted analysis, discrimination was reported more by the following groups: girls (RP = 1.27, 95%CI: 1.10-1.48), people identified by others as black (RP = 1.28, 95%CI: 1.04-1.57), poorer adolescents (RP = 1.58, 95%CI: 1.23-2.02), those who perceived themselves to be very thin or very fat (RP = 1.81 and 1.54 respectively), those whose families had financial trouble (RP = 1.76, 95%CI: 1.49-2.08), those who wore glasses (RP = 1.74, 95%CI: 1.45-2.10), those who thought their teeth looked bad (RP = 1.58, 95%CI: 1.21-2.07), those who had been reprimanded in school (RP = 1.23, 95%CI: 1.01- 1.51), and those who had been involved in fights in the past year (RP = 1.62, 95%CI: 1.36-1.94). The association between discrimination and nutritional status varied by sex (interaction P = 0.009). Thin children reported greater discrimination than those who were overweight or obese. Discrimination on the basis of obesity was higher among girls, with this effect more strongly felt among rich girls than among poor ones. Self-reported discrimination was prevalent and unequally distributed among the population. Actions to reduce experiences of discrimination must be implemented during the initial stages of life.

Lubrication of an 85-mm ball bearing with RP-1

NASA Technical Reports Server (NTRS)

Addy, Harold E., Jr.; Schuller, Fredrick T.

1993-01-01

A parametric experimental investigation of an 85 millimeter bore angular contact ball bearing running in RP-1 fuel was performed at speeds of 10,000 to 24,000 rpm. Thrust loads were varied from 4450 to 17,800 Newtons (1000 to 4000 lbs.). Radial loads were varied from 1335 to 13,350 Newtons (300 to 3000 lbs.). RP-1 lubrication for the bearing was provided through a stationary jet ring located adjacent to the test bearing outer ring. Increases in both the thrust and radial loads resulted in increased bearing temperature, while increases in shaft speed resulted in much more dramatic increases in bearing temperature. These trends are typical for ball bearings operating under these types of conditions. Results are given for outer ring temperatures of the test bearing at the various test conditions employed. In addition, the heat energy removed from the bearing by the RP-1 was determined by measuring the increase in temperature as the RP-1 passed through the bearing. Results showed that the amount of heat energy removed by the RP-1 increased with both shaft speed and RP-1 flow rate to the bearing.

Phenotype-genotype correlations in X linked retinitis pigmentosa.

PubMed Central

Kaplan, J; Pelet, A; Martin, C; Delrieu, O; Aymé, S; Bonneau, D; Briard, M L; Hanauer, A; Larget-Piet, L; Lefrançois, P

1992-01-01

Retinitis pigmentosa (RP) represents a group of clinically heterogeneous retinal degenerations in which all modes of inheritance have been described. We have previously found two different clinical profiles in X linked RP as a function of age and mode of onset. The first clinical form has very early onset with severe myopia. The second form starts later with night blindness with mild myopia or none. At least two genes have been identified in X linked forms, namely RP2 (linked to DXS7, DXS255, and DXS14) and RP3 (linked to DXS84 and OTC) on the short arm of the X chromosome. In order to contribute to phenotype-genotype correlations in X linked RP, we tested the hypothesis that the two clinical profiles could be accounted for by the two different gene loci. The present study provides evidence for linkage of the clinical form with early myopia as the onset symptom with the RP2 gene (pairwise linkage to DXS255: Z = 3.13 at theta = 0), while the clinical form with later night blindness as the onset symptom is linked to the RP3 gene (pairwise linkage to OTC: Z = 4.16 at theta = 0). Images PMID:1357178

Contemporary outcomes in women undergoing percutaneous coronary intervention for acute coronary syndromes.

PubMed

Al-Fiadh, Ali H; Andrianopoulos, Nick; Farouque, Omar; Yan, Bryan P; Duffy, Stephen J; Charter, Kerrie; Tongyoo, Surat; New, Gishel; Yip, Thomas; Brennan, Angela; Proimos, George; Reid, Christopher M; Ajani, Andrew E; Clark, David J

2011-09-01

Uncertainty remains as to whether females benefit as much as males from percutaneous coronary intervention (PCI) in the setting of an acute coronary syndrome (ACS). We compared 802 women with 2151 men presenting with ACS, undergoing PCI from April 2004 to October 2006 from the Melbourne Interventional Group registry. Clinical characteristics, in-hospital, 30-day and 1-year outcomes were compared. Women were older (69.6 ± 11.6 vs. 62.17 ± 12.3 years, p<0.001), and had more diabetes (27.1% vs. 19.6%, p<0.001) and hypertension (70.3% vs. 53.9%, p<0.001) than men. Women were less likely to present with ST-elevation myocardial infarction (30.5% vs. 37.9%, p<0.001). Bleeding (3.6% vs. 0.8%, p<0.001) was higher among women. Thirty-day mortality (4.7 vs. 2.4%, p<0.001) and MACE (10.1 vs. 6.4%, p<0.001) were higher in women. Gender was an independent predictor of overall MACE at 30 days (OR 1.45, 95% CI 1.04-2.02, p=0.03) but not death. At 12 months, there were no significant differences in mortality (6.4% vs. 4.8%, p=0.09), myocardial infarction (5.5% vs. 5.0%, p=0.64), target vessel revascularization (7.9% vs. 7.0%, p=0.42) and MACE (16.3% vs. 14%, p=0.13) between women and men. There is an early hazard amongst women undergoing PCI for ACS, but not at 12 months. These data suggest that gender should not affect the decision to offer PCI but further gender specific studies are warranted. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Environmental Enrichment Extends Photoreceptor Survival and Visual Function in a Mouse Model of Retinitis Pigmentosa

