To nearly come full circle: Nonoperative management of high-grade IV-V blunt splenic trauma is safe using a protocol with routine angioembolization.

PubMed

Bhullar, Indermeet S; Tepas, Joseph J; Siragusa, Daniel; Loper, Todd; Kerwin, Andrew; Frykberg, Eric R

2017-04-01

Nonoperative management (NOM) of hemodynamically stable high-grade (IV-V) blunt splenic trauma remains controversial given the high failure rates (19%) that persist despite angioembolization (AE) protocols. The NOM protocol was modified in 2011 to include mandatory AE of all grade (IV-V) injuries without contrast blush (CB) along with selective AE of grade (I-V) with CB. The purpose of this study was to determine if this new AE (NAE) protocol significantly lowered the failure rates for grade (IV-V) injuries allowing for safe observation without surgery and if the exclusion of grade III injuries allowed for the prevention of unnecessary angiograms without affecting the overall failure rates. The records of patients with blunt splenic trauma from January 2000 to October 2014 at a Level I trauma center were retrospectively reviewed. Patients were divided into two groups and failure of NOM (FNOM) rates compared: NAE protocol (2011-2014) with mandatory AE for all grade (IV-V) injuries without CB and selective AE for grade (I-V) with CB versus old AE (OAE) protocol (2000-2010) with selective AE for grade (I-V) with CB. Seven hundred twelve patients underwent NOM with 522 (73%) in the OAE group and 190 (27%) in the NAE group. Evolving from the OAE to the NAE strategy resulted in a significantly lower FNOM rate for the overall group (grade I-V) (OAE vs. NAE, 4% to 1%, p = 0.04) and the grade (IV-V) group (OAE vs. NAE, 19% vs. 3%, p = 0.01). Angiograms were avoided in 113 grade (I-III) injuries with no CB; these patients had NOM with observation alone and none failed. A protocol using mandatory AE of all high-grade (IV-V) injuries without CB and selective AE of grade (I-V) with CB may provide for optimum salvage with safe NOM of the high-grade injuries (IV-V) and limited unnecessary angiograms. Therapeutic study, level IV.

The Role of Independent V&V in Upstream Software Development Processes

NASA Technical Reports Server (NTRS)

Easterbrook, Steve

1996-01-01

This paper describes the role of Verification and Validation (V&V) during the requirements and high level design processes, and in particular the role of Independent V&V (IV&V). The job of IV&V during these phases is to ensure that the requirements are complete, consistent and valid, and to ensure that the high level design meets the requirements. This contrasts with the role of Quality Assurance (QA), which ensures that appropriate standards and process models are defined and applied. This paper describes the current state of practice for IV&V, concentrating on the process model used in NASA projects. We describe a case study, showing the processes by which problem reporting and tracking takes place, and how IV&V feeds into decision making by the development team. We then describe the problems faced in implementing IV&V. We conclude that despite a well defined process model, and tools to support it, IV&V is still beset by communication and coordination problems.

Intrathecal versus IV fentanyl in pediatric cardiac anesthesia.

PubMed

Pirat, Arash; Akpek, Elif; Arslan, Gülnaz

2002-11-01

Systemic large-dose opioids are widely used in pediatric cardiac anesthesia, but there are no randomized, prospective studies regarding the use of intrathecal (IT) opioids for these procedures. In this randomized, prospective study, we compared cardiovascular and neurohumoral responses during IT or IV fentanyl anesthesia for pediatric cardiac surgery. Thirty children aged 6 mo to 6 yr were anesthetized with an IV fentanyl bolus of 10 micro g/kg. This was followed by a fentanyl infusion of 10 micro g. kg(-1). h(-1) (Group IV; n = 10), 2 micro g/kg of IT fentanyl (Group IT; n = 10), or combined IV and IT protocols (Group IV + IT; n = 10). Heart rate, mean arterial blood pressure, additional fentanyl doses, time to first analgesic requirement, COMFORT and Children's Hospital of Eastern Ontario Pain Scale scores, and extubation time were recorded. Blood cortisol, insulin, glucose, and lactate levels were measured presurgery, poststernotomy, during the rewarming phase of cardiopulmonary bypass (CPB), and 6 and 24 h after surgery. The patients' urinary cortisol excretion rates were also measured during the first postoperative day. The findings in all three groups were statistically similar, except for higher blood glucose levels during CPB in Group IT compared with Group IV (P < 0.004). Group IV + IT was the only group in which the increases in heart rate and mean arterial blood pressure from presurgery to poststernotomy were not significant. The 24-h urinary cortisol excretion rates ( micro g. kg(-1). d(-1)) were 61.51 +/- 39, 92.54 +/- 67.55, and 40.15 +/- 29.69 for Groups IV, IT, and IV + IT, respectively (P > 0.05). A single IT injection of fentanyl 2 micro g/kg offers no advantage over systemic fentanyl (10 micro g/kg bolus and 10 micro g. kg(-1). h(-1)) with regard to hemodynamic stability or suppression of stress response. The combination of these two regimens may provide better hemodynamic stability during the pre-CPB period and may be associated with a decreased 24-h urinary cortisol excretion rate. In this prospective, randomized study, we investigated the adequacy of a single intrathecal injection of fentanyl for intraoperative analgesia, compared the effects of IT and IV fentanyl on stress response, and assessed for an additive effect of IT and IV fentanyl administration in pediatric cardiac anesthesia. The results with these three different anesthetic regimens were similar regarding anesthesia depth and level of stress response. However, the combination of IT and IV routes may provide better hemodynamic stability and a less pronounced stress response, as reflected by 24-h urinary cortisol excretion.

Math anxiety differentially affects WAIS-IV arithmetic performance in undergraduates.

PubMed

Buelow, Melissa T; Frakey, Laura L

2013-06-01

Previous research has shown that math anxiety can influence the math performance level; however, to date, it is unknown whether math anxiety influences performance on working memory tasks during neuropsychological evaluation. In the present study, 172 undergraduate students completed measures of math achievement (the Math Computation subtest from the Wide Range Achievement Test-IV), math anxiety (the Math Anxiety Rating Scale-Revised), general test anxiety (from the Adult Manifest Anxiety Scale-College version), and the three Working Memory Index tasks from the Wechsler Adult Intelligence Scale-IV Edition (WAIS-IV; Digit Span [DS], Arithmetic, Letter-Number Sequencing [LNS]). Results indicated that math anxiety predicted performance on Arithmetic, but not DS or LNS, above and beyond the effects of gender, general test anxiety, and math performance level. Our findings suggest that math anxiety can negatively influence WAIS-IV working memory subtest scores. Implications for clinical practice include the utilization of LNS in individuals expressing high math anxiety.

The Use of Immersive Visualization for the Control of Dental Anxiety During Oral Debridement.

PubMed

Padrino-Barrios, Carmelo; McCombs, Gayle; Diawara, Norou; De Leo, Gianluca

2015-12-01

The purpose of this study was to evaluate the effects of Immersive Visualization (IV) eyewear on anxious, adult patients during oral debridement. Thirty adult volunteers (n=23 females; n=7 males) were enrolled in the study. Participants were required to be 18 years or older, exhibit at least moderate anxiety (score 9 or higher) on the Corah's Dental Anxiety Scale-Revised (DAS-R), and be generally healthy. Individuals were excluded from participation if they presented with severe dental calculus, periodontal disease, or dental caries, were taking psychotropic drugs, had a history of convulsive disorders, vertigo, or equilibrium disorders, or required antibiotic pre-medication. Subjects received a full mouth oral prophylaxis (supra- and subgingival scaling and selective polishing) by a single experienced dental hygienist. A split mouth design was utilized whereby each subject served as their own control. Subjects were randomly divided into 2 groups: Group A used IV eyewear during the first one-half of the appointment (right side of the mouth) and Group B used IV eyewear during the second one-half of the appointment (left side of the mouth). At screening, medical and dental histories were obtained, full mouth oral examinations were performed, and DAS-R was scored to determine eligibility. At baseline, the DAS-R was re-scored to validate anxiety levels. The Calmness Scale was scored pre- and post-IV treatment on a Likert scale ranging from 1 (very calm) to 7 (less calm). At the end of the study, subjects completed a Post IV Opinion survey. Data were entered into Microsoft Excel for Mac 2011 (Microsoft Corporation Version 14.3.5) and analyzed using SAS® 9.3 statistical software. Thirty subjects with a mean age of 29.9 years completed the study. Data analysis indicated no statistically significant difference between Group A and B with regard to mean DAS-R anxiety levels at baseline (3.15 and 2.40, respectively), with a p-value of 0.07. Data showed a significant difference when comparing the calmness mean scores within Group A pre- and post-IV treatments (4.66 and 2.93, respectively), with a p-value 0.01. Within Group B the data revealed a statistically significant difference between pre- and post-IV treatments (p<0.01, 4.33 and 2.13, respectively). Both treatment groups experienced a decrease in anxiety levels from pre to post IV treatments. Moreover, combined mean calmness scores of the 30 subjects (Group A and B) expressed in mean standard deviation showed there was a decrease from 4.50±1.31 in pre-IV treatment to 2.53±1.17 in post-IV treatment. Further investigation of the data showed that there was a significant correlation between calmness and gender; females reported higher levels of anxiety than men before and after IV treatment. Results from this study support the use of IV eyewear as an effective technique to reduce anxiety in adults during oral debridement. The use of the IV eyewear was well received by all subjects. The portable, affordable and easy-to-operate IV system makes this technique an appealing approach of reducing dental anxiety. Copyright © 2015 The American Dental Hygienists’ Association.

Novel N-substituted aminobenzamide scaffold derivatives targeting the dipeptidyl peptidase-IV enzyme.

PubMed

Al-Balas, Qosay A; Sowaileh, Munia F; Hassan, Mohammad A; Qandil, Amjad M; Alzoubi, Karem H; Mhaidat, Nizar M; Almaaytah, Ammar M; Khabour, Omar F

2014-01-01

The dipeptidyl peptidase-IV (DPP-IV) enzyme is considered a pivotal target for controlling normal blood sugar levels in the body. Incretins secreted in response to ingestion of meals enhance insulin release to the blood, and DPP-IV inactivates these incretins within a short period and stops their action. Inhibition of this enzyme escalates the action of incretins and induces more insulin to achieve better glucose control in diabetic patients. Thus, inhibition of this enzyme will lead to better control of blood sugar levels. In this study, computer-aided drug design was used to help establish a novel N-substituted aminobenzamide scaffold as a potential inhibitor of DPP-IV. CDOCKER software available from Discovery Studio 3.5 was used to evaluate a series of designed compounds and assess their mode of binding to the active site of the DPP-IV enzyme. The designed compounds were synthesized and tested against a DPP-IV enzyme kit provided by Enzo Life Sciences. The synthesized compounds were characterized using proton and carbon nuclear magnetic resonance, mass spectrometry, infrared spectroscopy, and determination of melting point. Sixty-nine novel compounds having an N-aminobenzamide scaffold were prepared, with full characterization. Ten of these compounds showed more in vitro activity against DPP-IV than the reference compounds, with the most active compounds scoring 38% activity at 100 μM concentration. The N-aminobenzamide scaffold was shown in this study to be a valid scaffold for inhibiting the DPP-IV enzyme. Continuing work could unravel more active compounds possessing the same scaffold.

The relationship between the success rate of empirical antifungal therapy with intravenous itraconazole and clinical parameters, including plasma levels of itraconazole, in immunocompromised patients receiving itraconazole oral solution as prophylaxis: a multicenter, prospective, open-label, observational study in Korea.

PubMed

Kim, Jin Seok; Cheong, June-Won; Kim, Yeo-Kyeoung; Park, Jinny; Mun, Yeung-Chul; Kang, Hye Jin; Yi, Hyeon Gyu; Lee, Je-Hwan; Kim, Yang Soo; Ryoo, Hun-Mo; Kim, Sung-Hyun; Kim, Ho Young; Kim, Jin Young; Lee, Dong-Gun; Kim, Hoon-Gu; Kim, Hawk; Joo, Young-Don; Min, Yoo Hong

2014-01-01

To identify the role of therapeutic drug monitoring of itraconazole (ITZ) in the setting of empirical antifungal therapy with intravenous (IV) ITZ, we performed a multicenter, prospective study in patients with hematological malignancies who had received antifungal prophylaxis with ITZ oral solution (OS). We evaluated the plasma levels of ITZ and hydroxy (OH) ITZ both before initiation of IV ITZ and on days 5-7 of IV ITZ. A total of 181 patients showed an overall success rate of 68.0 %. Prolonged baseline neutropenia and accompanying cardiovascular comorbidity were significantly associated with poor outcomes of the empirical antifungal therapy (P = 0.005 and P = 0.001, respectively). A significantly higher trough plasma level of OH ITZ per body weight was found in the patients who achieved success with empirical antifungal therapy (P = 0.036). There were no significant correlations between plasma concentrations of ITZ/OH ITZ (baseline or trough levels) and toxicities. Seven patients had a discontinuation of ITZ therapy due to toxicity. This study demonstrated that IV ITZ as empirical antifungal therapy was effective and therapeutic drug monitoring was helpful to estimate the outcome of empirical antifungal therapy in patients receiving antifungal prophylaxis with ITZ OS. To predict the outcome of empirical antifungal therapy with IV ITZ, we should evaluate baseline clinical characteristics and also perform the therapeutic drug monitoring of both ITZ and OH ITZ.

Studies on the mechanism of salicylate-induced increase of insulin secretion in man.

PubMed

Giugliano, D; Cozzolino, D; Ceriello, A; Cerciello, T; Varano, R; Saccomanno, F; Torella, R

1988-01-01

Salicylate compounds are known to increase basal and stimulated insulin secretion in man. In our studies, infusion of lysine acetylsalicylate (72 mg/min) increased basal insulin levels and amplified insulin responses to glucose (5 g i.v.), arginine (5 g i.v.) and tolbutamide (1 g i.v.). Verapamil, an organic calcium antagonist, did not modify LAS-induced increase of basal insulin levels, but reduced the effect of LAS on glucose-induced insulin secretion. Calcitonin and somatostatin, two agents that inhibit basal and glucose-stimulated insulin secretion, inhibited the insulin response to glucose in presence of LAS infusion. The ability of salicylate compounds to augment insulin secretion might be due to multiple sites of action in the Beta-cells.

Selenite Enhances Immune Response against Pseudomonas aeruginosa PA14 via SKN-1 in Caenorhabditis elegans

PubMed Central

Huang, Chi-Wei; Wei, Chia-Cheng; Liao, Vivian Hsiu-Chuan

2014-01-01

Background Selenium (Se) is an important nutrient that carries out many biological processes including maintaining optimal immune function. Here, inorganic selenite (Se(IV)) was evaluated for its pathogen resistance and potential-associated factors in Caenorhabditis elegans. The immune effects of Se(IV) were investigated by examining the responses of C. elegans to Pseudomonas aerugonisa PA14 strain. Principal Findings Se(IV)-treated C. elegans showed increased survival under PA14 infection compared with untreated controls. The significant pathogen resistance of Se(IV) on C. elegans might not be attributed to the effects of Se(IV) on PA14 as Se(IV) showed no effect on bacterial quorum-sensing and virulence factors of PA14. This study showed that Se(IV) enhanced the expression of a gene pivotal for the innate immunity in C. elegans. The study found that the pathogen-resistant phenotypes contributed by Se(IV) was absent from the skn-1 mutant worms. Moreover, Se(IV) influenced the subcellular distribution of SKN-1/Nrf in C. elegans upon PA14 infection. Furthermore, Se(IV) increased mRNA levels of SKN-1 target genes (gst-4 and gcs-1). Conclusions This study found evidence of Se(IV) protecting C. elegans against P. aeruginosa PA14 infection by exerting effects on the innate immunity of C. elegans that is likely mediated via regulation of a SKN-1-dependent signaling pathway. PMID:25147937

Psychological variables and Wechsler Adult Intelligence Scale-IV performance.

PubMed

Gass, Carlton S; Gutierrez, Laura

2017-01-01

The MMPI-2 and WAIS-IV are commonly used together in neuropsychological evaluations yet little is known about their interrelationships. This study explored the potential influence of psychological factors on WAIS-IV performance in a sample of 180 predominantly male veteran referrals that underwent a comprehensive neuropsychological examination in a VA Medical Center. Exclusionary criteria included failed performance validity testing and self-report distortion on the MMPI-2. A Principal Components Analysis was performed on the 15 MMPI-2 content scales, yielding three broader higher-order psychological dimensions: Internalized Emotional Dysfunction (IED), Externalized Emotional Dysfunction (EED), and Fear. Level of IED was not related to performance on the WAIS-IV Full Scale IQ or its four indexes: (Verbal Comprehension, Perceptual Reasoning, Working Memory, and Processing Speed). EED was not related to WAIS-IV performance. Level of Fear, which encompasses health preoccupations (HEA) and distorted perceptions (BIZ), was significantly related to WAIS-IV Full Scale IQ and Verbal Comprehension. These results challenge the common use of high scores on the MMPI-2 IED measures (chiefly depression and anxiety) to explain deficient WAIS-IV performance. In addition, they provide impetus for further investigation of the relation between verbal intelligence and Fear.

Outcome Analysis of Patients With Oral Cavity Cancer and Extracapsular Spread in Neck Lymph Nodes

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

Liao, Chun-Ta, E-mail: liaoct@adm.cgmh.org.tw; Department of Head and Neck Oncology Group, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan; Lee, Li-Yu

Purpose: Extracapsular spread (ECS) in neck lymph nodes is a major adverse prognostic factor in patients with oral cavity squamous cell carcinoma (OSCC). We conducted a retrospective analysis of prognostic factors in this patient group and tried to identify a subset of patients with a worse prognosis suitable for more aggressive therapeutic interventions. Methods and Materials: Enrolled in the study were 255 OSCC patients with ECS in neck nodes and without evidence of distant metastasis. All participants were followed-up for at least 2 years or censored at last follow-up. The 5-year rates of control, distant metastasis, and survival were themore » main outcome measures. Results: Level IV/V lymph node metastases and tumor depth {>=}12 mm were independent predictors of 5-year survival and identified three prognostic groups. In the low-risk group (no level IV/V metastases and tumor depth <12 mm), the 5-year disease-free, disease-specific, and overall survival rates were 60%, 66%, and 50%, respectively. In the intermediate-risk group (no level IV/V metastases and tumor depth {>=}12 mm), the 5-year disease-free, disease-specific, and overall survival rates were 39%, 41%, and 28%, respectively. In the high-risk group (evidence of level IV/V metastases), the 5-year disease-free, disease-specific, and overall survival rates were 14%, 12%, and 10%, respectively. Conclusions: Among OSCC patients with ECS, those with level IV/V metastases appear to have the worst prognosis followed by without level IV/V metastases and tumor depth {>=}12 mm. An aggressive therapeutic approach may be suitable for intermediate- and high-risk patients.« less

Sport-specific outcomes after anterior cruciate ligament reconstruction.

PubMed

Warner, Stephen J; Smith, Matthew V; Wright, Rick W; Matava, Matthew J; Brophy, Robert H

2011-08-01

Although anterior cruciate ligament (ACL) reconstruction has been studied extensively in the literature, sport-specific outcomes have not been well-documented. The purpose of this systematic review was to assess sport-specific outcomes after ACL reconstruction in the literature. We performed a systematic review of the literature to identify studies reporting sport-specific outcomes after primary ACL reconstruction. Included studies were required to have reported standardized outcomes after primary ACL reconstruction for a single sport or comparing between different sports. In total 8 studies conformed to all inclusion criteria: 2 Level II studies, 1 Level III study, and 5 Level IV case series. Only 1 study reported comparisons of standardized outcomes between different sports, whereas 7 studies reported standardized outcomes in a single sport. Return to activity was the most common sport-specific outcome reported and varied from 19% (soccer) to 100% (bicycling and rugby), although the methods of measuring this outcome differed. Whereas return to activity after ACL reconstruction appears more likely for bicycling and jogging than for cutting and pivoting sports such as soccer and football, the literature on sport-specific outcomes from ACL reconstruction is limited with minimal data. Further studies are needed to report sport-specific outcomes and return to play after ACL reconstruction. Level IV, systematic review of Level II, III, and IV studies. Copyright © 2011 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Item Response Theory Analysis of DSM-IV Cannabis Abuse and Dependence Criteria in Adolescents

ERIC Educational Resources Information Center

Hartman, Christie A.; Gelhorn, Heather; Crowley, Thomas J.; Sakai, Joseph T.; Stallings, Michael; Young, Susan E.; Rhee, Soo Hyun; Corley, Robin; Hewitt, John K.; Hopfer, Christian J.

2008-01-01

A study to examine the DSM-IV criteria for cannabis abuse and dependence among adolescents is conducted. Results conclude that abuse and dependence criteria were not found to affect the different levels of severity in cannabis use.

Self-report assessment of the DSM-IV personality disorders. Measurement of trait and distress characteristics: the ADP-IV.

PubMed

Schotte, C K; de Doncker, D; Vankerckhoven, C; Vertommen, H; Cosyns, P

1998-09-01

Self-report instruments assessing the DSM personality disorders are characterized by overdiagnosis due to their emphasis on the measurement of personality traits rather than the impairment and distress associated with the criteria. The ADP-IV, a Dutch questionnaire, introduces an alternative assessment method: each test item assesses 'Trait' as well as 'Distress/impairment' characteristics of a DSM-IV criterion. This item format allows dimensional as well as categorical diagnostic evaluations. The present study explores the validity of the ADP-IV in a sample of 659 subjects of the Flemish population. The dimensional personality disorder subscales, measuring Trait characteristics, are internally consistent and display a good concurrent validity with the Wisconsin Personality Disorders Inventory. Factor analysis at the item-level resulted in 11 orthogonal factors, describing personality dimensions such as psychopathy, social anxiety and avoidance, negative affect and self-image. Factor analysis at the subscale-level identified two basic dimensions, reflecting hostile (DSM-IV Cluster B) and anxious (DSM-IV Cluster C) interpersonal attitudes. Categorical ADP-IV diagnoses are obtained using scoring algorithms, which emphasize the Trait or the Distress concepts in the diagnostic evaluation. Prevalences of ADP-IV diagnoses of any personality disorder according to these algorithms vary between 2.28 and 20.64%. Although further research in clinical samples is required, the present results support the validity of the ADP-IV and the potential of the measurement of trait and distress characteristics as a method for assessing personality pathology.

Chronic production of angiotensin IV in the brain leads to hypertension that is reversible with an angiotensin II AT1 receptor antagonist.

PubMed

Lochard, Nadheige; Thibault, Gaétan; Silversides, David W; Touyz, Rhian M; Reudelhuber, Timothy L

2004-06-11

Angiotensin IV (Ang IV) is a metabolite of the potent vasoconstrictor angiotensin II (Ang II). Because specific binding sites for this peptide have been reported in numerous tissues including the brain, it has been suggested that a specific Ang IV receptor (AT4) might exist. Bolus injection of Ang IV in brain ventricles has been implicated in learning, memory, and localized vasodilatation. However, the functions of Ang IV in a physiological context are still unknown. In this study, we generated a transgenic (TG) mouse model that chronically releases Ang IV peptide specifically in the brain. TG mice were found to be hypertensive by the tail-cuff method as compared with control littermates. Treatment with the angiotensin-converting enzyme inhibitor captopril had no effect on blood pressure, but surprisingly treatment with the Ang II AT1 receptor antagonist candesartan normalized the blood pressure despite the fact that the levels of Ang IV in the brains of TG mice were only 4-fold elevated over the normal endogenous level of Ang peptides. Calcium mobilization assays performed on cultured CHO cells chronically transfected with the AT1 receptor confirm that low-dose Ang IV can mobilize calcium via the AT1 receptor only in the presence of Ang II, consistent with an allosteric mechanism. These results suggest that chronic elevation of Ang IV in the brain can induce hypertension that can be treated with angiotensin II AT1 receptor antagonists.

AMD-like retinopathy associated with intravenous iron

PubMed Central

Song, Delu; Kanu, Levi N.; Li, Yafeng; Kelly, Kristen L.; Bhuyan, Rupak K.; Aleman, Tomas; Morgan, Jessica I. W.; Dunaief, Joshua L.

2016-01-01

Iron accumulation in the retina is associated with the development of age-related macular degeneration (AMD). IV iron is a common method to treat iron deficiency anemia in adults, and its retinal manifestations have not hitherto been identified. To assess whether IV iron formulations can be retina-toxic, we generated a mouse model for iron-induced retinal damage. Male C57BL/6J mice were randomized into groups receiving IV iron-sucrose (+Fe) or 30% sucrose (−Fe). Iron levels in neurosensory retina (NSR), retinal pigment epithelium (RPE), and choroid were assessed using immunofluorescence, quantitative PCR, and the Perls’ iron stain. Iron levels were most increased in the RPE and choroid while levels in the NSR did not differ significantly in +Fe mice compared to controls. Eyes from +Fe mice shared histological features with AMD, including Bruch’s membrane (BrM) thickening with complement C3 deposition, as well as RPE hypertrophy and vacuolization. This focal degeneration correlated with areas with high choroidal iron levels. Ultrastructural analysis provided further detail of the RPE/photoreceptor outer segment vacuolization and Bruch’s membrane thickening. Findings were correlated with a clinical case of a 43-year-old patient who developed numerous retinal drusen, the hallmark of AMD, within 11 months of IV iron therapy. Our results suggest that IV iron therapy may have the potential to induce or exacerbate a form of retinal degeneration. This retinal degeneration shares features with AMD, indicating the need for further study of AMD risk in patients receiving IV iron treatment. PMID:27565570

Prospective case-control study of efficacy of bilateral selective neck dissection in primary surgical treatment of supraglottic laryngeal cancers with clinically negative cervical findings (N0).

PubMed

Djordjevic, V; Bukurov, B; Arsovic, N; Dimitrijevic, M; Jesic, S; Nesic, V; Petrovic, Z

2016-12-01

To evaluate the efficacy of bilateral selective neck dissection of levels II-IV in elective and therapeutic management of the neck as a part of primary surgical treatment of patients with supraglottic laryngeal cancer and clinically negative cervical findings (N0). Institutional, observational, case-control study with historic control of patients who underwent primary supraglottic tumour surgery, and a prospective cohort of patient, who underwent, besides the operation of primary tumour, bilateral selective neck dissection (level II-IV). University, tertiary level hospital, national referral centre. The study included 193 patients with supraglottic cancer and without palpable or ultrasound positive cervical findings who were surgically treated from 1988 to 2005. Besides the operation of primary tumour, all patients in the study group underwent bilateral selective neck dissection (level II-IV). Patients in the control group (N = 51) underwent primary tumour operation only and were followed up regularly. In cases with postoperative regional recurrences, the radical neck dissection was performed. All patients with histopathological confirmation of occult metastases were administered radiotherapy treatment (60 Gy) in the postoperative period. Five-year overall survival rate. Occult cervical metastases were found in 18% of patients. They were present in level II in 77.5%, in level III in 20% of cases and in one patient in level IV (2.5%); the extracapsular spread was observed in 20% of cases. Postoperative regional metastases were found in 4.15% of cases in the study group, and in 11.8% in the control group, which proved to be significantly higher. The five-year overall survival rate showed no significant difference between the study group and the control group. The incidence of postoperative regional recurrences could be reduced by performing bilateral selective neck dissection simultaneously with primary tumour operation, but with no influence on the survival rate. © 2015 John Wiley & Sons Ltd.

Intravenous infusion of hexamethonium and atropine but not propranolol diminishes apolipoprotein A-IV gene expression in rat ileum.

PubMed

Sonoyama, K; Tajima, K; Fujiwara, R; Kasai, T

2000-03-01

To clarify the role of neural factors in the regulation of apolipoprotein (apo) A-IV expression in the small intestine, we investigated the effect of neural blockers on mRNA levels of apo A-IV in rat small intestine. Either ganglionic blocker (hexamethonium), cholinergic blocker (atropine) or beta-adrenergic blocker (propranolol) was infused intravenously to unrestrained conscious rats for 8 h, and then total RNA was isolated from the small intestine and analyzed using Northern hybridization. Apo A-IV mRNA levels in the ileum were significantly lower in hexamethonium- or atropine-infused rats than in saline- (control) or propranolol-infused rats. Immunoblot analysis showed no difference in plasma apo A-IV concentrations between hexamethonium- and saline-infused groups. The lower mRNA levels of apo A-IV in the ileum of hexamethonium-infused rats were observed even in bile-drained rats, indicating that the lower expression was not due to any changes in bile availability. The ileal apo A-IV mRNA levels were significantly higher in rats infused with lipid emulsion into the ileum than in rats infused with glucose-saline, and the concomitant infusion of intravenous hexamethonium did not affect the higher levels of apo A-IV mRNA. These results suggest that the basal expression of the ileal A-IV gene is at least partially regulated in a site-specific manner by cholinergic neurons.

Short and long-term effects of continuous versus intermittent loop diuretics treatment in acute heart failure with renal dysfunction.

PubMed

Palazzuoli, Alberto; Pellegrini, Marco; Franci, Beatrice; Beltrami, Matteo; Ruocco, Gaetano; Gonnelli, Stefano; Angelini, Gianni D; Nuti, Ranuccio

2015-02-01

Intravenous loop diuretics are still the cornerstone of therapy in acute decompensated heart failure, however, the optimal dosage and administration strategies remain poorly defined particularly in patients with an associated renal dysfunction. This is a single-center, pilot, randomized trial involving patients with acute HF and renal dysfunction. Patients were assigned to receive continuous furosemide infusion (cIV) or bolus injections of furosemide (iIV). Primary end points were the evaluation of urine output volumes, renal function, and b-type natriuretic peptide (BNP) levels during treatment time. Secondary end point included: weight loss, length of hospitalization, differences in plasma electrolytes, need for additional treatment, and evaluation of cardiac events during follow-up period. 57 patients were included in the study. The cIV group showed an increase in urine output (2,505 ± 796 vs 2140 ± 468 ml/day, p < 0.04) and a more significant decrease of BNP levels in respect to the iIV group (679.6 ± 397 vs 949 ± 548 pg/ml, p < 0.04). We observed a significant increase in creatinine levels (1.78 ± 0.5 vs 1.41 ± 0.3 mg/dl, p < 0.01), and a reduction of the estimated glomerular filtration rate in cIV (44.8 ± 6.1 vs 46.7 ± 6.1 ml/min, p < 0.05). We observed a significant difference in eGFR (p = 0.01), creatinine (p = 0.02) and BNP levels (p = 0.03) from baseline to the end of treatment in both groups. A significant increase of in-hospital additional treatment as well as length of hospitalization was observed in cIV. Finally, cIV revealed a higher rate of adverse events during the follow-up period (p < 0.03). cIV appears to provide a more efficient diuresis and BNP level reduction during hospitalization, however, it was associated with increased rate of worsening renal function during hospitalization. cIV also appears related to a longer hospitalization and an increased number of adverse events during follow-up. For all of these reasons, a larger multi-center study is required to determine whether high-dose diuretics are responsible for worsening renal function and to define the best modality of administration.

The APOA4 T347S variant is associated with reduced plasma TAOS in subjects with diabetes mellitus and cardiovascular disease.

PubMed

Wong, Wai-Man R; Stephens, Jeffrey W; Acharya, Jayshree; Hurel, Steven J; Humphries, Steve E; Talmud, Philippa J

2004-08-01

Apolipoprotein A-IV (apoA-IV) has been postulated to be antiatherogenic. Transgenic APOA4/Apoe-/- mice are protected against atherosclerosis, with plasma apoA-IV displaying antioxidant activity in vitro. In humans, there is an inverse relationship between apoA-IV levels and risk of coronary heart disease (CHD). Furthermore, the APOA4 T347S rare allele has been associated with increased risk of CHD and reduced apoA-IV levels. Reduced total antioxidant status (TAOS) due to increased oxidative stress is implicated in the process of atherogenesis. Thus, this study aimed to examine the association between the APOA4 T347S variant and TAOS in diabetic patients with (n = 196) or without (n = 509) cardiovascular disease (CVD). A higher percentage of CVD patients were present in the lowest quartile of TAOS, compared with the rest (P = 0.04). Overall, there was no association between genotype and TAOS. However, in patients with CVD, homozygotes for the S347 allele had significantly lower TAOS compared with TT and TS subjects (31.2 +/- 9.89% and 42.5 +/- 13.04% TAOS, respectively; P = 0.0024), an effect that was not seen in the patients without CVD. This study offers direct support for an antioxidant capacity of apoA-IV, thus providing some explanation for the antiatherogenic role of apoA-IV and the higher CVD risk in S347 homozygotes. Copyright 2004 American Society for Biochemistry and Molecular Biology, Inc.

Protective Efficacy of Selenite against Lead-Induced Neurotoxicity in Caenorhabditis elegans

PubMed Central

Tseng, I-Ling; Liao, Vivian Hsiu-Chuan

2013-01-01

Background Selenium is an essential micronutrient that has a narrow exposure window between its beneficial and toxic effects. This study investigated the protective potential of selenite (IV) against lead (Pb(II))-induced neurotoxicity in Caenorhabditis elegans. Principal Findings The results showed that Se(IV) (0.01 µM) pretreatment ameliorated the decline of locomotion behaviors (frequencies of body bends, head thrashes, and reversal ) of C. elegans that are damaged by Pb(II) (100 µM) exposure. The intracellular ROS level of C. elegans induced by Pb(II) exposure was significantly lowered by Se(IV) supplementation prior to Pb(II) exposure. Finally, Se(IV) protects AFD sensory neurons from Pb(II)-induced toxicity. Conclusions Our study suggests that Se(IV) has protective activities against Pb(II)-induced neurotoxicity through its antioxidant property. PMID:23638060

A study of low scores in Canadian children and adolescents on the Wechsler Intelligence Scale For Children, Fourth Edition (WISC-IV).

PubMed

Brooks, Brian L

2011-01-01

Knowing the prevalence of low neurocognitive scores for the WISC-IV Canadian normative sample (WISC-IV(CDN)) is an important supplement for clinical interpretation of test performance. On the WISC-IV(CDN), it is uncommon for children and adolescents to have 4 or more subtest scores or 2 or more Index scores ≤ 9th percentile when all scores on the battery are considered simultaneously. As the level of the child's intelligence increases or the number of years of parental education increases, the prevalence of low scores decreases. These results are consistent with existing studies of the base rates of low scores in children and adolescents on pediatric cognitive batteries, including the WISC-IV American normative sample. Tables provided are ready for clinical use.

Alterations of the levels of primary antioxidant enzymes in different grades of human astrocytoma tissues.

PubMed

Yen, Hsiu-Chuan; Lin, Chih-Lung; Chen, Bing-Shian; Chen, Chih-Wei; Wei, Kuo-Chen; Yang, Mei-Lin; Hsu, Jee-Ching; Hsu, Yung-Hsing

2018-06-03

Malignant astrocytoma is the most commonly occurring brain tumor in humans. Oxidative stress is implicated in the development of cancers. Superoxide dismutase 2 (SOD2) was found to exert tumor suppressive effect in basic research, but increased SOD2 protein level was associated with higher aggressiveness of human astrocytomas. However, studies reporting alterations of antioxidant enzymes in human astrocytomas often employed less accurate methods or included different types of tumors. Here we analyzed the mRNA levels, activities, and protein levels of primary antioxidant enzymes in control brain tissues and various grades of astrocytomas obtained from 40 patients. SOD1 expression, SOD1 activity, and SOD1 protein level were lower in Grade IV astrocytomas. SOD2 expression was lower in low-grade (Grades I and II) and Grade III astrocytomas than in controls, but SOD2 expression and SOD2 protein level were higher in Grade IV astrocytomas than in Grade III astrocytomas. Although there was no change in SOD2 activity and a lower activity of citrate synthase (CS), the MnSOD:CS ratio increased in Grade IV astrocytomas compared with controls and low-grade astrocytomas. Furthermore, SOD1 activity, CS activity, SOD1 expression, GPX4 expression, and GPX4 protein level were inversely correlated with the malignancy, whereas catalase activity, catalase protein, SOD2 protein level, and the SOD2:CS ratio were positively correlated with the degree of malignancy. Lower SOD2:CS ratio was associated with poor outcomes for Grade IV astrocytomas. This is the first study to quantify changes of various primary antioxidant enzymes in different grades of astrocytomas at different levels concurrently in human astrocytomas.

Level Energies, Oscillator Strengths and Lifetimes for Transitions in Pb IV

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

Colon, C.; Alonso-Medina, A.; Zanon, A.

2008-10-22

Oscillator strengths for several lines of astrophysical interest arising from some configurations and some levels radiative lifetimes of Pb IV have been calculated. These values were obtained in intermediate coupling (IC) and using ab initio relativistic Hartree-Fock calculations. We use for the IC calculations the standard method of least square fitting of experimental energy levels by means of computer codes from Cowan. Transition Probabilities and oscillator strengths obtained, although in general agreement with the rare experimental data, do present some noticeable discrepancies that are studied in the text.

Effect of impurities and processing on silicon solar cells. Volume 1: Characterization methods for impurities in silicon and impurity effects data base

NASA Technical Reports Server (NTRS)

Hopkins, R. H.; Davis, J. R.; Rohatgi, A.; Campbell, R. B.; Blais, P. D.; Rai-Choudhury, P.; Stapleton, R. E.; Mollenkopf, H. C.; Mccormick, J. R.

1980-01-01

Two major topics are treated: methods to measure and evaluate impurity effects in silicon and comprehensive tabulations of data derived during the study. Discussions of deep level spectroscopy, detailed dark I-V measurements, recombination lifetime determination, scanned laser photo-response, conventional solar cell I-V techniques, and descriptions of silicon chemical analysis are presented and discussed. The tabulated data include lists of impurity segregation coefficients, ingot impurity analyses and estimated concentrations, typical deep level impurity spectra, photoconductive and open circuit decay lifetimes for individual metal-doped ingots, and a complete tabulation of the cell I-V characteristics of nearly 200 ingots.

Revision to Planetary Protection Policy for Mars Missions

NASA Technical Reports Server (NTRS)

DeVincenzi, D. L.; Stabekis, P.; Barengoltz, J.; Morrison, David (Technical Monitor)

1994-01-01

Under existing COSPAR policy adopted in 1984, missions to Mars (landers, probes, and some orbiters) are designated as Category IV missions. As such, the procedures for implementing planetary protection requirements could include trajectory biasing, cleanrooms, bioload reduction, sterilization of hardware, and bioshields, i. e. requirements could be similar to Viking. However, in 1992, a U. S. National Academy of Sciences study recommended that controls on forward contamination of Mars be tied to specific mission objectives. The report recommended that Mars landers with life detection instruments be subject to at least Viking-level sterilization procedures for bioload reduction, while spacecraft (including orbiters) without life detection instruments be subject to at least Viking-level pre sterilization procedures for bioload reduction but need not be sterilized. In light of this, it is proposed that the current policy's Category IV missions and their planetary protection requirements be divided into two subcategories as follows: Category IV A, for missions comprising landers and probes without life detection experiments and some orbiters, which will meet a specified bioburden limit for exposed surfaces; Category IV B, for landers and probes with life detection experiments, which will require complete system sterilization. For Category IV A missions, bioburden specifications will be proposed and implementing procedures discussed. A resolution will be proposed to modify the existing COSPAR policy to reflect these changes. Similar specifications, procedures, and resolution for Category IV B missions will be the subject of a later study.

A Molecular-Genetic Study of the Arabidopsis Toc75 Gene Family1

PubMed Central

Baldwin, Amy; Wardle, Anthony; Patel, Ramesh; Dudley, Penny; Park, Soon Ki; Twell, David; Inoue, Kentaro; Jarvis, Paul

2005-01-01

Toc75 (translocon at the outer envelope membrane of chloroplasts, 75 kD) is the protein translocation channel at the outer envelope membrane of plastids and was first identified in pea (Pisum sativum) using biochemical approaches. The Arabidopsis (Arabidopsis thaliana) genome contains three Toc75-related sequences, termed atTOC75-I, atTOC75-III, and atTOC75-IV, which we studied using a range of molecular, genetic, and biochemical techniques. Expression of atTOC75-III is strongly regulated and at its highest level in young, rapidly expanding tissues. By contrast, atTOC75-IV is expressed uniformly throughout development and at a much lower level than atTOC75-III. The third sequence, atTOC75-I, is a pseudogene that is not expressed due to a gypsy/Ty3 transposon insertion in exon 1, and numerous nonsense, frame-shift, and splice-junction mutations. The expressed genes, atTOC75-III and atTOC75-IV, both encode integral envelope membrane proteins. Unlike atToc75-III, the smaller atToc75-IV protein is not processed upon targeting to the envelope, and its insertion does not require ATP at high concentrations. The atTOC75-III gene is essential for viability, since homozygous atToc75-III knockout mutants (termed toc75-III) could not be identified, and aborted seeds were observed at a frequency of approximately 25% in the siliques of self-pollinated toc75-III heterozygotes. Homozygous toc75-III embryos were found to abort at the two-cell stage. Homozygous atToc75-IV knockout plants (termed toc75-IV) displayed no obvious visible phenotypes. However, structural abnormalities were observed in the etioplasts of toc75-IV seedlings and atTOC75-IV overexpressing lines, and toc75-IV plants were less efficient at deetiolation than wild type. These results suggest some role for atToc75-IV during growth in the dark. PMID:15908591

Plasma and cerebrospinal fluid pharmacokinetic parameters after single-dose administration of intravenous, oral, or rectal acetaminophen.