PubMed Central

Barone, Ilaria; Novelli, Elena; Piano, Ilaria; Gargini, Claudia; Strettoi, Enrica

2012-01-01

Slow, progressive rod degeneration followed by cone death leading to blindness is the pathological signature of all forms of human retinitis pigmentosa (RP). Therapeutic schemes based on intraocular delivery of neuroprotective agents prolong the lifetime of photoreceptors and have reached the stage of clinical trial. The success of these approaches depends upon optimization of chronic supply and appropriate combination of factors. Environmental enrichment (EE), a novel neuroprotective strategy based on enhanced motor, sensory and social stimulation, has already been shown to exert beneficial effects in animal models of various disorders of the CNS, including Alzheimer and Huntington disease. Here we report the results of prolonged exposure of rd10 mice, a mutant strain undergoing progressive photoreceptor degeneration mimicking human RP, to such an enriched environment from birth. By means of microscopy of retinal tissue, electrophysiological recordings, visual behaviour assessment and molecular analysis, we show that EE considerably preserves retinal morphology and physiology as well as visual perception over time in rd10 mutant mice. We find that protective effects of EE are accompanied by increased expression of retinal mRNAs for CNTF and mTOR, both factors known as instrumental to photoreceptor survival. Compared to other rescue approaches used in similar animal models, EE is highly effective, minimally invasive and results into a long-lasting retinal protection. These results open novel perspectives of research pointing to environmental strategies as useful tools to extend photoreceptor survival. PMID:23209820

The novel nomogram of Gleason sum upgrade: possible application for the eligible criteria of low dose rate brachytherapy.

PubMed

Budäus, Lars; Graefen, Markus; Salomon, Georg; Isbarn, Hendrik; Lughezzani, Giovanni; Sun, Maxine; Chun, Felix K H; Schlomm, Thorsten; Steuber, Thomas; Haese, Alexander; Koellermann, Jens; Sauter, Guido; Fisch, Margit; Heinzer, Hans; Huland, Hartwig; Karakiewicz, Pierre I

2010-10-01

To examine the rate of Gleason sum upgrading (GSU) from a sum of 6 to a Gleason sum of ≥7 in patients undergoing radical prostatectomy (RP), who fulfilled the recommendations for low dose rate brachytherapy (Gleason sum 6, prostate-specific antigen ≤10 ng/mL, clinical stage ≤T2a and prostate volume ≤50 mL), and to test the performance of an existing nomogram for prediction of GSU in this specific cohort of patients. The analysis focused on 414 patients, who fulfilled the European Society for Therapeutic Radiation and Oncology and American Brachytherapy Society criteria for low dose rate brachytherapy (LD-BT) and underwent a 10-core prostate biopsy followed by RP. The rate of GSU was tabulated and the ability of available clinical and pathological parameters for predicting GSU was tested. Finally, the performance of an existing GSU nomogram was explored. The overall rate of GSU was 35.5%. When applied to LD-BT candidates, the existing nomogram was 65.8% accurate versus 70.8% for the new nomogram. In decision curve analysis tests, the new nomogram fared substantially better than the assumption that no patient is upgraded and better than the existing nomogram. GSU represents an important issue in LD-BT candidates. The new nomogram might improve patient selection for LD-BT and cancer control outcome by excluding patients with an elevated probability of GSU. © 2010 The Japanese Urological Association.

49 CFR 195.440 - Public awareness.

Code of Federal Regulations, 2014 CFR

2014-10-01

... Petroleum Institute's (API) Recommended Practice (RP) 1162 (incorporated by reference, see § 195.3). (b) The operator's program must follow the general program recommendations of API RP 1162 and assess the unique... general program recommendations, including baseline and supplemental requirements of API RP 1162, unless...

49 CFR 195.440 - Public awareness.

Code of Federal Regulations, 2013 CFR

2013-10-01

... Petroleum Institute's (API) Recommended Practice (RP) 1162 (incorporated by reference, see § 195.3). (b) The operator's program must follow the general program recommendations of API RP 1162 and assess the unique... general program recommendations, including baseline and supplemental requirements of API RP 1162, unless...

49 CFR 195.440 - Public awareness.

Code of Federal Regulations, 2012 CFR

2012-10-01

... Petroleum Institute's (API) Recommended Practice (RP) 1162 (incorporated by reference, see § 195.3). (b) The operator's program must follow the general program recommendations of API RP 1162 and assess the unique... general program recommendations, including baseline and supplemental requirements of API RP 1162, unless...

Formulation of an RP-1 Pyrolysis Surrogate from Shock Tube Measurements of Fuel and Ethylene Time Histories

DTIC Science & Technology

2012-04-01

They also provide modelers (in both kinetics and computational fluid dynamics) with a method of representing, during simulation, a fuel that may have...1 and RP-2 from [Huber 2009a] Composition, mole fraction Fluid RP-1 surrogate RP-2 surrogate -methyldecalin 0.354 0.354 5-methylnonane 0.150...modeling and experimental results. Experimental Thermal and Fluid Science, 28(7):701–708, 2004. L. F. Albright, B. L. Crynes, and W. H. Corcoran

Incorporating Functional Imaging Information into rpFNA Analysis for Breast Cancer Detection in High Risk Women

DTIC Science & Technology

2010-03-01

TITLE: INCORPORATING FUNCTIONAL IMAGING INFORMATION TO rpFNA ANALYSIS FOR BREAST CANCER DETECTION IN HIGH-RISK WOMEN PRINCIPAL INVESTIGATOR...Imaging Information into rpFNA 5a. CONTRACT NUMBER Analysis for Breast Cancer Detection in High Risk Women 5b. GRANT NUMBER W81XWH-08-1-0192 5c...results of random periareolar fine needle aspiration (rpFNA) in women at high risk for breast cancer. In this second year of work, efforts have been

Maize Homologs of CCoAOMT and HCT, Two Key Enzymes in Lignin Biosynthesis, Form Complexes with the NLR Rp1 Protein to Modulate the Defense Response1

PubMed Central

2016-01-01

Disease resistance (R) genes encode nucleotide binding Leu-rich-repeat (NLR) proteins that confer resistance to specific pathogens. Upon pathogen recognition they trigger a defense response that usually includes a so-called hypersensitive response (HR), a rapid localized cell death at the site of pathogen infection. Intragenic recombination between two maize (Zea mays) NLRs, Rp1-D and Rp1-dp2, resulted in the formation of a hybrid NLR, Rp1-D21, which confers an autoactive HR in the absence of pathogen infection. From a previous quantitative trait loci and genome-wide association study, we identified genes encoding two key enzymes in lignin biosynthesis, hydroxycinnamoyltransferase (HCT) and caffeoyl CoA O-methyltransferase (CCoAOMT), adjacent to the nucleotide polymorphisms that were highly associated with variation in the severity of Rp1-D21-induced HR. We have previously shown that the two maize HCT homologs suppress the HR conferred by Rp1-D21 in a heterologous system, very likely through physical interaction. Here, we show, similarly, that CCoAOMT2 suppresses the HR induced by either the full-length or by the N-terminal coiled-coil domain of Rp1-D21 also likely via physical interaction and that the metabolic activity of CCoAOMT2 is unlikely to be necessary for its role in suppressing HR. We also demonstrate that CCoAOMT2, HCTs, and Rp1 proteins can form in the same complexes. A model is derived to explain the roles of CCoAOMT and HCT in Rp1-mediated defense resistance. PMID:27208251

Maize Homologs of CCoAOMT and HCT, Two Key Enzymes in Lignin Biosynthesis, Form Complexes with the NLR Rp1 Protein to Modulate the Defense Response.

PubMed

Wang, Guan-Feng; Balint-Kurti, Peter J

2016-07-01

Disease resistance (R) genes encode nucleotide binding Leu-rich-repeat (NLR) proteins that confer resistance to specific pathogens. Upon pathogen recognition they trigger a defense response that usually includes a so-called hypersensitive response (HR), a rapid localized cell death at the site of pathogen infection. Intragenic recombination between two maize (Zea mays) NLRs, Rp1-D and Rp1-dp2, resulted in the formation of a hybrid NLR, Rp1-D21, which confers an autoactive HR in the absence of pathogen infection. From a previous quantitative trait loci and genome-wide association study, we identified genes encoding two key enzymes in lignin biosynthesis, hydroxycinnamoyltransferase (HCT) and caffeoyl CoA O-methyltransferase (CCoAOMT), adjacent to the nucleotide polymorphisms that were highly associated with variation in the severity of Rp1-D21-induced HR We have previously shown that the two maize HCT homologs suppress the HR conferred by Rp1-D21 in a heterologous system, very likely through physical interaction. Here, we show, similarly, that CCoAOMT2 suppresses the HR induced by either the full-length or by the N-terminal coiled-coil domain of Rp1-D21 also likely via physical interaction and that the metabolic activity of CCoAOMT2 is unlikely to be necessary for its role in suppressing HR. We also demonstrate that CCoAOMT2, HCTs, and Rp1 proteins can form in the same complexes. A model is derived to explain the roles of CCoAOMT and HCT in Rp1-mediated defense resistance. © 2016 American Society of Plant Biologists. All Rights Reserved.

ERG and other discriminators between advanced hydroxychloroquine retinopathy and retinitis pigmentosa.

PubMed

Nair, Archana A; Marmor, Michael F

2017-06-01

To study whether the ERG and other clinical findings help to distinguish between advanced hydroxychloroquine (HCQ) retinopathy and pericentral or diffuse retinitis pigmentosa (RP) with similar fundus appearance. We conducted a retrospective analysis of patients with advanced HCQ retinopathy (n = 11), pericentral RP (n = 8) and diffuse RP (n = 8). Pericentral RP was defined as having limited fundus damage and relatively normal flicker ERG time-to-peak. Diffuse RP had typical loss of the rod ERG and flicker timing delay. All patients showed reduced amplitude of the ISCEV responses in the full-field electroretinogram (ERG). Aspects of history, visual field results, fundus appearance, fundus autofluorescence and ocular coherence tomography were also compared. Relative to pericentral RP, patients with HCQ toxicity showed delayed flicker ERG time-to-peak and lower ERG amplitudes, particularly combined rod-cone responses. Relative to diffuse RP, most HCQ toxicity patients had some preserved rod ERG response, and there was no obvious predilection for rod over cone damage. In addition, patients with HCQ toxicity usually lacked markers of long-standing degeneration such as bone spicule figures or severe loss of peripheral field. History of familial disease and long-standing night blindness were specific to RP. While the early signs of HCQ damage are typically regional in the posterior pole, advanced disease is characteristically diffuse (unlike pericentral RP). This is appropriate for a systemic toxin, as is the finding that rods and cones were both affected in the ERG to a similar degree (unlike genetic rod-cone dystrophies). For patients with severe HCQ exposure and some of our discriminatory findings, and no family history or prior night blindness, HCQ toxicity is a sufficient diagnosis without invoking a second rare disease (Occam's razor).