PubMed

Singla, Neil K; Parulan, Cherri; Samson, Roselle; Hutchinson, Joel; Bushnell, Rick; Beja, Evelyn G; Ang, Robert; Royal, Mike A

2012-09-01

This is the first study to compare plasma and cerebrospinal fluid (CSF) pharmacokinetics of intravenous (IV), oral (PO), or rectal (PR) formulations of acetaminophen. Healthy male subjects (N = 6) were randomized to receive a single dose of IV (OFIRMEV(®) ; Cadence) 1,000 mg (15 minute infusion), PO (2 Tylenol(®) 500 mg caplets; McNeil Consumer Healthcare), or PR acetaminophen (2 Feverall(®) 650 mg suppositories; Actavis) with a 1-day washout period between doses. The 1,300 mg PR concentrations were standardized to 1,000 mg. Acetaminophen plasma and CSF levels were obtained at T0, 0.25, 0.5, 0.75, 1, 2, 3, 4, and 6 hours. IV acetaminophen showed earlier and higher plasma and CSF levels compared with PO or PR administration. CSF bioavailability over 6 hours (AUC(0-6)) for IV, PO, and PR 1 g was 24.9, 14.2, and 10.3 μg·h/mL, respectively. No treatment-related adverse events were reported. One subject was replaced because of premature failure of his lumbar spinal catheter. The mean CSF level in the IV group was similar to plasma from 3 to 4 hours and higher from 4 hours on. Absorption phase, variability in plasma, and CSF were greater in PO and PR groups than variability with IV administration. These results demonstrate that earlier and greater CSF penetration occurs as a result of the earlier and higher plasma peak with IV administration compared with PO or PR. © 2012 Lotus Clinical Research, LLC. Pain Practice © 2012 World Institute of Pain.

Evaluation of the effect of divalent metal transporter 1 gene polymorphism on blood iron, lead and cadmium levels

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

Kayaaltı, Zeliha, E-mail: kayaalti@ankara.edu.tr; Akyüzlü, Dilek Kaya; Söylemezoğlu, Tülin

Divalent metal transporter 1 (DMT1), a member of the proton-coupled metal ion transporter family, mediates transport of ferrous iron from the lumen of the intestine into the enterocyte and export of iron from endocytic vesicles. It has an affinity not only for iron but also for other divalent cations including manganese, cobalt, nickel, cadmium, lead, copper, and zinc. DMT1 is encoded by the SLC11a2 gene that is located on chromosome 12q13 in humans and express four major mammalian isoforms (1A/+IRE, 1A/-IRE, 2/+IRE and 2/-IRE). Mutations or polymorphisms of DMT1 gene may have an impact on human health by disturbing metalmore » trafficking. To study the possible association of DMT1 gene with the blood levels of some divalent cations such as iron, lead and cadmium, a single nucleotide polymorphism (SNP) (IVS4+44C/A) in DMT1 gene was investigated in 486 unrelated and healthy individuals in a Turkish population by method of polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). The genotype frequencies were found as 49.8% homozygote typical (CC), 38.3% heterozygote (CA) and 11.9% homozygote atypical (AA). Metal levels were analyzed by dual atomic absorption spectrometer system and the average levels of iron, lead and cadmium in the blood samples were 446.01±81.87 ppm, 35.59±17.72 ppb and 1.25±0.87 ppb, respectively. Individuals with the CC genotype had higher blood iron, lead and cadmium levels than those with AA and CA genotypes. Highly statistically significant associations were detected between IVS4+44 C/A polymorphism in the DMT1 gene and iron and lead levels (p=0.001 and p=0.036, respectively), but no association was found with cadmium level (p=0.344). This study suggested that DMT1 IVS4+44 C/A polymorphism is associated with inter-individual variations in blood iron, lead and cadmium levels. - Highlights: • DMT1 IVS4+44 C/A polymorphism is associated with inter-individual variations in blood iron, cadmium and lead levels. • Individuals with the DMT1 IVS4+44 CC genotype had higher blood iron, lead and cadmium levels. • Individuals with DMT1 IVS4+44 CC genotype may be more susceptible for metal toxicity.« less

Quality of abdominal computed tomography angiography: hand versus mechanical intravenous contrast administration in children.

PubMed

Ayyala, Rama S; Zurakowski, David; Lee, Edward Y

2015-11-01

Abdominal CT angiography has been increasingly used for evaluation of various conditions related to abdominal vasculature in the pediatric population. However, no direct comparison has evaluated the quality of abdominal CT angiography in children using hand versus mechanical administration of intravenous (IV) contrast agent. To compare hand versus mechanical administration of IV contrast agent in the quality of abdominal CT angiography in the pediatric population. We retrospectively reviewed the electronic medical record to identify pediatric patients (≤18 years) who had abdominal CT angiography between August 2012 and August 2013. The information obtained includes: (1) type of administration of IV contrast agent (hand [group 1] versus mechanical [group 2]), (2) size (gauge) of IV catheter, (3) amount of contrast agent administered and (4) rate of contrast agent administration (ml/s). Two reviewers independently performed qualitative and quantitative evaluation of abdominal CT angiography image quality. Qualitative evaluation of abdominal CT angiography image quality was performed by visual assessment of the degree of contrast enhancement in the region of interest (ROI) based on a 4-point scale. Quantitative evaluation of each CT angiography examination was performed by measuring the Hounsfield unit (HU) using an ROI within the abdominal aorta at two levels (celiac axis and the inferior mesenteric artery) for each child. Analysis of variance (ANOVA) using the F-test was applied to compare contrast enhancement within the abdominal aorta at two levels (celiac axis and inferior mesenteric artery) between hand administration and mechanical administration of IV contrast methods with adjustment for age. We identified 46 pediatric patients (24 male, 22 female; mean age 7.3 ± 5.5 years; range 5 weeks to 18 years) with abdominal CT angiography performed during the study period. Of these patients, 16 (35%; 1.7 ± 2.2 years; range 5 weeks to 5 years) had hand administration of IV contrast agent and 30 (65%; 10.2 ± 4.2 years; range 4-18 years) had mechanical administration of IV contrast agent. All 46 abdominal CT angiography studies were of diagnostic quality based on qualitative evaluation (all ≥3). All abdominal CT angiography studies from both groups showed diagnostic quality of contrast enhancement (>150 HU) at both the celiac axis and the inferior mesenteric artery (IMA) levels. The contrast enhancement of the abdominal aorta was not significantly different between the IV contrast administration methods at either the celiac axis level (360 ± 158 vs. 353 ± 116, P = 0.24) or the IMA level (340 ± 140 vs. 351 ± 90, P = 0.27), adjusting for age. Diagnostic-quality abdominal CT angiography can be achieved using hand administration of IV contrast agent in infants and young children (≤5 years).

Astragaloside IV prevents damage to human mesangial cells through the inhibition of the NADPH oxidase/ROS/Akt/NF‑κB pathway under high glucose conditions.

PubMed

Sun, Li; Li, Weiping; Li, Weizu; Xiong, Li; Li, Guiping; Ma, Rong

2014-07-01

Glomerular hypertrophy and hyperfiltration are the two major pathological characteristics of the early stages of diabetic nephropathy (DN), which are respectively related to mesangial cell (MC) proliferation and a decrease in calcium influx conducted by canonical transient receptor potential cation channel 6 (TRPC6). The marked increase in the production of reactive oxygen species (ROS) induced by hyperglycemia is the main sponsor of multiple pathological pathways in DN. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase is an important source of ROS production in MCs. Astragaloside IV (AS‑IV) is an active ingredient of Radix Astragali which has a potent antioxidative effect. In this study, we aimed to investigate whether high glucose (HG)‑induced NADPH oxidase activation and ROS production contribute to MC proliferation and the downregulation of TRPC6 expression; we also wished to determine the effects of AS‑IV on MCs under HG conditions. Using a human glomerular mesangial cell line, we found that treatment with AS‑IV for 48 h markedly attenuated HG‑induced proliferation and the hypertrophy of MCs in a dose‑dependent manner. The intracellular ROS level was also markedly reduced following treatment with AS‑IV. In addition, the enhanced activity of NADPH oxidase and the expression level of NADPH oxidase 4 (Nox4) protein were decreased. Treatment with AS‑IV also inhibited the phosphorylation level of Akt and IκBα in the MCs. In addition, TRPC6 protein expression and the intracellular free calcium concentration were also markedly reduced following treatment with AS‑IV under HG conditions. These results suggest that AS‑IV inhibits HG‑induced mesangial cell proliferation and glomerular contractile dysfunction through the NADPH oxidase/ROS/Akt/nuclear factor‑κB (NF‑κB) pathway, providing a new perspective for the clinical treatment of DN.

LPA gene: interaction between the apolipoprotein(a) size ('kringle IV' repeat) polymorphism and a pentanucleotide repeat polymorphism influences Lp(a) lipoprotein level.

PubMed

Røsby, O; Berg, K

2000-01-01

In order to search for factors influencing the Lp(a) lipoprotein level, we have examined the apolipoprotein(a) (apo(a)) size polymorphism as well as a pentanucleotide (TTTTA) repeat polymorphism in the 5' control region of the LPA gene. Lp(a) lipoprotein levels were compared between individuals with different genotypes as defined by pulsed field gel electrophoresis of DNA plugs, and PCR of DNA samples followed by polyacrylamide gel electrophoresis. DNA plugs and DNA were prepared from blood samples collected from blood donors. Twenty-seven different K IV repeat alleles were observed in the 71 women and 92 men from which apo(a) size polymorphism results were obtained. Alleles encoding 26-32 Kringle IV repeats were the most frequent. Alleles encoding seven to 11 TTTTA repeats were detected in the 84 women and 122 men included in the pentanucleotide polymorphism study, and homozygosity for eight TTTTA repeats was the most common genotype. The eight TTTTA repeat allele occurred with almost any apo(a) allele. An inverse relationship between number of K IV repeats and Lp(a) concentration was confirmed. The contributions of the apo(a) size polymorphism and the pentanucleotide repeat polymorphism to the interindividual variance of Lp(a) lipoprotein concentrations were 9.7 and 3.5%, respectively (type IV sum of squares). Nineteen per cent of the variance in Lp(a) lipoprotein level appeared to be the result of the multiplication product (interaction) between the apo(a) size polymorphism and the pentanucleotide repeat polymorphism. The contribution of the apo(a) size polymorphism alone to the variation in Lp(a) lipoprotein level was lower than previously reported. However, the multiplicative interaction effect between the K IV repeat polymorphism and the pentanucleotide repeat polymorphism may be an important factor explaining the variation in Lp(a) lipoprotein levels among the populations.

Glycated Apolipoprotein A-IV Induces Atherogenesis in Patients With CAD in Type 2 Diabetes.

PubMed

Dai, Yang; Shen, Ying; Li, Qing Run; Ding, Feng Hua; Wang, Xiao Qun; Liu, Hong Juan; Yan, Xiao Xiang; Wang, Ling Jie; Yang, Ke; Wang, Hai Bo; Chen, Qiu Jing; Shen, Wei Feng; Zhang, Rui Yan; Lu, Lin

2017-10-17

Nonenzymatic glycation of apolipoproteins plays a role in the pathogenesis of the vascular complications of diabetes. This study investigated whether apolipoprotein (apo) A-IV was glycated in patients with type 2 diabetes mellitus (T2DM) and whether apoA-IV glycation was related to coronary artery disease (CAD). The study also determined the biological effects of glycated apoA-IV. The authors consecutively enrolled 204 patients with T2DM without CAD (Group I), 515 patients with T2DM with CAD (Group II), and 176 healthy subjects (control group) in this study. ApoA-IV was precipitated from ultracentrifugally isolated high-density lipoprotein, and its glycation level was determined based on Western blotting densitometry (relative intensity of apoA-IV glycation). ApoA-IV NƐ-(carboxylmethyl) lysine (CML) modification sites were identified by mass spectrometry in 37 control subjects, 63 patients in Group I, and 138 patients in Group II. Saline or glycated apoA-IV (g-apoA-IV) generated by glyoxal culture was injected into apoE -/- mice to evaluate atherogenesis, and was also used for the cell experiments. The relative intensity and the abundance of apoA-IV glycation were associated with the presence and severity of CAD in patients with T2DM (all p < 0.05). The experiments showed that g-apoA-IV induced proinflammatory reactions in vitro and promoted atherogenesis in apoE -/- mice through the nuclear receptor NR4A3. G-apoA-IV with mutations (K-A) at high-frequency glycation sites exhibited more weakened proinflammatory and atherogenic effects than did g-apoA-IV both in vitro and in vivo. ApoA-IV glycation is associated with CAD severity in patients with T2DM, and g-apoA-IV induces atherogenesis through NR4A3 in apoE -/- mice. Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.

Prognostic values of common clinical parameters in advanced pancreatic ductal adenocarcinoma: a large multicenter cohort study of ten years.

PubMed

Zhang, Chenyue; Dong, Shu; Wang, Lei; Yu, Songlin; Zheng, Yuwei; Geng, Yanyan; Shen, Xiaoheng; Ying, Haifeng; Guo, Yuanbiao; Yu, Jinming; Deng, Qinglong; Meng, Zhiqiang; Li, Zhaoshen; Chen, Hao; Shen, Yehua; Chen, Qiwen

2018-03-01

We conducted a multicenter cohort study to investigate the prognostic value of some commonly-used laboratory indices in advanced pancreatic ductal adenocarcinoma (PDAC). A multicenter cohort study was conducted from 2004 to 2013. The associations between laboratory indices and prognosis of advanced PDAC were examined. This cohort consisted of 553 females (36.2%) and 973 males (63.8%). Patients at cancer stage III and IV were 595 (39.0%) and 931 (61.0%), respectively. The median survival of stage III patients was 9.0 months, with 3-, 6-, and 12-month survival rates of 94.5%, 73.4%, and 28.5%, respectively. The median survival of stage IV patients was 5.4 months, with 3-, 6-, and 12-month survival rates of 79.3%, 42.9%, and 15.0%, respectively. In multivariate analyses, primary tumor diameter, low albumin, and elevated CA19-9 were associated with decreased survival for stage III patients. Age, smoking, primary tumor diameter, elevated ALT or AST, low albumin, and elevated CA19-9 were associated with decreased survival for stage IV patients. Elevated CA19-9 level, decreased albumin level, and tumor size were associated with worse survival in stage III patients. Meanwhile, advanced age, smoking, and ALT or AST level were negatively correlated to prognosis in stage IV patients.

Prolonged Hypocalcemic Effect by Pulmonary Delivery of Calcitonin Loaded Poly(Methyl Vinyl Ether Maleic Acid) Bioadhesive Nanoparticles

PubMed Central

Varshosaz, J.; Minaiyan, M.; Forghanian, M.

2014-01-01

The purpose of the present study was to design a pulmonary controlled release system of salmon calcitonin (sCT). Therefore, poly(methyl vinyl ether maleic acid) [P(MVEMA)] nanoparticles were prepared by ionic cross-linking method using Fe2+ and Zn2+ ions. Physicochemical properties of nanoparticles were studied in vitro. The stability of sCT in the optimized nanoparticles was studied by electrophoretic gel method. Plasma calcium levels until 48 h were determined in rats as pulmonary-free sCT solution or nanoparticles (25 μg·kg−1), iv solution of sCT (5 μg·kg−1), and pulmonary blank nanoparticles. The drug remained stable during fabrication and tests on nanoparticles. The optimized nanoparticles showed proper physicochemical properties. Normalized reduction of plasma calcium levels was at least 2.76 times higher in pulmonary sCT nanoparticles compared to free solution. The duration of hypocalcemic effect of pulmonary sCT nanoparticles was 24 h, while it was just 1 h for the iv solution. There was not any significant difference between normalized blood calcium levels reduction in pulmonary drug solution and iv injection. Pharmacological activity of nanoparticles after pulmonary delivery was 65% of the iv route. Pulmonary delivery of P(MVEMA) nanoparticles of sCT enhanced and prolonged the hypocalcemic effect of the drug significantly. PMID:24701588

Exporting simulation technology to the Philippines: a comparative study of traditional versus simulation methods for teaching intravenous cannulation.

PubMed

Sotto, Juan Alejandro R; Ayuste, Eduardo C; Bowyer, Mark W; Almonte, Josefina R; Dofitas, Rodney B; Lapitan, Marie C M; Pimentel, Elisabeth A; Ritter, E Matthew; Wherry, David C

2009-01-01

This study examines effectiveness of a donated Laerdal Virtual I.V. simulator when compared with traditional methods of teaching intravenous (IV) cannulation to third year medical students in the Philippines. Forty novice Filipino medical students viewed an instructional video on how to start intravenous lines and were then randomly divided into two groups of twenty. The "Traditional" group observed an IV insertion on an actual patient performed by an experienced practitioner, and then subsequently performed an IV on an actual patient which was videotaped. The "Simulation" group practiced the Virtual I.V. simulator until they successfully completed level three using the "doctor" setting. These students then performed an IV on an actual patient which was videotaped. The videotapes for both groups were reviewed by two pre-trained (Inter-rater reliability of > or =0.84) observers who were blinded to the group using a previously validated checklist for IV insertion. Students trained on the Virtual I.V. showed significantly greater success in successfully starting an IV on an actual patient (40% VS. 15%, p<0.05), decreased constrictive band time (p<.05), increased raw score on the check list (p<.03), and decreased overall time to start an IV (p<.05). The technology was well received but wider application in the non western world is limited by lack of in country company support and the relative expense.

Astragaloside IV inhibits progression of glioma via blocking MAPK/ERK signaling pathway.

PubMed

Li, Bin; Wang, Fei; Liu, Ningtao; Shen, Wen; Huang, Tao

2017-09-09

Glioma is one of the most common primary brain tumors in adults with a high mortality rate and relapse rate. Thus, finding better effective approaches to treat glioma has become very urgent. Astragaloside IV (AS-IV), the major active triterpenoid in Radix Astragali, has shown anti-tumorigenic properties in certain cancers. However, its role in glioma remains unclear. Here, we studied the effects of AS-IV on glioma in vitro and in vivo, and explored the underlying mechanisms. Our results revealed that AS-IV dose-dependently inhibited the proliferation of U251 cells in vitro and attenuated tumor growth in vivo. In addition, the migration and invasion ability of U251 cell has been suppressed in presence of AS-IV. The levels of proliferating cell nuclear antigen (PCNA), Ki67, matrix metallopeptidase (MMP) -2, MMP-9 and vascular endothelial growth factor (VEGF) were decreased significantly by the treatment of different concentrations AS-IV. Furthermore, AS-IV also significantly weakened the activation of Mitogen-activated protein kinase/Extracellular regulated protein kinase (MAPK/ERK) signaling pathway in vitro and in vivo. Taken together our study has identified a novel function of AS-IV and provided a molecular basis for AS-IV potential applications in the treatment of glioma and other cancers. Copyright © 2017 Elsevier Inc. All rights reserved.

A qualitative study of the cultural appropriateness of the Diagnostic Interview Schedule for Children (DISC-IV) in South Africa

PubMed Central

Skinner, Donald; Serekoane, Motsaathebe; Ross, Michael W.

2012-01-01

Background The Diagnostic Interview Schedule for Children (DISC-IV) has been designed for use by trained laypersons. It therefore shows great promise for use in developing countries such as South Africa, where there is a lack of clinically trained and skilled professionals at the primary care level. Against this background, the aim of the current study was to investigate the sociocultural appropriateness of the DISC-IV for use with Sesotho families in South Africa. Methods Qualitative methodology of expert review and contextualized content analyses were used. Ten Sesotho-speaking clinicians were recruited through a snowball sampling technique to the review the DISC through expert review reports. Results Several themes emerged, including the structure of the DISC-IV, its computerized nature, Americanisms, problems in interpretation due to the adversity children live under, language problems, the effect of rural settings and education level, and cultural norms regarding psychiatric symptoms, gender, the experience of time, the expression of emotion, and family structure. Conclusion Recommendations for the sociocultural adaptation and translation of the DISC into Sesotho are made. PMID:20526764

Epidemiological and clinical relevance of insomnia diagnosis algorithms according to the DSM-IV and the International Classification of Sleep Disorders (ICSD).

PubMed

Ohayon, Maurice M; Reynolds, Charles F

2009-10-01

Although the epidemiology of insomnia in the general population has received considerable attention in the past 20 years, few studies have investigated the prevalence of insomnia using operational definitions such as those set forth in the ICSD and DSM-IV, specifying what proportion of respondents satisfied the criteria to reach a diagnosis of insomnia disorder. This is a cross-sectional study involving 25,579 individuals aged 15 years and over representative of the general population of France, the United Kingdom, Germany, Italy, Portugal, Spain and Finland. The participants were interviewed on sleep habits and disorders managed by the Sleep-EVAL expert system using DSM-IV and ICSD classifications. At the complaint level, too short sleep (20.2%), light sleep (16.6%), and global sleep dissatisfaction (8.2%) were reported by 37% of the subjects. At the symptom level (difficulty initiating or maintaining sleep and non-restorative sleep at least 3 nights per week), 34.5% of the sample reported at least one of them. At the criterion level, (symptoms+daytime consequences), 9.8% of the total sample reported having them. At the diagnostic level, 6.6% satisfied the DSM-IV requirement for positive and differential diagnosis. However, many respondents failed to meet diagnostic criteria for duration, frequency and severity in the two classifications, suggesting that multidimensional measures are needed. A significant proportion of the population with sleep complaints do not fit into DSM-IV and ICSD classifications. Further efforts are needed to identify diagnostic criteria and dimensional measures that will lead to insomnia diagnoses and thus provide a more reliable, valid and clinically relevant classification.

An External Independent Validation of APACHE IV in a Malaysian Intensive Care Unit.

PubMed

Wong, Rowena S Y; Ismail, Noor Azina; Tan, Cheng Cheng

2015-04-01

Intensive care unit (ICU) prognostic models are predominantly used in more developed nations such as the United States, Europe and Australia. These are not that popular in Southeast Asian countries due to costs and technology considerations. The purpose of this study is to evaluate the suitability of the acute physiology and chronic health evaluation (APACHE) IV model in a single centre Malaysian ICU. A prospective study was conducted at the single centre ICU in Hospital Sultanah Aminah (HSA) Malaysia. External validation of APACHE IV involved a cohort of 916 patients who were admitted in 2009. Model performance was assessed through its calibration and discrimination abilities. A first-level customisation using logistic regression approach was also applied to improve model calibration. APACHE IV exhibited good discrimination, with an area under receiver operating characteristic (ROC) curve of 0.78. However, the model's overall fit was observed to be poor, as indicated by the Hosmer-Lemeshow goodness-of-fit test (Ĉ = 113, P <0.001). Predicted in-ICU mortality rate (28.1%) was significantly higher than the actual in-ICU mortality rate (18.8%). Model calibration was improved after applying first-level customisation (Ĉ = 6.39, P = 0.78) although discrimination was not affected. APACHE IV is not suitable for application in HSA ICU, without further customisation. The model's lack of fit in the Malaysian study is attributed to differences in the baseline characteristics between HSA ICU and APACHE IV datasets. Other possible factors could be due to differences in clinical practice, quality and services of health care systems between Malaysia and the United States.

[Diagnostic values of serum type III procollagen N-terminal peptide in type IV gastric cancer].

PubMed

Akazawa, S; Fujiki, T; Kanda, Y; Kumai, R; Yoshida, S

1985-04-01

Since increased synthesis of collagen has been demonstrated in tissue of type IV gastric cancer, we attempted to distinguish type IV gastric cancer from other cancers by measuring serum levels of type III procollagen N-terminal peptide (type III-N-peptide). Mean serum levels in type IV gastric cancer patients without metastasis were found to be elevated above normal values and developed a tendency to be higher than those in types I, II and III gastric cancer patients without metastasis. Highly positive ratios were found in patients with liver diseases including hepatoma and colon cancer, biliary tract cancer, and esophageal cancer patients with liver, lung or bone metastasis, but only 2 out of 14 of these cancer patients without such metastasis showed positive serum levels of type III-N-peptide. Positive cases in patients with type IV gastric cancer were obtained not only in the group with clinical stage IV but also in the groups with clinical stages II and III. In addition, high serum levels of type III-N-peptide in patients with type IV gastric cancer were seen not only in the cases with liver, lung or bone metastasis but also in cases with disseminated peritoneal metastasis alone. These results suggest that if the serum level of type III-N-peptide is elevated above normal values, type IV gastric cancer should be suspected after ruling out liver diseases, myelofibrosis and liver, lung or bone metastasis.

Reliability and Construct Validity of the 6-Minute Racerunner Test in Children and Youth with Cerebral Palsy, GMFCS Levels III and IV.

PubMed

Bolster, Eline A M; Dallmeijer, Annet J; de Wolf, G Sander; Versteegt, Marieke; Schie, Petra E M van

2017-05-01

To determine the test-retest reliability and construct validity of a novel 6-Minute Racerunner Test (6MRT) in children and youth with cerebral palsy (CP) classified as Gross Motor Function Classification System (GMFCS) levels III and IV. The racerunner is a step-propelled tricycle. The participants were 38 children and youth with CP (mean age 11 y 2 m, SD 3 y 7 m; GMFCS III, n = 19; IV, n = 19). Racerunner capability was determined as the distance covered during the 6MRT on three occasions. The intraclass correlation coefficient (ICC), standard error of measurement (SEM), and smallest detectable differences (SDD) were calculated to assess test-retest reliability. The ICC for tests 2 and 3 were 0.89 (SDD 37%; 147 m) for children in level III and 0.91 for children in level IV (SDD 52%; 118 m). When the average of two separate test occasions was used, the SDDs were reduced to 26% (104 m; level III) and 37% (118 m; level IV). For tests 1 to 3, the mean distance covered increased from 345 m (SD 148 m) to 413 m (SD 137 m) for children in level III, and from 193 m (SD 100 m) to 239 m (SD 148 m) for children in level IV. Results suggest high test-retest reliability. However, large SDDs indicate that a single 6MRT measurement is only useful for individual evaluation when large improvements are expected, or when taking the average of two tests. The 6MRT discriminated the distance covered between children and youth in levels III and IV, supporting construct validity.

Significance of serum CA125 and TPS antigen levels for determination of overall survival after three chemotherapy courses in ovarian cancer patients during long-term follow-up.

PubMed

van Dalen, A; Favier, J; Hallensleben, E; Burges, A; Stieber, P; de Bruijn, H W A; Fink, D; Ferrero, A; McGing, P; Harlozinska, A; Kainz, Ch; Markowska, J; Molina, R; Sturgeon, C; Bowman, A; Einarsson, R; Goike, H

2009-01-01

To evaluate the prognostic significance for overall survival rate for the marker combination TPS and CA125 in ovarian cancer patients after three chemotherapy courses during long-term clinical follow-up. The overall survival of 212 (out of 213) ovarian cancer patients (FIGO Stages I-IV) was analyzed in a prospective multicenter study during a 10-year clinical follow-up by univariate and multivariate analysis. In patients with ovarian cancer FIGO Stage I (34 patients) or FIGO Stage II (30 patients) disease, the univariate and multivariate analysis of the 10-year overall survival data showed that CA125 and TPS serum levels were not independent prognostic factors. In the FIGO Stage III group (112 patients), the 10-year overall survival was 15.2%; while in the FIGO Stage IV group (36 patients) a 10-year overall survival of 5.6% was seen. Here, the tumor markers CA125 and TPS levels were significant prognostic factors in both univariate and multivariate analysis (p < 0.0001). In a combined FIGO Stage III + FIGO Stage IV group (60 patients with optimal debulking surgery), multivariate analysis demonstrated that CA125 and TPS levels were independent prognostic factors. For patients in this combined FIGO Stage III + IV group having both markers below respective discrimination level, 35.3% survived for more than ten years, as opposed to patients having one marker above the discrimination level where the 10-year survival was reduced to 10% of the patients. For patients showing both markers above the respective discrimination level, none of the patients survived for the 10-year follow-up time. In FIGO III and IV ovarian cancer patients, only patients with CA 125 and TPS markers below the discrimination level after three chemotherapy courses indicated a favorable prognosis. Patients with an elevated level of CA 125 or TPS or both markers after three chemotherapy courses showed unfavorable prognosis.

Artesunate modulates expression of matrix metalloproteinases and their inhibitors as well as collagen-IV to attenuate pulmonary fibrosis in rats.

PubMed

Wang, Y; Huang, G; Mo, B; Wang, C

2016-06-03

The aim of this study was to determine the effect of artesunate on extracellular matrix (ECM) accumulation and the expression of collagen-IV, matrix metalloproteinase (MMP), and tissue inhibitor of matrix metalloproteinase (TIMP) to understand the pharmacological role of artesunate in pulmonary fibrosis. Eighty Sprague-Dawley rats were randomly assigned to four groups that were administered saline alone, bleomycin (BLM) alone, BLM + artesunate, or artesunate alone for 28 days. Lung tissues from 10 rats in each group were used to obtain lung fibroblast (LF) primary cells, and the rest were used to analyze protein expression. The mRNA expression of collagen-IV, MMP-2, MMP-9, TIMP-1, and TIMP-2 in lung fibroblasts was detected by real-time quantitative reverse transcriptase polymerase chain reaction. The protein levels of collagen-IV, MMP-2, MMP-9, TIMP-1, and TIMP-2 protein in lung tissues were analyzed by western blotting. Artesunate treatment alleviated alveolitis and pulmonary fibrosis induced by bleomycin in rats, as indicated by a decreased lung coefficient and improvement of lung tissue morphology. Artesunate treatment also led to decreased collagen-IV protein levels, which might be a result of its downregulated expression and increased MMP-2 and MMP-9 protein and mRNA levels. Increased TIMP-1 and TIMP- 2 protein and mRNA levels were detected after artesunate treatment in lung tissues and primary lung fibroblast cells and may contribute to enhanced activity of MMP-2 and -9. These findings suggested that artesunate attenuates alveolitis and pulmonary fibrosis by regulating expression of collagen-IV, TIMP-1 and 2, as well as MMP-2 and -9, to reduce ECM accumulation.

Diagnostic efficiency of amylase and type IV collagen in predicting chronic pancreatitis.

PubMed

Das, Subir Kumar; Varadhan, Sowmya; Dhanya, L; Mukherjee, Sukhes; Mohana, S; Balakrishnan, V; Vasudevan, D M

2009-01-01

Chronic pancreatitis, an irreversible inflammatory disease of the pancreas, is associated with the replacement of the destroyed parenchyma by extended development of fibrosis. Despite marked progress in diagnostic tools, no consensus has been reached in diagnosis of chronic pancreatitis. In this study we examined the hematological and biochemical parameters among 40 chronic pancreatitis patients within 18 to 67 yrs. ESR level and ALP activity was elevated in 40% cases. Serum amylase activity increased in 32 patients and it showed significant correlation with ALP (r=0.458, p=0.003), CA-19.9 (r=0.556, p<0.001), and calcium level (r=-0.472, p=0.002). Type IV collagen level in chronic pancreatitis also elevated (164.4 ± 55.5 ng/ml) and showed negative significant correlation with calcium level (r= -0.505, p=0.001). However, no significant correlation was observed between amylase activity and type IV collagen (r=0.289, p= 0.07).

[EUROASPIRE-IV: European Society of Cardiology study of lifestyle, risk factors, and treatment approaches in patients with coronary artery disease: Data from Turkey].

PubMed

Tokgözoğlu, Lale; Kayıkçıoğlu, Meral; Altay, Servet; Aydoğdu, Sinan; Barçın, Cem; Bostan, Cem; Çakmak, Hüseyin Altuğ; Çatakoğlu, Alp Burak; Emet, Samim; Ergene, Oktay; Kalkan, Ali Kemal; Kaya, Barış; Tulunay Kaya, Cansın; Kaymaz, Cihangir; Koylan, Nevrez; Kültürsay, Hakan; Oğuz, Aytekin; Özpelit, Ebru; Ünlü, Serkan

2017-03-01

Data from EUROASPIRE-IV Turkey report investigating risk factors and adherence to guidelines in patients hospitalized for coronary artery disease are presented and results are compared with those of EUROASPIRE-III Turkey and EUROASPIRE-IV Europe. Study was performed in 24 European countries, including Turkey (17 centers). Patients (18-80 years old) hospitalized for coronary (index) event during preceding 3 years were identified from hospital records and interviewed ≥6 months later. Patient information regarding index event was acquired from hospital records. Anamnesis was obtained during the interview, and physical examination and laboratory analyses were performed. Median age at the index coronary event was 58.8 years, and it was significantly decreased compared with last EUROASPIRE-III study (60.5 years), which was conducted at the same centers 6 years earlier (p=0.017). Of all patients, 19.3% were under 50 years of age and mean age was lower than that of EUROASPIRE-IV Europe (62.5 years). Comparing EUROASPIRE-IV Turkey with EUROASPIRE-III Turkey, rate of smokers increased to 25.5% from 23.1% (p=0.499), obesity increased to 40.7% from 35.5% (p=0.211), total cholesterol level increased to 49.6% from 48.3% (p=0.767), and diabetes rate increased to 39.7% from 33.6% (p=0.139), however none of the differences reached a level of statistical significance. Only 11.7% of the smokers quit after coronary event. Rates for these factors were lower in EUROASPIRE-IV Europe (16% for smoking, 37.6% for obesity, and 26.8% for diabetes). EUROASPIRE-IV Turkey data revealed that secondary prevention was unsatisfactory and had progressed unfavorably compared with last EUROASPIRE study, some risk factors were more uncontrolled than overall European average, and coronary artery events at young age remain an important problem.

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

Liu, Xiu-Li, E-mail: usually.158@163.com; Hubei Key Laboratory of Tumor Biological Behaviors and Hubei Cancer Clinical Study Center, No 169 Donghu Road, Wuchang District, Wuhan 430071; Peng, Chun-Wei, E-mail: pqc278@163.com

Highlights: {yields} HER2 level is closely related to the biologic behaviors of breast cancer cells. {yields} A new method to simultaneously image HER2 and type IV collagen was established. {yields} HER2 status and type IV collagen degradation predict breast cancer invasion. {yields} The complex interactions between tumor and its environment were revealed. -- Abstract: It has been well recognized that human epidermal growth factor receptor 2 (HER2) level in breast cancer (BC) is closely related to the malignant biologic behaviors of the tumor, including invasion and metastasis. Yet, there has been a lack of directly observable evidence to support suchmore » notion. Here we report a quantum dots (QDs)-based double-color imaging technique to simultaneously show the HER2 level on BC cells and the type IV collagen in the tumor matrix. In benign breast tumor, the type IV collagen was intact. With the increasing of HER2 expression level, there has been a progressive decrease in type IV collagen around the cancer nest. At HER2 (3+) expression level, there has virtually been a total destruction of type IV collagen. Moreover, HER2 (3+) BC cells also show direct invasion into the blood vessels. This novel imaging method provides direct observable evidence to support the theory that the HER2 expression level is directly related to BC invasion.« less

Comparative study of topical vs. intravenous tranexamic acid regarding blood loss in total knee arthroplasty.

PubMed

Zekcer, Ari; Priori, Ricardo Del; Tieppo, Clauber; Silva, Ricardo Soares da; Severino, Nilson Roberto

2017-01-01

To compare topical vs. intravenous tranexamic acid (TA) in total knee arthroplasty regarding blood loss and transfusion. Ninety patients were randomized to receive TA intravenously (20 mg/kg in 100 mL of saline; group IV), topically (1.5 g in 50 mL of saline, sprayed over the operated site, before release of the tourniquet; topical group), or intravenous saline (100 mL with anesthesia; control group). The volume of drained blood in 48 h, the amount of transfused blood, and the serum levels of hemoglobin and hematocrit before and after surgery were evaluated. The groups were similar for gender, age, weight, laterality, and preoperative hemoglobin and hematocrit levels ( p  > 0.2). The hemoglobin level dropped in all groups when comparing the preoperative and the 48-h evaluations: the control group decreased 3.8 mg/dL on average, while the IV group had a decrease of 3.0, and the topical group, of 3.2 ( p  = 0.019). The difference between the control and IV groups was confirmed by Bonferroni test ( p  = 0.020). The difference between the control group and the topical group was not significant ( p  = 0.130), although there was less reduction in hemoglobin in the topical group; the comparison between the IV group and the topical group was also not significant ( p  = 1.000). Using topic and IV tranexamic acid decreased blood loss and the need for transfusion in total knee arthroplasty. Topical application showed results similar to IV use regarding the need for blood transfusion, but without the possible side effects of IV administration.

Two Validity Studies of CLEP Subject Examination in Elementary Computer Programming: Fortran IV, U. T. Austin, Spring 1979 and Spring 1982. Research Bulletin 82-8.

ERIC Educational Resources Information Center

Appenzellar, Anne B.; Kelley, H. Paul

Two validity studies of the College Board College-Level Examination Program (CLEP) Subject Examination in Elementary Computer Programming: Fortran IV determined that CLEP scores are appropriate for granting examination credit at the University of Texas at Austin. The standard-setting administration was in the spring of 1979, with a re-evaluation…

Efficacy of tacrolimus/mycophenolate mofetil as acute graft-versus-host disease prophylaxis and the impact of subtherapeutic tacrolimus levels in children after matched sibling donor allogeneic hematopoietic cell transplantation.

PubMed

Offer, Katharine; Kolb, Michelle; Jin, Zhezhen; Bhatia, Monica; Kung, Andrew L; George, Diane; Garvin, James H; Robinson, Chalitha; Sosna, Jean; Karamehmet, Esra; Satwani, Prakash

2015-03-01

Only a few studies in children have evaluated the efficacy of prophylactic regimens using tacrolimus on acute graft-versus-host disease (aGVHD). As a result, optimal tacrolimus levels in children after matched sibling donor allogeneic hematopoietic cell transplantation (alloHCT) are not well defined. We measured the association between subtherapeutic levels (<10 ng/mL) during weeks 1 to 4 after alloHCT and the cumulative incidence of grades II to IV aGVHD in children. Additionally, we identified optimal lower cutoff levels for tacrolimus. Sixty patients (median age, 8 years) received tacrolimus/mycophenolate mofetil between March 2003 and September 2012. Twenty-three had a malignant disease and 37 nonmalignant disorders. The stem cell source included peripheral blood stem cells (n = 12) and bone marrow or cord blood (n = 48). Conditioning regimen varied. Specifically, 38.3% received a myeloablative regimen, 36.7% receiving a reduced-toxicity regimen, and 25% receiving a reduced-intensity regimen. Tacrolimus was initiated at .03 mg/kg/day via continuous i.v. infusion or .12 mg/kg/day orally. The dose was adjusted to maintain daily steady state concentrations within a range of 10 to 20 ng/mL. The overall incidence of grades II to IV aGVHD was 33.3%. On multivariate analysis, a mean tacrolimus level < 10 ng/mL during week 3 (P = .042; 95% confidence interval, 1.051 to 14.28) was significantly associated with increased incidence of grades II to IV aGVHD. Using weekly receiver operator curves, the optimal lower cutoff for tacrolimus levels was 10 to 11.2 ng/mL. Further prospective studies are warranted to study the incidence of aGVHD comparing the conventional tacrolimus levels of 5 to 15 versus 10 to 15 ng/mL. Copyright © 2015 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

Alumni of a BSW-Level Specialized Title IV-E Program Voice Their Experiences in the Workplace

ERIC Educational Resources Information Center

Falk, Diane S.

2015-01-01

This study surveyed 289 alumni of a specialized Title IV-E program that prepares undergraduate social work students for careers in public child welfare, examining factors such as turnover rates, adherence to strengths-based practice principles, perceptions of work conditions, and intent to stay. Findings indicate that graduates of this program…

Coagulopathy in Zellweger spectrum disorders: a role for vitamin K.

PubMed

Zeynelabidin, Sara; Klouwer, Femke C C; Meijers, Joost C M; Suijker, Monique H; Engelen, Marc; Poll-The, Bwee Tien; van Ommen, C Heleen

2018-03-01

Zellweger spectrum disorders (ZSDs) are caused by an impairment of peroxisome biogenesis, resulting in multiple metabolic abnormalities. This leads to a range of symptoms, including hepatic dysfunction and coagulopathy. This study evaluated the incidence and severity of coagulopathy and the effect of vitamin K supplementation orally and IV in ZSD. Data were retrospectively retrieved from the medical records of 30 ZSD patients to study coagulopathy and the effect of vitamin K orally on proteins induced by vitamin K absence (PIVKA-II) levels. Five patients from the cohort with a prolonged prothrombin time, low factor VII, and elevated PIVKA-II levels received 10 mg of vitamin K IV. Laboratory results, including thrombin generation, at baseline and 72 h after vitamin K administration were examined. In the retrospective cohort, four patients (13.3%) experienced intracranial bleedings and 14 (46.7%) reported minor bleeding. No thrombotic events occurred. PIVKA-II levels decreased 38% after start of vitamin K therapy orally. In the five patients with a coagulopathy, despite treatment with oral administration of vitamin K, vitamin K IV caused an additional decrease (23%) of PIVKA-II levels and increased thrombin generation. Bleeding complications frequently occur in ZSD patients due to liver disease and vitamin K deficiency. Vitamin K deficiency is partly corrected by vitamin K supplementation orally, and vitamin K administered IV additionally improves vitamin K status, as shown by further decrease of PIVKA-II and improved thrombin generation.

Elucidating rifampin's inducing and inhibiting effects on glyburide pharmacokinetics and blood glucose in healthy volunteers: unmasking the differential effects of enzyme induction and transporter inhibition for a drug and its primary metabolite.

PubMed

Zheng, H X; Huang, Y; Frassetto, L A; Benet, L Z

2009-01-01

The effects of single doses of intravenous (IV) ciprofloxacin and rifampin and of multiple doses of rifampin on glyburide exposure and blood glucose levels were investigated in nine healthy volunteers. A single IV dose of rifampin significantly increased the area under the concentration-time curve (AUC) of glyburide and its metabolite. Blood glucose levels were significantly lower than those observed after dosing with glyburide alone. Multiple doses of rifampin induced an increase in liver enzyme levels, leading to a marked decrease in glyburide exposure and blood glucose levels. When IV rifampin was administered after multiple doses of rifampin, the inhibition of hepatic uptake transporters masked the induction effect; however, the relative changes in AUC for glyburide and its hydroxyl metabolite were similar to those seen under noninduced conditions. The studies reported here demonstrate how measurements of the levels of both the parent drug and its primary metabolite are useful in unmasking simultaneous drug-drug induction and inhibition effects and in characterizing enzymatic vs. transporter mechanisms.

DPP IV inhibitor treatment attenuates bone loss and improves mechanical bone strength in male diabetic rats.