Autosomal dominant retinitis pigmentosa with macular involvement associated with a disease haplotype that included a novel PRPH2 variant (p.Cys250Gly).

PubMed

Katagiri, Satoshi; Hayashi, Takaaki; Mizobuchi, Kei; Yoshitake, Kazutoshi; Iwata, Takeshi; Nakano, Tadashi

2018-06-01

It is known that PRPH2 variants appear to be rare causes of retinitis pigmentosa (RP) in the Japanese population. The purpose of this study was to describe clinical and genetic features in autosomal dominant RP (adRP) patients with a novel disease-causing variant in the PRHP2 gene. A total of 57 unrelated Japanese probands with adRP were investigated in this study. Comprehensive ophthalmic examinations include fundus photography, fundus autofluorescence imaging, spectral-domain optical coherence tomography, and electroretinography. Whole exome sequencing or Sanger sequencing for 25 targeted exons of multiple genes causing adRP was performed to identify disease-causing variants. Co-segregation and haplotype analyses were performed to determine a disease-causing gene variant and its haplotype. Genetic analysis identified a novel heterozygous PRPH2 variant (c.748T>G, p.Cys250Gly) as disease causing in four probands from four families. The variant co-segregated with the RP phenotype in the eight affected patients in all families. At least three of the four families shared the same haplotype for the variant allele. Clinically, seven of the eight affected patients exhibited typical RP presentation, as well as variable macular involvement including cystoid macular change, vitelliform-like appearance, choroidal neovascularization, and macular atrophy. The same disease haplotype that included a novel PRPH2 variant (p.Cys250Gly) was identified in three of the four Japanese families with adRP, suggesting a founder effect. Our clinical findings indicate that adRP caused by the p.Cys250Gly variant may accompany macular involvement with high frequency.

P2RP: a Web-based framework for the identification and analysis of regulatory proteins in prokaryotic genomes.

PubMed

Barakat, Mohamed; Ortet, Philippe; Whitworth, David E

2013-04-20

Regulatory proteins (RPs) such as transcription factors (TFs) and two-component system (TCS) proteins control how prokaryotic cells respond to changes in their external and/or internal state. Identification and annotation of TFs and TCSs is non-trivial, and between-genome comparisons are often confounded by different standards in annotation. There is a need for user-friendly, fast and convenient tools to allow researchers to overcome the inherent variability in annotation between genome sequences. We have developed the web-server P2RP (Predicted Prokaryotic Regulatory Proteins), which enables users to identify and annotate TFs and TCS proteins within their sequences of interest. Users can input amino acid or genomic DNA sequences, and predicted proteins therein are scanned for the possession of DNA-binding domains and/or TCS domains. RPs identified in this manner are categorised into families, unambiguously annotated, and a detailed description of their features generated, using an integrated software pipeline. P2RP results can then be outputted in user-specified formats. Biologists have an increasing need for fast and intuitively usable tools, which is why P2RP has been developed as an interactive system. As well as assisting experimental biologists to interrogate novel sequence data, it is hoped that P2RP will be built into genome annotation pipelines and re-annotation processes, to increase the consistency of RP annotation in public genomic sequences. P2RP is the first publicly available tool for predicting and analysing RP proteins in users' sequences. The server is freely available and can be accessed along with documentation at http://www.p2rp.org.

Airway assessment by volumetric computed tomography in snorers and subjects with obstructive sleep apnea in a Far-East Asian population (Chinese).

PubMed

Chen, Ning-Hung; Li, Kasey K; Li, Shia-Yu; Wong, Chao-Reng; Chuang, Ming-Lung; Hwang, Chung-Chi; Wu, Yao-Kaung

2002-04-01

To evaluate the airway dimension of simple snorers and subjects with obstructive sleep apnea (OSA) in a Far-East Asian population (Chinese). Prospective study of 117 near-consecutive patients evaluated for snoring and possible OSA from January 1998 to December 1998 in a sleep laboratory. Overnight polysomnography (PSG) was performed on all patients and the sleep parameters, including respiratory disturbance index (RDI), snoring index, minimal oxygen saturation (min O2), percentage of slow wave sleep (SWS), and rapid eye movement (REM) were recorded. Three-dimensional computerized tomography (CT) during awake periods was performed. The anteroposterior (AP) and the lateral distance of the retropalatal (RP) region in the oropharynx, the smallest area of RP, and retroglossal (RG) regions, and the total volume of the oropharynx were measured. Ninety-eight patients were diagnosed with OSA (mean RDI, 41.48 +/- 26.45 events per hour; min O2, 72.82 +/- 12.86%), whereas 19 were simple snorers. The AP and the lateral distance of the RP region, as well as the smallest area of the RP region, are significantly smaller in subjects with OSA. However, no differences in the RG region and the total volume of the oropharynx were found between the two groups. Linear regression analysis demonstrated that the lateral dimension and the smallest RP area in overweight subjects inversely correlated with the RDI, but only the AP dimension of the RP area was found to have an inverse correlation with the RDI in the underweight subjects. In Far-East Asians (Chinese), the RP airway was found to be the primary site of narrowing in subjects with OSA, and the narrowest RP area was inversely correlated with RDI. Furthermore, weight may influence the pattern of RP narrowing by contributing to lateral collapse.