PubMed

Glorie, Lorenzo; Behets, Geert J; Baerts, Lesley; De Meester, Ingrid; D'Haese, Patrick C; Verhulst, Anja

2014-09-01

Dipeptidyl peptidase IV (DPP IV) modulates protein activity by removing dipeptides. DPP IV inhibitors are currently used to improve glucose tolerance in type 2 diabetes patients. DPP IV substrates not only increase insulin secretion but also affect bone metabolism. In this study, the effect of DPP IV inhibitor sitagliptin on bone was evaluated in normal and streptozotocin-induced diabetic rats. This study included 64 male Wistar rats divided into four groups (n = 16): two diabetic and two control groups. One diabetic and one control group received sitagliptin through drinking water. Tibiae were scanned every 3 wk using an in vivo μCT scanner. After 6 and 12 wk, rats were euthanized for histomorphometric analysis of bone parameters. The mechanical resistance of femora to fracture was assessed using a three-point bending test, and serum levels of bone metabolic markers were measured. Efficient DPP IV inhibition was achieved in sitagliptin-treated groups. Trabecular bone loss, the decrease in trabecular number, and the increase in trabecular spacing was attenuated through sitagliptin treatment in diabetic rats, as shown by in vivo μCT. Bone histomorphometry was in line with these results. μCT analysis furthermore showed that sitagliptin prevented cortical bone growth stagnation in diabetic rats, resulting in stronger femora during three-point bending. Finally, the serum levels of the resorption marker CTX-I were significantly lower in sitagliptin-treated diabetic animals compared with untreated diabetic animals. In conclusion, sitagliptin treatment attenuates bone loss and increases bone strength in diabetic rats probably through the reduction of bone resorption and independent of glycemic management. Copyright © 2014 the American Physiological Society.

Intestinal expression of human apolipoprotein A-IV in transgenic mice fails to influence dietary lipid absorption or feeding behavior.

PubMed Central

Aalto-Setälä, K; Bisgaier, C L; Ho, A; Kieft, K A; Traber, M G; Kayden, H J; Ramakrishnan, R; Walsh, A; Essenburg, A D; Breslow, J L

1994-01-01

Two transgenic mouse lines, expressing low or high amounts of human apo A-IV were created. In low and high expressor HuAIVTg mice on a chow diet, serum human apo A-IV levels were 6 and 25 times the normal human level and on a high fat diet, they were 12 and 77 times higher. Human apo A-IV was equally distributed between lipoprotein (mainly HDL) and lipid-free fractions. Intestinal absorption of radiolabeled cholesterol and triglycerides was unaffected in HuAIVTg mice. Vitamin A, carried exclusively in chylomicrons and their remnants, was catabolized normally. When an intragastric vitamin E bolus is given to the HuAIVTg mice, the initial absorption and appearance in triglyceride-rich lipoproteins was similar to that observed in normal mice. However, elevated amounts of vitamin E were subsequently observed in the VLDL of the HuAIVTg mice. Furthermore, in the fed state, serum VLDL triglycerides were markedly elevated in HuAIVTg mice. This effect was greater in high expressor mice. Serum total cholesterol was not elevated, but the distribution was altered in the HuAIVTg mice; VLDL-C was increased at the expense of VLDL-C. Kinetic studies suggested a delayed clearance of VLDL in HuAIVTg mice. Apo A-IV has been suggested to be a satiety factor, but no effect on feeding behavior or weight gain was observed in these HuAIVTg mice. In summary, our studies with HuAIVTg mice show that additional apo A-IV does not effect intestinal absorption of fat and fat-soluble vitamins, and at least chronic elevation of plasma apo A-IV does not effect feeding behavior in this model system. Images PMID:8163677

Dose escalation study of intravenous and intra-arterial N-acetylcysteine for the prevention of oto- and nephrotoxicity of cisplatin with a contrast-induced nephropathy model in patients with renal insufficiency.

PubMed

Dósa, Edit; Heltai, Krisztina; Radovits, Tamás; Molnár, Gabriella; Kapocsi, Judit; Merkely, Béla; Fu, Rongwei; Doolittle, Nancy D; Tóth, Gerda B; Urdang, Zachary; Neuwelt, Edward A

2017-10-03

Cisplatin neuro-, oto-, and nephrotoxicity are major problems in children with malignant tumors, including medulloblastoma, negatively impacting educational achievement, socioemotional development, and overall quality of life. The blood-labyrinth barrier is somewhat permeable to cisplatin, and sensory hair cells and cochlear supporting cells are highly sensitive to this toxic drug. Several chemoprotective agents such as N-acetylcysteine (NAC) were utilized experimentally to avoid these potentially serious and life-long side effects, although no clinical phase I trial was performed before. The purpose of this study was to establish the maximum tolerated dose (MTD) and pharmacokinetics of both intravenous (IV) and intra-arterial (IA) NAC in adults with chronic kidney disease to be used in further trials on oto- and nephroprotection in pediatric patients receiving platinum therapy. Due to ethical considerations in pediatric tumor patients, we used a clinical population of adults with non-neoplastic disease. Subjects with stage three or worse renal failure who had any endovascular procedure were enrolled in a prospective, non-randomized, single center trial to determine the MTD for NAC. We initially aimed to evaluate three patients each at 150, 300, 600, 900, and 1200 mg/kg NAC. The MTD was defined as one dose level below the dose producing grade 3 or 4 toxicity. Serum NAC levels were assessed before, 5 and 15 min post NAC. Twenty-eight subjects (15 men; mean age 72.2 ± 6.8 years) received NAC IV (N = 13) or IA (N = 15). The first participant to experience grade 4 toxicity was at the 600 mg/kg IV dose, at which time the protocol was modified to add an additional dose level of 450 mg/kg NAC. Subsequently, no severe NAC-related toxicity arose and 450 mg/kg NAC was found to be the MTD in both IV and IA groups. Blood levels of NAC showed a linear dose response (p < 0.01). Five min after either IV or IA NAC MTD dose administration, serum NAC levels reached the 2-3 mM concentration which seemed to be nephroprotective in previous preclinical studies. In adults with kidney impairment, NAC can be safely given both IV and IA at a dose of 450 mg/kg. Additional studies are needed to confirm oto- and nephroprotective properties in the setting of cisplatin treatment. Clinical Trial Registration URL: https://eudract.ema.europa.eu . Unique identifier: 2011-000887-92.

An Item Response Theory Modeling of Alcohol and Marijuana Dependences: A National Drug Abuse Treatment Clinical Trials Network Study*

PubMed Central

Wu, Li-Tzy; Pan, Jeng-Jong; Blazer, Dan G.; Tai, Betty; Stitzer, Maxine L.; Brooner, Robert K.; Woody, George E.; Patkar, Ashwin A.; Blaine, Jack D.

2009-01-01

Objective: The aim of this study was to examine psychometric properties of the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), diagnostics criteria for alcohol and marijuana dependences among 462 alcohol users and 311 marijuana users enrolled in two multisite trials of the National Drug Abuse Treatment Clinical Trials Network. Method: Diagnostic questions were assessed by the DSM-IV checklist. Data were analyzed by the item response theory and the multiple indicators–multiple causes method procedures. Results: Criterion symptoms of alcohol and marijuana dependences exhibited a high level of internal consistency. All individual symptoms showed good discrimination in distinguishing alcohol or marijuana users between high and low severity levels of the continuum. In both groups, “withdrawal” appeared to measure the most severe symptom of the dependence continuum. There was little evidence of measurement nonequivalence in assessing symptoms of dependence by gender, age, race/ethnicity, and educational level. Conclusions: These findings highlight the clinical utility of the DSM-IV checklist in assessing alcohol- and marijuana-dependence syndromes among treatment-seeking substance users. PMID:19371493

Level of clinical evidence presented at the International Society for Hip Arthroscopy Annual Scientific Meeting over 5 years (2010–2014)

PubMed Central

Kay, Jeffrey; de SA, Darren; Shallow, Scott; Simunovic, Nicole; Safran, Marc R.; Philippon, Marc J.; Ayeni, Olufemi R.

2015-01-01

The International Society for Hip Arthroscopy (ISHA) Annual Scientific Meeting is at the forefront of informing today’s orthopaedic surgeons and society of the rapid advances in the exponentially growing field of hip arthroscopy. The purpose of this study was to evaluate and observe any trends in the level of clinical evidence in the papers and posters presented at the ISHA Annual Scientific Meeting from 2010 to 2014. The online abstracts of the paper and poster presentations presented at the ISHA Annual Scientific Meetings were independently evaluated by two reviewers (582 total resulting presentations). Two reviewers screened these results for clinical studies and graded the quality of evidence from level I (i.e. randomized trials) to IV (i.e. case series) based on the American Academy of Orthopaedic Surgeons classification system. Four hundred and twenty-eight presentations met the inclusion criteria and were evaluated. Overall, 10.1% of the presentations were level I, 12.8% were level II, 30.1% were level III and 47.0% were level IV evidence. Over time, from 2010 to 2014, we observed an increase in the percentage of level II paper presentations, an increase in the proportion of level III poster presentations, and a decrease in the proportion of both level IV paper and poster presentations. Significant non-random improvement in the level of evidence presented was noted for the poster presentations (P = 0.012) but not for the paper presentations (P = 0.61) over the study period. Statistical trends demonstrate ISHA’s increased awareness and commitment to presenting higher quality evidence as the availability of this evidence increases. PMID:27011857

Matrix metalloproteinase-2 and its correlation with basal membrane components laminin-5 and collagen type IV in paediatric burn patients measured with Surface Plasmon Resonance Imaging (SPRI) biosensors.

PubMed

Weremijewicz, Artur; Matuszczak, Ewa; Sankiewicz, Anna; Tylicka, Marzena; Komarowska, Marta; Tokarzewicz, Anna; Debek, Wojciech; Gorodkiewicz, Ewa; Hermanowicz, Adam

2018-06-01

The purpose of this study was the determination of matrix metalloproteinase-2 and its correlation with basal membrane components laminin-5 and collagen type IV in the blood plasma of burn patients measured with Surface Plasmon Resonance Imaging (SPRI) biosensors. 31 children scalded by hot water who were managed at the Department of Paediatric Surgery between 2014-2015, after primarily presenting with burns in 4-20% TBSA were included into the study (age 9 months up to 14 years, mean age 2,5+1 years). There were 10 girls and 21 boys. Venous blood samples were drawn 2-6h, and 12-16h after the thermal injury, and on the subsequent days 3, 5 and 7. The matrix metalloproteinase-2, collagen type IV and laminin-5 concentrations were assessed using Surface Plasmon Resonance Imaging by the investigators blinded to the other data. The MMP-2, laminin-5 and collagen type IV concentrations in the blood plasma of patients with burns, were highest 12-16h after thermal injury, the difference was statistically significant. The MMP-2, laminin-5 and collagen type IV concentrations measured 3 days, 5 days and 7 days after the thermal injury, slowly decreased over time, and on the 7th day reached the normal range, when compared with the concentration measured in controls. Current work is the first follow-up study regarding MMP-2 in burns. MMP-2, laminin-5 and collagen type IV levels were elevated early after burn injury in the plasma of studied patients, and were highest 12-16h after the injury. MMP-2, laminin-5 and collagen type IV levels were not proportional to the severity of the burn. We believe in the possibility that the gradual decrease of MMP-2, collagen type IV and laminin-5 concentrations could be connected with the process of healing, but to prove it, more investigation is needed in this area. The SPR imaging biosensor is a good diagnostic tool for determination of MMP-2, laminin-5 and collagen type IV in blood plasma of patients with burns. Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.

34 CFR 658.33 - What additional criterion does the Secretary apply to applications from organizations and...

Code of Federal Regulations, 2010 CFR

2010-07-01

... language at the undergraduate level. (b) The Secretary reviews each application for information that shows... studies and the study of modern foreign language at the undergraduate level. (1) The Secretary looks for... international studies or modern foreign languages at the undergraduate level; and (iv) The adequacy of the...

Lipid peroxidation and antioxidant status in colorectal cancer

PubMed Central

Skrzydlewska, Elzbieta; Sulkowski, Stanislaw; Koda, Mariusz; Zalewski, Bogdan; Kanczuga-Koda, Luiza; Sulkowska, Mariola

2005-01-01

AIM: Reactive oxygen species (ROS) can induce carcinogenesis via DNA injury. Both enzymatic and non-enzymatic parameters participate in cell protection against harmful influence of oxidative stress. The aim of the present study was to assess the levels of final lipid peroxidation products like malondialdehyde (MDA) and 4-hydroxy-2-nonenal (4-HNE) in primary colorectal cancer. Moreover, we analysed the activity of main antioxidative enzymes, superoxide dismutase (Cu, Zn-SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and glutathione reductase (GSSRG-R) and the level of non-enzymatic antioxidants (glutathione, vitamins C and E). METHODS: Investigations were conducted in 81 primary colorectal cancers. As a control, the same amount of sample was collected from macroscopically unchanged colon regions of the most distant location to the cancer. Homogenisation of specimens provided 10% homogenates for our evaluations. Activity of antioxidant enzymes and level of glutathione were determined by spectrophotometry. HPLC revealed levels of vitamins C and E and served as a method to detect terminal products of lipid peroxidation in colorectal cancer. RESULTS: Our studies demonstrated a statistically significant increase in the level of lipid peroxidation products (MDA-Adc.muc.-2.65±0.48 nmol/g, Adc.G3-2.15±0.44 nmol/g, clinical IV stage 4.04±0.47 nmol/g, P<0.001 and 4-HNE-Adc.muc. -0.44±0.07 nmol/g, Adc.G3-0.44±0.10 nmol/g, clinical IV stage 0.52±0.11 nmol/g, P<0.001) as well as increase of Cu,Zn-SOD (Adc.muc.-363±72 U/g, Adc.G3-318±48 U/g, clinical IV stage 421±58 U/g, P<0.001), GSH-Px (Adc.muc. -2143±623 U/g, Adc.G3-2005±591 U/g, clinical IV stage 2467±368 U/g, P<0.001) and GSSG-R (Adc.muc.-880±194 U/g, Adc.G3-795±228 U/g, clinical IV stage 951±243 U/g, P<0.001) in primary tumour comparison with normal colon (MDA-1.39±0.15 nmol/g, HNE-0.29±0.03 nmol/g, Cu, Zn-SOD-117±25 U/g, GSH-Px-1723±189 U/g, GSSG-R-625±112 U/g) especially in mucinous and G3-grade adenocarcinomas as well as clinical IV stage of colorectal cancer. We also observed a decrease of CAT activity (Adc.muc. -40±14 U/g, clinical IV stage 33±18 U/g vs 84±17 U/g, P<0.001) as well as a decreased level of reduced glutathione (clinical IV stage 150±48 nmol/g vs 167±15 nmol/g, P<0.05) and vitamins C and E (vit. C-clinical IV stage 325±92 nmol/g vs 513±64 nmol/g, P<0.001; vit. E-clinical IV stage 13.3±10.3 nmol/g vs 37.5±5.2 nmol/g). CONCLUSION: Colorectal carcinogenesis is associated with serious oxidative stress and confirms that gradual advancement of oxidative-antioxidative disorders is followed by progression of colorectal cancer. PMID:15637754

E3024, 3-but-2-ynyl-5-methyl-2-piperazin-1-yl-3,5-dihydro-4H-imidazo[4,5-d]pyridazin-4-one tosylate, is a novel, selective and competitive dipeptidyl peptidase-IV inhibitor.

PubMed

Yasuda, Nobuyuki; Nagakura, Tadashi; Inoue, Takashi; Yamazaki, Kazuto; Katsutani, Naruo; Takenaka, Osamu; Clark, Richard; Matsuura, Fumiyoshi; Emori, Eita; Yoshikawa, Seiji; Kira, Kazunobu; Ikuta, Hironori; Okada, Toshimi; Saeki, Takao; Asano, Osamu; Tanaka, Isao

2006-10-24

Dipeptidyl peptidase IV (DPP-IV) inhibitors are expected to become a useful new class of anti-diabetic agent. The aim of the present study is to characterize the in vitro and in vivo profile of E3024, 3-but-2-ynyl-5-methyl-2-piperazin-1-yl-3,5-dihydro-4H-imidazo[4,5-d]pyridazin-4-one tosylate, which is a novel imidazopyridazinone-derived DPP-IV inhibitor. E3024 inhibited recombinant human and mouse DPP-IV with IC50 values of approximately 100 nM. E3024 inhibited DPP-IV in human, mouse, rat and canine plasma with IC50 values of 140 to 400 nM. In contrast, E3024 did not inhibit DPP-8 or DPP-9 activity. Kinetic analysis indicated that E3024 is a competitive DPP-IV inhibitor. In Zucker fa/fa rats, E3024 (1 mg/kg) reduced glucose excursion after glucose load, with increases in plasma insulin and active glucagon-like peptide-1 levels. In fasted rats, this compound did not cause hypoglycemia. In a rat 4-week toxicological study, no notable changes were found at doses up to 750 mg/kg. The present preclinical studies indicate that E3024 is a novel selective DPP-IV inhibitor with anti-diabetic effects and a good safety profile.

Health Occupations Education I. Module No. IV-A to IV-F.

ERIC Educational Resources Information Center

Dunmeyer, Kathryn; And Others

This set of 6 modules on patient body mechanics is 1 of 11 sets in the Health Occupations Education I instructional package for the first year of a 2-year course of study. The materials are designed to prepare students through individualized instruction for entry-level job opportunities on health care teams in a variety of practice settings. Each…

Parkin promotes proteasomal degradation of synaptotagmin IV by accelerating polyubiquitination.

PubMed

Kabayama, Hiroyuki; Tokushige, Naoko; Takeuchi, Makoto; Kabayama, Miyuki; Fukuda, Mitsunori; Mikoshiba, Katsuhiko

2017-04-01

Parkin is an E3 ubiquitin ligase whose mutations cause autosomal recessive juvenile Parkinson's disease (PD). Unlike the human phenotype, parkin knockout (KO) mice show no apparent dopamine neuron degeneration, although they demonstrate reduced expression and activity of striatal mitochondrial proteins believed to be necessary for neuronal survival. Instead, parkin-KO mice show reduced striatal evoked dopamine release, abnormal synaptic plasticity, and non-motor symptoms, all of which appear to mimic the preclinical features of Parkinson's disease. Extensive studies have screened candidate synaptic proteins responsible for reduced evoked dopamine release, and synaptotagmin XI (Syt XI), an isoform of Syt family regulating membrane trafficking, has been identified as a substrate of parkin in humans. However, its expression level is unaltered in the striatum of parkin-KO mice. Thus, the target(s) of parkin and the molecular mechanisms underlying the impaired dopamine release in parkin-KO mice remain unknown. In this study, we focused on Syt IV because of its highly homology to Syt XI, and because they share an evolutionarily conserved lack of Ca 2+ -binding capacity; thus, Syt IV plays an inhibitory role in Ca 2+ -dependent neurotransmitter release in PC12 cells and neurons in various brain regions. We found that a proteasome inhibitor increased Syt IV protein, but not Syt XI protein, in neuron-like, differentiated PC12 cells, and that parkin interacted with and polyubiquitinated Syt IV, thereby accelerating its protein turnover. Parkin overexpression selectively degraded Syt IV protein, but not Syt I protein (indispensable for Ca 2+ -dependent exocytosis), thus enhancing depolarization-dependent exocytosis. Furthermore, in parkin-KO mice, the level of striatal Syt IV protein was increased. Our data indicate a crucial role for parkin in the proteasomal degradation of Syt IV, and provide a potential mechanism of parkin-regulated, evoked neurotransmitter release. Copyright © 2017 Elsevier Inc. All rights reserved.

U.S. Level III and IV Ecoregions (U.S. EPA)

EPA Pesticide Factsheets

This map service displays Level III and Level IV Ecoregions of the United States and was created from ecoregion data obtained from the U.S. Environmental Protection Agency Office of Research and Development's Western Ecology Division. The original ecoregion data was projected from Albers to Web Mercator for this map service. To download shapefiles of ecoregion data (in Albers), please go to: ftp://newftp.epa.gov/EPADataCommons/ORD/Ecoregions/. IMPORTANT NOTE ABOUT LEVEL IV POLYGON LEGEND DISPLAY IN ARCMAP: Due to the limitations of Graphical Device Interface (GDI) resources per application on Windows, ArcMap does not display the legend in the Table of Contents for the ArcGIS Server service layer if the legend has more than 100 items. As of December 2011, there are 968 unique legend items in the Level IV Ecoregion Polygon legend. Follow this link (http://support.esri.com/en/knowledgebase/techarticles/detail/33741) for instructions about how to increase the maximum number of ArcGIS Server service layer legend items allowed for display in ArcMap. Note the instructions at this link provide a slightly incorrect path to Maximum Legend Count. The correct path is HKEY_CURRENT_USER > Software > ESRI > ArcMap > Server > MapServerLayer > Maximum Legend Count. When editing the Maximum Legend Count, update the field, Value data to 1000. To download a PDF version of the Level IV ecoregion map and legend, go to ftp://newftp.epa.gov/EPADataCommons/ORD/Ecoregions/us/Eco_Level_IV

Effectiveness of external cold and vibration for procedural pain relief during peripheral intravenous cannulation in pediatric patients.

PubMed

Canbulat, Nejla; Ayhan, Fatma; Inal, Sevil

2015-02-01

The aim of this study was to investigate the effect of external cold and vibration stimulation via Buzzy on the pain and anxiety level of children during peripheral intravenous (IV) cannulation. This study was a prospective, randomized controlled trial. The sample consisted of 176 children ages 7 to 12 years who were randomly assigned to two groups: a control group that received no peripheral IV cannulation intervention and an experimental group that received external cold and vibration via Buzzy. The same nurse conducted the peripheral IV cannulation in all the children, and the same researcher applied the external cold and vibration to all the children. The external cold and the vibration were applied 1 minute before the peripheral IV cannulation procedure and continued until the end of the procedure. Preprocedural anxiety was assessed using the Children's Fear Scale, along with reports by the children, their parents, and an observer. Procedural anxiety was assessed with the Children's Fear Scale and the parents' and the observer's reports. Procedural pain was assessed using the Wong Baker Faces Scale and the visual analog scale self-reports of the children. Preprocedural anxiety did not differ significantly. Comparison of the two groups showed significantly lower pain and anxiety levels in the experimental group than in the control group during the peripheral IV cannulation. Buzzy can be considered to provide an effective combination of coldness and vibration. This method can be used during pediatric peripheral IV cannulation by pediatric nurses. Copyright © 2015 American Society for Pain Management Nursing. Published by Elsevier Inc. All rights reserved.

Astragaloside IV Attenuates Glutamate-Induced Neurotoxicity in PC12 Cells through Raf-MEK-ERK Pathway.

PubMed

Yue, Rongcai; Li, Xia; Chen, Bingyang; Zhao, Jing; He, Weiwei; Yuan, Hu; Yuan, Xing; Gao, Na; Wu, Guozhen; Jin, Huizi; Shan, Lei; Zhang, Weidong

2015-01-01

Astragaloside IV (AGS-IV) is a main active ingredient of Astragalus membranaceus Bunge, a medicinal herb prescribed as an immunostimulant, hepatoprotective, antiperspirant, a diuretic or a tonic as documented in Chinese Materia Medica. In the present study, we employed a high-throughput comparative proteomic approach based on 2D-nano-LC-MS/MS to investigate the possible mechanism of action involved in the neuroprotective effect of AGS-IV against glutamate-induced neurotoxicity in PC12 cells. Differential proteins were identified, among which 13 proteins survived the stringent filter criteria and were further included for functional discussion. Two proteins (vimentin and Gap43) were randomly selected, and their expression levels were further confirmed by western blots analysis. The results matched well with those of proteomics. Furthermore, network analysis of protein-protein interactions (PPI) and pathways enrichment with AGS-IV associated proteins were carried out to illustrate its underlying molecular mechanism. Proteins associated with signal transduction, immune system, signaling molecules and interaction, and energy metabolism play important roles in neuroprotective effect of AGS-IV and Raf-MEK-ERK pathway was involved in the neuroprotective effect of AGS-IV against glutamate-induced neurotoxicity in PC12 cells. This study demonstrates that comparative proteomics based on shotgun approach is a valuable tool for molecular mechanism studies, since it allows the simultaneously evaluate the global proteins alterations.

Surgical approach to cervical spondylotic myelopathy on the basis of radiological patterns of compression: prospective analysis of 129 cases

PubMed Central

Chaudhary, Kshitij; Sharma, Amit; Laheri, Vinod

2008-01-01

This is a prospective analysis of 129 patients operated for cervical spondylotic myelopathy (CSM). Paucity of prospective data on surgical management of CSM, especially multilevel CSM (MCM), makes surgical decision making difficult. The objectives of the study were (1) to identify radiological patterns of cord compression (POC), and (2) to propose a surgical protocol based on POC and determine its efficacy. Average follow-up period was 2.8 years. Following POCs were identified: POC I: one or two levels of anterior cord compression. POC II: one or two levels of anterior and posterior compression. POC III: three levels of anterior compression. POC III variant: similar to POC III, associated with significant medical morbidity. POC IV: three or more levels of anterior compression in a developmentally narrow canal or with multiple posterior compressions. POC IV variant: similar to POC IV with one or two levels, being more significant than the others. POC V: three or more levels of compression in a kyphotic spine. Anterior decompression and reconstruction was chosen for POC I, II and III. Posterior decompression was chosen in POC III variant because they had more incidences of preoperative morbidity, in spite of being radiologically similar to POC III. Posterior surgery was also performed for POC IV and IV variant. For POC IV variant a targeted anterior decompression was considered after posterior decompression. The difference in the mJOA score before and after surgery for patients in each POC group was statistically significant. Anterior surgery in MCM had better result (mJOA = 15.9) versus posterior surgery (mJOA = 14.96), the difference being statistically significant. No major graft-related complications occurred in multilevel groups. The better surgical outcome of anterior surgery in MCM may make a significant difference in surgical outcome in younger and fitter patients like those of POC III whose expectations out of surgery are more. Judicious choice of anterior or posterior approach should be made after individualizing each case. PMID:18946692

Connection between nitrogen and manganese cycles revealed by transcriptomic analysis in Shewanella algae C6G3

NASA Astrophysics Data System (ADS)

Michotey, V.; Aigle, A.; Armougom, F.; Mejean, V.; Guasco, S.; Bonin, P.

2016-02-01

In sedimentary systems, the repartition of terminal electron-accepting molecules is often stratified on a permanent or seasonal basis. Just below to oxic zone, the suboxic one is characterized by high concentrations of oxidized inorganic compounds such as nitrate, manganese oxides (MnIII/IV) and iron oxides that are in close vicinity. Several studies have reported unexpected anaerobic nitrite/nitrate production at the expense of ammonium mediated by MnIII/IV, however this transient processes is difficult to discern and poorly understood. In the frame of this study, genes organization of nitrate and MnIII/IV respiration was investigated in S.algae. Additional genes were identified in S. algae compare to S. oneidensis: genes coding for nitrate and nitrite reductase (napA-a and nrfA-2) and an OMC protein (mtrH). In contrast to S. oneidensis, an anaerobic transitory nitrite accumulation at the expense of ammonium was observed in S. algae during growth with MnIII/IV, concomitantly with expression of nitrate/nitrite reductase genes (napA, nrfA, nrfA-2). Among the hypothesis explaining this data, the potential putative expression of unidentified gene able to perform ammonium oxidation was not observed on the global transcriptional level, however several signs of oxidative stress were detected and the existence of a secondary reaction generated by a putative oxidative s could not be excluded. Another option could be the action of reverse reaction by an enzyme such as NrfA or NrfA-2 due to the electron flow equilibrium. Whatever the electron acceptor (Nitrate/ MnIII/IV), the unexpected expression level of of omcA, mtrF, mtrH, mtrC was observed and peaked at the end of the exponential phase. Different expression patterns of the omc genes were observed depending on electron acceptor and growth phase. Only mtrF-2 gene was specifically expressed in Mn(III/IV) condition. Nitrate and Mn(III/IV) respirations seem connected at physiological as well as at transcriptional level

Genetic Ablation of Apolipoprotein A-IV Accelerates Alzheimer's Disease Pathogenesis in a Mouse Model

PubMed Central

Cui, Yujie; Huang, Mingwei; He, Yingbo; Zhang, Shuyan; Luo, Yongzhang

2011-01-01

The link between lipoprotein metabolism and Alzheimer's disease (AD) has been established. Apolipoprotein A-IV (apoA-IV), a component of lipoprotein particles similar to apolipoprotein E, has been suggested to play an important role in brain metabolism. Although there are clinical debates on the function of its polymorphism in AD, the pathologic role of apoA-IV in AD is still unknown. Here, we report that genetic ablation of apoA-IV is able to accelerate AD pathogenesis in mice. In a mouse model that overexpresses human amyloid precursor protein (APP) and presenilin 1, genetic reduction of apoA-IV augments extracellular amyloid-β peptide (Aβ) burden and aggravates neuron loss in the brain. In addition, genetic ablation of apoA-IV also accelerates spatial learning deficits and increases the mortality of mice. We have found that apoA-IV colocalizes within Aβ plaques in APP/presenilin 1 transgenic mice and binds to Aβ in vitro. Subsequent studies show that apoA-IV in this model facilitates Aβ uptake in the Aβ clearance pathway mediated by astrocytes rather than the amyloidogenic pathway of APP processing. Taken together, we conclude that apoA-IV deficiency increases Aβ deposition and results in cognitive damage in the mouse model. Enhancing levels of apoA-IV may have therapeutic potential in AD treatment. PMID:21356380

Dissemination and Implementation of Cognitive Behavioral Therapy for Stimulant Dependence: A Randomized Trial Comparison of Three Approaches

PubMed Central

Rawson, Richard A.; Rataemane, Solomon; Rataemane, Lusanda; Ntlhe, Nomvuyo; Fox, Ruthlyn Sodano; McCuller, Jason; Brecht, Mary-Lynn

2012-01-01

This study evaluated the effectiveness of 3 approaches to transferring cognitive behavioral therapy (CBT) to addiction clinicians in the Republic of South Africa (RSA). Clinicians (N = 143) were assigned to 3 training conditions: (1) An in vivo (IV) approach in which clinicians received in-person training and coaching; (2) A distance learning (DL) approach providing training via video conference and coaching through teleconferencing; and (3) A control condition (C) providing a manual and 2-hour orientation. Frequency of use of CBT skills increased significantly with the IV and DL approaches compared to the C approach, and the IV approach facilitated greater use of CBT skills than the DL approach. During the active phase of the study, skill quality declined significantly for clinicians trained in the C condition, whereas those in the DL approach maintained skill quality and those in the IV approach improved skill quality. After coaching was discontinued, clinicians in the IV and DL approaches declined in skill quality. However, those in the IV approach maintained a higher level of skill quality compared to the other approaches. Cost of the IV condition was double that of the DL condition and 10 times greater than the C condition. PMID:23577903

48 CFR 1532.006-1 - General.

Code of Federal Regulations, 2010 CFR

2010-10-01

... Activity, if that individual is not below Level IV of the Executive Schedule. If the Head of the Contracting Activity is below Level IV of the Executive Schedule, then Agency responsibilities and...

The dependence of C IV broad absorption line properties on accompanying Si IV and Al III absorption: relating quasar-wind ionization levels, kinematics, and column densities

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

Filiz Ak, N.; Brandt, W. N.; Schneider, D. P.

2014-08-20

We consider how the profile and multi-year variability properties of a large sample of C IV Broad Absorption Line (BAL) troughs change when BALs from Si IV and/or Al III are present at corresponding velocities, indicating that the line of sight intercepts at least some lower ionization gas. We derive a number of observational results for C IV BALs separated according to the presence or absence of accompanying lower ionization transitions, including measurements of composite profile shapes, equivalent width (EW), characteristic velocities, composite variation profiles, and EW variability. We also measure the correlations between EW and fractional-EW variability for Cmore » IV, Si IV, and Al III. Our measurements reveal the basic correlated changes between ionization level, kinematics, and column density expected in accretion-disk wind models; e.g., lines of sight including lower ionization material generally show deeper and broader C IV troughs that have smaller minimum velocities and that are less variable. Many C IV BALs with no accompanying Si IV or Al III BALs may have only mild or no saturation.« less

48 CFR 1532.006-1 - General.

Code of Federal Regulations, 2011 CFR

2011-10-01

... Contracting Activity, if that individual is not below Level IV of the Executive Schedule. If the Head of the Contracting Activity is below Level IV of the Executive Schedule, then Agency responsibilities and...

Level III and IV Ecoregions by State

EPA Pesticide Factsheets

Information and links to downloadable maps and datasets for Level III and IV ecoregions, listed by state. Ecoregions are areas of general similarity in the type, quality, and quantity of environmental resources.

Level III and IV Ecoregions by EPA Region

EPA Pesticide Factsheets

Information and downloadable maps and datasets for Level III and IV ecoregions, listed by EPA region. Ecoregions are areas of general similarity in the type, quality, and quantity of environmental resources.

Expanding the Therapeutic Potential of the Iron Chelator Deferasirox in the Development of Aqueous Stable Ti(IV) Anticancer Complexes.

PubMed

Loza-Rosas, Sergio A; Vázquez-Salgado, Alexandra M; Rivero, Kennett I; Negrón, Lenny J; Delgado, Yamixa; Benjamín-Rivera, Josué A; Vázquez-Maldonado, Angel L; Parks, Timothy B; Munet-Colón, Charlene; Tinoco, Arthur D

2017-07-17

The recent X-ray structure of titanium(IV)-bound human serum transferrin (STf) exhibiting citrate as a synergistic anion reveals a difference in Ti(IV) coordination versus iron(III), the metal endogenously delivered by the protein to cells. This finding enriches our bioinspired drug design strategy for Ti(IV)-based anticancer therapeutics, which applies a family of Fe(III) chelators termed chemical transferrin mimetic (cTfm) ligands to inhibit Fe bioavailability in cancer cells. Deferasirox, a drug used for iron overload disease, is a cTfm ligand that models STf coordination to Fe(III), favoring Fe(III) binding versus Ti(IV). This metal affinity preference drives deferasirox to facilitate the release of cytotoxic Ti(IV) intracellularly in exchange for Fe(III). An aqueous speciation study performed by potentiometric titration from pH 4 to 8 with micromolar levels of Ti(IV) deferasirox at a 1:2 ratio reveals exclusively Ti(deferasirox) 2 in solution. The predominant complex at pH 7.4, [Ti(deferasirox) 2 ] 2- , exhibits the one of the highest aqueous stabilities observed for a potent cytotoxic Ti(IV) species, demonstrating little dissociation even after 1 month in cell culture media. UV-vis and 1 H NMR studies show that the stability is unaffected by the presence of biomolecular Ti(IV) binders such as citrate, STf, and albumin, which have been shown to induce dissociation or regulate cellular uptake and can alter the activity of other antiproliferative Ti(IV) complexes. Kinetic studies on [Ti(deferasirox) 2 ] 2- transmetalation with Fe(III) show that a labile Fe(III) source is required to induce this process. The initial step of this process occurs on the time scale of minutes, and equilibrium for the complete transmetalation is reached on a time scale of hours to a day. This work reveals a mechanism to deliver Ti(IV) compounds into cells and trigger Ti(IV) release by a labile Fe(III) species. Cellular studies including other cTfm ligands confirm the Fe(III) depletion mechanism of these compounds and show their ability to induce early and late apoptosis.

Early absorption of enteral ranitidine after major laparotomy.

PubMed

Kulber, D A; Bentt, L; Repique, E; Dubin, S B; Wittman, M; Treiman, R; Shabot, M M

1991-12-01

Thirty-six patients were studied following abdominal aortic surgery to determine if a commonly used medication could be absorbed from the gastrointestinal (GI) tract in the early postoperative period. Patients were randomized into two groups: Group I received ranitidine elixir 3 mg/kg via nasogastric tube every 12 hours; Group II received intravenous (IV) ranitidine 1 mg/kg every 8 hours. Ranitidine serum levels were measured with high performance liquid chromatography 1 hour after administration of the first three doses. Gastric pH was measured every 4 hours. It was found that serum ranitidine levels generally regarded as clinically effective were achieved in both groups. Although the levels were significantly higher following intravenous (IV) administration (Group II), there were no differences in average gastric pH. The authors conclude that within 24 hours of aortic surgery enterally administered ranitidine is effectively absorbed and provides prophylaxis equivalent to IV administration of the drug at lower cost. Other medications might be deliverable via the GI tract in the early postoperative period.

DSM-IV hypochondriasis in primary care.

PubMed

Escobar, J I; Gara, M; Waitzkin, H; Silver, R C; Holman, A; Compton, W

1998-05-01

The object of this study was to assess the prevalence and correlates of the DSM-IV diagnosis of hypochondriasis in a primary care setting. A large sample (N = 1456) of primary care users was given a structured interview to make diagnoses of mood, anxiety, and somatoform disorders and estimate levels of disability. The prevalence of hypochondriasis (DSM-IV) was about 3%. Patients with this disorder had higher levels of medically unexplained symptoms (abridged somatization) and were more impaired in their physical functioning than patients without the disorder. Of the various psychopathologies examined, major depressive syndromes were the most frequent among patients with hypochondriasis. Interestingly, unlike somatization disorder, hypochondriasis was not related to any demographic factor. Hypochondriasis is a relatively rare condition in primary care that is largely separable from somatization disorder but seems closely intertwined with the more severe depressive syndromes.

Intensity, perception, and descriptive characteristics of chronic pain in children with cerebral palsy.

PubMed

Houlihan, Christine M; Hanson, Amber; Quinlan, Nicole; Puryear, Carol; Stevenson, Richard D

2008-01-01

Children with cerebral palsy (CP) experience bodily pain, leading to functional impairment and decreased quality of life. The purpose of this study is to characterize subjective descriptors of chronic pain in children with CP. One hundred fifty-seven children were invited to participate in a quantitative pilot survey. Parents were mailed the Varni-Thompson Pediatric Pain Questionnaire, designed to assess three dimensions of pain: sensory (physical aspects), affective (emotional response), and evaluative (the combined intensity of the emotional and physical responses). Parents assessed their child's pain using non-verbal and verbal cues. Fifty-two families responded (33% return rate). Thirty-eight children ages 6-8 years with CP and Gross Motor Function Classification System (GMFCS) levels I-V were included. Ninety percent of families reported that their child was experiencing some pain at the time of the survey. At the time of assessment the children's pain was mild. Their pain, at its worst, was in the distressing range. The two largest GMFCS groups of children, levels I and IV, were compared in both severity and intensity of pain experienced. Increasing intensity of pain was reported in children in the level IV group compared to children classified as level I. Pain severity in all dimensions was reported as increasing in Level IV children compared to Level I. Children with CP experience frequent pain, which increases with worsening impairment. Descriptive qualifiers of pain help to elucidate the etiology of various types of pain which would lead to the development of more effective approaches to pain management and treatment.

Blood Levels of Trace Elements in Children with Attention-Deficit Hyperactivity Disorder: Results from a Case-Control Study.

PubMed

Yang, Rongwang; Zhang, Yanyi; Gao, Weijia; Lin, Nannan; Li, Rong; Zhao, Zhengyan

2018-06-16

Some trace elements may participate in the pathogenesis of attention-deficit hyperactivity disorder (ADHD). This study aimed to investigate the trace element status of zinc (Zn), copper (Cu), iron (Fe), magnesium (Mg), and lead (Pb) in children with ADHD, and to compare them with normal controls. Associations between examined elements and SNAP-IV rating scores of ADHD symptoms were also assessed. Four hundred nineteen children with ADHD (8.8 ± 2.1 years) and 395 matched normal controls (8.9 ± 1.7 years) were recruited in the study. The concentrations of Zn, Fe, Cu, Mg, and Pb in the whole blood were measured by atomic absorption spectrometry. Lower zinc levels (P < 0.001) and the number out of normal ranges (P = 0.015) were found in children with ADHD when compared with the normal control group. The difference remained when adjusting the factor of BMI z-score. No significant between-group differences were found in levels of other elements. Zinc levels were negatively correlated with parent-rated scores of inattentive subscale of SNAP-IV (r = - 0.40) as well as with total score of SNAP-IV (r = - 0.24). Other significant associations were not observed. The present results indicated that there were alterations in blood levels of zinc, which was associated with the symptom scores of ADHD.

Control of human energy expenditure by cytochrome c oxidase subunit IV-2.

PubMed

Schiffer, Tomas A; Peleli, Maria; Sundqvist, Michaela L; Ekblom, Björn; Lundberg, Jon O; Weitzberg, Eddie; Larsen, Filip J

2016-09-01

Resting metabolic rate (RMR) in humans shows pronounced individual variations, but the underlying molecular mechanism remains elusive. Cytochrome c oxidase (COX) plays a key role in control of metabolic rate, and recent studies of the subunit 4 isoform 2 (COX IV-2) indicate involvement in the cellular response to hypoxia and oxidative stress. We evaluated whether the COX subunit IV isoform composition may explain the pronounced individual variations in resting metabolic rate (RMR). RMR was determined in healthy humans by indirect calorimetry and correlated to levels of COX IV-2 and COX IV-1 in vastus lateralis. Overexpression and knock down of the COX IV isoforms were performed in primary myotubes followed by evaluation of the cell respiration and production of reactive oxygen species. Here we show that COX IV-2 protein is constitutively expressed in human skeletal muscle and strongly correlated to RMR. Primary human myotubes overexpressing COX IV-2 displayed markedly (>60%) lower respiration, reduced (>50%) cellular H2O2 production, higher resistance toward both oxidative stress, and severe hypoxia compared with control cells. These results suggest an important role of isoform COX IV-2 in the control of energy expenditure, hypoxic tolerance, and mitochondrial ROS homeostasis in humans. Copyright © 2016 the American Physiological Society.

Hormones, Nicotine and Cocaine: Clinical Studies

PubMed Central

Mello, Nancy K.

2009-01-01

Nicotine and cocaine each stimulate hypothalamic-pituitary-adrenal and -gonadal axis hormones, and there is increasing evidence that the hormonal milieu may modulate the abuse-related effects of these drugs. This review summarizes some clinical studies of the acute effects of cigarette smoking or IV cocaine on plasma drug and hormone levels, and subjective effects ratings. The temporal covariance between these dependent measures was assessed with a rapid (two min) sampling procedure in nicotine-dependent volunteers or current cocaine users. Cigarette smoking and IV cocaine each stimulated a rapid increase in LH and ACTH, followed by gradual increases in cortisol and DHEA. Positive subjective effects ratings increased immediately after initiation of cigarette smoking or IV cocaine administration. However, in contrast to cocaine’s sustained positive effects (< 20 min), ratings of “High” and “Rush” began to decrease within one or two puffs of a high nicotine cigarette while nicotine levels were increasing. Peak nicotine levels increased progressively after each of three successive cigarettes smoked at 60 min intervals, but the magnitude of the subjective effects ratings and peak ACTH and cortisol levels diminished. Only DHEA increased consistently after successive cigarettes. The possible influence of neuroactive hormones on nicotine dependence and cocaine abuse, and implications for treatment of these addictive disorders is discussed. PMID:19835877

Brief Report: The Euro-Lupus Low-Dose Intravenous Cyclophosphamide Regimen Does Not Impact the Ovarian Reserve, as Measured by Serum Levels of Anti-Müllerian Hormone.

PubMed

Tamirou, Farah; Husson, Séverine Nieuwland; Gruson, Damien; Debiève, Frédéric; Lauwerys, Bernard R; Houssiau, Frédéric A

2017-06-01

The Euro-Lupus regimen of low-dose intravenous cyclophosphamide (IV CYC) (cumulative dose of 3 gm) was developed to reduce gonadal toxicity. To address the possibility of a marginal effect on the ovarian reserve, we measured serum titers of anti-Müllerian hormone (AMH) in patients with systemic lupus erythematosus (SLE) treated with the Euro-Lupus regimen and compared them with those measured in patients who were treated with higher doses of IV CYC or were never treated with IV CYC. Serum AMH levels were measured by enzyme-linked immunosorbent assay in a cohort of 155 premenopausal SLE patients; 30 of these patients had been treated with the Euro-Lupus regimen, and 24 had received higher doses of IV CYC. None had received oral CYC. AMH levels were age-adjusted using a slope computed from levels measured across the group of SLE patients who had not been treated with IV CYC. Demographic and clinical data were collected. Serum titers of AMH measured in SLE patients treated with the Euro-Lupus IV CYC regimen (median dose 1.46 ng/ml) did not differ from those measured in patients never treated with the cytotoxic drug (median 1.85 ng/ml). As expected, patients given >6 gm of IV CYC had significantly lower serum titers of AMH (median 0.83 ng/ml) compared with those never treated with IV CYC (P = 0.047). Median serum AMH titers did not change before (1.24 ng/ml) and after (2.50 ng/ml) treatment with the Euro-Lupus IV CYC regimen in the subset of patients for whom paired samples could be tested (P = 0.43). The Euro-Lupus regimen of low-dose IV CYC does not impact the ovarian reserve of SLE patients and can therefore be proposed as treatment in patients seeking to become pregnant. © 2017, American College of Rheumatology.

Intravenous volume tomographic pulmonary angiography imaging

NASA Astrophysics Data System (ADS)

Ning, Ruola; Strang, John G.; Chen, Biao; Conover, David L.; Yu, Rongfeng

1999-05-01

This study presents a new intravenous (IV) tomographic angiography imaging technique, called intravenous volume tomographic digital angiography (VTDA) for cross sectional pulmonary angiography. While the advantages of IV-VTDA over spiral CT in terms of volume scanning time and resolution have been validated and reported in our previous papers for head and neck vascular imaging, the superiority of IV-VTDA over spiral CT for cross sectional pulmonary angiography has not been explored yet. The purpose of this study is to demonstrate the advantage of isotropic resolution of IV-VTDA in the x, y and z directions through phantom and animal studies, and to explore its clinical application for detecting clots in pulmonary angiography. A prototype image intensifier-based VTDA imaging system has been designed and constructed by modifying a GE 8800 CT scanner. This system was used for a series of phantom and dog studies. A pulmonary vascular phantom was designed and constructed. The phantom was scanned using the prototype VTDA system for direct 3D reconstruction. Then the same phantom was scanned using a GE CT/i spiral CT scanner using the routine pulmonary CT angiography protocols. IV contrast injection and volume scanning protocols were developed during the dog studies. Both VTDA reconstructed images and spiral CT images of the specially designed phantom were analyzed and compared. The detectability of simulated vessels and clots was assessed as the function of iodine concentration levels, oriented angles, and diameters of the vessels and clots. A set of 3D VTDA reconstruction images of dog pulmonary arteries was obtained with different IV injection rates and isotropic resolution in the x, y and z directions. The results of clot detection studies in dog pulmonary arteries have also been shown. This study presents a new tomographic IV angiography imaging technique for cross sectional pulmonary angiography. The results of phantom and animal studies indicate that IV-VTDA is superior to spiral CT for cross sectional pulmonary angiography.

Isolation, characterization and comparative genomics of bacteriophage SfIV: a novel serotype converting phage from Shigella flexneri

PubMed Central

2013-01-01

Background Shigella flexneri is the major cause of shigellosis in the developing countries. The O-antigen component of the lipopolysaccharide is one of the key virulence determinants required for the pathogenesis of S. flexneri. The glucosyltransferase and/or acetyltransferase genes responsible for the modification of the O-antigen are encoded by temperate serotype converting bacteriophage present in the S. flexneri genome. Several serotype converting phages have previously been isolated and characterized, however, attempts to isolate a serotype converting phage which encodes the modification genes of serotypes 4a strain have not been successful. Results In this study, a novel temperate serotype converting bacteriophage SfIV was isolated. Lysogenisation of phage SfIV converted serotype Y strain to serotype 4a. Electron microscopy indicated that SfIV belongs to Myoviridae family. The 39,758 bp genome of phage SfIV encompasses 54 open reading frames (orfs). Protein level comparison of SfIV with other serotype converting phages of S. flexneri revealed that SfIV is similar to phage SfII and SfV. The comparative analysis also revealed that SfIV phage contained five proteins which were not found in any other phages of S. flexneri. These proteins were: a tail fiber assembly protein, two hypothetical proteins with no clear function, and two other unknown proteins which were encoded by orfs present on a moron, that presumably got introduced in SfIV genome from another species via a transposon. These unique proteins of SfIV may play a role in the pathogenesis of the host. Conclusions This study reports the isolation and complete genome sequence analysis of bacteriophage SfIV. The SfIV phage has a host range significantly different from the other phages of Shigella. Comparative genome analysis identified several proteins unique to SfIV, which may potentially be involved in the survival and pathogenesis of its host. These findings will further our understanding on the evolution of these phages, and will also facilitate studies on development of new phage vectors and therapeutic agents to control infections caused by S. flexneri. PMID:24090466

LEVEL IV ECOREGION DELINEATION FOR THE STATE OF WYOMING

EPA Science Inventory

Level III ecoregions were refined and subdivided into level IV for the state of Wyoming in a manner consistent with ecoregion revision and subdivision that has been completed or is on-going in 37 of the conterminous United States. The project was collaborative, involving the scie...

Doxorubicin: Comparison between 3-h continuous and bolus intravenous administration paradigms on cardio-renal axis, mitochondrial sphingolipids and pathology

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

Kamendi, Harriet, E-mail: harriet_kamendi@kandih.com; Zhou, Ying, E-mail: yingzhou526@gmail.com; Crosby, Meredith, E-mail: Meredith.crosby@astrazeneca.com

Doxorubicin (DOX) is a potent and effective broad-spectrum anthracycline antitumor agent, but its clinical usefulness is restricted by cardiotoxicity. This study compared pharmacokinetic, functional, structural and biochemical effects of single dose DOX bolus or 3-h continuous iv infusion (3-h iv) in the Han–Wistar rat to characterize possible treatment-related differences in drug safety over a 72 h observation period. Both DOX dosing paradigms significantly altered blood pressure, core body temperature and QA interval (indirect measure of cardiac contractility); however, there was no recovery observed in the bolus iv treatment group. Following the 3-h iv treatment, blood pressures and QA interval normalizedmore » by 36 h then rose above baseline levels over 72 h. Both treatments induced biphasic changes in heart rate with initial increases followed by sustained decreases. Cardiac injury biomarkers in plasma were elevated only in the bolus iv treatment group. Tissue cardiac injury biomarkers, cardiac mitochondrial complexes I, III and V and cardiac mitochondrial sphingolipids were decreased only in the bolus iv treatment group. Results indicate that each DOX dosing paradigm deregulates sinus rhythm. However, slowing the rate of infusion allows for functional compensation of blood pressure and may decrease the likelihood of cardiac myocyte necrosis via a mechanism associated with reduced mitochondrial damage. - Highlights: • Despite damaging cardiomyocytes, continuous iv doxorubicin improves cardiovascular outcomes. • This study supports administration of doxorubicin via slow continuous iv infusion limits acute cardio-toxicity. • This study supports use of metabolomic-derived lipid biomarkers for improved quantification of cardiovascular risk. • This study supports systems-based physiological approach to generate a data that can greatly inform risk assessments.« less

Level III and IV Ecoregions of the Continental United States

EPA Pesticide Factsheets

Information and downloadable maps and datasets for Level III and IV ecoregions of the continental United States. Ecoregions are areas of general similarity in the type, quality, and quantity of environmental resources.

Diagnostic accuracy of level IV portable sleep monitors versus polysomnography for obstructive sleep apnea: a systematic review and meta-analysis.

PubMed

Abrahamyan, Lusine; Sahakyan, Yeva; Chung, Suzanne; Pechlivanoglou, Petros; Bielecki, Joanna; Carcone, Steven M; Rac, Valeria E; Fitzpatrick, Michael; Krahn, Murray

2018-01-09

Obstructive sleep apnea (OSA) is the most common sleep-related breathing disorder. In-laboratory, overnight type I polysomnography (PSG) is the current "gold standard" for diagnosing OSA. Home sleep apnea testing (HSAT) using portable monitors (PMs) is an alternative testing method offering better comfort and lower costs. We aimed to systematically review the evidence on diagnostic ability of type IV PMs compared to PSG in diagnosing OSA. Participants: patients ≥16 years old with symptoms suggestive of OSA;intervention: type IV PMs (devices with < 2 respiratory channels); comparator: in-laboratory PSG; outcomes: diagnostic accuracy measures;studies: cross-sectional, prospective observational/experimental/quasi-experimental studies; information sources: MEDLINE and Cochrane Library from January 1, 2010 to May 10, 2016. All stages of review were conducted independently by two investigators. We screened 6054 abstracts and 117 full-text articles to select 24 full-text articles for final review. These 24 studies enrolled a total of 2068 patients with suspected OSA and evaluated 10 different PMs with one to six channels. Only seven (29%) studies tested PMs in the home setting. The mean difference (bias) between PSG-measured and PM-measured apnea-hypopnea index (AHI) ranged from - 14.8 to 10.6 events/h. At AHI ≥ 5 events/h, the sensitivity of type IV PMs ranged from 67.5-100% and specificity ranged from 25 to 100%. While current evidence is not very strong for the stand-alone use of level IV PMs in clinical practice, they can potentially widen access to diagnosis and treatment of OSA. Policy recommendations regarding HSAT use should also consider the health and broader social implications of false positive and false negative diagnoses.

Change in mobility function and its causes in adults with cerebral palsy by Gross Motor Function Classification System level: A cross-sectional questionnaire study.

PubMed

Himuro, Nobuaki; Mishima, Reiko; Seshimo, Takashi; Morishima, Toshibumi; Kosaki, Keisuke; Ibe, Shigeharu; Asagai, Yoshimi; Minematsu, Koji; Kurita, Kazuhiro; Okayasu, Tsutomu; Shimura, Tsukasa; Hoshino, Kotaro; Suzuki, Toshiro; Yanagizono, Taiichiro

2018-04-07

The prognosis for mobility function by Gross Motor Function Classification System (GMFCS) level is vital as a guide to rehabilitation for people with cerebral palsy. This study sought to investigate change in mobility function and its causes in adults with cerebral palsy by GMFCS level. We conducted a cross-sectional questionnaire study. A total of 386 participants (26 y 8 m, SD 5 y 10 m) with cerebral palsy were analyzed. Participant numbers by GMFCS level were: I (53), II (139), III (74) and IV (120). The median age of participants with peak mobility function in GMFCS level III was younger than that in the other levels. 48% had experienced a decline in mobility. A Kaplan-Meier plot showed the risk of mobility decline increased in GMFCS level III; the hazard ratio was 1.97 (95% CI, 1.20-3.23) compared with level I. The frequently reported causes of mobility decline were changes in environment, and illness and injury in GMFCS level III, stiffness and deformity in level IV, and reduced physical activity in level II and III. Peak mobility function and mobility decline occurred at a younger age in GMFCS level III, with the cause of mobility decline differing by GMFCS level.

Modified BEAM with triple autologous stem cell transplantation for patients with relapsed aggressive non-Hodgkin lymphoma.

PubMed

Hohloch, Karin; Zeynalova, Samira; Chapuy, Björn; Pfreundschuh, Michael; Loeffler, Markus; Ziepert, Marita; Feller, Alfred C; Trümper, Lorenz; Hasenclever, Dirk; Wulf, Gerald; Schmitz, Norbert

2016-06-01

Treatment of relapse and primary progression in aggressive lymphoma remains unsatisfactory; outcome is still poor. Better treatment strategies are much needed for this patient population. The R1 study is a prospective multi-center phase I/II study evaluating a dose finding approach with a triple transplant regimen in four BEAM dose levels in patients with relapsed aggressive non-Hodgkin lymphoma. The aim of the study was to determine feasibility, toxicity, and remission rate. In a total of 39 patients (pts.) enrolled in the study, 24 pts. were evaluated in the following analysis. Twenty pts. had aggressive B cell lymphoma, and two pts. had T cell lymphoma. All evaluated patients responded to DexaBEAM with a sufficient stem cell harvest. The phase I/II study was started with BEAM dose level II. Four patients were treated at dose level II, and 20 pts. were treated at dose level III. Due to the early termination of the study, dose levels I and IV were never administered. Sixteen pts. completed therapy according to protocol, and eight pts. (33.3 %) stopped treatment early. Infections (27 %) and stomatitis (13 %) were the most frequent grade III/IV non-hematologic toxicities. Thirteen percent of patients presented with severe grade III/IV lung toxicity during modified BEAM (m-BEAM). Fourteen pts. achieved a complete response (CR), one pt. achieved no change (NC), six pts. had progressive disease (PD), and two pts. died; for one pt., outcome is not known. One-year and 3-year event-free survival (EFS) was 38 and 33 %, respectively. Overall survival (OS) after 1 and 3 years was 50 and 38 %. In conclusion, dose escalation of standard BEAM is not feasible due to toxicity.

Treatment of patients with cardiovascular disease with L-4F, an apo-A1 mimetic, did not improve select biomarkers of HDL function[S

PubMed Central

Watson, Catherine E.; Weissbach, Nicole; Kjems, Lise; Ayalasomayajula, Surya; Zhang, Yiming; Chang, Ih; Navab, Mohamad; Hama, Susan; Hough, Greg; Reddy, Srinivasa T.; Soffer, Daniel; Rader, Daniel J.; Fogelman, Alan M.; Schecter, Alison

2011-01-01

L-4F, an apolipoprotein A-I (apoA-I) mimetic peptide (also known as APL180), was administered daily by either intravenous (IV) infusion for 7 days or by subcutaneous (SC) injection for 28 days in patients with coronary heart disease in two distinct clinical studies. L-4F was well tolerated at all doses tested. Despite achieving plasma levels (mean maximal plasma concentration of 2,907 ng/ml and 395 ng/ml, following IV infusion and SC injection, respectively), that were effective in previously published animal models, treatment with L-4F, as assessed by biomarkers of HDL function such as HDL-inflammatory index (HII), and paraoxonase activity, did not improve. Paradoxically, there was a 49% increase in high-sensitivity C-reactive protein (hs-CRP) levels after seven IV infusions of 30 mg L-4F (P < 0.05; compared with placebo) and a trend for hs-CRP increase in subjects receiving 30 mg SC injection for 28 days. In a subsequent, ex vivo study, addition of L-4F at concentrations of 150, 375, or 1,000 ng/ml to plasma from subjects prior to L-4F treatment resulted in significant dose-dependent HII improvement. In conclusion, in vivo L-4F treatment, delivered by either SC injection or IV infusion, did not improve HDL functional biomarkers despite achieving plasma levels that improved identical biomarkers ex vivo and in animal models. PMID:21068008

Irradiation Alters MMP-2/TIMP-2 System and Collagen Type IV Degradation in Brain

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

Lee, Won Hee; Warrington, Junie P.; Sonntag, William E.

Purpose: Blood-brain barrier (BBB) disruption is one of the major consequences of radiation-induced normal tissue injury in the central nervous system. We examined the effects of whole-brain irradiation on matrix metalloproteinases (MMPs)/tissue inhibitors of metalloproteinases (TIMPs) and extracellular matrix (ECM) degradation in the brain. Methods and Materials: Animals received either whole-brain irradiation (a single dose of 10 Gy {gamma}-rays or a fractionated dose of 40 Gy {gamma}-rays, total) or sham-irradiation and were maintained for 4, 8, and 24 h following irradiation. mRNA expression levels of MMPs and TIMPs in the brain were analyzed by real-time reverse transcriptase-polymerase chain reaction (PCR).more » The functional activity of MMPs was measured by in situ zymography, and degradation of ECM was visualized by collagen type IV immunofluorescent staining. Results: A significant increase in mRNA expression levels of MMP-2, MMP-9, and TIMP-1 was observed in irradiated brains compared to that in sham-irradiated controls. In situ zymography revealed a strong gelatinolytic activity in the brain 24 h postirradiation, and the enhanced gelatinolytic activity mediated by irradiation was significantly attenuated in the presence of anti-MMP-2 antibody. A significant reduction in collagen type IV immunoreactivity was also detected in the brain at 24 h after irradiation. In contrast, the levels of collagen type IV were not significantly changed at 4 and 8 h after irradiation compared with the sham-irradiated controls. Conclusions: The present study demonstrates for the first time that radiation induces an imbalance between MMP-2 and TIMP-2 levels and suggests that degradation of collagen type IV, a major ECM component of BBB basement membrane, may have a role in the pathogenesis of brain injury.« less

Venous glucose, serum lactate and base deficit as biochemical predictors of mortality in patients with polytrauma.

PubMed

Saad, Sameh; Mohamed, Naglaa; Moghazy, Amr; Ellabban, Gouda; El-Kamash, Soliman

2016-01-01

The trauma and injury severity score (TRISS) and Acute Physiology and Chronic Health Evaluation IV (APACHE IV) are accurate but complex. This study aimed to compare venous glucose, levels of serum lactate, and base deficit in polytraumatized patients as simple parameters to predict the mortality in these patients versus (TRISS) and (APACHE IV). This was a comparative cross-sectional study of 282 patients with polytrauma presented to the Emergency Department (ED). The best cut off value of TRISS probability of survival score for prediction of mortality among poly-traumatized patients was ≤90. APACHE IV demonstrated 67% sensitivity and 95% specificity at 95% CI at cut off point 99. The best cutoff value of Random Blood Sugar was >140 mg/dl, with 89% sensitivity, 49% specificity; base deficit was less than -5.6 with 64% sensitivity, 93% specificity; lactate was >2.6 mmol/L with 92%, sensitivity, 42% specificity. Venous glucose, serum lactate and base deficit are easy and rapid biochemical predictors of mortality in patients with polytrauma. These predictors could be used as TRISS and APACHE IV in predicting mortality.

"Claw your way"--Machiavellianism among the medical community.

PubMed

Bratek, Agnieszka; Bonk, Magdalena; Bulska, Weronika; Tyrała, Kinga; Seweryn, Mariusz; Krysta, Krzysztof

2015-09-01

Machiavellianism is a personality trait characterized by emotional detachment and tendency to manipulate others to achieve one's own goal. It is presumed that people high in Machiavellianism would more likely choose business-related occupations, whereas low Machiavellians would prefer helping professions, therefore medical professionals are expected to be low-Machs. This is a questionnaire study on 509 respondents: medical school candidates (16.1%), medical students (65%), medical trainees (9.8%), residents (6.3%) and specialists (2.8%) aimed at assessing the level of Machiavellianism, as measured with Mach-IV score, a self-report questionnaire. The overall mean Mach-IV score was 59.24±6.07. The highest mean Mach-IV score, 61.80±6.94, was found in the group of medical school candidates. The lowest mean Mach-IV score, 57.61±7.88, was reported in the group of registered specialists. Male gender was found to be positively correlated with the mean Mach-IV score, which in women was 58.97±6.08 and in men it was 60.16±6.01. There was a negative correlation between the mean Mach-IV score and the age of post-graduate participants. When we divided all participants into subgroups of "low Machs" (<60 points) and " high Machs" (≥60 points), we found that both subgroups were similarly numerous--49.5% and 50.5%, accordingly. The highest representation of "high Machs" was found in the subgroup of medical studies candidates (65.85%), then in the students (47.73%) and in the group of post-graduates (45.16%). Gender differences remained statistically significant--47.33% of women and 60.18% of men were "high Machs". Machiavellianism level among medical candidates, students and doctors is relatively high, however is gradually decreasing with the progress of career.

Self-consistent-field study of conduction through conjugated molecules

NASA Astrophysics Data System (ADS)

Paulsson, Magnus; Stafström, Sven

2001-07-01

Current-voltage (I-V) characteristics of individual molecules connected by metallic leads are studied theoretically. Using the Pariser-Parr-Pople quantum chemical method to model the molecule enables us to include electron-electron interactions in the Hartree approximation. The self-consistent-field method is used to calculate charging together with other properties for the total system under bias. Thereafter the Landauer formula is used to calculate the current from the transmission amplitudes. The most important parameter to understand charging is the position of the chemical potentials of the leads in relation to the molecular levels. At finite bias, the main part of the potential drop is located at the molecule-lead junctions. Also, the potential of the molecule is shown to partially follow the chemical potential closest to the highest occupied molecular orbital (HOMO). Therefore, the resonant tunneling steps in the I-V curves are smoothed giving a I-V resembling a ``Coulomb-gap.'' However, the charge of the molecule is not quantized since the molecule is small with quite strong interactions with the leads. The calculations predict an increase in the current at the bias corresponding to the energy gap of the molecule irrespective of the metals used in the leads. When the bias is increased further, charge is redistributed from the HOMO level to the lowest unoccupied molecular orbital of the molecule. This gives a step in the I-V curves and a corresponding change in the potential profile over the molecule. Calculations were mainly performed on polyene molecules. Molecules asymmetrically coupled to the leads model the I-V curves for molecules contacted by a scanning tunneling microscopy tip. I-V curves for pentapyrrole and another molecule that show negative differential conductance are also analyzed. The charging of these two systems depends on the shape of the molecular wave functions.

Validity of DSM-IV attention–deficit/hyperactivity disorder symptom dimensions and subtypes

PubMed Central

Willcutt, Erik G.; Nigg, Joel T.; Pennington, Bruce F.; Solanto, Mary V.; Rohde, Luis A.; Tannock, Rosemary; Loo, Sandra K.; Carlson, Caryn L.; McBurnett, Keith; Lahey, Benjamin B.

2013-01-01

DSM-IV criteria for ADHD specify two dimensions of inattention and hyperactivity-impulsivity symptoms that are used to define three nominal subtypes: predominantly hyperactive-impulsive type (ADHD-H), predominantly inattentive type (ADHD-I), and combined type (ADHD-C). To aid decision-making for DSM-5 and other future diagnostic systems, a comprehensive literature review and meta-analysis of 546 studies was completed to evaluate the validity of the DSM-IV model of ADHD. Results indicated that DSM-IV criteria identify individuals with significant and persistent impairment in social, academic, occupational, and adaptive functioning when intelligence, demographic factors, and concurrent psychopathology are controlled. Available data overwhelmingly support the concurrent, predictive, and discriminant validity of the distinction between inattention and hyperactivity-impulsivity symptoms, and indicate that nearly all differences among the nominal subtypes are consistent with the relative levels of inattention and hyperactivity-impulsivity symptoms that define the subtypes. In contrast, the validity of the DSM-IV subtype model is compromised by weak evidence for the validity of ADHD-H after first grade, minimal support for the distinction between ADHD-I and ADHD-C in studies of etiological influences, academic and cognitive functioning, and treatment response, and the marked longitudinal instability of all three subtypes. Overall, it is concluded that the DSM-IV ADHD subtypes provide a convenient clinical shorthand to describe the functional and behavioral correlates of current levels of inattention and hyperactivity-impulsivity symptoms, but do not identify discrete subgroups with sufficient long-term stability to justify the classification of distinct forms of the disorder. Empirical support is stronger for an alternative model that would replace the subtypes with dimensional modifiers that reflect the number of inattention and hyperactivity-impulsivity symptoms at the time of assessment. PMID:22612200

Levels of Evidence in Orthopaedic Trauma Literature.

PubMed

Scheschuk, Joseph P; Mostello, Andrew J; Lombardi, Nicholas J; Maltenfort, Mitchell G; Freedman, Kevin B; Tjoumakaris, Fotios P

2016-07-01

To review and critically assess trends observed regarding the levels of evidence in published articles in orthopaedic traumatology literature. The Journal of Orthopaedic Trauma, Journal of Bone and Joint Surgery-American, and Clinical Orthopaedics and Related Research. All articles from the years 1998, 2003, 2008, and 2013 in The Journal of Orthopaedic Trauma (JOT) and orthopaedic trauma-related articles from The Journal of Bone and Joint Surgery-American (JBJS-A) and Clinical Orthopaedics and Related Research (CORR) were analyzed. Articles were categorized by type and ranked for level of evidence according to guidelines from the Centre for Evidence-Based Medicine. Study type and standardized level of evidence were determined for each article. Articles were subcategorized as high-level evidence (I, II), moderate-level evidence (III), and low-level evidence (IV, V). During the study period, Journal of Bone and Joint Surgery-American reduced its low-level studies from 80% to 40% (P = 0.00015), Clinical Orthopaedics and Related Research decreased its low-level studies from 70% to 27%, and Journal of Orthopaedic Trauma decreased its low-level studies from 78% to 45%. Level IV and V therapeutic, prognostic, and diagnostic studies demonstrated significant decreases during the study period (P = 0.0046, P < 0.0001, P = 0.026). The percentage of high-level studies increased from 13% to 19%; however, this was not significant (P = 0.42). There was a trend showing an increase in level I and II studies for therapeutic, prognostic, and diagnostic studies (P = 0.06). There has been a statistically significant decrease in lower level of evidence studies published in the orthopaedic traumatology literature over the past 15 years.

Relativistic solar particle events during STIP (study of travelling interplanetary phenomena) intervals II and IV

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

Shea, M.A.; Smart, D.F.

1982-12-27

Using spaceship 'Earth' as a detector located at 1 AU, the relativistic solar cosmic ray events of 30 April 1976 and 22 November 1977 are compared to deduce the relativistic solar particle flux anisotropy and pitch angle characteristics in the interplanetary medium. These two ground level events occurred during STIP Interval II and IV respectively - periods of time of coordinated and cooperative scientific efforts.

A plant based protective antigen [PA(dIV)] vaccine expressed in chloroplasts demonstrates protective immunity in mice against anthrax.

PubMed

Gorantala, Jyotsna; Grover, Sonam; Goel, Divya; Rahi, Amit; Jayadev Magani, Sri Krishna; Chandra, Subhash; Bhatnagar, Rakesh

2011-06-15

The currently available anthrax vaccines are limited by being incompletely characterized, potentially reactogenic and have an expanded dosage schedule. Plant based vaccines offer safe alternative for vaccine production. In the present study, we expressed domain IV of Bacillus anthracis protective antigen gene [PA(dIV)] in planta (by nuclear agrobacterium and chloroplast transformation) and E. coli [rPA(dIV)]. The presence of transgene and the expression of PA(dIV) in planta was confirmed by molecular analysis. Expression levels up to 5.3% of total soluble protein (TSP) were obtained with AT rich (71.8% AT content) PA(dIV) gene in transplastomic plants while 0.8% of TSP was obtained in nuclear transformants. Further, we investigated the protective response of plant and E. coli derived PA(dIV) in mice by intraperitoneal (i.p.) and oral immunizations with or without adjuvant. Antibody titers of >10(4) were induced upon i.p. and oral immunizations with plant derived PA(dIV) and oral immunization with E. coli derived PA(dIV). Intraperitoneal injections with adjuvanted E. coli derived PA(dIV), generated highest antibody titers of >10(5). All the immunized groups demonstrated predominant IgG1 titers over IgG2a indicating a polarized Th2 type response. We also evaluated the mucosal antibody response in orally immunized groups. When fecal extracts were analyzed, low sIgA titer was demonstrated in adjuvanted plant and E. coli derived PA(dIV) groups. Further, PA(dIV) antisera enhanced B. anthracis spore uptake by macrophages in vitro and also demonstrated an anti-germinating effect suggesting a potent role at mucosal surfaces. The antibodies from various groups were efficient in neutralizing the lethal toxin in vitro. When mice were challenged with B. anthracis, mice immunized with adjuvanted plant PA(dIV) imparted 60% and 40% protection while E. coli derived PA(dIV) conferred 100% and 80% protection upon i.p. and oral immunizations. Thus, our study is the first attempt in highlighting the efficacy of plant expressed PA(dIV) by oral immunization in murine model. Copyright © 2011 Elsevier Ltd. All rights reserved.

Comparing the Personality Disorder Interview for DSM-IV (PDI-IV) and SCID-II borderline personality disorder scales: an item-response theory analysis.

PubMed

Huprich, Steven K; Paggeot, Amy V; Samuel, Douglas B

2015-01-01

One-hundred sixty-nine psychiatric outpatients and 171 undergraduate students were assessed with the Personality Disorder Interview-IV (PDI-IV; Widiger, Mangine, Corbitt, Ellis, & Thomas, 1995) and the Structured Clinical Interview for DSM-IV Axis II disorders (SCID-II; First, Gibbon, Spitzer, Williams, & Benjamin, 1997) for borderline personality disorder (BPD). Eighty individuals met PDI-IV BPD criteria, whereas 34 met SCID-II BPD criteria. Dimensional ratings of both measures were highly intercorrelated (rs = .78, .75), and item-level interrater reliability fell in the good to excellent range. An item-response theory analysis was performed to investigate whether properties of the items from each interview could help understand these differences. The limited agreement seemed to be explained by differences in the response options across the two interviews. We found that suicidal behavior was among the most discriminating criteria on both instruments, whereas dissociation and difficulty controlling anger had the 2 lowest alpha parameter values. Finally, those meeting BPD criteria on both interviews had higher levels of anxiety, depression, and more impairments in object relations than those meeting criteria on just the PDI-IV. These findings suggest that the choice of measure has a notable effect on the obtained diagnostic prevalence and the level of BPD severity that is detected.

The effect of two different doses comprising the simultaneous administration of intravenous B-complex vitamins and oral folic acid on serum homocysteine levels in hemodialysis patients.

PubMed

Sombolos, Kostas; Papaioannou, Anna; Christidou, Fotini; Natse, Taisir; Bamichas, Gerasimos; Gionanlis, Lazaros; Katsaris, George; Progia, Evagelia

2006-01-01

Several regimens using different doses of folic acid (FA) alone or supplemented with B-complex vitamins (BCVs) have been tested for their ability to reduce total homocysteine (tHcy) serum levels in hemodialysis (HD) patients. In the present study, we assessed the effect of two different doses comprising the simultaneous administration of intravenous (IV) BCVs and an oral FA supplementation on serum tHCy levels in HD patients. In a cohort of 49 patients (31 male, 18 female) undergoing chronic HD treatment for a mean of 40.0+/-40.7 months, serum concentrations of tHcy, folate and vitamin-B12 (vB12) were determined at the end of three sequential periods as follows: 20 weeks without any BCV and/or FA supplementation (period A), 20 weeks with a dose comprising the simultaneous administration of IV BCVs and an oral supplementation of 5 mg of FA once a week (period B), and 20 weeks with a dose comprising the simultaneous administration of IV BCVs and an oral supplementation of 5 mg of FA thrice a week (period C). An IV dose of BCVs consisting of a 5 mL solution containing vitamin B1 (250 mg), vitamin B6 (250 mg) and vitamin B12 (1.5 mg) was administered at the end of hemodialysis. Mean serum tHcy levels were significantly higher at the end of period A relative to levels at the end of periods B and C (35.8+/-23 micromol/L vs. 22.0+/-17.6 and 15.0+/-4.5 micromol/L, respectively; p<0.000001). Mean serum folate levels and mean serum vB12 levels were significantly lower at the end of period A relative to levels at the end of periods B and C (p<0.000001). Mean serum tHcy levels were lowest at the end of period C (p<0.000001 in comparison to periods A and B), and 26 of the 49 HD patients (67.3%) possessed tHcy levels below 16 micromol/L. In HD patients, high doses consisting of the simultaneous administration of IV BCVs and an oral FA supplementation resulted in the efficient reduction of serum tHcy levels.

The effects of intravenous, enteral and combined administration of glutamine on malnutrition in sepsis: a randomized clinical trial.

PubMed

Koksal, Guniz Meyancı; Erbabacan, Emre; Tunali, Yusuf; Karaoren, Gulsah; Vehid, Suphi; Oz, Huseyin

2014-01-01

Our aim was to compare the effects of intravenous, enteral, and enteral plus intravenous supplemented glutamine on plasma transferrin, nitrogen balance, and creatinine/height index in septic patients with malnutrition. Blood and urine samples were collected for transferrin, urea and creatinine measurements. Samples, SOFA score and protein-calorie intake values were repeated on days 7 and 15. Patients (n:120) were randomly divided into 4 groups. Group I received 30 g/day IV glutamine, group II received 30 g/day enteral glutamine, group III received 15 g/day IV and 15 g/day enteral glutamine. Group IV received only enteral feeding as a control group. Transferrin levels decreased in group IV (p<0.01 0-7 days, p<0.01 7-15 days, p<0.01 0-15 days). Nitrogen balance levels were highest in group IV when compared with group I (p<0.05, p<0.001), group II (p<0.001), and group III (p<0.05, p<0.001) on days 7-15. Creatinine/height indexes increased in group I (p<0.001), group II (p<0.001), group III (p<0.001), and group IV (p<0.05) on day 15. In group III the creatinine/height index was higher than in groups I and II (p<0.05). In group IV, creatinine/height index was lower than in group I (p<0.01) and group II (p<0.001). Protein-calorie intake in group IV was higher than others on day 7 (p<0.05). SOFA scores of group IV were higher than the other groups on day 15 (p<0.05). This study demonstrated, that combined route of gln supplementation resulted in the most positive outcome to transferrin, creatine/height index and nitrogen balance (on days 7 and 15) during the catabolic phase of septic patients with malnutrition.

Increased levels of circulating platelet-derived microparticles are associated with metastatic cutaneous melanoma.

PubMed

Moreau, Joséphine; Pelletier, Fabien; Biichle, Sabeha; Mourey, Guillaume; Puyraveau, Marc; Badet, Nicolas; Caubet, Matthieu; Laresche, Claire; Garnache-Ottou, Francine; Saas, Philippe; Seilles, Estelle; Aubin, François

2017-10-01

We investigated the plasma levels of PMPs in patients with 45 stage III and 45 stage IV melanoma. PMPs were characterised by flow cytometry and their thrombogenic activity. We also investigated the link between PMPs circulating levels and tumor burden. The circulating levels of PMPs were significantly higher in stage IV (8500 μL -1 ) than in patients with stage III (2041 μL -1 ) melanoma (P=.0001). We calculated a highly specific (93.3%) and predictive (91.7%) cut-off value (5311 μL -1 ) allowing the distinction between high-risk stage III and metastatic stage IV melanoma. The thrombogenic activity of PMPs was significantly higher in patients with stage IV melanoma (clotting time: 40.7 second vs 65 second, P=.0001). There was no significant association between the radiological tumoral syndrome and the plasma level of PMPs. Our data suggest the role of PMPs in metastatic progression of melanoma. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Comparison of efficacies of a dipeptidyl peptidase IV inhibitor and alpha-glucosidase inhibitors in oral carbohydrate and meal tolerance tests and the effects of their combination in mice.

PubMed

Yamazaki, Kazuto; Inoue, Takashi; Yasuda, Nobuyuki; Sato, Yoshiaki; Nagakura, Tadashi; Takenaka, Osamu; Clark, Richard; Saeki, Takao; Tanaka, Isao

2007-05-01

E3024 (3-but-2-ynyl-5-methyl-2-piperazin-1-yl-3,5-dihydro-4H-imidazo[4,5-d]pyridazin-4-one tosylate) is a dipeptidyl peptidase IV (DPP-IV) inhibitor. Since the target of both DPP-IV inhibitors and alpha-glucosidase inhibitors is the lowering of postprandial hyperglycemia, we compared antihyperglycemic effects for E3024 and alpha-glucosidase inhibitors in various oral carbohydrate and meal tolerance tests using normal mice. In addition, we investigated the combination effects of E3024 and voglibose on blood glucose levels in a meal tolerance test using mice fed a high-fat diet. ER-235516-15 (the trifluoroacetate salt form of E3024, 1 mg/kg) lowered glucose excursions consistently, regardless of the kind of carbohydrate loaded. However, the efficacy of acarbose (10 mg/kg) and of voglibose (0.1 mg/kg) varied with the type of carbohydrate administered. The combination of E3024 (3 mg/kg) and voglibose (0.3 mg/kg) improved glucose tolerance additively, with the highest plasma active glucagon-like peptide-1 levels. This study shows that compared to alpha-glucosidase inhibitors, DPP-IV inhibitors may have more consistent efficacy to reduce postprandial hyperglycemia, independent of the types of carbohydrate contained in a meal, and that the combination of a DPP-IV inhibitor and an alpha-glucosidase inhibitor is expected to be a promising option for lowering postprandial hyperglycemia.

Assessment of the effect of Allium sativum on serum nitric oxide level and hepatic histopathology in experimental cystic echinococcosis in mice.

PubMed

Ali, Nehad Mahmoud; Ibrahim, Ayman Nabil; Ahmed, Naglaa Samier

2016-09-01

The current study was carried out to evaluate the prophylactic and therapeutic effects of Allium sativum on experimental cystic echinococcosis by measuring the serum nitric oxide level and studying hepatic histopathological changes. The experimental animals were divided into five groups, ten mice in each, group (I): prophylactic; group (II): therapeutic; group (III): prophylactic and therapeutic; group (IV): infected nontreated; group (V): non infected non treated. The results showed that serum nitric oxide was significantly increased as a result of infection in all infected groups compared to group V. Statistical significant difference was noted in serum nitrate level in group I at 1st and 8th week post infection compared to the same time interval in group IV. In group II, statistical significance was noticed only at the 1st week post infection. Statistical significant difference was noted in serum nitrate level in group III at 1st, 4th, 6th and 8th week post infection compared to same time interval in group IV. Hydatid cysts developed in livers of mice of group IV as early as 4 weeks of infection while no cysts were found in groups I,II and III. Histopathologically there were moderate pathological changes in group I and group II as hepatocytes showed moderate steatosis, moderate venous congestion and inflammatory cellular infiltrate with foci of degeneration and necrosis. While livers of mice of group III showed mild steatosis, mild venous congestion, mild inflammatory cellular infiltrate, no necrosis and no biliary hyperplasia. Accordingly, that garlic (Allium sativum) may be a promising phototherapeutic agent for cystic echinococcosis.

Intravenous versus topical tranexamic acid administration in primary total knee arthroplasty: a meta-analysis.

PubMed

Shin, Young-Soo; Yoon, Jung-Ro; Lee, Hoon-Nyun; Park, Se-Hwan; Lee, Dae-Hee

2017-11-01

This meta-analysis was designed to compare the effectiveness and safety of intravenous (IV) versus topical administration of tranexamic acid (TXA) in patients undergoing primary total knee arthroplasty (TKA) by evaluating the need for allogenic blood transfusion, incidence of postoperative complications, volume of postoperative blood loss, and change in haemoglobin levels. Studies were included in this meta-analysis to check whether they assessed the allogenic blood transfusion rate, postoperative complications including pulmonary thromboembolism (PTE) or deep vein thrombosis (DVT), volume of postoperative blood loss via drainage, estimated blood loss, total blood loss, and change in haemoglobin levels before and after surgery in primary TKA with TXA administered through both the IV and topical routes. Ten studies were included in this meta-analysis. The proportion of patients requiring allogenic blood transfusion (OR 1.34, 95 % CI 0.63-2.81; n.s.) and the proportion of patients who developed postoperative complications including PTE or DVT (OR 0.85, 95 % CI 0.41 to 1.77; n.s.) did not significantly differ between the two groups. There was 52.3 mL less blood loss via drainage (95 % CI -50.74 to 185.66 mL; n.s.), 52.1 mL greater estimated blood loss (95 % CI -155.27 to 51.03 mL; n.s.), and 51.4 mL greater total blood loss (95 % CI -208.16 to 105.31 mL; n.s.) in the topical TXA group as compared to the IV TXA group. The two groups were also similar in terms of the change in haemoglobin levels (0.02 g/dL, 95 % CI -0.36 to 0.39 g/dL; n.s.). In primary TKA, there are no significant differences in the transfusion requirement, postoperative complications, blood loss, and change in haemoglobin levels between the IV and topical administration of TXA. In addition, results from subgroup analysis evaluating the effect of the times of TXA administration through the IV route suggested that double IV dose of TXA is more effective than single dose in terms of the transfusion requirements and blood loss via drainage. The current meta-analysis indicates that IV administration of 10 mg/kg of TXA 20 min before inflation of the tourniquet followed by 10 mg/kg of TXA 15 min before deflation of the tourniquet is effective and safe. The topical administration of 2 g of TXA mixed with 100 mL of normal saline after wound closure could be an alternative option in patients at greater risk of thromboembolic complications. Meta-analysis, Level III.