Rhinoplasty from a rhinologist's perspective: Need for recognition of associated sinonasal conditions

PubMed Central

Picavet, Valerie A.; Grietens, Jente; Jorissen, Mark

2012-01-01

Background: Facial plastic surgeons may primarily focus on esthetic improvement of the nasal shape in patients seeking rhinoplasty (RP). However, medical conditions inside the nasal cavity should not be neglected because they may lead to unresolved sinonasal problems and, hence, dissatisfaction after esthetic RP. This observational study investigated the prevalence of sinonasal symptoms and endonasal pathology in patients requesting esthetic RP. Methods: Patients seeking RP (n = 269) were given a questionnaire evaluating nasal obstruction and sinonasal symptoms using visual analog scales and the 22-item Sino-Nasal Outcome Test. In addition, patients underwent nasal endoscopy to evaluate anatomic and/or mucosal disease and skin-prick testing in case of clinical suspicion of allergy. Two control groups consisted of patients with an otological or general ear/nose/throat problem (n = 65) and patients who planned for endoscopic sinus surgery (ESS; n = 90). Results: The general appraisal of nasal breathing on a scale from 0–10 in patients seeking RP was as low as 4.3 ± 3.1. Structural pathology was found in 62% of RP patients, with septal deviation being the most frequent problem encountered (54%), followed by internal nasal valve dysfunction (14%). Mucosal disease was present in 28% of RP patients. The mean SNOT-22 score of RP patients (31.8 ± 23.3) was significantly higher than the control group (11.6 ± 7.9; p < 0.001), but lower than the ESS patients (48.5 ± 22.0; p < 0.001). Conclusion: The prevalence of endonasal structural or mucosal pathology in patients seeking RP is high and should not be overlooked at the time of planning surgery. PMID:23232202

Long-Term Rock Phosphate Fertilization Impacts the Microbial Communities of Maize Rhizosphere

PubMed Central

Silva, Ubiana C.; Medeiros, Julliane D.; Leite, Laura R.; Morais, Daniel K.; Cuadros-Orellana, Sara; Oliveira, Christiane A.; de Paula Lana, Ubiraci G.; Gomes, Eliane A.; Dos Santos, Vera L.

2017-01-01

Phosphate fertilization is a common practice in agriculture worldwide, and several commercial products are widely used. Triple superphosphate (TSP) is an excellent soluble phosphorus (P) source. However, its high cost of production makes the long-term use of crude rock phosphate (RP) a more attractive alternative in developing countries, albeit its influence on plant-associated microbiota remains unclear. Here, we compared long-term effects of TSP and RP fertilization on the structure of maize rhizosphere microbial community using next generation sequencing. Proteobacteria were dominant in all conditions, whereas Oxalobacteraceae (mainly Massilia and Herbaspirillum) was enriched in the RP-amended soil. Klebsiella was the second most abundant taxon in the RP-treated soil. Burkholderia sp. and Bacillus sp. were enriched in the RP-amended soil when compared to the TSP-treated soil. Regarding fungi, Glomeromycota showed highest abundance in RP-amended soils, and the main genera were Scutellospora and Racocetra. These taxa are already described as important for P solubilization/acquisition in RP-fertilized soil. Maize grown on TSP and RP-treated soil presented similar productivity, and a positive correlation was detected for P content and the microbial community of the soils. The results suggest changes of the microbial community composition associated to the type of phosphate fertilization. Whilst it is not possible to establish causality relations, our data highlights a few candidate taxa that could be involved in RP solubilization and plant growth promotion. Moreover, this can represent a shorter path for further studies aiming the isolation and validation of the taxa described here concerning P release on the soil plant system and their use as bioinoculants. PMID:28744264

Effects of reference pricing in pharmaceutical markets: a review.

PubMed

Galizzi, Matteo Maria; Ghislandi, Simone; Miraldo, Marisa

2011-01-01

This work aims to provide a systematic and updated survey of original scientific studies on the effect of the introduction of reference pricing (RP) policies in Organisation for Economic Co-operation and Development (OECD) countries. We searched PubMed, EconLit and Web of Knowledge for articles on RP. We reviewed studies that met the inclusion criteria established in the search strategy. From a total of 468 references, we selected the 35 that met all of the inclusion criteria. Some common themes emerged in the literature. The first was that RP was generally associated with a decrease in the prices of the drugs subject to the policy. In particular, price drops seem to have been experienced in virtually every country that implemented a generic RP (GRP) policy. A GRP policy applies only to products with expired patents and generic competition, and clusters drugs according to chemical equivalence (same form and active compound). More significant price decreases were observed in the sub-markets in which drugs were already facing generic competition prior to RP. Price drops varied widely according to the amount of generic competition and industrial strategies: brand-named drugs originally priced above RP values decreased their prices to a greater extent. A second common theme was that both therapeutic RP (TRP) and GRP have been associated with significant and consistent savings in the first years of application. A third general result is that generic market shares significantly increased whenever the firms producing brand-named drugs did not adopt one of the following strategies: lowering prices to RP values; launching new dosages and/or formulations; or marketing substitute drugs still under patent protection. Finally, concerning TRP, although more evidence is needed, studies based on a large number of patient-level observations showed no association between the RP policy and health outcomes.