Hierarchical subdivisions of the Columbia Plateau and Blue Mountains ecoregions, Oregon and Washington.

Treesearch

Sharon E. Clarke; Sandra A. Bryce

1997-01-01

This document presents two spatial scales of a hierarchical, ecoregional framework and provides a connection to both larger and smaller scale ecological classifications. The two spatial scales are subregions (1:250,000) and landscape-level ecoregions (1:100,000), or Level IV and Level V ecoregions. Level IV ecoregions were developed by the Environmental Protection...

A Genetic Selection for dinB Mutants Reveals an Interaction between DNA Polymerase IV and the Replicative Polymerase That Is Required for Translesion Synthesis.

PubMed

Scotland, Michelle K; Heltzel, Justin M H; Kath, James E; Choi, Jung-Suk; Berdis, Anthony J; Loparo, Joseph J; Sutton, Mark D

2015-09-01

Translesion DNA synthesis (TLS) by specialized DNA polymerases (Pols) is a conserved mechanism for tolerating replication blocking DNA lesions. The actions of TLS Pols are managed in part by ring-shaped sliding clamp proteins. In addition to catalyzing TLS, altered expression of TLS Pols impedes cellular growth. The goal of this study was to define the relationship between the physiological function of Escherichia coli Pol IV in TLS and its ability to impede growth when overproduced. To this end, 13 novel Pol IV mutants were identified that failed to impede growth. Subsequent analysis of these mutants suggest that overproduced levels of Pol IV inhibit E. coli growth by gaining inappropriate access to the replication fork via a Pol III-Pol IV switch that is mechanistically similar to that used under physiological conditions to coordinate Pol IV-catalyzed TLS with Pol III-catalyzed replication. Detailed analysis of one mutant, Pol IV-T120P, and two previously described Pol IV mutants impaired for interaction with either the rim (Pol IVR) or the cleft (Pol IVC) of the β sliding clamp revealed novel insights into the mechanism of the Pol III-Pol IV switch. Specifically, Pol IV-T120P retained complete catalytic activity in vitro but, like Pol IVR and Pol IVC, failed to support Pol IV TLS function in vivo. Notably, the T120P mutation abrogated a biochemical interaction of Pol IV with Pol III that was required for Pol III-Pol IV switching. Taken together, these results support a model in which Pol III-Pol IV switching involves interaction of Pol IV with Pol III, as well as the β clamp rim and cleft. Moreover, they provide strong support for the view that Pol III-Pol IV switching represents a vitally important mechanism for regulating TLS in vivo by managing access of Pol IV to the DNA.

Needleless connectors substantially reduce flow of crystalloid and red blood cells during rapid infusion.

PubMed

Lehn, Robert A; Gross, Jeffrey B; McIsaac, Joseph H; Gipson, Keith E

2015-04-01

Although needleless connectors (NC) are frequently used in the perioperative setting, the potential of modern NCs to slow delivery of IV fluids has not been thoroughly studied. We examined flow characteristics of 5 NC models during pressurized delivery of crystalloid and banked red blood cells from a Level 1 warmer through various IV catheters. Crystalloid flow rates were reduced by 29% to 85% from control in catheters >18 gauge, while red blood cell flow reductions ranged from 22% to 76% in these catheters (all P < 0.0050). We suggest that practitioners consider eliminating NCs when large IV catheters are inserted for rapid fluid administration.

Effects of the combination of a dipeptidyl peptidase IV inhibitor and an insulin secretagogue on glucose and insulin levels in mice and rats.

PubMed

Yamazaki, Kazuto; Yasuda, Nobuyuki; Inoue, Takashi; Yamamoto, Eiichi; Sugaya, Yukiko; Nagakura, Tadashi; Shinoda, Masanobu; Clark, Richard; Saeki, Takao; Tanaka, Isao

2007-02-01

Several combination therapies have been tried for treating of type 2 diabetes to control more effectively fasting hyperglycemia and postprandial hyperglycemia. In this study, we have examined the effects of combining a novel, selective, and competitive dipeptidyl peptidase IV (DPP-IV) inhibitor, 3-but-2-ynyl-5-methyl-2-piperazin-1-yl-3,5-dihydro-4H-imidazo[4,5-d]pyridazin-4-one tosylate (E3024), with a representative of one of two types of insulin secretagogues, i.e., either glybenclamide (a sulfonylurea) or nateglinide (a rapid-onset/short-duration insulin secretagogue), on glucose and insulin levels in an oral glucose tolerance test (OGTT) using mice fed a high-fat diet. In addition, we have investigated the effects of these combinations on blood glucose levels in fasting rats. Two-way analysis of variance showed that the combination of E3024 and glybenclamide improved glucose tolerance additively and also caused a synergistic increase in insulin levels in the OGTT in mice fed a high-fat diet. In a similar way, the combination of E3024 and nateglinide ameliorated glucose tolerance additively and raised insulin levels additively. In fasting rats, coadministration of E3024 with glybenclamide or nateglinide treatment did not affect the glucose-lowering effects of the insulin secretagogues. Therefore, a DPP-IV inhibitor in combination with glybenclamide or nateglinide may be a promising option for the treatment of type 2 diabetes, and particularly, for controlling postprandial hyperglycemia in the clinic.

Pharmacologic conversion of atrial fibrillation: a systematic review of available evidence.

PubMed

Slavik, R S; Tisdale, J E; Borzak, S

2001-01-01

This report reviews the efficacy of currently available antiarrhythmic agents for conversion of atrial fibrilation (AF) to normal sinus rhythm (NSR). A systematic search of literature in the English language was done on computerized databases, such as MEDLINE, EMBASE, and Current Contents, in reference lists, by manual searching, and in contact with expert informants. Published studies involving humans that described the use of antiarrhythmic therapy for conversion of AF to NSR were considered and only studies that examined the use of agents currently available in the United States were included. Studies exclusively describing antiarrhythmic therapy for conversion of postsurgical AF were excluded. The methodology and results of each trial were assessed and attempts were made to acquire additional information from investigators when needed. Assessment of methodological quality was incorporated into a levels-of-evidence scheme. Eighty-eight trials were included, of which 34 (39%) included a placebo group (level I data). We found in recent-onset AF of less than 7 days, intravenous (i.v.) procainamide, high-dose i.v. or high-dose combination i.v. and oral amiodarone, oral quinidine, oral flecainide, oral propafenone, and high-dose oral amiodarone are more effective than placebo for converting AF to NSR. In recent-onset AF of less than 90 days, i.v. ibutilide is more effective than placebo and i.v. procainamide. In chronic AF, oral dofetilide converts AF to NSR within 72 hours, and oral propafenone and amiodarone are effective after 30 days of therapy. We conclude than for conversion of recent-onset AF of less than 7 days, procainamide may be considered a preferred i.v. agent and propafenone a preferred oral agent. For conversion of recent-onset AF of longer duration (less than 90 days), i.v. ibutilide may be considered a preferred agent. For patients with chronic AF and left ventricular dysfunction, direct current cardioversion is the preferred conversion method. Larger, well-designed randomized controlled trials with clinically important endpoints in specific populations of AF patients are needed. Copyright 2001 by W.B. Saunders Company

Annual changes in radiographic indices of the spine in cerebral palsy patients.

PubMed

Lee, Seung Yeol; Chung, Chin Youb; Lee, Kyoung Min; Kwon, Soon-Sun; Cho, Kyu-Jung; Park, Moon Seok

2016-03-01

We estimated the annual changes in radiographic indices of the spine in cerebral palsy (CP) patients and analyzed the factors that influence its progression rate. We included CP patients who had undergone whole-spine radiography more than twice and were followed for at least 1 year. The scoliosis Cobb angle, coronal balance, apical vertebral translation, apical rotation, and pelvic obliquity were measured on anteroposterior (AP) radiographs; thoracic kyphosis and lumbar lordosis angles, and sagittal balance was measured on lateral radiographs; and migration percentage was measured on AP hip radiographs to determine hip instability. For each gross motor function classification system (GMFCS) level, the Cobb angles, apical vertebral translation, coronal and sagittal balance, and pelvic obliquity were adjusted by multiple factors with a linear mixed model. A total of 184 patients (774 radiographs) were included in this study. There was no significant annual change in scoliosis Cobb, thoracic kyphosis, and lumbar lordosis angles in the GMFCS level I-II and III groups. In the GMFCS level IV-V group, there was an annual increase of 3.4° in the scoliosis Cobb angle (p = 0.020). The thoracic kyphosis angle increased by 2.2° (p = 0.018) annually in the GMFCS level IV-V group. Apical vertebral translation increased by 5.4 mm (p = 0.029) annually in the GMFCS level IV-V group. Progression of coronal and sagittal balance and pelvic obliquity with aging were not statistically significant. Sex, hip instability, hip surgery, and triradiate cartilage did not affect the progression of scoliosis and the balance of the spine and pelvis. The scoliosis Cobb angle, thoracic kyphosis angle, and apical vertebral translation in the GMFCS level IV-V CP patients progressed with age. These findings can predict radiographic progression of scoliosis in CP patients.

Approximating a DSM-5 Diagnosis of PTSD Using DSM-IV Criteria

PubMed Central

Rosellini, Anthony J.; Stein, Murray B.; Colpe, Lisa J.; Heeringa, Steven G.; Petukhova, Maria V.; Sampson, Nancy A.; Schoenbaum, Michael; Ursano, Robert J.; Kessler, Ronald C.

2015-01-01

Background Diagnostic criteria for DSM-5 posttraumatic stress disorder (PTSD) are in many ways similar to DSM-IV criteria, raising the possibility that it might be possible to closely approximate DSM-5 diagnoses using DSM-IV symptoms. If so, the resulting transformation rules could be used to pool research data based on the two criteria sets. Methods The Pre-Post Deployment Study (PPDS) of the Army Study to Assess Risk and Resilience in Servicemembers (Army STARRS) administered a blended 30-day DSM-IV and DSM-5 PTSD symptom assessment based on the civilian PTSD Checklist for DSM-IV (PCL-C) and the PTSD Checklist for DSM-5 (PCL-5). This assessment was completed by 9,193 soldiers from three US Army Brigade Combat Teams approximately three months after returning from Afghanistan. PCL-C items were used to operationalize conservative and broad approximations of DSM-5 PTSD diagnoses. The operating characteristics of these approximations were examined compared to diagnoses based on actual DSM-5 criteria. Results The estimated 30-day prevalence of DSM-5 PTSD based on conservative (4.3%) and broad (4.7%) approximations of DSM-5 criteria using DSM-IV symptom assessments were similar to estimates based on actual DSM-5 criteria (4.6%). Both approximations had excellent sensitivity (92.6-95.5%), specificity (99.6-99.9%), total classification accuracy (99.4-99.6%), and area under the receiver operating characteristic curve (0.96-0.98). Conclusions DSM-IV symptoms can be used to approximate DSM-5 diagnoses of PTSD among recently-deployed soldiers, making it possible to recode symptom-level data from earlier DSM-IV studies to draw inferences about DSM-5 PTSD. However, replication is needed in broader trauma-exposed samples to evaluate the external validity of this finding. PMID:25845710

Did the DSM-5 Improve the Traumatic Stressor Criterion?: Association of DSM-IV and DSM-5 Criterion A with Posttraumatic Stress Disorder Symptoms.

PubMed

Larsen, Sadie E; Berenbaum, Howard

2017-01-01

A recent meta-analysis found that DSM-III- and DSM-IV-defined traumas were associated with only slightly higher posttraumatic stress disorder (PTSD) symptoms than nontraumatic stressors. The current study is the first to examine whether DSM-5-defined traumas were associated with higher levels of PTSD than DSM-IV-defined traumas. Further, we examined theoretically relevant event characteristics to determine whether characteristics other than those outlined in the DSM could predict PTSD symptoms. One hundred six women who had experienced a trauma or significant stressor completed questionnaires assessing PTSD, depression, impairment, and event characteristics. Events were rated for whether they qualified as DSM-IV and DSM-5 trauma. There were no significant differences between DSM-IV-defined traumas and stressors. For DSM-5, effect sizes were slightly larger but still nonsignificant (except for significantly higher hyperarousal following traumas vs. stressors). Self-reported fear for one's life significantly predicted PTSD symptoms. Our results indicate that the current DSM-5 definition of trauma, although a slight improvement from DSM-IV, is not highly predictive of who develops PTSD symptoms. Our study also indicates the importance of individual perception of life threat in the prediction of PTSD. © 2017 S. Karger AG, Basel.

Instrumental variable approaches to identifying the causal effect of educational attainment on dementia risk

PubMed Central

Nguyen, Thu T.; Tchetgen Tchetgen, Eric J.; Kawachi, Ichiro; Gilman, Stephen E.; Walter, Stefan; Liu, Sze Y.; Manly, Jennifer; Glymour, M. Maria

2015-01-01

Purpose Education is an established correlate of cognitive status in older adulthood, but whether expanding educational opportunities would improve cognitive functioning remains unclear given limitations of prior studies for causal inference. Therefore, we conducted instrumental variable (IV) analyses of the association between education and dementia risk, using for the first time in this area, genetic variants as instruments as well as state-level school policies. Methods IV analyses in the Health and Retirement Study cohort (1998–2010) used two sets of instruments: 1) a genetic risk score constructed from three single nucleotide polymorphisms (SNPs) (n=8,054); and 2) compulsory schooling laws (CSLs) and state school characteristics (term length, student teacher ratios, and expenditures) (n=13,167). Results Employing the genetic risk score as an IV, there was a 1.1% reduction in dementia risk per year of schooling (95% CI: −2.4, 0.02). Leveraging compulsory schooling laws and state school characteristics as IVs, there was a substantially larger protective effect (−9.5%; 95% CI: −14.8, −4.2). Analyses evaluating the plausibility of the IV assumptions indicated estimates derived from analyses relying on CSLs provide the best estimates of the causal effect of education. Conclusion IV analyses suggest education is protective against risk of dementia in older adulthood. PMID:26633592

Comparison of Mortality Associated with Sepsis in the Burn, Trauma, and General Intensive Care Unit Patient: A Systematic Review of the Literature

DTIC Science & Technology

2012-01-01

sepsis 14/175 (8%), 14/79 (18%); septic shock 16/175 (9%), 16/79 (20%) Miller et al . (20) 2006 1995 2005 Retro review/level IV/grade B 70 Center, 30 US...deaths, 97 autopsies 43/97 (44%) fungal elements identified Sharma et al . (22) 2006 2000 2004 Retro review/ level IV/grade A Single center; India Five...2,857,476 (G1%) Esper et al . (43) 2006 1979 2003 Retro review/level IV/grade A US/NR Factors that may influence health care disparities on incidence of

Reduced aortic lesions and elevated high density lipoprotein levels in transgenic mice overexpressing mouse apolipoprotein A-IV.

PubMed Central

Cohen, R D; Castellani, L W; Qiao, J H; Van Lenten, B J; Lusis, A J; Reue, K

1997-01-01

Transgenic mouse lines carrying several copies of the mouse apo A-IV gene were produced. Lipoprotein composition and function, and aortic lesion development were examined. Apo A-IV levels in the plasma of transgenic mice were elevated threefold compared with nontransgenic littermates on a chow diet, and sixfold in mice fed an atherogenic diet. Plasma concentrations of total cholesterol, HDL cholesterol, triglycerides, and free fatty acids were similar in transgenic and control mice fed a chow diet. However, with the atherogenic diet, male transgenic mice exhibited significantly higher levels of plasma triglycerides (P < 0.05), total cholesterol (P < 0.01), HDL cholesterol (P < 0.0001), and free fatty acids (P < 0.05), and lower levels of unesterified cholesterol (P < 0.05), than nontransgenic littermates. Expression of the apo A-IV transgene had a protective effect against the formation of diet-induced aortic lesions, with transgenics exhibiting lesion scores of approximately 30% those seen in control mice. HDL-sized lipoproteins isolated from transgenic mice fed the atherogenic diet promoted cholesterol efflux from cholesterol-loaded human monocytes more efficiently than comparable lipoproteins from nontransgenic counterparts. Plasma from transgenics also exhibited higher endogenous cholesterol esterification rates. Taken together, these results suggest that apo A-IV levels influence the metabolism and antiatherogenic properties of HDL. PMID:9109435

Blending of palm oil, palm stearin and palm kernel oil in the preparation of table and pastry margarine.

PubMed

Norlida, H M; Md Ali, A R; Muhadhir, I

1996-01-01

Palm oil (PO ; iodin value = 52), palm stearin (POs1; i.v. = 32 and POs2; i.v. = 40) and palm kernel oil (PKO; i.v. = 17) were blended in ternary systems. The blends were then studied for their physical properties such as melting point (m.p.), solid fat content (SFC), and cooling curve. Results showed that palm stearin increased the blends melting point while palm kernel oil reduced it. To produce table margarine with melting point (m.p.) below 40 degrees C, the POs1 should be added at level of < or = 16%, while POs2 at level of < or = 20%. At 10 degrees C, eutectic interaction occur between PO and PKO which reach their maximum at about 60:40 blending ratio. Within the eutectic region, to maintain the SFC at 10 degrees C to be < or = 50%, POs1 may be added at level of < or = 7%, while POs2 at level of < or = 12%. The addition of palm stearin increased the blends solidification Tmin and Tmax values, while PKO reduced them. Blends which contained high amount of palm stearin showed melting point and cooling curves quite similar to that of pastry margarine.

An Explorative Study on Environmental Literacy among the Secondary Level Students in Bangladesh

ERIC Educational Resources Information Center

Sarkar, Md. Mahbub Alam; Ara, Quazi Afroz Jahan; Raihan, Jahir; Ozaki, Koji

2008-01-01

This study was intended to explore the environmental literacy among the secondary level students of Bangladesh. Specifically, it was designed to: i) determine environmental knowledge of the secondary students, ii) explore their environmental attitude, iii) find out their environment related practices, and iv) explore school's environment-friendly…

Effects of low-level laser therapy on stem cells from human exfoliated deciduous teeth.

PubMed

Fernandes, Ana Paula; Junqueira, Marina de Azevedo; Marques, Nádia Carolina Teixeira; Machado, Maria Aparecida Andrade Moreira; Santos, Carlos Ferreira; Oliveira, Thais Marchini; Sakai, Vivien Thiemy

2016-01-01

This study aimed to evaluate the influence of different laser therapy energy densities on SHED viability and proliferation. SHED were irradiated according to the groups: I (1.2 J/cm2 - 0.5 mW - 10 s), II (2.5 J/cm2 - 10 mW - 10 s), III (3.7 J/cm2 - 15 mW - 10 s), IV (5.0 J/cm2 - 20 mW - 10 s), V (6.2 J/cm2 - 25 mW - 10 s), and VI (not irradiated - control group). Cell viability was assessed 6 and 24 h after irradiation measuring the mitochondrial activity and using the Crystal Violet assay. Cell proliferation was assessed after 24, 48, and 72 h of irradiation by SRB assay. MTT assay demonstrated differences from 6 to 24 hours after irradiation. After 24 h, groups I and IV showed higher absorbance values than those of control group. Crystal Violet assay showed statistically differences in the absorbance rate from 6 to 24 h after irradiation for groups III and VI. At 24 h after irradiation, Group III absorbance rate was greater than that of groups I, II, and IV. Group VI absorbance rate was greater than that of groups I and IV. SRB assay showed that the group I had higher rates than those of groups II, III, V, and VI, at 24 h after irradiation. After 48 h, group I exhibited the greatest cell proliferation rate followed by groups III, V, and VI. After 72 h, group III exhibited the lowest cell proliferation rate than those of groups II, IV, and V. The Low-Level Laser Therapy energy densities used in this study did not cause loss of cell viability and stimulated SHED proliferation within the parameters described in this study.

Adipokine Profile in Patients with Type 2 Diabetes Depends on Degree of Obesity

PubMed Central

Kocot, Joanna; Dziemidok, Piotr; Kiełczykowska, Małgorzata; Hordyjewska, Anna; Szcześniak, Grzegorz; Musik, Irena

2017-01-01

Background The fast pace of life, promoting fast food consumption and low physical activity, has resulted in obesity and/or diabetes as being serious social problems. The aim of the present study was to evaluate concentrations of selected adipokines (leptin, adiponectin, resistin, and visfatin) and to assess the leptin/adiponectin ratio in plasma of type 2 diabetes (T2D) patients in relation to degree of obesity. Material/Methods The study comprised 92 T2D subjects divided into 4 groups according to BMI value – I (normal body weight), II (overweight), III (obesity), and IV (severe obesity) – and 20 healthy volunteers (control group). Each group was divided into male and female subgroups. Plasma concentrations of adipokines were determined by enzyme-linked immunosorbent assay. Results In women, leptin concentration was significantly higher in group IV, whereas in men it was higher in groups III and IV than in the control group and groups I and II. Irrespective of sex, a significant decrease in adiponectin level was observed in group III vs. control. There was no significant difference in resistin levels. In women visfatin was markedly enhanced in group III, whereas in men in groups II, III and IV vs. control. Leptin/adiponectin ratio was increased in groups III and IV vs. control in women, whereas in men vs. both control and group I. Conclusions The obese type 2 diabetic patients presented a disturbed adipokine profile, which seems to be an important link between obesity and T2D. The future studies concerning the question if regulating of adipokines’ concentrations could be a promising approach for managing metabolic disorders seem to be well-grounded. PMID:29049270

Phenotypic and Genomic Analysis of Hypervirulent Human-associated Bordetella bronchiseptica

PubMed Central

2012-01-01

Background B. bronchiseptica infections are usually associated with wild or domesticated animals, but infrequently with humans. A recent phylogenetic analysis distinguished two distinct B. bronchiseptica subpopulations, designated complexes I and IV. Complex IV isolates appear to have a bias for infecting humans; however, little is known regarding their epidemiology, virulence properties, or comparative genomics. Results Here we report a characterization of the virulence of human-associated complex IV B. bronchiseptica strains. In in vitro cytotoxicity assays, complex IV strains showed increased cytotoxicity in comparison to a panel of complex I strains. Some complex IV isolates were remarkably cytotoxic, resulting in LDH release levels in A549 cells that were 10- to 20-fold greater than complex I strains. In vivo, a subset of complex IV strains was found to be hypervirulent, with an increased ability to cause lethal pulmonary infections in mice. Hypercytotoxicity in vitro and hypervirulence in vivo were both dependent on the activity of the bsc T3SS and the BteA effector. To clarify differences between lineages, representative complex IV isolates were sequenced and their genomes were compared to complex I isolates. Although our analysis showed there were no genomic sequences that can be considered unique to complex IV strains, there were several loci that were predominantly found in complex IV isolates. Conclusion Our observations reveal a T3SS-dependent hypervirulence phenotype in human-associated complex IV isolates, highlighting the need for further studies on the epidemiology and evolutionary dynamics of this B. bronchiseptica lineage. PMID:22863321

Improved Acoustic Blanket Developed and Tested

NASA Technical Reports Server (NTRS)

1996-01-01

Acoustic blankets are used in the payload fairing of expendable launch vehicles to reduce the fairing's interior acoustics and the subsequent vibration response of the spacecraft. The Cassini spacecraft, to be launched on a Titan IV in October 1997, requires acoustic levels lower than those provided by the standard Titan IV blankets. Therefore, new acoustic blankets were recently developed and tested to reach NASA's goal of reducing the Titan IV acoustic environment to the allowable levels for the Cassini spacecraft.

Retrospective Analysis of the Risk Factors for Grade IV Neutropenia in Oesophageal Cancer Patients Treated with a Docetaxel, Cisplatin, and 5-Fluorouracil Regimen.

PubMed

Naito, Masahito; Yamamoto, Tomoya; Shimamoto, Chikao; Miwa, Yoshihiro

2017-01-01

Previous Japanese trials of the docetaxel, cisplatin, and 5-fluorouracil regimen for oesophageal cancer have demonstrated that a large proportion of patients also develop grade IV neutropenia. Our aim was to examine the risk factors for neutropenia in patients treated with this regimen. We retrospectively analysed the risk factors for developing grade IV neutropenia in 66 patients with oesophageal cancer using a multivariate analysis. After administering the docetaxel, cisplatin, and 5-fluorouracil regimen, 49 patients (74.2%) developed grade IV neutropenia. Grade IV neutropenia was significantly associated with platelet count (p < 0.01), alanine transaminase level (p = 0.05), and proton-pump inhibitor administration (p < 0.05). Receiver operating characteristic curve analysis confirmed a platelet count of 290 × 103/μL as the optimal diagnostic cut-off value for grade IV neutropenia. The receiver operating characteristic area for grade IV neutropenia was increased by including patients that were administered a proton-pump inhibitor and alanine transaminase level (updated model; sensitivity and specificity, 75.5 and 88.2%, respectively). Our findings suggest that a platelet count is the most significant predictor of grade IV neutropenia. © 2017 S. Karger AG, Basel.

Heterogeneous levels of oxidative phosphorylation enzymes in rat adrenal glands.

PubMed

Ogawa, Koichi; Harada, Keita; Endo, Yutaka; Sagawa, Sueko; Inoue, Masumi

2011-01-01

Mitochondria are organelles that produce ATP and reactive oxygen species, which are thought to be responsible for a decline in physiological function with aging. In this study, we morphologically and biochemically examined mitochondria in the rat adrenal gland. Immunohistochemistry showed that the rank order for intensity of immunolabelling for complex IV was zona reticularis > zona fasciculata > adrenal medulla, whereas for complex V α and β subunits, it was zona fasciculata > zona reticularis and adrenal medulla. The immunolabelling for complex I was homogeneous in the adrenal gland. The difference in immunolabelling between complexes I and IV indicates that the ratio of levels of complex I to that of complex IV in the zona reticularis was smaller than that in the zona fasciculata and the adrenal medulla. Electron microscopy revealed that aging rats had zona reticularis cells with many lysosomes and irregular nuclei. The result suggests that the level of proteins involved in oxidative phosphorylation is coordinated within the complex, but differs between the complexes. This might be responsible for degeneration of zona reticularis cells with aging. Copyright © 2009 Elsevier GmbH. All rights reserved.

Irinotecan Loaded in Eluting Beads: Preclinical Assessment in a Rabbit VX2 Liver Tumor Model

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

Rao, Pramod P.; Pascale, Florentina; Seck, Atman

2012-12-15

Purpose: The purpose of this study was to study the pharmacokinetics of irinotecan injected intravenously, intra-arterially, or loaded onto a delivery platform. Material and Methods: Fifty-four New Zealand White rabbits with VX2 liver tumor, divided in 3 groups of 17 rabbits, each received irinotecan either by intravenous (IV) route, intra-arterial hepatic (IA) route, or loaded on drug-eluting beads (DEBIRI). Animals were killed at 1, 6, and 24 h. Irinotecan and SN-38 concentrations were measured at different time points in serum, tumor, and normal liver.ResultsTwelve milligrams of irinotecan were injected IV and IA, whereas 6-16.5 mg were injected loaded onto DEBIRI.more » Normalized serum irinotecan reached a peak of 333 ng/ml (range 198.8-502.5) for IV, 327.1 ng/ml (range 277.1-495.6) for IA, and 189.7 ng/ml (range 111.1-261.9) for DEBIRI (P < 0.001) delivery. The area-under-the-curve value from 10 to 60 min of serum irinotecan concentration was significantly lower for DEBIRI (P = 0.0009). Tumor irinotecan levels for IV, IA, and DEBIRI (in ng/200 mg of tissue followed by ranges in parentheses) were, respectively, 23.6 (0.3-24.9), 36.5 (7.7-1914.1), and 20.2 (2.9-319) at 1 h; 4.2 (1-27.9), 99.3 (46.6-159.5), and 42.1 (11.3-189) at 6 h; and 2.7 (2.5-6.9), 18.3 (1.5-369.1), and 174.4 (3.4-5147.3) at 24 h (P = 0.02). At 24 h, tumor necrosis was 25% (10-30), 60% (40-91.25), and 95% (76.25-95) for IV, IA, and DEBIRI, respectively (P = 0.03). Conclusion: Compared with IV or IA, DEBIRI induces lower early serum levels of irinotecan, a high and prolonged intratumoral level of irinotecan, and a greater rate of tumor necrosis at 24 h. Further evaluation of the clinical benefit of DEBIRI is warranted.« less

A clinicopathological study of the expression of extracellular matrix components in urothelial carcinoma.

PubMed

Ioachim, Elli; Michael, Michalis; Stavropoulos, Nicolaos E; Kitsiou, Evangelia; Salmas, Marios; Malamou-Mitsi, Vasiliki

2005-03-01

To measure the immunohistochemical expression of the extracellular matrix (ECM) components tenascin, fibronectin, collagen type IV and laminin in urothelial carcinomas, and to correlate their expression with clinicopathological features to clarify the prognostic value of these molecules and their role in tumour progression. Tumour specimens obtained during transurethral resection of bladder tumour (TURBT) from 103 patients (82 men and 2 1 women, mean age 66.7 years, range 27-89) were studied retrospectively. The expression of tenascin, fibronectin, collagen type IV and laminin was correlated with clinicopathological features (tumour grade and stage, multiplicity, simultaneous in situ component, the proliferative activity as estimated by the two proliferation associated indices, Ki-67 and proliferating cell nuclear antigen, the recurrence rate, and the progression of invading tumour). Specimens investigated for tenascin expression from patients with superficial bladder cancers were categorized into 28 treated by TURBT only and 53 who had TURBT followed by intravesical instillations of interferon. Cytoplasmic tenascin expression was detected in tumour cells in 20% of specimens. Tenascin was expressed in the tumour stroma in 76% of specimens, and was positively correlated with tumour grade and stage. Stromal tenascin expression was positively correlated with proliferative activity, and with the expression of fibronectin and collagen type IV. Fibronectin was expressed in the tumour stroma in 89% of specimens and was positively correlated with tumour stage, proliferative activity, and expression of collagen type IV and laminin. Collagen type IV was expressed in 93% of specimens, and was positively correlated with tumour grade and stage. Laminin was expressed in 78% of specimens and had no significant correlation with the clinicopathological features. Patients treated with TURBT alone and who had low levels of tenascin had a longer tumour-free interval than those with high levels of tenascin. Levels of tenascin might be valuable for predicting the risk of early recurrence. The expression of tenascin, fibronectin and collagen type IV seems to be correlated with more aggressive tumour behaviour. Furthermore, their interrelationships could indicate that they are involved in the remodelling of bladder cancer tissue, probably influencing tumour progression.

Apolipoprotein A-IV concentrations and clinical outcomes in haemodialysis patients with type 2 diabetes mellitus--a post hoc analysis of the 4D Study.

PubMed

Kollerits, B; Krane, V; Drechsler, C; Lamina, C; März, W; Ritz, E; Wanner, C; Kronenberg, F

2012-12-01

Apolipoprotein A-IV (apoA-IV) is an anti-atherogenic and anti-oxidative plasma glycoprotein involved in reverse cholesterol transport. The aim of this study was to examine the association between apoA-IV and all-cause mortality, cardiovascular endpoints and parameters of protein-energy wasting and nutrition in haemodialysis patients. This post hoc analysis was performed in the German Diabetes Dialysis Study (4D Study) evaluating atorvastatin in 1255 haemodialysis patients with type 2 diabetes mellitus, followed for a median of 4 years. The association between apoA-IV and relevant outcomes was analysed using Cox proportional hazards regression analyses. Body mass index (BMI) was used as a marker of protein-energy wasting. In addition, a definition of extended wasting was applied, combining median values of BMI, serum albumin, creatinine and sensitive C-reactive protein, to classify patients. Mean (±SD) apoA-IV concentration was 49.8 ± 14.2 mg dL(-1). Age- and gender-adjusted apoA-IV concentrations were strongly associated with the presence of congestive heart failure at baseline [odds ratio = 0.81, 95% confidence interval (CI) 0.74-0.88 per 10 mg dL(-1) increase; P < 0.001). During the prospective follow-up, the strongest association was found for all-cause mortality [hazard ratio (HR) = 0.89, 95% CI 0.85-0.95, P = 0.001), which was mainly because of patients with BMI > 23 kg m(-2) (HR = 0.87, 95% CI 0.82-0.94, P < 0.001) and those in the nonwasting group according to the extended definition (HR = 0.89, 95% CI 0.84-0.96, P = 0.001). This association remained significant after additionally adjusting for parameters associated with apoA-IV at baseline. Further associations were observed for sudden cardiac death. ApoA-IV was less strongly associated with atherogenic events such as myocardial infarction. Low apoA-IV levels seem to be a risk predictor of all-cause mortality and sudden cardiac death. This association might be modified by nutritional status. © 2012 The Association for the Publication of the Journal of Internal Medicine.

Determining the Effect of Gutkha on Serum Levels of Vitamin B12 and Folic Acid as Compared to Smoking among Chronic Periodontitis Subjects : A Cross-Sectional Study

PubMed Central

Warad, Shivaraj; Kalburgi, Nagaraj B; Kalburgi, Veena C; Koregol, Arati C; Patanashetti, Jyoti; Rao, Subramaniam; Kokatnur, M. Vijayalaxmi

2014-01-01

Background: Periodontitis, being a common inflammatory disease has a multifactorial origin , with smoking and gutkha as few of the causative entities. The role of smoking as a risk factor for periodontitis is been well documented in literature. Cigarette smoke also affects vitamin B12 and folic acid mechanisms. Nutritionally derived vitamin B12 occurs mainly as either hydroxycobalamin or deoxyadenosycobalmin. Folic acid is also heat sensitive and water soluble, closely linked to vitamin B12 in its metabolism. However, effect of smokeless tobacco in form of gutkha on serum levels of vitamin B12 and folic acid is yet to be explored. Aims and Objectives: To estimate and correlate serum vitamin B12 (VB12) and folic acid (FA) levels among periodontally healthy subjects and Chronic Periodontitis (CP) subjects with habit of smoking and gutkha chewing. Materials and Methods: The study included 111 subjects ranging in age from 18 to 60 y. Participants were divided into four groups: 30 healthy subjects (Group I), 29 subjects with CP (Group II), 25 smokers with CP (Group III) and 27 gutkha chewers with CP (Group IV). Clinical parameters included pocket probing depth (PPD), clinical attachment level (CAL) & gingival index (GI) following which VB12 and FA levels were estimated through UV-spectrophotometry method and data was analysed using Statistical Package for Social Scientists software, Mann-Whitney U-test and Pearson correlation coefficient. p-values less than 0.05 were considered as significant. Results : Pairwise comparison by Mann-Whitney U-test showed an increase in the serum VB12 in Group IV when compared to Group I (p=0.01) and Group II (p=0.01). Although serum FA levels were found to be low in Group III (7.61 ug/ml) & Group IV (8.64 ug/ml), Group III was found to be statistically significant (P=0.046). The clinical parameters GI, PPD and CAL among the four groups of patients were also statistically significant (p < 0.05). Conclusion: The study results suggested that among the patients with periodontal disease, serum VB12 levels are directly related while serum FA levels are inversely related to inflammation and tissue destruction in periodontium as occurred in Group IV. PMID:25654040

Outerbridge Grade IV Cartilage Lesions in the Hip Identified at Arthroscopy.

PubMed

Bhatia, Sanjeev; Nowak, Douglas D; Briggs, Karen K; Patterson, Diana C; Philippon, Marc J

2016-05-01

To determine factors associated with grade IV cartilage defects in the hip in patients undergoing hip arthroscopy with joint pain. Data from consecutive patients who underwent hip arthroscopy performed by a single surgeon over a period of 4 years were included in this study. The study group included 1,097 patients (491 women and 606 men; mean age, 37 years) who underwent hip arthroscopy for pain, had no prior hip surgery, and were aged 18 years or older. Preoperative radiographs, patient demographic characteristics, and operative details were used to identify risk factors for cartilage defects. Grade IV chondral defects were present in 308 of 1,097 hips (28%). Isolated chondral lesions were more frequently observed on the acetabulum (76%) than on the femoral head (24%). Defects of the acetabulum were more commonly anterosuperior (94.7%) and less commonly posterolateral (5.3%). Patients with less than 2 mm of joint space on preoperative radiographs were 8 times more likely to have a grade IV lesion than those with more than 2 mm. Men were more likely than women to have grade IV lesions (35% v 19%, P = .0001); patients with grade IV lesions were older than those without (42 years v 34 years, P = .0001). Hips with grade IV lesions had significantly higher alpha angles than those without (74° v 70°, P = .0001). Patients with grade IV defects reported a longer duration of symptoms than those without (37 months v 27 months, P = .007). Independent risk factors for the presence of grade IV chondral defects were less than 2 mm of joint space, male gender, increasing age, larger alpha angle, and longer duration of symptoms. Grade IV chondral defects in patients undergoing hip arthroscopy were associated with decreased joint space, increased time from symptom onset to arthroscopy, male gender, and larger alpha angles associated with femoroacetabular impingement. Level IV, prognostic case series. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Mapping of epitopes and structural analysis of antigenic sites in the nucleoprotein of rabies virus.

PubMed

Goto, H; Minamoto, N; Ito, H; Ito, N; Sugiyama, M; Kinjo, T; Kawai, A

2000-01-01

Linear epitopes on the rabies virus nucleoprotein (N) recognized by six MAbs raised against antigenic sites I (MAbs 6-4, 12-2 and 13-27) and IV (MAbs 6-9, 7-12 and 8-1) were investigated. Based on our previous studies on sites I and IV, 24 consecutively overlapping octapeptides and N- and C-terminal-deleted mutant N proteins were prepared. Results showed that all three site I epitopes studied and two site IV epitopes (for MAbs 8-1 and 6-9) mapped to aa 358-367, and that the other site IV epitope of MAb 7-12 mapped to aa 375-383. Tests using chimeric and truncated proteins showed that MAb 8-1 also requires the N-terminal sequence of the N protein to recognize its binding region more efficiently. Immunofluorescence studies demonstrated that all three site I-specific MAbs and one site IV-specific MAb (7-12) stained the N antigen that was diffusely distributed in the whole cytoplasm; the other two site IV-specific MAbs (6-9 and 8-1) detected only the N antigen in the cytoplasmic inclusion bodies (CIB). An antigenic site II-specific MAb (6-17) also detected CIB-associated N antigen alone. Furthermore, the level of diffuse N antigens decreased after treatment of infected cells with cycloheximide. These results suggest that epitopes at site I are expressed on the immature form of the N protein, but epitope structures of site IV MAbs 6-9 and 8-1 are created and/or exposed only after maturation of the N protein.

A protocol for the 0.9% saline versus Plasma-Lyte 148 for intensive care fluid therapy (SPLIT) study.

PubMed

Reddy, Sumeet K; Bailey, Michael J; Beasley, Richard W; Bellomo, Rinaldo; Henderson, Seton J; Mackle, Diane M; McArthur, Colin J; Mehrtens, Jan E; Myburgh, John A; McGuinness, Shay P; Psirides, Alex J; Young, Paul J

2014-12-01

0.9% saline is the most commonly used intravenous (IV) fluid in the world. However, recent data raise the possibility that, compared with buffered crystalloid fluids such as Plasma-Lyte 148, the administration of 0.9% saline to intensive care unit patients might increase their risk of acute kidney injury (AKI). To describe the protocol for the 0.9% Saline v Plasma-Lyte 148 for ICU Fluid Therapy (SPLIT) study. This is a multicentre, cluster-randomised, double crossover feasibility study to be conducted in four New Zealand tertiary ICUs over a 28-week period and will enroll about 2300 participants. All ICU patients who need crystalloid IV fluid therapy (except those with established renal failure needing dialysis and those admitted to the ICU for palliative care) will be enrolled. Participating ICUs will be randomly assigned to 0.9% saline or Plasma-Lyte 148 as the routine crystalloid IV fluid, in a blinded fashion, in four alternating 7-week blocks. The primary outcome will be the proportion of patients who develop AKI in the ICU. Secondary outcomes will include the difference between the most recent serum creatinine level measured before study enrollment and the peak serum creatinine level in the ICU; use of renal replacement therapy; and ICU and in hospital mortality. All analyses will be conducted on an intention-to-treat basis. The SPLIT study started on 1 April 2014 and will provide preliminary data on the comparative effectiveness of using 0.9% saline v Plasma- Lyte 148 as the routine IV fluid therapy in ICU patients.

Efficacy and safety of i.v. sodium benzoate in urea cycle disorders: a multicentre retrospective study.

PubMed

Husson, Marie-Caroline; Schiff, Manuel; Fouilhoux, Alain; Cano, Aline; Dobbelaere, Dries; Brassier, Anais; Mention, Karine; Arnoux, Jean-Baptiste; Feillet, François; Chabrol, Brigitte; Guffon, Nathalie; Elie, Caroline; de Lonlay, Pascale

2016-09-23

The efficacy and safety of intra-venous (i.v.) sodium benzoate for treating acute episodes of hyperammonemia in urea cycle enzyme disorders (UCD) is well known. However, published data do not provide a clear picture of the benefits and risks of this drug. We report a retrospective multicentre study on the use of i.v. sodium benzoate in patients treated for UCD between 2000 and 2010 in the 6 French reference centres for metabolic diseases. Sixty-one patients with UCDs - 22 ornithine transcarbamylase (20 confirmed, 2 suspected), 18 arginino-succinate synthetase, 15 carbamoyl phosphate synthetase, 3 arginosuccinate lyase, 1 arginase deficiency, 1 N-acetylglutamate synthetase, 1 HHH syndrome - required i.v. sodium benzoate over the course of 95 acute episodes (NH3 > 100 μmol/L or high-risk situations, i.e., gastroenteritis, surgery). Forty out of 61 patients experienced only one episode of decompensation (neonatal coma, 68.6 %). The most frequent cause of late decompensation was infection (55.5 %). A loading dose of i.v. sodium benzoate (median 250 mg/kg over 2 h) was administered for 41/95 acute episodes. The median maintenance dose was 246.1 mg/kg/day, administered via peripheral venous infusion in all cases except one via a central line. The total median duration of i.v. sodium benzoate treatment per episode was 2 days (0-13 days). The median durations of hospitalization in intensive care and metabolic units were 4 days (0-17 days) and 10 days (0-70 days), respectively. Eight patients died during the neonatal coma (n = 6) or surgery (n = 2). The median plasma ammonium level before treatment was 245.5 μmol/L (20.0-2274.0 μmol/L); it decreased to 40.0 μmol/L in patients who were alive (13.0-181.0 μmol/L) at the end of treatment with i.v. sodium benzoate. A decrease in ammonium level to ≤ 100 μmol/L was obtained in 92.8 % of episodes (64/69 of the episodes recorded for the 53 surviving patients). Five patients required another treatment for hyperammonemia (sodium phenylacetate + sodium benzoate, haemofiltration). Eighteen side effects were reported related to the i.v. infusion (local diffusion, oedema). This 10-year retrospective study shows that i.v. sodium benzoate associated with an emergency regimen is an effective and safe treatment for acute episodes of UCD.

Investigation of the factor structure of the Wechsler Adult Intelligence Scale--Fourth Edition (WAIS-IV): exploratory and higher order factor analyses.

PubMed

Canivez, Gary L; Watkins, Marley W

2010-12-01

The present study examined the factor structure of the Wechsler Adult Intelligence Scale--Fourth Edition (WAIS-IV; D. Wechsler, 2008a) standardization sample using exploratory factor analysis, multiple factor extraction criteria, and higher order exploratory factor analysis (J. Schmid & J. M. Leiman, 1957) not included in the WAIS-IV Technical and Interpretation Manual (D. Wechsler, 2008b). Results indicated that the WAIS-IV subtests were properly associated with the theoretically proposed first-order factors, but all but one factor-extraction criterion recommended extraction of one or two factors. Hierarchical exploratory analyses with the Schmid and Leiman procedure found that the second-order g factor accounted for large portions of total and common variance, whereas the four first-order factors accounted for small portions of total and common variance. It was concluded that the WAIS-IV provides strong measurement of general intelligence, and clinical interpretation should be primarily at that level.

Comparison of Depression and Burnout Levels of Mothers of Children with Attention-Deficit Hyperactivity Disorder Before and After Treatment.

PubMed

Gokcen, Cem; Coskun, Seyma; Kutuk, Meryem Ozlem

2018-06-01

This study aimed to compare the depression and burnout levels of mothers of children having attention-deficit/hyperactivity disorder (ADHD) between the child's pre- and posttreatment periods. The study sample consisted of 40 children aged between 4 and 10 years and their mothers. Initially, 40 cases participated, but during the follow-up, 19 cases dropped out. The Beck Depression Inventory (BDI), the Maslach Burnout Inventory (MBI), and the Turgay DSM-IV Based Child and Adolescent Behaviour Disorders Screening and Rating Scale (T-DSM-IV-S) were used. Among the mothers, posttreatment BDI scores, MBI-emotional exhaustion, and personal accomplishment were significantly lower than the pretreatment scores. In the treatment's second month, all T-DSM-IV-S subscale scores showed a statistically significant decrease. It was concluded that treatment of children with ADHD would have a favorable impact on their mothers' depressive symptoms, which would consequently decrease negative parental attitudes, hence reducing the risk of behavioral disorder in children with ADHD and exerting a positive effect on their treatment.

Prevalence of and Risk Factors for Asymptomatic Inflammatory (NIH-IV) Prostatitis in Chinese Men

PubMed Central

Wu, Chunlei; Zhang, Zhifu; Lu, Zheng; Liao, Ming; Zhang, Youjie; Xie, Yuanliang; Guo, Xuefeng; Yu, Xiaoxiang; Yang, Xiaobo; Gao, Yong; Tan, Aihua; Mo, Zengnan

2013-01-01

Background While many investigators have studied symptomatic prostatitis, little research has been done with regard to asymptomatic (NIH-IV) prostatitis. Purpose To describe the prevalence of and risk factors for NIH-IV prostatitis among a large male population. Methods The study population was comprised of 1,868 men at the second phase recruitment of a population-based cohort in China. Asymptomatic and symptomatic men were defined by the National Institutes of Health Chronic Prostatitis (CP) Symptom Index. Meanwhile, EPS specimens and their leukocyte count were collected. Lifestyle and demographic characteristics were obtained through a questionnaire. Results Prevalence of NIH-IV prostatitis was 21.1% among 1,868 asymptomatic men aged 19–78 years and increased with age. After adjusteing for potential confounding variables (age, smoking habits, alcohol drinking habits, education, physical activity, hypertension, dyslipidemia, obesity and diabetes), age remained a significant factor for NIH-IV prostatitis (OR = 1.35; 95% CI = 1.06–1.71; P = 0.01) and the risk of NIH-IV prostatitis was significantly higher in smokers≧15 pack/years than non-smokers (OR = 1.33; 95% CI = 1.01–1.75; P = 0.03). In addition, compared with non-drinkers, the OR of NIH-IV prostatitis in drinkers ≧1 drinks/week was 1.35 (95% CI = 1.03, 1.77, p = 0.02) after adjusting for the other variables above. In addition, having less than a college education may be a risk factor for NIH-IV prostatitis, although a statistically significant difference did not exist in our data (OR = 1.22; 95% CI = 0.97–1.52; P = 0.08). Conclusions Our findings suggest that NIH-IV prostatitis is prevalent in China. Age, smoking, drinking and lower education levels were associated with an increased risk of NIH-IV prostatitis. The prevalence of NIH-IV prostatitis should be taken into account when estimating the total prevalence of CP in future studies. PMID:23967188

LPA and PLG sequence variation and kringle IV-2 copy number in two populations.

PubMed

Crawford, Dana C; Peng, Ze; Cheng, Jan-Fang; Boffelli, Dario; Ahearn, Magdalena; Nguyen, Dan; Shaffer, Tristan; Yi, Qian; Livingston, Robert J; Rieder, Mark J; Nickerson, Deborah A

2008-01-01

Lp(a) levels have long been recognized as a potential risk factor for coronary heart disease that is almost completely under genetic control. Much of the genetics impacting Lp(a) levels has been attributed to the highly polymorphic LPA kringle IV-2 copy number variant, and most of the variance in Lp(a) levels in populations of European-descent is inversely correlated with kringle IV copy number. However, less of the variance is explained in African-descent populations for the same structural variation. African-descent populations have, on average, higher levels of Lp(a), suggesting other genetic factors contribute to Lp(a) level variability across populations. To identify potential cis-acting factors, we re-sequenced the gene LPA for single nucleotide polymorphism (SNP) discovery in 23 European-Americans and 24 African-Americans. We also re- sequenced the neighboring gene plasminogen (PLG) and genotyped the kringle IV copy number variant in the same reference samples. These data are the most comprehensive description of sequence variation in LPA and its relationship with the kringle IV copy number variant. With these data, we demonstrate that only a fraction of LPA sequence diversity has been previously documented. Also, we identify several high frequency SNPs present in the African-American sample but absent in the European-American sample. Finally, we show that SNPs within PLG are not in linkage disequilibrium with SNPs in LPA, and we show that kringle IV copy number variation is not in linkage disequilibrium with either LPA or PLG SNPs. Together, these data suggest that LPA SNPs could independently contribute to Lp(a) levels in the general population. Copyright (c) 2008 S. Karger AG, Basel.

Maternal intravenous treatment with either azithromycin or solithromycin clears Ureaplasma parvum from the amniotic fluid in an ovine model of intrauterine infection.

PubMed

Miura, Yuichiro; Payne, Matthew S; Keelan, Jeffrey A; Noe, Andres; Carter, Sean; Watts, Rory; Spiller, Owen B; Jobe, Alan H; Kallapur, Suhas G; Saito, Masatoshi; Stock, Sarah J; Newnham, John P; Kemp, Matthew W

2014-09-01

Intrauterine infection with Ureaplasma spp. is strongly associated with preterm birth and adverse neonatal outcomes. We assessed whether combined intraamniotic (IA) and maternal intravenous (IV) treatment with one of two candidate antibiotics, azithromycin (AZ) or solithromycin (SOLI), would eradicate intrauterine Ureaplasma parvum infection in a sheep model of pregnancy. Sheep with singleton pregnancies received an IA injection of U. parvum serovar 3 at 85 days of gestational age (GA). At 120 days of GA, animals (n=5 to 8/group) received one of the following treatments: (i) maternal IV SOLI with a single IA injection of vehicle (IV SOLI only); (ii) maternal IV SOLI with a single IA injection of SOLI (IV+IA SOLI); (iii) maternal IV AZ and a single IA injection of vehicle (IV AZ only); (iv) maternal IV AZ and a single IA injection of AZ (IV+IA AZ); or (v) maternal IV and single IA injection of vehicle (control). Lambs were surgically delivered at 125 days of GA. Treatment efficacies were assessed by U. parvum culture, quantitative PCR, enzyme-linked immunosorbent assay, and histopathology. Amniotic fluid (AF) from all control animals contained culturable U. parvum. AF, lung, and chorioamnion from all AZ- or SOLI-treated animals (IV only or IV plus IA) were negative for culturable U. parvum. Relative to the results for the control, the levels of expression of interleukin 1β (IL-1β), IL-6, IL-8, and monocyte chemoattractant protein 2 (MCP-2) in fetal skin were significantly decreased in the IV SOLI-only group, the MCP-1 protein concentration in the amniotic fluid was significantly increased in the IV+IA SOLI group, and there was no significant difference in the histological inflammation scoring of lung or chorioamnion among the five groups. In the present study, treatment with either AZ or SOLI (IV only or IV+IA) effectively eradicated macrolide-sensitive U. parvum from the AF. There was no discernible difference in antibiotic therapy efficacy between IV-only and IV+IA treatment regimens relative to the results for the control. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Effect of insulin on human skeletal muscle mitochondrial ATP production, protein synthesis, and mRNA transcripts

NASA Astrophysics Data System (ADS)

Stump, Craig S.; Short, Kevin R.; Bigelow, Maureen L.; Schimke, Jill M.; Sreekumaran Nair, K.

2003-06-01

Mitochondria are the primary site of skeletal muscle fuel metabolism and ATP production. Although insulin is a major regulator of fuel metabolism, its effect on mitochondrial ATP production is not known. Here we report increases in vastus lateralis muscle mitochondrial ATP production capacity (32-42%) in healthy humans (P < 0.01) i.v. infused with insulin (1.5 milliunits/kg of fat-free mass per min) while clamping glucose, amino acids, glucagon, and growth hormone. Increased ATP production occurred in association with increased mRNA levels from both mitochondrial (NADH dehydrogenase subunit IV) and nuclear [cytochrome c oxidase (COX) subunit IV] genes (164-180%) encoding mitochondrial proteins (P < 0.05). In addition, muscle mitochondrial protein synthesis, and COX and citrate synthase enzyme activities were increased by insulin (P < 0.05). Further studies demonstrated no effect of low to high insulin levels on muscle mitochondrial ATP production for people with type 2 diabetes mellitus, whereas matched nondiabetic controls increased 16-26% (P < 0.02) when four different substrate combinations were used. In conclusion, insulin stimulates mitochondrial oxidative phosphorylation in skeletal muscle along with synthesis of gene transcripts and mitochondrial protein in human subjects. Skeletal muscle of type 2 diabetic patients has a reduced capacity to increase ATP production with high insulin levels. cytochrome c oxidase | NADH dehydrogenase subunit IV | amino acids | citrate synthase

Methylation of CIITA promoter IV causes loss of HLA-II inducibility by IFN-γ in promyelocytic cells

PubMed Central

De Ambrosis, Alessandro; Banelli, Barbara; Pira, Giuseppina Li; Aresu, Ottavia; Romani, Massimo; Ferrini, Silvano; Accolla, Roberto S.

2008-01-01

The human promyelocytic cell line THP-1 expresses high level of HLA class II (HLA-II) molecules after IFN-γ treatment. Here, we report a variant of THP-1 that does not express HLA-II after IFN-γ. The variant's HLA-II phenotype is constant over time in culture and it is not related to a defective IFN-γ-signalling pathway. Transfection of CIITA, the HLA-II transcriptional activator, under the control of a cytomegalovirus promoter rescues high level of HLA-DR surface expression in the variant indicating that the biosynthetic block resides in the expression of CIITA and not in the CIITA-dependent transactivation of the HLA-II promoters. Treatment of the variant with 5-azacytidine (5-aza), which inhibits CpG methylation, restores inducibility of HLA-II by IFN-γ both at transcriptional and phenotypic level and antigen presenting and processing function of the variant. DNA studies demonstrate that the molecular defect of the THP-1 variant originates from the methylation of the CIITA promoter IV. Furthermore, treatment with 5-aza produces a substantial demethylation of CIITA promoter IV and a significant increase of IFN-γ-dependent HLA-II expression in another myelomonocytic cell line, U937. Therefore hyper-methylation of CIITA promoter IV may be a relevant mechanism of epigenetic control preventing HLA-II IFN-γ inducibility in the myelomonocytic cell lineage. PMID:18829986

Prolyl oligopeptidase and dipeptidyl peptidase II/dipeptidyl peptidase IV ratio in the cerebrospinal fluid in Parkinson's disease: historical overview and future prospects.

PubMed

Nagatsu, Toshiharu

2017-06-01

Prolyl oligopeptidase (also named prolyl endopeptidase; PREP) hydrolyzes the Pro-Xaa bonds of biologically active oligopeptides on their carboxyl side. In 1987, we detected PREP activity in human cerebrospinal fluid (CSF) using highly sensitive liquid chromatography-fluorometry with succinyl-Gly-Pro-4-methyl-coumarin amide as a new synthetic substrate, and found a marked decrease in its activity in the cerebrospinal fluid (CSF) from patients with Parkinson's disease (PD) as compared with its level in control patients without neurological diseases. In 2013, Hannula et al. found co-localization of PREP with α-synuclein in the postmortem PD brain. Several recent studies also suggest that the level of PREP in the brain of PD patients may be related to dopamine (DA) cell death via promotion of α-synuclein oligomerization and that inhibitors of PREP may play a neuroprotective role in PD. Although the relationship between another family of prolyl oligopeptidase enzymes, dipeptidyl peptidase II (DPP II) and dipeptidyl peptidase IV (DPP IV), and α-synuclein in the PD brain is not yet clear, we found that the DPP II activity/DPP IV activity ratio in the CSF was significantly increased in PD patients. This review discusses the possibility of PREP as well as the DPP II/DPP IV ratio in the CSF as potential biomarkers of PD.

Nutrient-dependent increased dendritic arborization of somatosensory neurons.

PubMed

Watanabe, Kaori; Furumizo, Yuki; Usui, Tadao; Hattori, Yukako; Uemura, Tadashi

2017-01-01

Suboptimal nutrition imposes developmental constraints on infant animals, which marshal adaptive responses to eventually become mature adults. Such responses are mounted at multiple levels from systemic to cellular. At the cellular level, the underlying mechanisms of cell proliferation control have been intensively studied. However, less is known about how growth of postmitotic and morphologically complex cells, such as neurons, is controlled by nutritional status. We address this question using Class I and Class IV dendritic arborization neurons in Drosophila larvae. Class IV neurons have been shown to sense nociceptive thermal, mechanical and light stimuli, whereas Class I neurons are proprioceptors. We reared larvae on diets with different protein and carbohydrate content throughout larval stages and examined how morphologies of Class I or Class IV neurons were affected. Dendritic arbors of Class IV neurons became more complex when larvae were reared on a low-yeast diet, which contains lower amounts of amino acids and other ingredients, compared to a high-yeast diet. In contrast, such low-yeast-dependent hyperarborization was not seen in Class I neurons. The physiological and metabolic implications of the hyperarborization phenotype are discussed in relation to a recent hypothesis that Class IV neurons sense protein-deficient stress and to our characterization of how the dietary yeast contents impacted larval metabolism. © 2016 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

Vitamin D Status in Patients With Stage IV Colorectal Cancer: Findings From Intergroup Trial N9741

PubMed Central

Ng, Kimmie; Sargent, Daniel J.; Goldberg, Richard M.; Meyerhardt, Jeffrey A.; Green, Erin M.; Pitot, Henry C.; Hollis, Bruce W.; Pollak, Michael N.; Fuchs, Charles S.

2011-01-01

Purpose Previous studies have suggested that higher plasma 25-hydroxyvitamin D3 [25(OH)D] levels are associated with decreased colorectal cancer risk and improved survival, but the prevalence of vitamin D deficiency in advanced colorectal cancer and its influence on outcomes are unknown. Patients and Methods We prospectively measured plasma 25(OH)D levels in 515 patients with stage IV colorectal cancer participating in a randomized trial of chemotherapy. Vitamin D deficiency was defined as 25(OH)D lower than 20 ng/mL, insufficiency as 20 to 29 ng/mL, and sufficiency as ≥ 30 ng/mL. We examined the association between baseline 25(OH)D level and selected patient characteristics. Cox proportional hazards models were used to calculate hazard ratios (HR) for death, disease progression, and tumor response, adjusted for prognostic factors. Results Among 515 eligible patients, 50% of the study population was vitamin D deficient, and 82% were vitamin D insufficient. Plasma 25(OH)D levels were lower in black patients compared to white patients and patients of other race (median, 10.7 v 21.1 v 19.3 ng/mL, respectively; P < .001), and females compared to males (median, 18.3 v 21.7 ng/mL, respectively; P = .0005). Baseline plasma 25(OH)D levels were not associated with patient outcome, although given the distribution of plasma levels in this cohort, statistical power for survival analyses were limited. Conclusion Vitamin D deficiency is highly prevalent among patients with stage IV colorectal cancer receiving first-line chemotherapy, particularly in black and female patients. PMID:21422438

Vitamin D status in patients with stage IV colorectal cancer: findings from Intergroup trial N9741.

PubMed

Ng, Kimmie; Sargent, Daniel J; Goldberg, Richard M; Meyerhardt, Jeffrey A; Green, Erin M; Pitot, Henry C; Hollis, Bruce W; Pollak, Michael N; Fuchs, Charles S

2011-04-20

Previous studies have suggested that higher plasma 25-hydroxyvitamin D(3) [25(OH)D] levels are associated with decreased colorectal cancer risk and improved survival, but the prevalence of vitamin D deficiency in advanced colorectal cancer and its influence on outcomes are unknown. We prospectively measured plasma 25(OH)D levels in 515 patients with stage IV colorectal cancer participating in a randomized trial of chemotherapy. Vitamin D deficiency was defined as 25(OH)D lower than 20 ng/mL, insufficiency as 20 to 29 ng/mL, and sufficiency as ≥ 30 ng/mL. We examined the association between baseline 25(OH)D level and selected patient characteristics. Cox proportional hazards models were used to calculate hazard ratios (HR) for death, disease progression, and tumor response, adjusted for prognostic factors. Among 515 eligible patients, 50% of the study population was vitamin D deficient, and 82% were vitamin D insufficient. Plasma 25(OH)D levels were lower in black patients compared to white patients and patients of other race (median, 10.7 v 21.1 v 19.3 ng/mL, respectively; P < .001), and females compared to males (median, 18.3 v 21.7 ng/mL, respectively; P = .0005). Baseline plasma 25(OH)D levels were not associated with patient outcome, although given the distribution of plasma levels in this cohort, statistical power for survival analyses were limited. Vitamin D deficiency is highly prevalent among patients with stage IV colorectal cancer receiving first-line chemotherapy, particularly in black and female patients.

An Analysis of Type IV Precision Measurement Equipment Laboratory Logistical Support Relative to the Implementation of F-15/F-16 Two-Level Maintenance

DTIC Science & Technology

1994-09-01

wife, Margie, for her patience and understanding. Graduate school definitely affects the family . Margie allowed me to use many valuable family hours...Consolidations and reorganizations, in which the face of logistics is changing day -by- day , are taking place throughout the Department of Defense. Two...will focus on Type IV F-15 and Type IV F-16 PMELs. Imporane of Research The two-level maintenance concept significantly alters the structure of

GENES AS INSTRUMENTS FOR STUDYING RISK BEHAVIOR EFFECTS: AN APPLICATION TO MATERNAL SMOKING AND OROFACIAL CLEFTS

PubMed Central

Jugessur, Astanand; Murray, Jeffrey C.; Moreno, Lina; Wilcox, Allen; Lie, Rolv T.

2011-01-01

This study uses instrumental variable (IV) models with genetic instruments to assess the effects of maternal smoking on the child’s risk of orofacial clefts (OFC), a common birth defect. The study uses genotypic variants in neurotransmitter and detoxification genes relateded to smoking as instruments for cigarette smoking before and during pregnancy. Conditional maximum likelihood and two-stage IV probit models are used to estimate the IV model. The data are from a population-level sample of affected and unaffected children in Norway. The selected genetic instruments generally fit the IV assumptions but may be considered “weak” in predicting cigarette smoking. We find that smoking before and during pregnancy increases OFC risk substantially under the IV model (by about 4–5 times at the sample average smoking rate). This effect is greater than that found with classical analytic models. This may be because the usual models are not able to consider self-selection into smoking based on unobserved confounders, or it may to some degree reflect limitations of the instruments. Inference based on weak-instrument robust confidence bounds is consistent with standard inference. Genetic instruments may provide a valuable approach to estimate the “causal” effects of risk behaviors with genetic-predisposing factors (such as smoking) on health and socioeconomic outcomes. PMID:22102793

49 CFR 555.6 - Basis for application.

Code of Federal Regulations, 2011 CFR

2011-10-01

... achieved either by design changes or termination of production of nonconforming vehicles; and (v) The total... failure to meet the standard, expressed as comparative performance levels; and (iv) Reasons why the... standard, expressed as comparative performance levels; (iv) The results of any tests conducted on the...

49 CFR 555.6 - Basis for application.

Code of Federal Regulations, 2013 CFR

2013-10-01

... achieved either by design changes or termination of production of nonconforming vehicles; and (v) The total... failure to meet the standard, expressed as comparative performance levels; and (iv) Reasons why the... standard, expressed as comparative performance levels; (iv) The results of any tests conducted on the...

49 CFR 555.6 - Basis for application.

Code of Federal Regulations, 2012 CFR

2012-10-01

... achieved either by design changes or termination of production of nonconforming vehicles; and (v) The total... failure to meet the standard, expressed as comparative performance levels; and (iv) Reasons why the... standard, expressed as comparative performance levels; (iv) The results of any tests conducted on the...

49 CFR 555.6 - Basis for application.

Code of Federal Regulations, 2010 CFR

2010-10-01

... achieved either by design changes or termination of production of nonconforming vehicles; and (v) The total... failure to meet the standard, expressed as comparative performance levels; and (iv) Reasons why the... standard, expressed as comparative performance levels; (iv) The results of any tests conducted on the...

49 CFR 555.6 - Basis for application.

Code of Federal Regulations, 2014 CFR

2014-10-01

... achieved either by design changes or termination of production of nonconforming vehicles; and (v) The total... failure to meet the standard, expressed as comparative performance levels; and (iv) Reasons why the... standard, expressed as comparative performance levels; (iv) The results of any tests conducted on the...

7 CFR 760.633 - 2008 SURE guarantee calculation.

Code of Federal Regulations, 2010 CFR

2010-01-01

... percent of the NAP established price for the crop; (2) Coverage level in § 760.631(a)(1)(iv) is 70 percent... the NAP established price for the crop; and (ii) Coverage level in §§ 760.631(a)(1)(iv) and 760.634(a...

Temporal Synchronization Analysis for Improving Regression Modeling of Fecal Indicator Bacteria Levels

EPA Science Inventory

Multiple linear regression models are often used to predict levels of fecal indicator bacteria (FIB) in recreational swimming waters based on independent variables (IVs) such as meteorologic, hydrodynamic, and water-quality measures. The IVs used for these analyses are traditiona...

How can we improve stroke thrombolysis rates? A review of health system factors and approaches associated with thrombolysis administration rates in acute stroke care.

PubMed

Paul, Christine L; Ryan, Annika; Rose, Shiho; Attia, John R; Kerr, Erin; Koller, Claudia; Levi, Christopher R

2016-04-08

Thrombolysis using intravenous (IV) tissue plasminogen activator (tPA) is one of few evidence-based acute stroke treatments, yet achieving high rates of IV tPA delivery has been problematic. The 4.5-h treatment window, the complexity of determining eligibility criteria and the availability of expertise and required resources may impact on treatment rates, with barriers encountered at the levels of the individual clinician, the social context and the health system itself. The review aimed to describe health system factors associated with higher rates of IV tPA administration for ischemic stroke and to identify whether system-focussed interventions increased tPA rates for ischemic stroke. Published original English-language research from four electronic databases spanning 1997-2014 was examined. Observational studies of the association between health system factors and tPA rates were described separately from studies of system-focussed intervention strategies aiming to increase tPA rates. Where study outcomes were sufficiently similar, a pooled meta-analysis of outcomes was conducted. Forty-one articles met the inclusion criteria: 7 were methodologically rigorous interventions that met the Cochrane Collaboration Evidence for Practice and Organization of Care (EPOC) study design guidelines and 34 described observed associations between health system factors and rates of IV tPA. System-related factors generally associated with higher IV tPA rates were as follows: urban location, centralised or hub and spoke models, treatment by a neurologist/stroke nurse, in a neurology department/stroke unit or teaching hospital, being admitted by ambulance or mobile team and stroke-specific protocols. Results of the intervention studies suggest that telemedicine approaches did not consistently increase IV tPA rates. Quality improvement strategies appear able to provide modest increases in stroke thrombolysis (pooled odds ratio = 2.1, p = 0.05). In order to improve IV tPA rates in acute stroke care, specific health system factors need to be targeted. Multi-component quality improvement approaches can improve IV tPA rates for stroke, although more thoughtfully designed and well-reported trials are required to safely increase rates of IV tPA to eligible stroke patients.

CSF drug levels for children with acute lymphoblastic leukemia treated by 5 g/m2 methotrexate. A study from the EORTC Children's Leukemia Cooperative Group.

PubMed

Milano, G; Thyss, A; Serre Debeauvais, F; Laureys, G; Benoit, Y; Deville, A; Dutour, C; Robert, A; Otten, J; Behar, C

1990-04-01

A multicenter EORTC study was conducted in children with acute lymphocytic leukemia to determine whether 5 g/m2 of methotrexate (MTX) (24 h i.v. infusion, four cycles) is an appropriate dosage for obtaining CSF drug concentrations approaching the critical cytotoxic level of 10(-6) M. A total of 193 cycles were analyzed for 58 patients. At the end of the 24 h infusion, the mean MTX serum level was 65.27 +/- 33.11 microM; the mean CSF MTX level was 1.47 +/- 1.1 microM; no significant difference in CSF MTX levels was observed between patients with (n = 20) and those without i.v. Ara-C (n = 38). The mean CSF MTX/serum MTX ratio was 0.029 +/- 0.027. CSF drug concentrations greater than or equal to 10(-6) M were achieved in 81% of the courses. The highest level was 8.4 X 10(-6) M. Only 5% of patients failed to achieve this drug concentration in at least one cycle. No significant correlation was observed between blood and CSF MTX levels. Mean CSF MTX levels were comparable from one cycle to another.

A toxicity profile of osteoprotegerin in the cynomolgus monkey.

PubMed

Smith, Brenda B; Cosenza, Mary Ellen; Mancini, Audrey; Dunstan, Colin; Gregson, Richard; Martin, Steven W; Smith, Susan Y; Davis, Harold

2003-01-01

Osteoprotegerin (OPG) is a novel secreted glycoprotein of the tumor necrosis factor (TNF) receptor superfamily that acts as an antiresorptive agent inhibiting osteoclast maturation. OPG acts by competitively inhibiting the association of the OPG ligand with the RANK receptor on osteoclasts and osteoclast precursors. This inhibition of osteoclasts can lead to excess accumulation of newly synthesized bone and cartilage in vivo. The purpose of this study was to investigate the potential toxicity of a human recombinant form of OPG in the young cynomolgus monkey. OPG was administered by intravenous (i.v.) or subcutaneous (s.c.) injection three times per week for either 4 or 13 weeks. There were no deaths during the study, no clinical signs related to treatment, no effect on body weight, appetence, or ophthalmology. No toxicologically relevant changes in routine laboratory investigations, organ weights, or gross or histopathological findings were observed. Serum ionized calcium and phosphorus were decreased at all dose levels. Evaluations were performed to monitor biochemical markers of bone resorption (N-telopeptide [NTx], deoxypyridinoline [DPD]), bone formation (skeletal alkaline phosphatase [sALP], osteocalcin [OC]), parathyroid hormone [PTH], and bone density of the proximal tibia and distal radius in vivo. Dose-related decreases in NTx and/or DPD were observed at each dose level, with up to a 90% decrease in NTx noted for animals treated i.v. or s.c. at 15 mg/kg. Similar decreases were observed for sALP and OC. PTH was increased for animals treated at 5 and 15 mg/kg (i.v. or s.c.). Trabecular bone density was increased for the majority of males and females treated i.v. or s.c. at 15 mg/kg and males treated i.v. at 5 mg/kg. Microscopic examination of the sternebrae revealed corresponding increases in bone. Decreases in markers of bone turnover, and corresponding increases in bone density, were consistent with the pharmacological action of OPG as an osteoclast inhibitor. The no-observable-adverse-effect level (NOAEL) of OPG was 15 mg/kg.

Transforming Growth Factor-Beta Inhibition Reduces Progression of Early Choroidal Neovascularization Lesions in Rats: P17 and P144 Peptides

PubMed Central

Zarranz-Ventura, Javier; Fernández-Robredo, Patricia; Recalde, Sergio; Salinas-Alamán, Angel; Borrás-Cuesta, Francisco; Dotor, Javier; García-Layana, Alfredo

2013-01-01

The purpose of this study was to assess the effects of transforming growth factor beta (TGF-β) inhibitor peptides (P17 & P144) on early laser-induced choroidal neovascularization (LI-CNV) lesions in rats, two weeks after laser CNV induction. Seventy-one Long Evans rats underwent diode laser application in an established LI-CNV model. Baseline fluorescein angiography (FA) was performed 14 days following laser procedure, and treatments were administered 16 days post-laser application via different administration routes. Intravenous groups included control (IV-Control), P17 (IV-17), and P144 (IV-144) groups, whereas intravitreal groups included P17 (IVT-17), P144 (IVT-144), and a mixture of both peptides (IVT-17+144) (with fellow eyes receiving vehicle alone). CNV evolution was assessed using FA performed weekly for four weeks after treatment. Following sacrifice, VEGF, TGF-β, COX-2, IGF-1, PAI-1, IL-6, MMP-2, MMP-9, and TNF-α gene expression was assessed using RT-PCR. VEGF and p-SMAD2 protein levels were also assessed by western-blot, while MMP-2 activity was assessed with gelatin zymography. Regarding the FA analysis, the mean CNV area was lower from the 3rd week in IVT-17 and IVT-144 groups, and also from the 2nd week in IVT-17+144. Biochemical analysis revealed that gene expression was lower for VEGF and COX-2 genes in IV-17 and IV-144 groups, VEGF gene in IVT-17+144 group and MMP-2 gene in IVT-17 and IVT-144 groups. VEGF protein expression was also decreased in IV-17, IV-144, IVT-17 and IVT-144, whereas pSMAD-2 levels were lower in IV-17, IV-144 and IVT-17+144 groups. Zymogram analysis revealed decreased MMP-2 activity in IV-17, IV-144, IVT-17 and IVT-144 groups. These data suggest that the use of TGF-β inhibitor peptides (P17 & P144) decrease the development of early CNV lesions by targeting different mediators than those typically affected using current anti-angiogenic therapies. Its potential role in the treatment of early CNV appears promising as a single therapy or adjuvant to anti-VEGF drugs. PMID:23741494

Correlations between skin hydration parameters and corneocyte-derived parameters to characterize skin conditions.

PubMed

Masaki, Hitoshi; Yamashita, Yuki; Kyotani, Daiki; Honda, Tatsuya; Takano, Kenichi; Tamura, Toshiyasu; Mizutani, Taeko; Okano, Yuri

2018-03-30

Skin hydration is generally assessed using the parameters of skin surface water content (SWC) and trans-epidermal water loss (TEWL). To date, few studies have characterized skin conditions using correlations between skin hydration parameters and corneocyte parameters. The parameters SWC and TEWL allow the classification of skin conditions into four distinct Groups. The purpose of this study was to assess the characteristics of skin conditions classified by SWC and TEWL for correlations with parameters from corneocytes. A human volunteer test was conducted that measured SWC and TEWL. As corneocyte-derived parameters, the size and thick abrasion ratios, the ratio of sulfhydryl groups and disulfide bonds (SH/SS) and CP levels were analyzed. Volunteers were classified by their median SWC and TEWL values into 4 Groups: Group I (high SWC/low TEWL), Group II (high SWC/high TEWL), Group III (low SWC/low TEWL), and Group IV (low SWC/high TEWL). Group IV showed a significantly smaller size of corneocytes. Groups III and IV had significantly higher thick abrasion ratios and CP levels. Group I had a significantly lower SH/SS value. The SWC/TEWL value showed a decline in order from Group I to Group IV. Groups classified by their SWC and TEWL values showed characteristic skin conditions. We propose that the SWC and TEWL ratio is a comprehensive parameter to assess skin conditions. © 2018 Wiley Periodicals, Inc.

Adult height, coronary heart disease and stroke: a multi-locus Mendelian randomization meta-analysis

PubMed Central

Nüesch, Eveline; Dale, Caroline; Palmer, Tom M; White, Jon; Keating, Brendan J; van Iperen, Erik PA; Goel, Anuj; Padmanabhan, Sandosh; Asselbergs, Folkert W; Verschuren, WM; Wijmenga, C; Van der Schouw, YT; Onland-Moret, NC; Lange, Leslie A; Hovingh, GK; Sivapalaratnam, Suthesh; Morris, Richard W; Whincup, Peter H; Wannamethe, Goya S; Gaunt, Tom R; Ebrahim, Shah; Steel, Laura; Nair, Nikhil; Reiner, Alexander P; Kooperberg, Charles; Wilson, James F; Bolton, Jennifer L; McLachlan, Stela; Price, Jacqueline F; Strachan, Mark WJ; Robertson, Christine M; Kleber, Marcus E; Delgado, Graciela; März, Winfried; Melander, Olle; Dominiczak, Anna F; Farrall, Martin; Watkins, Hugh; Leusink, Maarten; Maitland-van der Zee, Anke H; de Groot, Mark CH; Dudbridge, Frank; Hingorani, Aroon; Ben-Shlomo, Yoav; Lawlor, Debbie A; Amuzu, A; Caufield, M; Cavadino, A; Cooper, J; Davies, TL; Drenos, F; Engmann, J; Finan, C; Giambartolomei, C; Hardy, R; Humphries, SE; Hypponen, E; Kivimaki, M; Kuh, D; Kumari, M; Ong, K; Plagnol, V; Power, C; Richards, M; Shah, S; Shah, T; Sofat, R; Talmud, PJ; Wareham, N; Warren, H; Whittaker, JC; Wong, A; Zabaneh, D; Davey Smith, George; Wells, Jonathan C; Leon, David A; Holmes, Michael V; Casas, Juan P

2016-01-01

Abstract Background: We investigated causal effect of completed growth, measured by adult height, on coronary heart disease (CHD), stroke and cardiovascular traits, using instrumental variable (IV) Mendelian randomization meta-analysis. Methods: We developed an allele score based on 69 single nucleotide polymorphisms (SNPs) associated with adult height, identified by the IBCCardioChip, and used it for IV analysis against cardiovascular risk factors and events in 21 studies and 60 028 participants. IV analysis on CHD was supplemented by summary data from 180 height-SNPs from the GIANT consortium and their corresponding CHD estimates derived from CARDIoGRAMplusC4D. Results: IV estimates from IBCCardioChip and GIANT-CARDIoGRAMplusC4D showed that a 6.5-cm increase in height reduced the odds of CHD by 10% [odds ratios 0.90; 95% confidence intervals (CIs): 0.78 to 1.03 and 0.85 to 0.95, respectively],which agrees with the estimate from the Emerging Risk Factors Collaboration (hazard ratio 0.93; 95% CI: 0.91 to 0.94). IV analysis revealed no association with stroke (odds ratio 0.97; 95% CI: 0.79 to 1.19). IV analysis showed that a 6.5-cm increase in height resulted in lower levels of body mass index (P < 0.001), triglycerides (P < 0.001), non high-density (non-HDL) cholesterol (P < 0.001), C-reactive protein (P = 0.042), and systolic blood pressure (P = 0.064) and higher levels of forced expiratory volume in 1 s and forced vital capacity (P < 0.001 for both). Conclusions: Taller individuals have a lower risk of CHD with potential explanations being that taller people have a better lung function and lower levels of body mass index, cholesterol and blood pressure. PMID:25979724

Potential role of pre- and postnatal testosterone levels in attention-deficit/hyperactivity disorder: is there a sex difference?

PubMed

Wang, Liang-Jen; Chou, Miao-Chun; Chou, Wen-Jiun; Lee, Min-Jing; Lee, Sheng-Yu; Lin, Pao-Yen; Lee, Yi-Hsuan; Yang, Yi-Hsin; Yen, Cheng-Fang

2017-01-01

Both prenatal testosterone (T) exposure and postnatal T levels have been associated with developing neural circuitry and behavioral systems. This study examined the potential correlation between pre- and postnatal T levels and behavioral and neurocognitive profiles of children with attention-deficit/hyperactivity disorder (ADHD). Two hundred ADHD patients with a mean age of 8.7±2.0 years (158 boys and 42 girls) were recruited. The ratio of the length of the right index finger (2D) to that of the right ring finger (4D) (2D/4D ratio) served as a surrogate of prenatal T exposure, and postnatal T was determined using salivary T concentration. Behavioral symptoms were evaluated using the Swanson, Nolan, and Pelham - Version IV Scale for ADHD (SNAP-IV). Neurocognitive function was assessed using the Wechsler Intelligence Scale for Children - Fourth Edition (WISC-IV) and Conners' Continuous Performance Test (CPT). Lower 2D/4D ratios were associated with comorbid disruptive behavior disorders ( t =2.15, P =0.033) in all participants. Among the boys with ADHD, neither 2D/4D ratios nor salivary T levels were associated with behavioral symptoms or neurocognitive function. Among the girls with ADHD, the salivary T level was positively correlated with the Perceptual Reasoning Index of the WISC-IV ( r =0.48, P =0.001) and the Confidence Index ( r =0.37, P =0.017) and Omission Errors of the CPT ( r =0.62, P <0.001). Findings suggest that a higher prenatal T exposure is associated with a greater risk of developing disruptive behavior disorders, and T may exert differential neurocognitive effects between boys and girls with ADHD. However, the neurobiological mechanisms of T involved in the pathogenesis of ADHD warrant further investigation.

Evaluation of Different Disinfactants on Dimensional Accuracy and Surface Quality of Type IV Gypsum Casts Retrieved from Elastomeric Impression Materials.

PubMed

Pal, P K; Kamble, Suresh S; Chaurasia, Ranjitkumar Rampratap; Chaurasia, Vishwajit Rampratap; Tiwari, Samarth; Bansal, Deepak

2014-06-01

The present study was done to evaluate the dimensional stability and surface quality of Type IV gypsum casts retrieved from disinfected elastomeric impression materials. In an in vitro study contaminated impression material with known bacterial species was disinfected with disinfectants followed by culturing the swab sample to assess reduction in level of bacterial colony. Changes in surface detail reproduction of impression were assessed fallowing disinfection. All the three disinfectants used in the study produced a 100% reduction in colony forming units of the test organisms. All the three disinfectants produced complete disinfection, and didn't cause any deterioration in surface detail reproduction. How to cite the article: Pal PK, Kamble SS, Chaurasia RR, Chaurasia VR, Tiwari S, Bansal D. Evaluation of dimensional stability and surface quality of type IV gypsum casts retrieved from disinfected elastomeric impression materials. J Int Oral Health 2014;6(3):77-81.

Patient satisfaction with intravenous acetaminophen: a pooled analysis of five randomized, placebo-controlled studies in the acute postoperative setting.

PubMed

Apfel, Christian C; Souza, Kimberly; Portillo, Juan; Dalal, Poorvi; Bergese, Sergio D

2015-01-01

Intravenous (IV) acetaminophen has been shown to reduce postoperative pain and opioid consumption, which may lead to increased patient satisfaction. To determine the effect IV acetaminophen has on patient satisfaction, a pooled analysis from methodologically homogenous studies was conducted. We obtained patient-level data from five randomized, placebo-controlled studies in adults undergoing elective surgery in which patient satisfaction was measured using a 4-point categorical rating scale. The primary endpoint was "excellent" satisfaction and the secondary endpoint was "good" or "excellent" satisfaction at 24 hr after first study drug administration. Bivariate analyses were conducted using the chi-square test and Student's t-test and multivariable analyses were conducted using logistic regression analysis. Patients receiving IV acetaminophen were more than twice as likely as those who received placebo to report "excellent" patient satisfaction ratings (32.3% vs. 15.9%, respectively). Of all variables that remained statistically significant in the multivariable analysis (i.e., type of surgery, duration of anesthesia, last pain rating, and opioid consumption), IV acetaminophen had the strongest positive effect on "excellent" patient satisfaction with an odds ratio of 2.76 (95% CI 1.81-4.23). Results for "excellent" or "good" satisfaction were similar. When given as part of a perioperative analgesic regimen, IV acetaminophen was associated with significantly improved patient satisfaction.

The willingness of patients to pay for intravenous patient-controlled analgesia in Korea.