A pilot assessment of relapse prevention for heroin addicts in a Chinese rehabilitation center.

PubMed

Min, Zhao; Xu, Li; Chen, Hanhui; Ding, Xu; Yi, Zhang; Mingyuang, Zhang

2011-05-01

To conduct a pilot assessment of relapse prevention (RP) group therapy for heroin-dependent patients in a drug rehabilitation center in China. A randomized case-control study was conducted to assess the efficacy of RP delivered over a 2-month period to male heroin addicts (n = 50, RP group) in the Shanghai Labor Drug Rehabilitation Center (LDRC) compared with an equal number of participants (n = 50, labor rehabilitation (LR) group) in the LDRC program receiving standard-of-care treatment. Outcomes were assessed by the Beck Depression Inventory (BDI), the Self-Rating Anxiety Scale (SAS), the Self-Efficacy Scale (SE), and the Self-Esteem Scale (SES) after completion of RP, and by the Addiction Severity Index (ASI) and abstinence rates of heroin use at 3-month follow-up post release from the LDRC for both groups. Significant improvements in scores on SAS, SE, and SES were found in the RP group after completion of the 2-month RP group therapy compared with the LR group (SAS 7.85 ± 6.20 vs 1.07 ± 5.42, SE 3.88 ± 3.60 vs .08 ± 2.89, and SES 3.83 ± 3.31 vs .78 ± 2.55). At 3-month follow-up, the RP group participants had more improvements on ASI scores in most domains and had higher abstinence rates than that in the LR group (37.2% vs 16.7%). An RP component can be effective in increasing abstinence rates among post-program heroin-dependent individuals and may help reduce anxiety and improve self-esteem and self-efficacy during and following treatment. This study suggests RP as a potentially effective component of treatment for heroin addicts.

Biorhythms, deciduous enamel thickness, and primary bone growth: a test of the Havers-Halberg Oscillation hypothesis.

PubMed

Mahoney, Patrick; Miszkiewicz, Justyna J; Pitfield, Rosie; Schlecht, Stephen H; Deter, Chris; Guatelli-Steinberg, Debbie

2016-06-01

Across mammalian species, the periodicity with which enamel layers form (Retzius periodicity) in permanent teeth corresponds with average body mass and the pace of life history. According to the Havers-Halberg Oscillation hypothesis (HHO), Retzius periodicity (RP) is a manifestation of a biorhythm that is also expressed in lamellar bone. Potentially, these links provide a basis for investigating aspects of a species' biology from fossilized teeth. Here, we tested intra-specific predictions of this hypothesis on skeletal samples of human juveniles. We measured daily enamel growth increments to calculate RP in deciduous molars (n = 25). Correlations were sought between RP, molar average and relative enamel thickness (AET, RET), and the average amount of primary bone growth (n = 7) in humeri of age-matched juveniles. Results show a previously undescribed relationship between RP and enamel thickness. Reduced major axis regression reveals RP is significantly and positively correlated with AET and RET, and scales isometrically. The direction of the correlation was opposite to HHO predictions as currently understood for human adults. Juveniles with higher RPs and thicker enamel had increased primary bone formation, which suggests a coordinating biorhythm. However, the direction of the correspondence was, again, opposite to predictions. Next, we compared RP from deciduous molars with new data for permanent molars, and with previously published values. The lowermost RP of 4 and 5 days in deciduous enamel extends below the lowermost RP of 6 days in permanent enamel. A lowered range of RP values in deciduous enamel implies that the underlying biorhythm might change with age. Our results develop the intra-specific HHO hypothesis. © 2016 Anatomical Society.

Right versus left parasternal electrode position in the entirely subcutaneous ICD.

PubMed

Bettin, Markus; Dechering, Dirk; Frommeyer, Gerrit; Larbig, Robert; Löher, Andreas; Reinke, Florian; Köbe, Julia; Eckardt, Lars

2018-05-01

The subcutaneous implantable cardioverter defibrillator (S-ICD ® ) has been established as an alternative to conventional transvenous ICD for the prevention of sudden cardiac death. Initial studies have shown safety and efficacy of the system with a left parasternal (LP) electrode. However, several case studies reported a right parasternal (RP) position. The purpose of this study was to analyze shock efficacy and safety of an RP electrode position. Between June 2010 and May 2016, 120 S-ICD ® were implanted at our institution. On the basis of the heart location on preoperative chest radiography (CXR), the investigators decided on an RP (n = 52) or LP electrode position (n = 68). All perioperative induced VF episodes, and spontaneous appropriate and inappropriate episodes during follow-up were analyzed. Patients with an RP electrode did not differ in terms of age, sex, or ejection fraction. A statistically significant difference in underlying cardiac disease was observed between the RP and LP electrode group, with more patients with channelopathies in the RP electrode group and more patients with non-ischemic cardiomyopathy in the LP electrode group. During a mean follow-up of 24.3 ± 19.5 months, 27 appropriate (19 in the LP group and 8 in the RP group) and 28 inappropriate (18 LP and 10 RP) ICD shocks occurred (p value = NS). In the present study, an RP electrode position was chosen on the basis of chest radiographic characteristics and was efficient in terms of sensing and shock efficacy. Thus, a right-sided electrode implant might be an alternative if a left-sided electrode implant is inadequate. It might also be favorable for young patients with narrow heart silhouettes in the midsagittal position.

Online combination of reversed-phase/reversed-phase and porous graphitic carbon liquid chromatography for multicomponent separation of proteomics and glycoproteomics samples.

PubMed

Lam, Maggie P Y; Lau, Edward; Siu, S O; Ng, Dominic C M; Kong, Ricky P W; Chiu, Philip C N; Yeung, William S B; Lo, Clive; Chu, Ivan K

2011-11-01

In this paper, we describe an online combination of reversed-phase/reversed-phase (RP-RP) and porous graphitic carbon (PGC) liquid chromatography (LC) for multicomponent analysis of proteomics and glycoproteomics samples. The online RP-RP portion of this system provides comprehensive 2-D peptide separation based on sequence hydrophobicity at pH 2 and 10. Hydrophilic components (e.g. glycans, glycopeptides) that are not retained by RP are automatically diverted downstream to a PGC column for further trapping and separation. Furthermore, the RP-RP/PGC system can provide simultaneous extension of the hydropathy range and peak capacity for analysis. Using an 11-protein mixture, we found that the system could efficiently separate native peptides and released N-glycans from a single sample. We evaluated the applicability of the system to the analysis of complex biological samples using 25 μg of the lysate of a human choriocarcinoma cell line (BeWo), confidently identifying a total of 1449 proteins from a single experiment and up to 1909 distinct proteins from technical triplicates. The PGC fraction increased the sequence coverage through the inclusion of additional hydrophilic sequences that accounted for up to 6.9% of the total identified peptides from the BeWo lysate, with apparent preference for the detection of hydrophilic motifs and proteins. In addition, RP-RP/PGC is applicable to the analysis of complex glycomics samples, as demonstrated by our analysis of a concanavalin A-extracted glycoproteome from human serum; in total, 134 potentially N-glycosylated serum proteins, 151 possible N-glycosylation sites, and more than 40 possible N-glycan structures recognized by concanavalin A were simultaneously detected. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Pre-Radiation Therapy Fluorine 18 Fluorodeoxyglucose PET Helps Identify Patients with Esophageal Cancer at High Risk for Radiation Pneumonitis.

PubMed

Castillo, Richard; Pham, Ngoc; Castillo, Edward; Aso-Gonzalez, Samantha; Ansari, Sobiya; Hobbs, Brian; Palacio, Diana; Skinner, Heath; Guerrero, Thomas M

2015-06-01

To examine the association between pre-radiation therapy (RT) fluorine 18 fluorodeoxyglucose (FDG) uptake and post-RT symptomatic radiation pneumonitis (RP). In accordance with the retrospective study protocol approved by the institutional review board, 228 esophageal cancer patients who underwent FDG PET/CT before chemotherapy and RT were examined. RP symptoms were evaluated by using the Common Terminology Criteria for Adverse Events, version 4.0, from the consensus of five clinicians. By using the cumulative distribution of standardized uptake values (SUVs) within the lungs, those values greater than 80%-95% of the total lung voxels were determined for each patient. The effect of pre-chemotherapy and RT FDG uptake, dose, and patient or treatment characteristics on RP toxicity was studied by using logistic regression. The study subjects were treated with three-dimensional conformal RT (n = 36), intensity-modulated RT (n = 135), or proton therapy (n = 57). Logistic regression analysis demonstrated elevated FDG uptake at pre-chemotherapy and RT was related to expression of RP symptoms. Study subjects with elevated 95% percentile of the SUV (SUV95) were more likely to develop symptomatic RP (P < .000012); each 0.1 unit increase in SUV95 was associated with a 1.36-fold increase in the odds of symptomatic RP. Receiver operating characteristic (ROC) curve analysis resulted in area under the ROC curve of 0.676 (95% confidence interval: 0.58, 0.77), sensitivity of 60%, and specificity of 71% at the 1.17 SUV95 threshold. CT imaging and dosimetric parameters were found to be poor predictors of RP symptoms. The SUV95, a biomarker of pretreatment pulmonary metabolic activity, was shown to be prognostic of symptomatic RP. Elevation in this pretreatment biomarker identifies patients at high risk for posttreatment symptomatic RP. RSNA, 2015

Determination of pterins in urine by HPLC with UV and fluorescent detection using different types of chromatographic stationary phases (HILIC, RP C8, RP C18).