PubMed

Lim, Hyungsun; Lee, Duck-Hyoung; Lee, Jeongwoo; Han, Young Jin; Choe, Huhn; Son, Ji-Seon

2012-06-01

The use of intravenous patient-controlled analgesia (IV-PCA) has been increasing because it has advantages such as improved pain relief, greater patient satisfaction, and fewer postoperative complications. However, current research has not considered the patients' thoughts about IV-PCA's cost-effectiveness. The purpose of this study was to investigate the willingness to pay (WTP) for IV-PCA and the relationship between patients' characteristics and WTP in Korea. We enrolled 400 adult patients who were scheduled for elective surgery. The patient was requested to indicate a series of predefined amounts of money (Korean won; 30,000/50,000/100,000/150,000/200,000/300,000/500,000). We also recorded patient characteristics, such as age, sex, type of surgery, IV-PCA history, education level, the person responsible for medical expenses, type of insurance, net annual income, and residential area. Three days after surgery, we asked about the degree of satisfaction and the WTP for IV-PCA. For IV-PCA, the median WTP was 100,000 won (25-75%; 50,000-200,000 won: US$1 = W1078.04; July 19, 2011) before surgery. All patients' characteristics were not related to preoperative WTP for IV-PCA, whereas the increase in WTP after surgery showed a tendency correlated to higher IV-PCA satisfaction. The median WTP was 100,000 won. The satisfaction of IV-PCA increased patients' WTP after surgery, but the WTP may be independent of patient characteristics in Korea.

Early trends from the Study to Evaluate the Prospective Payment System Impact on Small Dialysis Organizations (STEPPS).

PubMed

Brunelli, Steven M; Monda, Keri L; Burkart, John M; Gitlin, Matthew; Neumann, Peter J; Park, Grace S; Symonian-Silver, Margarita; Yue, Susan; Bradbury, Brian D; Rubin, Robert J

2013-06-01

Launched in January 2011, the prospective payment system (PPS) for the US Medicare End-Stage Renal Disease Program bundled payment for services previously reimbursed independently. Small dialysis organizations may be particularly susceptible to the financial implications of the PPS. The ongoing Study to Evaluate the Prospective Payment System Impact on Small Dialysis Organizations (STEPPS) was designed to describe trends in care and outcomes over the period of PPS implementation. This report details early results between October 2010 and June 2011. Prospective observational cohort study of patients from a sample of 51 small dialysis organizations. 1,873 adult hemodialysis and peritoneal dialysis patients. Secular trends in processes of care, anemia, metabolic bone disease management, and red blood cell transfusions. Facility-level data are collected quarterly. Patient characteristics were collected at enrollment and scheduled intervals thereafter. Clinical outcomes are collected on an ongoing basis. Over time, no significant changes were observed in patient to staff ratios. There was a temporal trend toward greater use of peritoneal dialysis (from 2.4% to 3.6%; P = 0.09). Use of cinacalcet, phosphate binders, and oral vitamin D increased; intravenous (IV) vitamin D use decreased (P for trend for all <0.001). Parathyroid hormone levels increased (from 273 to 324 pg/dL; P < 0.001). Erythropoiesis-stimulating agent doses decreased (P < 0.001 for IV epoetin alfa and IV darbepoetin alfa), particularly high doses. Mean hemoglobin levels decreased (P < 0.001), the percentage of patients with hemoglobin levels <10 g/dL increased (from 12.7% to 16.8%), and transfusion rates increased (from 14.3 to 19.6/100 person-years; P = 0.1). Changes in anemia management were more pronounced for African American patients. Limited data were available for the prebundle period. Secular trends may be subject to the ecologic fallacy and are not causal in nature. In the period after PPS implementation, IV vitamin D use decreased, use of oral therapies for metabolic bone disease increased, erythropoiesis-stimulating agent use and hemoglobin levels decreased, and transfusion rates increased numerically. Copyright © 2013 National Kidney Foundation, Inc. Published by Elsevier Inc. All rights reserved.

Muscle RAS oncogene homolog (MRAS) recurrent mutation in Borrmann type IV gastric cancer.

PubMed

Yasumoto, Makiko; Sakamoto, Etsuko; Ogasawara, Sachiko; Isobe, Taro; Kizaki, Junya; Sumi, Akiko; Kusano, Hironori; Akiba, Jun; Torimura, Takuji; Akagi, Yoshito; Itadani, Hiraku; Kobayashi, Tsutomu; Hasako, Shinichi; Kumazaki, Masafumi; Mizuarai, Shinji; Oie, Shinji; Yano, Hirohisa

2017-01-01

The prognosis of patients with Borrmann type IV gastric cancer (Type IV) is extremely poor. Thus, there is an urgent need to elucidate the molecular mechanisms underlying the oncogenesis of Type IV and to identify new therapeutic targets. Although previous studies using whole-exome and whole-genome sequencing have elucidated genomic alterations in gastric cancer, none has focused on comprehensive genetic analysis of Type IV. To discover cancer-relevant genes in Type IV, we performed whole-exome sequencing and genome-wide copy number analysis on 13 patients with Type IV. Exome sequencing identified 178 somatic mutations in protein-coding sequences or at splice sites. Among the mutations, we found a mutation in muscle RAS oncogene homolog (MRAS), which is predicted to cause molecular dysfunction. MRAS belongs to the Ras subgroup of small G proteins, which includes the prototypic RAS oncogenes. We analyzed an additional 46 Type IV samples to investigate the frequency of MRAS mutation. There were eight nonsynonymous mutations (mutation frequency, 17%), showing that MRAS is recurrently mutated in Type IV. Copy number analysis identified six focal amplifications and one homozygous deletion, including insulin-like growth factor 1 receptor (IGF1R) amplification. The samples with IGF1R amplification had remarkably higher IGF1R mRNA and protein expression levels compared with the other samples. This is the first report of MRAS recurrent mutation in human tumor samples. Our results suggest that MRAS mutation and IGF1R amplification could drive tumorigenesis of Type IV and could be new therapeutic targets. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Additional intraarticular tranexamic acid further reduced postoperative blood loss compared to intravenous and topical bathed tranexamic acid in total hip arthroplasty: a retrospective sequential series study.

PubMed

Nakura, Nariaki; Hirakawa, Kazuo; Takayanagi, Satoshi; Saito, Akira; Tsuji, Koji; Tamaki, Yasunobu; Ochiai, Shunsuke; Mihara, Masahiko

2017-04-01

Topical tranexamic acid (TXA) administration has been described to be effective in decreasing blood loss in total hip arthroplasty (THA). The aim of this retrospective study was to evaluate whether topical intraarticular TXA administration in addition to intravenous (IV) and topical bathed TXA further reduces blood loss in THA patients. Four-hundred patients were enrolled in this sequential series study with two different phases during four different time periods. Patients were divided based on TXA usage and route of administration: those with and without IV TXA (IVTA-I and no-IVTA groups, respectively) and those with and without intraarticular TXA (TITA and IVTA-II groups, respectively). Both IVTA-II and TITA groups had IV TXA, and all four groups used topical bathed TXA. These four groups had 100 cases each. The primary outcomes were evaluated with total blood loss and postoperative hemoglobin level. The total blood loss was 1106 and 875 mL in the no-IVTA and IVTA-I groups, respectively (p < 0.05). Postoperative Hb was 10.9 and 11.51 g/dL in the no-IVTA and IVTA-I groups, respectively (p < 0.05). Total blood loss was 813 and 646 mL in the IVTA-II and TITA groups, respectively (p < 0.05). Intraarticular with IV and bathed TXA administration was more effective than IV and bathed TXA in reducing blood loss. This study suggests that the combined administration of topical intraarticular, bathed, and IV TXA was effective in reducing blood loss in THA patients. © 2016 AABB.

Carvacrol and Pomegranate Extract in Treating Methotrexate-Induced Lung Oxidative Injury in Rats

PubMed Central

Şen, Hadice Selimoğlu; Şen, Velat; Bozkurt, Mehtap; Türkçü, Gül; Güzel, Abdulmenap; Sezgi, Cengizhan; Abakay, Özlem; Kaplan, Ibrahim

2014-01-01

Background This study was designed to evaluate the effects of carvacrol (CRV) and pomegranate extract (PE) on methotrexate (MTX)-induced lung injury in rats. Material/Methods A total of 32 male rats were subdivided into 4 groups: control (group I), MTX treated (group II), MTX+CRV treated (group III), and MTX+PE treated (group IV). A single dose of 73 mg/kg CRV was administered intraperitoneally to rats in group III on Day 1 of the investigation. To group IV, a dose of 225 mg/kg of PE was administered via orogastric gavage once daily over 7 days. A single dose of 20 mg/kg of MTX was given intraperitoneally to groups II, III, and IV on Day 2. The total duration of experiment was 8 days. Malondialdehyde (MDA), total oxidant status (TOS), total antioxidant capacity (TAC), and oxidative stress index (OSI) were measured from rat lung tissues and cardiac blood samples. Results Serum and lung specimen analyses demonstrated that MDA, TOS, and OSI levels were significantly greater in group II relative to controls. Conversely, the TAC level was significantly reduced in group II when compared to the control group. Pre-administering either CRV or PE was associated with decreased MDA, TOS, and OSI levels and increased TAC levels compared to rats treated with MTX alone. Histopathological examination revealed that lung injury was less severe in group III and IV relative to group II. Conclusions MTX treatment results in rat lung oxidative damage that is partially counteracted by pretreatment with either CRV or PE. PMID:25326861

Prevalence and severity of eating disorders: A comparison of DSM-IV and DSM-5 among German adolescents.

PubMed

Ernst, Verena; Bürger, Arne; Hammerle, Florian

2017-11-01

Changes in the DSM-5 eating disorders criteria sought to increase the clarity of the diagnostic categories and to decrease the preponderance of nonspecified eating disorders. The first objective of this study was to analyze how these revisions affect threshold and EDNOS/OSFED eating disorder diagnoses in terms of prevalence, sex ratios, and diagnostic distribution in a student sample. Second, we aimed to compare the impairment levels of participants with a threshold, an EDNOS/OSFED and no diagnosis using both DSM-IV and DSM-5. A sample of 1654 7th and 8th grade students completed self-report questionnaires to determine diagnoses and impairment levels in the context of an eating disorder prevention program in nine German secondary schools. Height and weight were measured. The prevalence of threshold disorders increased from .48% (DSM-IV) to 1.15% (DSM-5). EDNOS disorders increased from 2.90 to 6.23% when using OSFED-categories. A higher proportion of girls was found throughout all the diagnostic categories, and the sex ratios remained stable. The effect sizes of DSM-5 group differences regarding impairment levels were equal to or larger than those of the DSM-IV comparisons, ranging from small to medium. We provide an in-depth overview of changes resulting from the revisions of DSM eating disorder criteria in a German adolescent sample. Despite the overall increase in prevalence estimates, the results suggest that the DSM-5 criteria differentiate participants with threshold disorders and OSFED from those no diagnosis as well as or even more distinctly than the DSM-IV criteria. © 2017 Wiley Periodicals, Inc.

Resolving the paradigm crisis in intravenous iron and erythropoietin management.

PubMed

Besarab, A

2006-05-01

Despite the proven benefits of intravenous (i.v.) iron therapy in anemia management, it remains underutilized in the hemodialysis population. Although overall i.v. iron usage continues to increase slowly, monthly usage statistics compiled by the US Renal Data System suggest that clinicians are not implementing continued dosing regimens following repletion of iron stores. Continued therapy with i.v. iron represents a key opportunity to improve patient outcomes and increase the efficiency of anemia treatment. Regular administration of low doses of i.v. iron prevents the recurrence of iron deficiency, enhances response to recombinant human erythropoietin therapy, minimizes fluctuation of hemoglobin levels, hematocrit levels, and iron stores, and may reduce overall costs of care. This article reviews the importance of i.v. iron dosing on a regular basis in the hemodialysis patient with iron-deficiency anemia and explores reasons why some clinicians may still be reluctant to employ these protocols in the hemodialysis setting.

Optimizing IV and V for Mature Organizations

NASA Technical Reports Server (NTRS)

Fuhman, Christopher

2003-01-01

NASA is intending for its future software development agencies to have at least a Level 3 rating in the Carnegie Mellon University Capability Maturity Model (CMM). The CMM has built-in Verification and Validation (V&V) processes that support higher software quality. Independent Verification and Validation (IV&V) of software developed by mature agencies can be therefore more effective than for software developed by less mature organizations. How is Independent V&V different with respect to the maturity of an organization? Knowing a priori the maturity of an organization's processes, how can IV&V planners better identify areas of need choose IV&V activities, etc? The objective of this research is to provide a complementary set of guidelines and criteria to assist the planning of IV&V activities on a project using a priori knowledge of the measurable levels of maturity of the organization developing the software.

Infusion volume control and calculation using metronome and drop counter based intravenous infusion therapy helper.

PubMed

Park, Kyungnam; Lee, Jangyoung; Kim, Soo-Young; Kim, Jinwoo; Kim, Insoo; Choi, Seung Pill; Jeong, Sikyung; Hong, Sungyoup

2013-06-01

This study assessed the method of fluid infusion control using an IntraVenous Infusion Controller (IVIC). Four methods of infusion control (dial flow controller, IV set without correction, IV set with correction and IVIC correction) were used to measure the volume of each technique at two infusion rates. The infused fluid volume with a dial flow controller was significantly larger than other methods. The infused fluid volume was significantly smaller with an IV set without correction over time. Regarding the concordance correlation coefficient (CCC) of infused fluid volume in relation to a target volume, IVIC correction was shown to have the highest level of agreement. The flow rate measured in check mode showed a good agreement with the volume of collected fluid after passing through the IV system. Thus, an IVIC could assist in providing an accurate infusion control. © 2013 Wiley Publishing Asia Pty Ltd.

Effects of low-level laser therapy on stem cells from human exfoliated deciduous teeth

PubMed Central

FERNANDES, Ana Paula; JUNQUEIRA, Marina de Azevedo; MARQUES, Nádia Carolina Teixeira; MACHADO, Maria Aparecida Andrade Moreira; SANTOS, Carlos Ferreira; OLIVEIRA, Thais Marchini; SAKAI, Vivien Thiemy

2016-01-01

ABSTRACT Low-Level Laser Therapy stimulates the proliferation of a variety of types of cells. However, very little is known about its effect on stem cells from human exfoliated deciduous teeth (SHED). Objective This study aimed to evaluate the influence of different laser therapy energy densities on SHED viability and proliferation. Material and Methods SHED were irradiated according to the groups: I (1.2 J/cm2 - 0.5 mW – 10 s), II (2.5 J/cm2 – 10 mW – 10 s), III (3.7 J/cm2 – 15 mW – 10 s), IV (5.0 J/cm2 – 20 mW – 10 s), V (6.2 J/cm2 – 25 mW – 10 s), and VI (not irradiated – control group). Cell viability was assessed 6 and 24 h after irradiation measuring the mitochondrial activity and using the Crystal Violet assay. Cell proliferation was assessed after 24, 48, and 72 h of irradiation by SRB assay. Results MTT assay demonstrated differences from 6 to 24 hours after irradiation. After 24 h, groups I and IV showed higher absorbance values than those of control group. Crystal Violet assay showed statistically differences in the absorbance rate from 6 to 24 h after irradiation for groups III and VI. At 24 h after irradiation, Group III absorbance rate was greater than that of groups I, II, and IV. Group VI absorbance rate was greater than that of groups I and IV. SRB assay showed that the group I had higher rates than those of groups II, III, V, and VI, at 24 h after irradiation. After 48 h, group I exhibited the greatest cell proliferation rate followed by groups III, V, and VI. After 72 h, group III exhibited the lowest cell proliferation rate than those of groups II, IV, and V. Conclusions The Low-Level Laser Therapy energy densities used in this study did not cause loss of cell viability and stimulated SHED proliferation within the parameters described in this study. PMID:27556203

Hierarchy of evidence relating to hand surgery in Brazilian orthopedic journals.

PubMed

Moraes, Vinícius Ynoe de; Belloti, João Carlos; Moraes, Fábio Ynoe de; Galbiatti, José Antonio; Palácio, Evandro Pereira; Santos, João Baptista Gomes Dos; Faloppa, Flávio

2011-03-01

There is no systematic assessment of the quality of scientific production in the specialty of hand surgery in our setting. This study aimed to systematically assess the status of evidence generation relating to hand surgery and to evaluate the reproducibility of the classification method based on an evidence pyramid. Secondary study conducted at Universidade Federal de São Paulo (Unifesp) and Faculdade Estadual de Medicina de Marília (Famema). Two researchers independently conducted an electronic database search for hand surgery studies published between 2000 and 2009 in the two main Brazilian orthopedic journals (Acta Ortopédica Brasileira and Revista Brasileira de Ortopedia). The studies identified were subsequently classified according to methodological design (systematic review of the literature, randomized clinical trial, cohort study, case-control study, case series and other studies) and evidence level (I to V). A total of 1,150 articles were evaluated, and 83 (7.2%) were included in the final analysis. Studies with evidence level IV (case series) accounted for 41 (49%) of the published papers. Studies with evidence level V (other studies) accounted for 12 (14.5%) of the papers. Only two studies (2.4%) were ranked as level I or II. The inter-rater reproducibility was excellent (k = 0.94). Hand surgery articles corresponded to less than one tenth of Brazilian orthopedic production. Studies with evidence level IV were the commonest type. The reproducibility of the classification stratified by evidence level was almost perfect.

Parenteral irons versus transfused red blood cells for treatment of anemia during canine experimental bacterial pneumonia.

PubMed

Suffredini, Dante A; Xu, Wanying; Sun, Junfeng; Barea-Mendoza, Jesús; Solomon, Steven B; Brashears, Samuel L; Perlegas, Andreas; Kim-Shapiro, Daniel B; Klein, Harvey G; Natanson, Charles; Cortés-Puch, Irene

2017-10-01

No studies have been performed comparing intravenous (IV) iron with transfused red blood cells (RBCs) for treating anemia during infection. In a previous report, transfused older RBCs increased free iron release and mortality in infected animals when compared to fresher cells. We hypothesized that treating anemia during infection with transfused fresh RBCs, with minimal free iron release, would prove superior to IV iron therapy. Purpose-bred beagles (n = 42) with experimental Staphylococcus aureus pneumonia rendered anemic were randomized to be transfused RBCs stored for 7 days or one of two IV iron preparations (7 mg/kg), iron sucrose, a widely used preparation, or ferumoxytol, a newer formulation that blunts circulating iron levels. Both irons increased the alveolar-arterial oxygen gradient at 24 to 48 hours (p = 0.02-0.001), worsened shock at 16 hours (p = 0.02-0.003, respectively), and reduced survival (transfusion 56%; iron sucrose 8%, p = 0.01; ferumoxytol 9%, p = 0.04). Compared to fresh RBC transfusion, plasma iron measured by non-transferrin-bound iron levels increased with iron sucrose at 7, 10, 13, 16, 24, and 48 hours (p = 0.04 to p < 0.0001) and ferumoxytol at 7, 24, and 48 hours (p = 0.04 to p = 0.004). No significant differences in cardiac filling pressures or performance, hemoglobin (Hb), or cell-free Hb were observed. During canine experimental bacterial pneumonia, treatment of mild anemia with IV iron significantly increased free iron levels, shock, lung injury, and mortality compared to transfusion of fresh RBCs. This was true for iron preparations that do or do not blunt circulating free iron level elevations. These findings suggest that treatment of anemia with IV iron during infection should be undertaken with caution. © 2017 AABB.

A pilot study differentiating recurrent major depression from bipolar disorder cycling on the depressive pole.

PubMed

Hinz, Marty; Stein, Alvin; Uncini, Thomas

2010-11-09

A novel method for differentiating and treating bipolar disorder cycling on the depressive pole from patients who are suffering a major depressive episode is explored in this work. To confirm the diagnosis of type 1 or type 2 bipolar disorder, the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria require that at least one manic or hypomanic episode be identified. History of one or more manic or hypomanic episodes may be impossible to obtain, representing a potential blind spot in the DSM-IV diagnostic criteria. Many bipolar patients who cycle primarily on the depressive side for many years carry a misdiagnosis of recurrent major depression, leading to treatment with antidepressants that achieve little or no relief of symptoms. This article discusses a novel approach for diagnosing and treating patients with bipolar disorder cycling on the depressive pole versus patients with recurrent major depression. Patients involved in this study were formally diagnosed with recurrent major depression under DSM-IV criteria and had no medical history of mania or hypomania to support the diagnosis of bipolar disorder. All patients had suffered multiple depression treatment failures in the past, when evaluated under DSM-IV guidelines, secondary to administration of antidepressant drugs and/or serotonin with dopamine amino acid precursors. This study contained 1600 patients who were diagnosed with recurrent major depression under the DSM-IV criteria. All patients had no medical history of mania or hypomania. All patients experienced no relief of depression symptoms on level 3 amino acid dosing values of the amino acid precursor dosing protocol. Of 1600 patients studied, 117 (7.3%) nonresponder patients were identified who experienced no relief of depression symptoms when the serotonin and dopamine amino acid precursor dosing values were adjusted to establish urinary serotonin and urinary dopamine levels in the Phase III therapeutic ranges. All of the 117 nonresponders who achieved no relief of depression symptoms were continued on this amino acid dosing value, and a mood-stabilizing drug was started. At this point, complete relief of depression symptoms, under evaluation with DSM-IV criteria, was noted in 114 patients within 1-5 days. With further dose adjustment of the mood-stabilizing drug, the remaining three nonresponders achieved relief of depression symptoms. Resolution of depression symptoms with the addition of a mood-stabilizing drug in combination with proper levels of serotonin and dopamine amino acid precursors was the basis for a clinical diagnosis of bipolar disorder cycling on the depressive pole.

A pilot study differentiating recurrent major depression from bipolar disorder cycling on the depressive pole

PubMed Central

Hinz, Marty; Stein, Alvin; Uncini, Thomas

2010-01-01

Purpose A novel method for differentiating and treating bipolar disorder cycling on the depressive pole from patients who are suffering a major depressive episode is explored in this work. To confirm the diagnosis of type 1 or type 2 bipolar disorder, the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria require that at least one manic or hypomanic episode be identified. History of one or more manic or hypomanic episodes may be impossible to obtain, representing a potential blind spot in the DSM-IV diagnostic criteria. Many bipolar patients who cycle primarily on the depressive side for many years carry a misdiagnosis of recurrent major depression, leading to treatment with antidepressants that achieve little or no relief of symptoms. This article discusses a novel approach for diagnosing and treating patients with bipolar disorder cycling on the depressive pole versus patients with recurrent major depression. Patients and methods Patients involved in this study were formally diagnosed with recurrent major depression under DSM-IV criteria and had no medical history of mania or hypomania to support the diagnosis of bipolar disorder. All patients had suffered multiple depression treatment failures in the past, when evaluated under DSM-IV guidelines, secondary to administration of antidepressant drugs and/or serotonin with dopamine amino acid precursors. Results This study contained 1600 patients who were diagnosed with recurrent major depression under the DSM-IV criteria. All patients had no medical history of mania or hypomania. All patients experienced no relief of depression symptoms on level 3 amino acid dosing values of the amino acid precursor dosing protocol. Of 1600 patients studied, 117 (7.3%) nonresponder patients were identified who experienced no relief of depression symptoms when the serotonin and dopamine amino acid precursor dosing values were adjusted to establish urinary serotonin and urinary dopamine levels in the Phase III therapeutic ranges. All of the 117 nonresponders who achieved no relief of depression symptoms were continued on this amino acid dosing value, and a mood-stabilizing drug was started. At this point, complete relief of depression symptoms, under evaluation with DSM-IV criteria, was noted in 114 patients within 1–5 days. With further dose adjustment of the mood-stabilizing drug, the remaining three nonresponders achieved relief of depression symptoms. Conclusion Resolution of depression symptoms with the addition of a mood-stabilizing drug in combination with proper levels of serotonin and dopamine amino acid precursors was the basis for a clinical diagnosis of bipolar disorder cycling on the depressive pole. PMID:21173882

Parallel Architectures and Parallel Algorithms for Integrated Vision Systems. Ph.D. Thesis

NASA Technical Reports Server (NTRS)

Choudhary, Alok Nidhi

1989-01-01

Computer vision is regarded as one of the most complex and computationally intensive problems. An integrated vision system (IVS) is a system that uses vision algorithms from all levels of processing to perform for a high level application (e.g., object recognition). An IVS normally involves algorithms from low level, intermediate level, and high level vision. Designing parallel architectures for vision systems is of tremendous interest to researchers. Several issues are addressed in parallel architectures and parallel algorithms for integrated vision systems.

Quality of Life and Health-Related Quality of Life of Adolescents with Cerebral Palsy

ERIC Educational Resources Information Center

Rosenbaum, Peter L.; Livingston, Michael H.; Palisano, Robert J.; Galuppi, Barbara E.; Russell, Dianne J.

2007-01-01

This study assessed quality of life (QOL) and health-related quality of life (HRQOL) of 203 adolescents with cerebral palsy (111 males, 92 females; mean age 16y [SD 1y 9mo]). Participants were classified using the Gross Motor Function Classification System (GMFCS), as Level I (n=60), Level II (n=33), Level III (n=28), Level IV (n=50), or Level V…

Effect of Peppermint Oil on Serum Lipid Peroxidation and Hepatic Enzymes after Immobility Stress in Mice

PubMed Central

Marjani, Abdoljalal; Rahmati, Reza; Mansourian, Azad Reza; Veghary, Gholamreza

2012-01-01

This study was undertaken to determine the influences of various doses of peppermint oil on the hepatic en-zymes, alanine transaminase, apartate tranaminase, alkaline phosphotase and gamma glutamyl transferase and the level of malondialdehyde in the serum of mice with and without immobility stress. The mice exposed to drink water, 0.9, 27 and 60 mg/kg peppermint oil from the days 1 to 5 for a period of 4 h before and after immobility stress. Serum MDA in-creased in treatment group II, III and IV after immobility stress. There was a significant decrease in ALT in treatment group III and IV after immobility stress. There were also significant decreases in ALP and GGT in treatment group IV af-ter immobility stress. This result may suggest that, MDA level is higher in immobilization stress group than in the un-immobilized animals in serum and this results show that enzyme activities decreased after immobilization stress. PMID:22654997

Monthly oral ibandronate 100 mg is as effective as monthly intravenous ibandronate 1 mg in patients with various pathologies in the MOVEST study.

PubMed

Hagino, Hiroshi; Ito, Masako; Hashimoto, Junko; Yamamoto, Masao; Endo, Koichi; Katsumata, Kyoko; Asao, Yoshihiro; Matsumoto, Rumiko; Nakano, Tetsuo; Mizunuma, Hideki; Nakamura, Toshitaka

2018-05-01

The non-inferiority of oral ibandronate 100 mg to intravenous (i.v.) ibandronate 1 mg in increasing lumbar spine (LS) bone mineral density (BMD) after 12 months of treatment was demonstrated in the randomized, phase III MOVEST study. We conducted subgroup analyses in the per-protocol set of the study (n = 183 oral ibandronate; n = 189 i.v. ibandronate). In patients with LS BMD T score ≥ -3.0 or < -3.0 at screening, LS BMD gains from baseline were 4.42 and 5.79%, respectively, with oral ibandronate, and 4.60 and 5.83%, respectively, with i.v. ibandronate. LS BMD gains in patients with or without prevalent vertebral fractures were 5.21 and 5.23%, respectively, with oral ibandronate, and 5.01 and 5.49%, respectively, with i.v. ibandronate. In patients aged <75 or ≥75 years, LS BMD gains were 5.46 and 4.51%, respectively, with oral ibandronate, and 5.25 and 5.77%, respectively, with i.v. ibandronate. LS BMD gains in patients with baseline 25-hydroxyvitamin D levels ≥20 or <20 ng/mL were 5.35 and 4.76%, respectively, with oral ibandronate, and 5.05 and 6.57%, respectively, with i.v. ibandronate. Similar results were obtained in patients with or without prior bisphosphonate (BP) treatment, and in those receiving osteoporosis drug treatment other than BPs. In conclusion, oral ibandronate 100 mg demonstrated comparable BMD gains with monthly i.v. ibandronate, and thus shows high utility in the lifestyle and disease conditions associated with osteoporosis in Japanese patients.

A Two-Year Randomized Trial of Interventions to Decrease Stress Hormone Vasopressin Production in Patients with Meniere's Disease-A Pilot Study.

PubMed

Kitahara, Tadashi; Okamoto, Hidehiko; Fukushima, Munehisa; Sakagami, Masaharu; Ito, Taeko; Yamashita, Akinori; Ota, Ichiro; Yamanaka, Toshiaki

2016-01-01

Meniere's disease, a common inner ear condition, has an incidence of 15-50 per 100,000. Because mental/physical stress and subsequent increase in the stress hormone vasopressin supposedly trigger Meniere's disease, we set a pilot study to seek new therapeutic interventions, namely management of vasopressin secretion, to treat this disease. We enrolled 297 definite Meniere's patients from 2010 to 2012 in a randomized-controlled and open-label trial, assigning Group-I (control) traditional oral medication, Group-II abundant water intake, Group-III tympanic ventilation tubes and Group-IV sleeping in darkness. Two hundred sixty-three patients completed the planned 2-year-follow-up, which included assessment of vertigo, hearing, plasma vasopressin concentrations and changes in stress/psychological factors. At 2 years, vertigo was completely controlled in 54.3% of patients in Group-I, 81.4% in Group-II, 84.1% in Group-III, and 80.0% in Group-IV (statistically I < II = III = IV). Hearing was improved in 7.1% of patients in Group-I, 35.7% in Group-II, 34.9% in Group-III, and 31.7% in Group-IV (statistically I < II = III = IV). Plasma vasopressin concentrations decreased more in Groups-II, -III, and -IV than in Groups-I (statistically I < II = III = IV), although patients' stress/psychological factors had not changed. Physicians have focused on stress management for Meniere's disease. However, avoidance of stress is unrealistic for patients who live in demanding social environments. Our findings in this pilot study suggest that interventions to decrease vasopressin secretion by abundant water intake, tympanic ventilation tubes and sleeping in darkness is feasible in treating Meniere's disease, even though these therapies did not alter reported mental/physical stress levels. ClinicalTrials.gov NCT01099046.

Levels-of-growing-stock cooperative study in Douglas-fir: report no. 18--Rocky Brook, 1963-2006.

Treesearch

Robert O. Curtis; David D. Marshall

2009-01-01

This report documents the history and results of the Rocky Brook installation of the cooperative levels-of-growing-stock (LOGS) study in Douglas-fir (Pseudotsuga menziesii (Mirb.) Franco), over the 41-year period 1965 to 2006. This 1938 plantation is one of the two site-IV installations among the nine installations in the study. Much public...

Validity of DSM-IV attention deficit/hyperactivity disorder symptom dimensions and subtypes.

PubMed

Willcutt, Erik G; Nigg, Joel T; Pennington, Bruce F; Solanto, Mary V; Rohde, Luis A; Tannock, Rosemary; Loo, Sandra K; Carlson, Caryn L; McBurnett, Keith; Lahey, Benjamin B

2012-11-01

Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) criteria for attention deficit/hyperactivity disorder (ADHD) specify two dimensions of inattention and hyperactivity-impulsivity symptoms that are used to define three nominal subtypes: predominantly hyperactive-impulsive type (ADHD-H), predominantly inattentive type (ADHD-I), and combined type (ADHD-C). To aid decision making for DSM-5 and other future diagnostic systems, a comprehensive literature review and meta-analysis of 546 studies was completed to evaluate the validity of the DSM-IV model of ADHD. Results indicated that DSM-IV criteria identify individuals with significant and persistent impairment in social, academic, occupational, and adaptive functioning when intelligence, demographic factors, and concurrent psychopathology are controlled. Available data overwhelmingly support the concurrent, predictive, and discriminant validity of the distinction between inattention and hyperactivity-impulsivity symptoms, and indicate that nearly all differences among the nominal subtypes are consistent with the relative levels of inattention and hyperactivity-impulsivity symptoms that define the subtypes. In contrast, the DSM-IV subtype model is compromised by weak evidence for the validity of ADHD-H after first grade, minimal support for the distinction between ADHD-I and ADHD-C in studies of etiological influences, academic and cognitive functioning, and treatment response, and the marked longitudinal instability of all three subtypes. Overall, we conclude that the DSM-IV ADHD subtypes provide a convenient clinical shorthand to describe the functional and behavioral correlates of current levels of inattention and hyperactivity-impulsivity symptoms, but do not identify discrete subgroups with sufficient long-term stability to justify the classification of distinct forms of the disorder. Empirical support is stronger for an alternative model that would replace the subtypes with dimensional modifiers that reflect the number of inattention and hyperactivity-impulsivity symptoms at the time of assessment. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

Hemorrhoids and matrix metalloproteinases: A multicenter study on the predictive role of biomarkers.

PubMed

Serra, Raffaele; Gallelli, Luca; Grande, Raffaele; Amato, Bruno; De Caridi, Giovanni; Sammarco, Giuseppe; Ferrari, Francesco; Butrico, Lucia; Gallo, Gaetano; Rizzuto, Antonia; de Franciscis, Stefano; Sacco, Rosario

2016-02-01

An association between hemorrhoidal disease and matrix metalloproteinases (MMPs) has been described previously. MMPs regulate extracellular structural proteins and tissue remodeling. Neutrophil gelatinase-associated lipocalin (NGAL) is involved in the regulation of MMP activity. The aim of this work was to study the relationship between tissue immunoreactive levels of MMPs and NGAL and different stages of hemorrhoids. In a multicenter, open-label, prospective study, the population under investigation consisted of 2 groups: group I (with symptomatic hemorrhoids; Goligher grade I-IV) and group II (healthy volunteers). We enrolled 97 patients with hemorrhoids: 21 with grade I hemorrhoids, 37 with grade II, 14 with grade III, and 25 with grade IV. Finally, 90 healthy volunteers (53 males and 37 females; age range, 19-70 years; median, 56) were enrolled in group II. Enzyme-linked immunosorbent assay and Western blot analysis revealed greater levels of immunoreactive MMPs and NGAL in all patients with hemorrhoids. We recorded significantly greater levels of MMP-1 and MMP-3 in grade I and II patients compared with control, and greater levels of MMP-3, MMP-7, MMP-8, and MMP-9 in grade III compared with grade II. MMP-9 and NGAL were particularly increased in patients with grade IV especially in case of thrombosed hemorrhoids. These results provide potentially important insights into the understanding of the natural history of hemorrhoids. MMPs and NGAL play a role in development of disease and may represent molecular markers for the complications such as hemorrhoidal thrombosis. Copyright © 2016 Elsevier Inc. All rights reserved.

Validating the proposed diagnostic and statistical manual of mental disorders, 5th edition, severity indicator for personality disorder.

PubMed

Morey, Leslie C; Bender, Donna S; Skodol, Andrew E

2013-09-01

The authors sought to determine whether a 5-point global rating of personality dysfunction on the Level of Personality Functioning Scale proposed as a severity index for Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5), would be related to DSM-IV personality disorder diagnosis as well as to other key clinical judgments. Data were collected from a national sample of 337 mental health clinicians who provided complete diagnostic information relevant to DSM-IV and proposed DSM-5 personality disorder diagnoses, as well as demographic information and other clinical judgments, on one of their patients. Of the 337 patients described, 248 met criteria for 1 of the 10 specific DSM-IV personality disorders. A "moderate" or greater rating of impairment in personality functioning on the Level Scale demonstrated 84.6% sensitivity and 72.7% specificity for identifying patients meeting criteria for a specific DSM-IV personality disorder. The Level of Personality Functioning Scale had significant and substantial validity correlations with other measures of personality pathology and with clinical judgments regarding functioning, risk, prognosis, and optimal treatment intensity. Furthermore, the single-item Level of Personality Functioning rating was viewed as being as clinically useful as the 10 DSM-IV categories for treatment planning and patient description and was a better predictor of clinician ratings of broad psychosocial functioning than were the 10 DSM-IV categories combined. These results confirm hypotheses that the single-item Level of Personality Functioning Scale rating provides an indication of severity of personality pathology that predicts both assignment of personality disorder diagnosis and clinician appraisals of functioning, risk, prognosis, and needed treatment intensity.

Streptozotocin-Induced Adaptive Modification of Mitochondrial Supercomplexes in Liver of Wistar Rats and the Protective Effect of Moringa oleifera Lam.

PubMed

Alejandra Sánchez-Muñoz, María; Valdez-Solana, Mónica Andrea; Campos-Almazán, Mara Ibeth; Flores-Herrera, Óscar; Esparza-Perusquía, Mercedes; Olvera-Sánchez, Sofia; García-Arenas, Guadalupe; Avitia-Domínguez, Claudia; Téllez-Valencia, Alfredo; Sierra-Campos, Erick

2018-01-01

The increasing prevalence of diabetes continues to be a major health issue worldwide. Alteration of mitochondrial electron transport chain is a recognized hallmark of the diabetic-associated decline in liver bioenergetics; however, the molecular events involved are only poorly understood. Moringa oleifera is used for the treatment of diabetes. However, its role on mitochondrial functionality is not yet established. This study was aimed to evaluate the effect of M. oleifera extract on supercomplex formation, ATPase activity, ROS production, GSH levels, lipid peroxidation, and protein carbonylation. The levels of lipid peroxidation and protein carbonylation were increased in diabetic group. However, the levels were decreased in Moringa -treated diabetic rats. Analysis of in-gel activity showed an increase in all complex activities in the diabetic group, but spectrophotometric determinations of complex II and IV activities were unaffected in this treatment. However, we found an oxygen consumption abolition through complex I-III-IV pathway in the diabetic group treated with Moringa . While respiration with succinate feeding into complex II-III-IV was increased in the diabetic group. These findings suggest that hyperglycemia modifies oxygen consumption, supercomplexes formation, and increases ROS levels in mitochondria from the liver of STZ-diabetic rats, whereas M. oleifera may have a protective role against some alterations.

Streptozotocin-Induced Adaptive Modification of Mitochondrial Supercomplexes in Liver of Wistar Rats and the Protective Effect of Moringa oleifera Lam

PubMed Central

Alejandra Sánchez-Muñoz, María; Flores-Herrera, Óscar; Esparza-Perusquía, Mercedes; Olvera-Sánchez, Sofia; García-Arenas, Guadalupe; Téllez-Valencia, Alfredo

2018-01-01

The increasing prevalence of diabetes continues to be a major health issue worldwide. Alteration of mitochondrial electron transport chain is a recognized hallmark of the diabetic-associated decline in liver bioenergetics; however, the molecular events involved are only poorly understood. Moringa oleifera is used for the treatment of diabetes. However, its role on mitochondrial functionality is not yet established. This study was aimed to evaluate the effect of M. oleifera extract on supercomplex formation, ATPase activity, ROS production, GSH levels, lipid peroxidation, and protein carbonylation. The levels of lipid peroxidation and protein carbonylation were increased in diabetic group. However, the levels were decreased in Moringa-treated diabetic rats. Analysis of in-gel activity showed an increase in all complex activities in the diabetic group, but spectrophotometric determinations of complex II and IV activities were unaffected in this treatment. However, we found an oxygen consumption abolition through complex I-III-IV pathway in the diabetic group treated with Moringa. While respiration with succinate feeding into complex II-III-IV was increased in the diabetic group. These findings suggest that hyperglycemia modifies oxygen consumption, supercomplexes formation, and increases ROS levels in mitochondria from the liver of STZ-diabetic rats, whereas M. oleifera may have a protective role against some alterations. PMID:29686903

Capacities of metabotropic glutamate modulators in counteracting soman-induced seizures in rats.

PubMed

Myhrer, Trond; Mariussen, Espen; Enger, Siri; Aas, Pål

2013-10-15

Current treatment of nerve agent poisoning with ionotropic drugs proves inadequate, and alternative treatment strategies are searched for. Based on positive findings with metabotropic glutamate modulators in microinfusion studies, the present study was initiated to examine anticonvulsant effects of MPEP (2-Methyl-6-(phenylethynyl)pyridine hydrochloride), a metabotropic glutamate receptor 5 antagonist, and DCG-IV ((2S,2'R,3'R)-2-(2',3'-dicarboxycyclopropyl)glycine), a metabotropic glutamate receptor 2/3 agonist, when administered systemically in combinations with HI-6 (1-[([4-(aminocarbonyl)pyridino]methoxy)methyl]-2-[(hydroxyimino)methyl]pyridinium) and procyclidine or HI-6 and levetiracetam relative to the combination of HI-6, procyclidine, and levetiracetam. The results showed that MPEP or DCG-IV combined with HI-6 and procyclidine resulted in substantial antidotal efficacy when administered 20 min after onset of seizures elicited by soman. MPEP or DCG-IV combined with HI-6 and levetiracetam did not terminate seizures and preserve lives. When given 20 min before challenge with soman, DCG-IV in combination with HI-6 and procyclidine provided protection, whereas MPEP combined with HI-6 and procyclidine did not. Combinations with metabotropic glutamate receptor modulators did not achieve the same high level of antidotal efficacy as the combination of HI-6, procyclidine, and levetiracetam. MPEP alone inhibited pseudocholinesterase activity in the brain markedly. A positive correlation was found between latency to seizure onset or full protection and level of pseudocholinesterase activity in brain. MPEP and DCG-IV can serve as effective anticonvulsants against nerve agent poisoning when combined with HI-6 and procyclidine. Metabotropic glutamate receptor modulators may represent an alternative or supplement to treatment with ionotropic drugs. © 2013 Elsevier B.V. All rights reserved.

Assessment of the levels of serum Hsp 70 and ghrelin in children with simple febrile convulsions.

PubMed

Kilic, Mehmet; Gündüzalp, Mehmet; Taskin, Erdal; Aydin, Süleyman; Serin, Hepsen M

2016-04-01

In this study we aimed to evaluate the serum levels of Heat-shock protein (Hsp) 70 and acylated and desacylated ghrelin in patients suffering from a simple febrile convulsion. This cross-sectional study included patients who were diagnosed with a simple febrile convulsion, afebrile tonic-clonic epileptic seizure and upper respiratory tract infection when admitted to our hospital. All patients were aged between six months and 60 months. Patients enrolled in this study were divided into five groups. Group I: patients with a simple febrile convulsion and body temperature of 38º C to 39° C; group II: patients with a simple febrile convulsion and body temperature of 39.1° C to 41° C; group III: patients with primary generalised tonic-clonic seizure and normal body temperature; group IV: patients with upper respiratory infection without convulsion and a body temperature of 38° C to 39° C; and group V: patients with upper respiratory infection without convulsion and a body temperature of 39.1° C to 41° C. The control group included healthy children who were followed up in the healthy children polyclinic. Serum levels of Hsp70 and acylated and des-acylated ghrelin were studied from the blood samples collected from the patients and control group. Serum levels of Hsp70 were higher in the febrile convulsion (groups I, II) and epileptic convulsion and infection (groups IV, V) groups than in the controls (P<0.0001). Moreover, serum levels of acylated and desacylated ghrelin were higher in the simple febrile convulsion (groups I and II) and epileptic convulsion and infection (groups IV and V) groups than in the control (P<0.05). We demonstrated that serum levels of Hsp70 and acylated and desacylated ghrelin increased in patients with a simple febrile convulsion.