PubMed

Kośliński, Piotr; Jarzemski, Piotr; Markuszewski, Michał J; Kaliszan, Roman

2014-03-01

Pterins are a class of potential cancer biomarkers. New methods involving hydrophilic interaction liquid chromatography (HILIC) and reversed phase (RP) high-performance liquid chromatography have been developed for analysis of eight pterin compounds: 6,7-dimethylpterin, pterin, 6-OH-methylpterin, biopterin, isoxanthopterin, neopterin, xanthopterin, and pterin-6-carboxylic acid. The effect of mobile phase composition, buffer type, pH and concentration on retention using HILIC, C8 and C18 RP stationary phases were examined. Separation of pterins on RP and HILIC stationary phase was performed and optimized. Eight pterins were successfully separated on HILIC Luna diol-bonded phases, Aquasil C18 RP column and LiChrospher C8 RP column. Determination and separation of the pterins from urine samples were performed on HILIC Luna and LiChrospher C8 RP columns which were chosen as the most appropriate ones. Finally, LiChrospher C8 RP column with fluorescence detection was selected for further validation of the method. The optimum chromatographic condition was mobile phase methanol (A)/phosphoric buffer pH 7, 10mM (B), isocratic elution 0-15min 5% A flow=0.5ml/min 15-17min. 5% A, flow=0.5-1ml/min the linearity (R(2)>0.997) and retention time repeatability (RSD%<1) were at satisfactory level. The precision of peak areas expressed as RSD in % was between 0.55 and 14. Pterins detection limits varied from 0.041ng/ml to 2.9ng/ml. Finally, HPLC method was used for the analysis of pterins in urine samples with two different oxidation procedures. Concentration levels of pterin compounds in bladder cancer patients and healthy subjects were compared. Copyright © 2013 Elsevier B.V. All rights reserved.

Cigarette smoking in British men and selection for coronary artery bypass surgery.

PubMed Central

Morris, R. W.; McCallum, A. K.; Walker, M.; Whincup, P. H.; Ebrahim, S.; Shaper, A. G.

1996-01-01

OBJECTIVE: To examine the relation between smoking status, clinical need, and likelihood of coronary artery bypass grafting in middle aged men. DESIGN: A prospective study of cardiovascular disease in British men aged 40 to 59 years, screened in 1978-80 and followed until December 1991. SUBJECTS AND SETTING: 7735 men drawn from one general practice in each of 24 British towns. MAIN OUTCOME MEASURE: Coronary artery bypass graft surgery. RESULTS: Of the 3185 current smokers, 38 (1.03/1000/year) underwent coronary artery bypass surgery compared with 47 of 2715 (1.45/1000/year) ex-smokers, and 19 of 1817 (0.85/1000/year) never-smokers. Ex-smokers had a lower incidence of major ischaemic heart disease during follow up than current smokers. After adjustment for incidence of ischaemic heart disease during follow up, the hazard ratio of coronary artery bypass surgery for ex-smokers compared with smokers was 1.52 (95% confidence interval 0.99 to 2.34). Ex-smokers were more likely at screening to recall a doctor diagnosis of ischaemic heart disease than smokers (7.1% v 5.3%), but among those who recalled a doctor diagnosis, smokers were less likely to undergo coronary artery bypass surgery than ex-smokers (9.4% v 3.5%, P = 0.026). By 1992, men defined as smokers at screening were no less likely than ex-smokers to have been referred to a cardiologist (18.5% v 18.8%), nor to report having undergone coronary angiography less frequently than ex-smokers (12.7% v 11.4%). CONCLUSION: Even allowing for the strong relation between coronary artery bypass surgery and clinical need, continuing smokers were less likely to undergo coronary artery bypass surgery than ex-smokers. A complex interplay exists between the men's experience of heart disease, the decision to stop smoking, and the willingness of doctors to consider coronary artery bypass surgery. PMID:8697156

Infarct size, left ventricular function, and prognosis in women compared to men after primary percutaneous coronary intervention in ST-segment elevation myocardial infarction: results from an individual patient-level pooled analysis of 10 randomized trials.

PubMed

Kosmidou, Ioanna; Redfors, Björn; Selker, Harry P; Thiele, Holger; Patel, Manesh R; Udelson, James E; Magnus Ohman, E; Eitel, Ingo; Granger, Christopher B; Maehara, Akiko; Kirtane, Ajay; Généreux, Philippe; Jenkins, Paul L; Ben-Yehuda, Ori; Mintz, Gary S; Stone, Gregg W

2017-06-01

Studies have reported less favourable outcomes in women compared with men after primary percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI). Whether sex-specific differences in the magnitude or prognostic impact of infarct size or post-infarction cardiac function explain this finding is unknown. We pooled patient-level data from 10 randomized primary PCI trials in which infarct size was measured within 1 month (median 4 days) by either cardiac magnetic resonance imaging or technetium-99m sestamibi single-photon emission computed tomography. We assessed the association between sex, infarct size, and left ventricular ejection fraction (LVEF) and the composite rate of death or heart failure (HF) hospitalization within 1 year. Of 2632 patients with STEMI undergoing primary PCI, 587 (22.3%) were women. Women were older than men and had a longer delay between symptom onset and reperfusion. Infarct size did not significantly differ between women and men, and women had higher LVEF. Nonetheless, women had a higher 1-year rate of death or HF hospitalization compared to men, and while infarct size was a strong independent predictor of 1-year death or HF hospitalization (P < 0.0001), no interaction was present between sex and infarct size or LVEF on the risk of death or HF hospitalization. In this large-scale, individual patient-level pooled analysis of patients with STEMI undergoing primary PCI, women had a higher 1-year rate of death or HF hospitalization compared to men, a finding not explained by sex-specific differences in the magnitude or prognostic impact of infarct size or by differences in post-infarction cardiac function. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.