Perioperative epidural or intravenous ketamine does not improve the effectiveness of thoracic epidural analgesia for acute and chronic pain after thoracotomy.

PubMed

Tena, Beatriz; Gomar, Carmen; Rios, Jose

2014-06-01

Persistent postsurgical pain (PPP) after thoracotomy effect 50% to 80%. Nerve damage and central sensitization involving NDMDAr activation may play an important role. This study evaluates the efficacy of adding intravenous (IV) or epidural ketamine to thoracic epidural analgesia (TEA) after thoracotomy. Double-blind randomized study on patients undergoing thoracotomy allocated to one of the following: group Kiv (IV racemic ketamine 0.5 mg/kg preincisional +0.25 mg/kg/h for 48 h), group Kep (epidural racemic ketamine 0.5 mg/kg preincisional +0.25 mg/kg/h for 48 h), or group S (saline). Postoperative analgesia was ensured by TEA with ropivacaine and fentanyl. Pain visual analog scales (VAS), Neuropathic Pain Symptom Inventory, Catastrophizing Scale, and Quantitative Sensory Testing, measuring both the peri-incisional and distant hyperalgesia area, were conducted preoperatively and postoperatively until 6 months. Plasma ketamine levels and stability of the analgesic solutions were analyzed. A total of 104 patients were included. PPP incidence was 20% at 6 months. Pain scores on coughing were significantly lower in Kiv and Kep than in S at 24 and 72 hours, but there were no differences afterwards. There were no significant differences in pain at rest, Neuropathic Pain Symptom Inventory, and Catastrophizing Scale, or in the area of mechanical allodynia at any time. Adverse effects were mild. Plasma ketamine levels did not differ significantly between groups. Analgesic solutions were stable. Adding epidural or IV racemic ketamine to TEA after thoracotomy did not lead to any reduction in PPP or allodynia. Epidural administration produced similar plasma ketamine levels to the IV route.

SAFETY AND ACTIVITY OF TEMSIROLIMUS AND BEVACIZUMAB IN PATIENTS WITH ADVANCED RENAL CELL CARCINOMA PREVIOUSLY TREATED WITH TYROSINE KINASE INHIBITORS: A PHASE 2 CONSORTIUM STUDY

PubMed Central

Merchan, Jaime R.; Qin, Rui; Pitot, Henry; Picus, Joel; Liu, Glenn; Fitch, Tom; Maples, William J.; Flynn, Patrick J.; Fruth, Briant F.; Erlichman, Charles

2015-01-01

Purpose Bevacizumab or Temsirolimus regimens have clinical activity in the first line treatment of advanced renal cell carcinoma (RCC). This phase I/II trial was conducted to determine the safety of combining both agents and its efficacy in RCC patients who progressed on at least one prior anti-VEGF receptor tyrosine kinase inhibitor (RTKI) agent. Methods In the phase I portion, eligible patients were treated with Temsirolimus (25 mg IV weekly) and escalating doses of IV Bevacizumab (level 1=5mg/kg; level 2=10 mg/kg) every other week. The primary endpoint for the phase II portion (RTKI resistant patients) was the 6-month progression free rate. Secondary endpoints were response rate, toxicity evaluation, PFS and OS. Results MTD was not reached at the maximum dose administered in 12 phase I patients. Forty evaluable patients were treated with the phase II recommended dose (Temsirolimus 25 mg IV weekly and Bevacizumab 10 mg/kg IV every two weeks). The 6-month progression free rate was 40% (16/40 pts). Median PFS was 5.9 (4-7.8) months, and median OS was 20.6 (11.5-23.7) months. Partial response/stable/progressive disease were seen in 23%/63%/14% of patients. Most common grade 3-4 AEs included fatigue (17.8%), hypertriglyceridemia (11.1%), stomatitis (8.9%), proteinuria (8.9%), abdominal pain (6.7%), and anemia (6.7%). Baseline levels of serum sFLT-1 and VEGF-A were inversely correlated with PFS and OS, respectively. Conclusions Temsirolimus and Bevacizumab is a feasible combination in patients with advanced RCC previously exposed to oral anti-VEGF agents. The safety and efficacy results warrant further confirmatory studies in this patient population. PMID:25556030

[Comparison of effects on the oxidant/antioxidant system of sevoflurane, desflurane and propofol infusion during general anesthesia].

PubMed

Erbas, Mesut; Demiraran, Yavuz; Yildirim, Hayriye Ak; Sezen, Gulbin; Iskender, Abdulkadir; Karagoz, Ibrahim; Kandis, Hayati

2015-01-01

Desflurane and sevoflurane are frequently used for maintenance of anesthesia and studies have shown that these anesthetics cause a variety of changes to the oxidative stress and antioxidative defense mechanisms. This study aims to compare the effects of sevoflurane, desflurane and propofol infusion anesthesia on the oxidant and antioxidant systems of patients undergoing laparoscopic cholecystectomy. 45 patients between 18 and 50 years with planned laparoscopic cholecystectomy under general anesthetic were included in the study. Patients were divided into three groups on the way to surgery: propofol (group P, n=15), sevoflurane (group S, n=15) and desflurane (group D, n=15). All groups were given hypnotic 2mg/kg propofol IV, 1mcg/kg fentanyl IV and 0.1mg/kg vecuronium IV for induction. For maintenance of anesthesia group S were ventilated with 2% sevoflurane, group D cases were given 6% desflurane and group P were given propofol infusions of 12mg/kg/h for the first 10minutes, 9mg/kg/h for the second 10minutes and 6mg/kg/h after that. Before induction and after the operation venous blood samples were taken to evaluate the levels of glutation peroxidase, total oxidants and antioxidants. The 45 patients included in the study were 22 male and 23 female patients. The demographic characteristics of the groups were similar. In the postoperative period we observed that while sevoflurane and propofol increased antioxidants by a statistically significant level, desflurane increased the total oxidants level by a significant amount compared to levels before the operation. Copyright © 2014 Sociedade Brasileira de Anestesiologia. Publicado por Elsevier Editora Ltda. All rights reserved.

76 FR 45710 - Pay in Nonforeign Areas

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-01

... for the purpose of computing nonforeign area COLAs and post differentials, a retained rate established... limited by the normally applicable Executive Schedule level IV (EX-IV) cap on special rates ($155,500 in... special rate in excess of the EX-IV cap at the end of the transition period must be converted to a...

Ground-level falls: 9-year cumulative experience in a regionalized trauma system

PubMed Central

Cade, Angela; King, Brad; Berne, John; Fernandez, Luis; Norwood, Scott

2012-01-01

Ground-level falls (GLFs) are the leading cause of nonfatal hospitalized injuries in the US. We hypothesized that risk-adjusted mortality would not vary between levels of trauma center verification if regional triage functioned appropriately. Data were collected from our regional trauma registry for the years 2001 through 2009. A multilevel mixed-effects logistic regression model was developed to compare risk-adjusted mortality rates by trauma center level and by year. GLF patients numbered 8202 over 9 years with 2.1% mortality. Mean age was 74.5 years and mean probability of death was 0.021 (95% confidence interval [CI], 0.020–0.021). The level I center–treated patients had the highest probability of death (0.033) compared to levels II and III/IV patients (0.023 and 0.018, respectively; P < 0.001), with the highest mortality (6.0%, 3.1%, and 1.1% for levels I, II, and III/IV; P < 0.001). The adjusted odds ratio of mortality was lowest at the level I center (0.71; 95% CI, 0.56–0.91), while no difference existed between level II (1.17; 95% CI, 0.90–1.51) and level III/IV centers (1.22; 95% CI, 0.90–1.66). The 95% CIs for risk-adjusted mortality by year overlapped the 1.0 reference line for each year from 2002 to 2009. In conclusion, regional risk-adjusted mortality for GLF has varied little since 2002. More study is warranted to understand the lower risk-adjusted GLF mortality at the level I center for this growing patient population. PMID:22275774

Renal tubular acidosis type IV in hyperkalaemic patients--a fairy tale or reality?

PubMed

Haas, Christian S; Pohlenz, Inga; Lindner, Ulrich; Muck, Philip M; Arand, Jovana; Suefke, Sven; Lehnert, Hendrik

2013-05-01

Hyperkalaemia is a common feature in hospitalized patients and often attributed to drugs antagonizing the renin-angiotensin-aldosterone system (RAAS) and/or acute kidney injury (AKI), despite significantly preserved glomerular filtration rate (GFR). The objective of this study was to determine the prevalence and role of renal tubular acidosis type IV (RTA IV) in the development of significant hyperkalaemia. A single-centre retrospective study. Patients admitted to a University Hospital over 12 months. Patients with a potassium value > 6·0 mm were identified. Clinical and laboratory data were revisited, and patients with a normal anion gap metabolic acidosis were evaluated for the existence of RTA IV. A total of 57 patients having significant hyperkalaemia (>6·0 mm) were identified. Twelve patients had end-stage renal disease, while 21 patients had solely AKI or progressive chronic renal failure. RTA IV was present in 24 patients (42%), of whom 71% had pre-existing renal insufficiency because of diabetic nephropathy or tubulointerstitial nephritis. All hyperkalaemic patients with urinary/serum electrolytes suggestive of RTA IV had evidence of AKI, but creatinine levels were significantly lower (P < 0·05), while the number of drugs antagonizing the RAAS was comparable. We demonstrated that RTA IV (i) is very common in patients with hyperkalaemia; (ii) should always be suspected in hyperkalaemic patients with only moderately impaired GFR; and (iii) may result in significant hyperkalaemia in the presence of both AKI and drugs antagonizing the RAAS. © 2012 Blackwell Publishing Ltd.

Association of DPP4 Gene Polymorphisms with Type 2 Diabetes Mellitus in Malaysian Subjects

PubMed Central

Ahmed, Radwan H.; Huri, Hasniza Zaman; Al-Hamodi, Zaid; Salem, Sameer D.; Al-absi, Boshra; Muniandy, Sekaran

2016-01-01

Background Genetic polymorphisms of the Dipeptidyl Peptidase 4 (DPP4) gene may play a role in the etiology of type 2 diabetes mellitus (T2DM). This study aimed to investigate the possible association of single nucleotide polymorphisms (SNPs) of the DPP4 gene in Malaysian subjects with T2DM and evaluated whether they had an effect on the serum levels of soluble dipeptidyl peptidase 4 (sDPP-IV). Method Ten DPP4 SNPs were genotyped by TaqMan genotyping assays in 314 subjects with T2DM and 235 controls. Of these, 71 metabolic syndrome (MetS) subjects were excluded from subsequent analysis. The odds ratios (ORs) and their 95% confidence interval (CIs) were calculated using multiple logistic regression for the association between the SNPs of DPP4 and T2DM. In addition, the serum levels of sDPP-IV were investigated to evaluate the association of the SNPs of DPP4 with the sDPP-IV levels. Results Dominant, recessive, and additive genetic models were employed to test the association of DPP4 polymorphisms with T2DM, after adjusting for age, race, gender and BMI. The rs12617656 was associated with T2DM in Malaysian subjects in the recessive genetic model (OR = 1.98, p = 0.006), dominant model (OR = 1.95, p = 0.008), and additive model (OR = 1.63, p = 0.001). This association was more pronounced among Malaysian Indians, recessive (OR = 3.21, p = 0.019), dominant OR = 3.72, p = 0.003) and additive model (OR = 2.29, p = 0.0009). The additive genetic model showed that DPP4 rs4664443 and rs7633162 polymorphisms were associated with T2DM (OR = 1.53, p = 0.039), and (OR = 1.42, p = 0.020), respectively. In addition, the rs4664443 G>A polymorphism was associated with increased sDPP-IV levels (p = 0.042) in T2DM subjects. Conclusions DPP4 polymorphisms were associated with T2DM in Malaysian subjects, and linked to variations in sDPP-IV levels. In addition, these associations were more pronounced among Malaysian Indian subjects. PMID:27111895

Association of DPP4 Gene Polymorphisms with Type 2 Diabetes Mellitus in Malaysian Subjects.

PubMed

Ahmed, Radwan H; Huri, Hasniza Zaman; Al-Hamodi, Zaid; Salem, Sameer D; Al-Absi, Boshra; Muniandy, Sekaran

2016-01-01

Genetic polymorphisms of the Dipeptidyl Peptidase 4 (DPP4) gene may play a role in the etiology of type 2 diabetes mellitus (T2DM). This study aimed to investigate the possible association of single nucleotide polymorphisms (SNPs) of the DPP4 gene in Malaysian subjects with T2DM and evaluated whether they had an effect on the serum levels of soluble dipeptidyl peptidase 4 (sDPP-IV). Ten DPP4 SNPs were genotyped by TaqMan genotyping assays in 314 subjects with T2DM and 235 controls. Of these, 71 metabolic syndrome (MetS) subjects were excluded from subsequent analysis. The odds ratios (ORs) and their 95% confidence interval (CIs) were calculated using multiple logistic regression for the association between the SNPs of DPP4 and T2DM. In addition, the serum levels of sDPP-IV were investigated to evaluate the association of the SNPs of DPP4 with the sDPP-IV levels. Dominant, recessive, and additive genetic models were employed to test the association of DPP4 polymorphisms with T2DM, after adjusting for age, race, gender and BMI. The rs12617656 was associated with T2DM in Malaysian subjects in the recessive genetic model (OR = 1.98, p = 0.006), dominant model (OR = 1.95, p = 0.008), and additive model (OR = 1.63, p = 0.001). This association was more pronounced among Malaysian Indians, recessive (OR = 3.21, p = 0.019), dominant OR = 3.72, p = 0.003) and additive model (OR = 2.29, p = 0.0009). The additive genetic model showed that DPP4 rs4664443 and rs7633162 polymorphisms were associated with T2DM (OR = 1.53, p = 0.039), and (OR = 1.42, p = 0.020), respectively. In addition, the rs4664443 G>A polymorphism was associated with increased sDPP-IV levels (p = 0.042) in T2DM subjects. DPP4 polymorphisms were associated with T2DM in Malaysian subjects, and linked to variations in sDPP-IV levels. In addition, these associations were more pronounced among Malaysian Indian subjects.

What makes a hospital manager competent at the middle and senior levels?

PubMed

Liang, Zhanming; Leggat, Sandra G; Howard, Peter F; Koh, Lee

2013-11-01

The purpose of this paper is to confirm the core competencies required for middle to senior level managers in Victorian public hospitals in both metropolitan and regional/rural areas. This exploratory mixed-methods study used a three-step approach which included position description content analysis, focus group discussions and online competency verification and identification survey. The study validated a number of key tasks required for senior and middle level hospital managers (levels II, III and IV) and identified and confirmed the essential competencies for completing these key tasks effectively. As a result, six core competencies have been confirmed as common to the II, III and IV management levels in both the Melbourne metropolitan and regional/rural areas. Six core competencies are required for middle to senior level managers in public hospitals which provide guidance to the further development of the competency-based educational approach for training the current management workforce and preparing future health service managers. With the detailed descriptions of the six core competencies, healthcare organisations and training institutions will be able to assess the competency gaps and managerial training needs of current health service managers and develop training programs accordingly.

Selective thoracic surgery in the Lenke type 1A: King III and King IV type curves.

PubMed

Parisini, P; Di Silvestre, M; Lolli, F; Bakaloudis, G

2009-06-01

Pedicle screw fixation enables enhanced three-dimensional correction of spinal deformities and effectively shortens the distal fusion level. However, the choice of distal fusion level is still controversial in single thoracic idiopathic scoliosis with the lumbar compensatory curve not crossing the middle line (Lenke type 1 with modifier A or King type III and IV curves).The authors retrospectively analyzed 31 patients treated by segmental pedicular instrumentation alone, affected by a single thoracic adolescent idiopathic scoliosis with a compensatory lumbar curve not crossing the midline (Lenke 1A), with an average age of 16.3 years (range 10-22 years). The patients with regard to the King classification were also assessed. A statistical analysis was performed to determine whether the two groups (King III, King IV) presented differences concerning the level of the stable vertebra (SV), end vertebra (EV), and neutral vertebra (NV) and were also analyzed the results at follow-up regarding the relationships between the SV, EV, and lowest instrumented vertebra (LIV). The statistical analysis showed a significant difference between the two curve types. In the King III type curve the SV, EV, and NV appeared to be more proximal than those of the King IV type curve and the segments between the SV, EV, and NV appeared to be reduced in King III curves compared with King IV curves. At a follow-up of 3.2 years (range 2.2-5) the thoracic curve showed a correction of 58.4% (from 62.3 degrees to 26.6 degrees ) and compensatory lumbar curve an average spontaneous correction of 52.4% (from 38.1 degrees to 18.1 degrees ).The position of the LIV was shorter than the position of the SV in 30 patients (97%) with an average "salvage" of 2.1 (from 1 to 4) distal fusion levels. Four cases (13%), all affected by a King IV type curve, presented at follow-up an unsatisfactory results due to an "adding on" phenomenon. The statistical analysis confirmed that this phenomenon was correlated with The King IV curve (P = 0.043; Chi-square test) and that the only predictive parameter for its onset was the LIV-SV difference (odds ratio = 0.093; with a confidence interval of 0.008-1): every time that in King IV curve type the LIV was three or more levels shorter than the stable vertebra at follow-up the "adding on" phenomenon was present. The authors conclude that Lenke's type 1 with modifier A includes two kinds of curves, King III and King IV and that the Lenke's type 2 curves and King V with the lumbar curve not crossing the middle line have a similar behavior. Therefore, it is of authors' opinion that "the adding on phenomenon" could be prevented by more rigidly defining K. IV versus K. III curves. In Lenke's 1/2 A-K. IV/V type with the rotation of the first vertebra just below the thoracic lower EV in the same direction as the thoracic curve, and when SV and EV show more than two levels of difference, it is necessary to extend the lower fusion down to L2 or L3 (not more than two levels shorter than the SV). Whereas in Lenke's 1/2 A-K. III/V with the rotation of the first proximal vertebra of lumbar curve in the opposite direction to the thoracic apex and when SV and EV show not more than two level gap differences, the position of the lowest instrumented vertebra can be two or three levels shorter than the stable vertebra with satisfactory postoperative spinal balance. Therefore, the stable vertebra and the rotation of lumbar curve are considered to be a reliable guide for selecting the lower level of fusion.

The nature of electron acceptor (MnIV/NO3) triggers differential expression of genes associated with stress and ammonium limitation responses in Shewanella algae C6G3.

PubMed

Aigle, Axel; Bonin, Patricia; -Nunez, Nicolas Fernandez; Loriod, Béatrice; Guasco, Sophie; Bergon, Aurélie; Armougom, Fabrice; Iobbi-Nivol, Chantal; Imbert, Jean; Michotey, Valérie

2018-03-16

Shewanella algae C6G3 can reduce dissimilatively nitrate into ammonium and manganese-oxide (MnIV) into MnII. It has the unusual ability to produce anaerobically nitrite from ammonium in the presence of MnIV. To gain insight into their metabolic capabilities, global mRNA expression patterns were investigated by RNA-seq and qRT-PCR in cells growing with lactate and ammonium as carbon and nitrogen sources and with either MnIV or nitrate as electron acceptors. Gene exhibiting higher expression levels in the presence of MnIV belonged to functional categories of carbohydrate, coenzyme, lipid metabolisms and inorganic ion transport. Comparative transcriptomic pattern between MnIV and NO3 revealed that the strain presented an ammonium limitation status with MnIV, despite the presence of non-limiting concentration of ammonium under both culture conditions. In addition, in presence of MnIV, ntrB/nrtC regulators, ammonium channel, nitrogen regulatory protein P-II, glutamine synthetase and asparagine synthetase glutamine dependent genes were over-represented. Under nitrate condition, the expression of genes involved in the synthesis of several amino acids was increased. Finally, expression level of genes associated with the general stress response was also amplified and among them, katE, a putative catalase/peroxidase present on several Shewanella genomes, was highly expressed with a relative median value higher in MnIV condition.

Participation in home, extracurricular, and community activities among children and young people with cerebral palsy.

PubMed

Orlin, Margo N; Palisano, Robert J; Chiarello, Lisa A; Kang, Lin-Ju; Polansky, Marcia; Almasri, Nihad; Maggs, Jill

2010-02-01

Participation in home, extracurricular, and community activities is a desired outcome of rehabilitation services for children and young people with cerebral palsy (CP). The purpose of this study was to investigate the effect of age and gross motor function on participation among children and young people with CP. Five hundred participants (277 males, 223 females) were grouped by age and Gross Motor Function Classification System (GMFCS) level. There were 291 children aged 6 to 12 years and 209 young people aged 13 to 21 years. There were 128 participants in GMFCS level I, 220 in levels II/III, and 152 in levels IV/V. Participants completed the Children's Assessment of Participation and Enjoyment to measure number of activities (diversity) and how often they were performed (intensity) in the past 4 months. Children had higher overall participation diversity and intensity than young people (p<0.001). Children and young people in GMFCS level I had the highest overall participation, followed by children and young people in levels II/III and IV/V. Children had higher participation in recreational (p<0.001) but not formal (such as team sports or clubs) or physical activities. Children (p<0.01) and young people (p<0.001) in level I had the highest participation in physical activities; diversity and intensity were generally low. The findings provide evidence of the effect of age and gross motor function on participation of children and young people with CP. Low participation in physical activities may have implications for fitness and health, especially for children and young people in GMFCS levels IV and V.

Oral versus intravenous iron replacement therapy distinctly alters the gut microbiota and metabolome in patients with IBD

PubMed Central

Lee, Thomas; Clavel, Thomas; Smirnov, Kirill; Schmidt, Annemarie; Lagkouvardos, Ilias; Walker, Alesia; Lucio, Marianna; Michalke, Bernhard; Schmitt-Kopplin, Philippe; Fedorak, Richard; Haller, Dirk

2017-01-01

Objective Iron deficiency is a common complication in patients with IBD and oral iron therapy is suggested to exacerbate IBD symptoms. We performed an open-labelled clinical trial to compare the effects of per oral (PO) versus intravenous (IV) iron replacement therapy (IRT). Design The study population included patients with Crohn's disease (CD; N=31), UC (N=22) and control subjects with iron deficiency (non-inflamed, NI=19). After randomisation, participants received iron sulfate (PO) or iron sucrose (IV) over 3 months. Clinical parameters, faecal bacterial communities and metabolomes were assessed before and after intervention. Results Both PO and IV treatments ameliorated iron deficiency, but higher ferritin levels were observed with IV. Changes in disease activity were independent of iron treatment types. Faecal samples in IBD were characterised by marked interindividual differences, lower phylotype richness and proportions of Clostridiales. Metabolite analysis also showed separation of both UC and CD from control anaemic participants. Major shifts in bacterial diversity occurred in approximately half of all participants after IRT, but patients with CD were most susceptible. Despite individual-specific changes in phylotypes due to IRT, PO treatment was associated with decreased abundances of operational taxonomic units assigned to the species Faecalibacterium prausnitzii, Ruminococcus bromii, Dorea sp. and Collinsella aerofaciens. Clear IV-specific and PO-specific fingerprints were evident at the level of metabolomes, with changes affecting cholesterol-derived host substrates. Conclusions Shifts in gut bacterial diversity and composition associated with iron treatment are pronounced in IBD participants. Despite similar clinical outcome, oral administration differentially affects bacterial phylotypes and faecal metabolites compared with IV therapy. Trial registration number clinicaltrial.gov (NCT01067547). PMID:26848182

Clinical value of DSM IV and DSM 5 criteria for diagnosing the most prevalent somatoform disorders in patients with medically unexplained physical symptoms (MUPS).

PubMed

van Dessel, Nikki Claassen-; van der Wouden, Johannes C; Dekker, Joost; van der Horst, Henriette E

2016-03-01

This study aimed (1) to describe frequencies of DSM IV somatisation disorder, undifferentiated somatoform disorder and pain disorder versus DSM 5 somatic symptom disorder (SSD) in a multi-setting population of patients with medically unexplained physical symptoms (MUPS), (2) to investigate differences in sociodemographic and (psycho)pathological characteristics between these diagnostic groups and (3) to explore the clinical relevance of the distinction between mild and moderate DSM 5 SSD. We used baseline data of a cohort of 325 MUPS patients. Measurements included questionnaires about symptom severity, physical functioning, anxiety, depression, health anxiety and illness perceptions. These questionnaires were used as proxy measures for operationalization of DSM IV and DSM 5 diagnostic criteria. 92.9% of participants fulfilled criteria of a DSM IV somatoform disorder, while 45.5% fulfilled criteria of DSM 5 SSD. Participants fulfilling criteria of DSM 5 SSD suffered from more severe symptoms than those only fulfilling criteria of a DSM IV somatoform disorder(mean PHQ-15 score of 13.98 (SD 5.17) versus 11.23 (SD 4.71), P-value<0.001). Furthermore their level of physical functioning was significantly lower. Compared to patients with mild SSD, patients with moderate SSD suffered from significantly lower physical functioning and higher levels of depression. Within a population of MUPS patients DSM 5 SSD criteria are more restrictive than DSM IV criteria for somatoform disorders. They are associated with higher symptom severity and lower physical functioning. However, further specification of the positive psychological criteria of DSM 5 SSD may improve utility in research and practice. Copyright © 2016 Elsevier Inc. All rights reserved.

Combination of TS-021 with metformin improves hyperglycemia and synergistically increases pancreatic β-cell mass in a mouse model of type 2 diabetes.

PubMed

Tajima, Atsushi; Hirata, Takashi; Taniguchi, Kazuo; Kondo, Yukiko; Kato, Sota; Saito-Hori, Masako; Ishimoto, Tsuyoshi; Yamamoto, Koji

2011-10-24

The objectives of this study were to elucidate the effects of a potent dipeptidyl peptidase (DPP)-IV inhibitor, TS-021, combined with/without metformin on glycemic control and pathological changes in pancreatic islets in high-fat diet and streptozotocin-induced (HFD-STZ) diabetic mice. The anti-diabetic effects of TS-021 and/or metformin in HFD-STZ mice were examined in both acute and chronic treatment studies. In addition, we performed immunohistochemical analysis after repeated administration of TS-021 and/or metformin to HFD-STZ mice twice a day for 5 weeks. In the acute treatment study, TS-021 and/or metformin significantly improved glucose tolerance and glucagon-like peptide-1 (GLP-1) level, and TS-021 alone or in combination with metformin significantly increased the plasma insulin level after nutrient ingestion. In the chronic treatment study, TS-021 in combination with metformin significantly lowered the glycosylated hemoglobin level, plasma insulin level, and α-cell-to-β-cell area ratio in pancreatic islets. In particular, the combined treatment synergistically increased the insulin-positive area in pancreatic islets from 32.3% in diabetic mice treated with the vehicle to 51.1% (TS-021 alone, 35.3%; metformin alone, 30.6%). The present study demonstrated that the coadministration of TS-021 and metformin synergistically improved the islet morphology by increasing the circulating level of biologically active GLP-1, which is thought to result from two different mechanisms (namely, an increase in GLP-1 secretion and DPP-IV inhibition). These findings strongly support the rationale for combined treatment with DPP-IV inhibitors plus metformin in clinical practice by clearly demonstrating an anti-diabetic effect associated with the remarkable improvement in pancreatic β-cell morphology. Copyright © 2011 Elsevier Inc. All rights reserved.

Return to Sport Following Shoulder Surgery in the Elite Pitcher

PubMed Central

Harris, Joshua D.; Frank, Jonathan M.; Jordan, Mark A.; Bush-Joseph, Charles A.; Romeo, Anthony A.; Gupta, Anil K.; Abrams, Geoffrey D.; McCormick, Frank M.; Bach, Bernard R.

2013-01-01

Context: The ability to return to elite pitching, performance, and clinical outcomes of shoulder surgery in elite baseball pitchers are not definitively established. Objective: To determine (1) the rate of return to sport (RTS) in elite pitchers following shoulder surgery, (2) postoperative clinical outcomes upon RTS, and (3) performance upon RTS and to compare RTS rates in different types of shoulder surgery. Data Sources: Using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and checklist, Medline, SciVerse Scopus, SportDiscus, and Cochrane Central Register of Controlled Trials were searched. Study Selection: Levels I-IV evidence were eligible for inclusion if performance-based (eg, RTS) and/or clinical outcome–based reporting of outcomes were reported following surgical treatment of shoulder pathology in elite pitchers (major or minor league or collegiate). Data Extraction: Subject, shoulder, and pre- and postoperative performance-based variables of interest were extracted. All shoulder surgery types were potentially inclusive (eg, open, arthroscopic, rotator cuff, labrum, biceps, acromioclavicular joint, fracture). Study methodological quality was analyzed using the Modified Coleman Methodology Score (MCMS). Results: Six studies were analyzed (287 elite male pitchers [mean age, 27 years] who underwent shoulder surgery, with 99% on the dominant, throwing shoulder). MCMS was 38 (poor). Most pitchers were professional, with a mean career length of 6.58 years and postoperative clinical follow-up of 3.62 years. In 5 of 6 studies, multiple diagnoses were addressed concomitantly at surgery. Rate of RTS was 68% at mean 12 months following surgery. Twenty-two percent of Major League Baseball (MLB) pitchers never RTS in MLB. Overall performance did improve following surgery; however, this did not improve to pre-injury levels. Conclusion: In this systematic review, the rate of return to elite baseball pitching following surgery was established. Performance tended to decrease prior to surgery and gradually improve postoperatively, though not reaching pre-injury levels of pitching. Level of Evidence: IV (systematic review of studies level I-IV evidence), therapeutic. PMID:24459557

Efficacy and safety of intravenous secukinumab in noninfectious uveitis requiring steroid-sparing immunosuppressive therapy.

PubMed

Letko, Erik; Yeh, Steven; Foster, C Stephen; Pleyer, Uwe; Brigell, Mitchell; Grosskreutz, Cynthia L

2015-05-01

Secukinumab, a fully human anti-interleukin-17A monoclonal antibody, exhibited promising activity in a proof-of-concept study when administered in intravenous (IV) doses to patients with active, chronic, noninfectious uveitis. This study compared the efficacy and safety of different IV and subcutaneous (SC) doses of secukinumab in patients with noninfectious uveitis. Multicenter, randomized, double-masked, dose-ranging, phase 2 clinical trial. Thirty-seven patients with active noninfectious intermediate uveitis, posterior uveitis, or panuveitis who required corticosteroid-sparing immunosuppressive therapy. Patients were randomized to secukinumab 300 mg SC every 2 weeks for 4 doses, secukinumab 10 mg/kg IV every 2 weeks for 4 doses, or secukinumab 30 mg/kg IV every 4 weeks for 2 doses. Intravenous or SC saline was administered to maintain masking. Efficacy was assessed on day 57 (2-4 weeks after last dose). Percentage of patients with treatment response, defined as (1) at least a 2-grade reduction in vitreous haze score or trace or absent vitreous haze in the study eye without an increase in corticosteroid dose and without uveitis worsening or (2) reduction in corticosteroid dosages to prespecified levels without uveitis worsening. Percentage of patients with remission, defined as anterior chamber cell and vitreous haze scores of 0 or 0.5+ in both eyes without corticosteroid therapy or uveitis worsening. Secukinumab 30 mg/kg IV and 10 mg/kg IV, compared with the 300 mg SC dose, produced higher responder rates (72.7% and 61.5% vs. 33.3%, respectively) and remission rates (27.3% and 38.5% vs. 16.7%, respectively). Statistical and clinical superiority for the 30 mg/kg IV dose compared with the 300 mg SC dose was established in a Bayesian probability model. Other measures, including time to response onset, change in visual acuity, and change in vitreous haze score, showed numeric trends favoring IV dosing. Secukinumab, administered in IV or SC formulations, appeared safe and was well tolerated. Intravenous secukinumab was effective and well tolerated in noninfectious uveitis requiring systemic corticosteroid-sparing immunosuppressive therapy. Greater activity with IV dosing suggests that patients may not receive sufficient drug with SC administration. High-dose IV secukinumab may be necessary to deliver secukinumab in therapeutic concentrations. Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Resonance lines and energy levels of Cs III, Ba IV, and La V

NASA Technical Reports Server (NTRS)

Epstein, G. L.; Reader, J.

1976-01-01

Spectra of Cs III, Ba IV, and La V were photographed in a low-voltage sliding spark on a 10.7 m normal-incidence vacuum spectrograph. These ions are isoelectronic with neutral iodine and display a halogen-like energy level structure. Detailed isoelectronic comparisons, level transition diagrams, and tabular data on the transitions of the ions and percentage compositions of Cs III configurations are presented.

Subchronic Exposure to Arsenic Represses the TH/TRβ1-CaMK IV Signaling Pathway in Mouse Cerebellum.

PubMed

Guan, Huai; Li, Shuangyue; Guo, Yanjie; Liu, Xiaofeng; Yang, Yi; Guo, Jinqiu; Li, Sheng; Zhang, Cong; Shang, Lixin; Piao, Fengyuan

2016-01-26

We previously reported that arsenic (As) impaired learning and memory by down-regulating calmodulin-dependent protein kinase IV (CaMK IV) in mouse cerebellum. It has been documented that the thyroid hormone receptor (TR)/retinoid X receptor (RXR) heterodimer and thyroid hormone (TH) may be involved in the regulation of CaMK IV. To investigate whether As affects the TR/RXR heterodimer and TH, we determined As concentration in serum and cerebellum, 3,5,3'-triiodothyronine (T3) and thyroxin (T4) levels in serum, and expression of CaMK IV, TR and RXR in cerebellum of mice exposed to As. Cognition function was examined by the step-down passive avoidance task and Morris water maze (MWM) tests. Morphology of the cerebellum was observed by Hematoxylin-Eosin staining under light microscope. Our results showed that the concentrations of As in the serum and cerebellum of mice both increased with increasing As-exposure level. A significant positive correlation was found between the two processes. Adeficit in learning and memory was found in the exposed mice. Abnormal morphologic changes of Purkinje cells were observed in cerebellum of the exposed mice. Moreover, the cerebellar expressions of CaMK IV protein and the TRβ gene, and TRβ1 protein were significantly lower in As-exposed mice than those in controls. Subchronic exposure to As appears to increase its level in serum and cerebella of mice, impairing learning and memory and down-regulating expression of TRβ1 as well as down-stream CaMK IV. It is also suggested that the increased As may be responsible for down-regulation of TRβ1 and CaMK IV in cerebellum and that the down-regulated TRβ1 may be involved in As-induced impairment of learning and memory via inhibiting CaMK IV and its down-stream pathway.

Substance P and neurokinin A metabolism by cultured human skeletal muscle myocytes and fibroblasts.

PubMed

Russell, J S; Chi, H; Lantry, L E; Stephens, R E; Ward, P E

1996-01-01

A recent study determined that cultured human skeletal muscle adult myoblasts, myotubes, and fibroblasts degraded angiotensins and kinins via neutral endopeptidase-24.11 (NEP-24.11: EC 3.4.24.11) and aminopeptidase N (APN: EC 3.4.11.2). Due to the possible importance of other peptides to skeletal muscle blood flow and function, the present study looked specifically at the metabolism of the neurokinins substance P (SP) and neurokinin A (NKA) by skeletal muscle peptidases. The results show that SP is degraded not only by NEP-24.11, but also sequentially by dipeptidyl(amino)peptidase IV (DAP IV: EC 3.4.14.5)/APN. NKA is unaffected by DAP IV but is metabolized by NEP-24.11 and APN. NEP-24.11 was inhibited by phosphoramidon (IC50 = 80 nM), thiorphan and ZINCOV, DAP IV by diprotin A (IC50 = 8 microM), and APN by amastatin (IC50 = 50 nM) and bestatin (IC50 = 100 microM). Skeletal muscle myocyte and fibroblast metabolism of SP and NKA may regulate local skeletal muscle vascular and extravascular functions including SP- and NKA-mediated nerve-induced vasodilation. Inhibition of both NEP-24.11 and DAP IV/APN may increase skeletal muscle blood flow and decrease peripheral vascular resistance via potentiation of local neurokinin levels.

Arabidopsis RNA Polymerase V Mediates Enhanced Compaction and Silencing of Geminivirus and Transposon Chromatin during Host Recovery from Infection.

PubMed

Coursey, Tami; Regedanz, Elizabeth; Bisaro, David M

2018-04-01

Plants employ RNA-directed DNA methylation (RdDM) and dimethylation of histone 3 lysine 9 (H3K9me2) to silence geminiviruses and transposable elements (TEs). We previously showed that canonical RdDM (Pol IV-RdDM) involving RNA polymerases IV and V (Pol IV and Pol V) is required for Arabidopsis thaliana to recover from infection with Beet curly top virus lacking a suppressor protein that inhibits methylation (BCTV L2 - ). Recovery, which is characterized by reduced viral DNA levels and symptom remission, allows normal floral development. Here, we used formaldehyde-assisted isolation of regulatory elements (FAIRE) to confirm that >90% of BCTV L2 - chromatin is highly compacted during recovery, and a micrococcal nuclease-chromatin immunoprecipitation assay showed that this is largely due to increased nucleosome occupancy. Physical compaction correlated with augmented cytosine and H3K9 methylation and with reduced viral gene expression. We additionally demonstrated that these phenomena are dependent on Pol V and by extension the Pol IV-RdDM pathway. BCTV L2 - was also used to evaluate the impact of viral infection on host loci, including repressed retrotransposons Ta3 and Athila6A Remarkably, an unexpected Pol V-dependent hypersuppression of these TEs was observed, resulting in transcript levels even lower than those detected in uninfected plants. Hypersuppression is likely to be especially important for natural recovery from wild-type geminiviruses, as viral L2 and AL2 proteins cause ectopic TE expression. Thus, Pol IV-RdDM targets both viral and TE chromatin during recovery, simultaneously silencing the majority of viral genomes and maintaining host genome integrity by enforcing tighter control of TEs in future reproductive tissues. IMPORTANCE In plants, RdDM pathways use small RNAs to target cytosine and H3K9 methylation, thereby silencing DNA virus genomes and transposable elements (TEs). Further, Pol IV-RdDM involving Pol IV and Pol V is a key aspect of host defense that can lead to recovery from geminivirus infection. Recovery is characterized by reduced viral DNA levels and symptom remission and thus allows normal floral development. Studies described here demonstrate that the Pol V-dependent enhanced viral DNA and histone methylation observed during recovery result in increased chromatin compaction and suppressed gene expression. In addition, we show that TE-associated chromatin is also targeted for hypersuppression during recovery, such that TE transcripts are reduced below the already low levels seen in uninfected plants. Thus, Pol IV-RdDM at once silences the majority of viral genomes and enforces a tight control over TEs which might otherwise jeopardize genome integrity in future reproductive tissue. Copyright © 2018 American Society for Microbiology.

Dipeptidyl peptidase IV (DPP-IV) inhibition prevents fibrosis in adipose tissue of obese mice.

PubMed

Marques, Ana Patrícia; Cunha-Santos, Janete; Leal, Helena; Sousa-Ferreira, Lígia; Pereira de Almeida, Luís; Cavadas, Cláudia; Rosmaninho-Salgado, Joana

2018-03-01

During the development of obesity the expansion of white adipose tissue (WAT) leads to a dysregulation and an excessive remodeling of extracellular matrix (ECM), leading to fibrosis formation. These ECM changes have high impact on WAT physiology and may change obesity progression. Blocking WAT fibrosis may have beneficial effects on the efficacy of diet regimen or therapeutical approaches in obesity. Since dipeptidyl peptidase IV (DPP-IV) inhibitors prevent fibrosis in tissues, such as heart, liver and kidney, the objective of this study was to assess whether vildagliptin, a DPP-IV inhibitor, prevents fibrosis in WAT in a mouse model of obesity, and to investigate the mechanisms underlying this effect. We evaluated the inhibitory effect of vildagliptin on fibrosis markers on WAT of high-fat diet (HFD)-induced obese mice and on 3T3-L1 cell line of mouse adipocytes treated with a fibrosis inducer, transforming growth factor beta 1 (TGFβ1). Vildagliptin prevents the increase of fibrosis markers in WAT of HFD-fed mice and reduces blood glucose, serum triglycerides, total cholesterol and leptin levels. In the in vitro study, the inhibition of DPP-IV with vildagliptin, neuropeptide Y (NPY) treatment and NPY Y 1 receptor activation prevents ECM deposition and fibrosis markers increase induced by TGFβ1 treatment. Vildagliptin prevents fibrosis formation in adipose tissue in obese mice, at least partially through NPY and NPY Y 1 receptor activation. This study highlights the importance of vildagliptin in the treatment of fibrosis that occur in obesity. Copyright © 2017 Elsevier B.V. All rights reserved.

Continued expansion of USA300-like methicillin-resistant Staphylococcus aureus (MRSA) among hospitalized patients in the United States.

PubMed

Tickler, Isabella A; Goering, Richard V; Mediavilla, Jose R; Kreiswirth, Barry N; Tenover, Fred C

2017-08-01

We characterized spa types, SCCmec types, and antimicrobial resistance patterns of 516 methicillin-resistant Staphylococcus aureus (MRSA) isolates, collected between 2011 and 2014 from nares and blood cultures of United States patients. Among nares isolates, 45 spa types were observed; 29.9% were t002/SCCmec II and 30.9% were t008/SCCmec IV. Among blood isolates, 40 spa types were identified; 24.4% were t002/SCCmec II and 39.9% were type t008/SCCmec IV. Compared to data from our 2009-2010 survey, the percentage of t008/SCCmec IV isolates from nares increased significantly (20.4%-30.9%; P=0.004) while the percentage from positive blood cultures remained similar (39.2% versus 39.9%; P=0.921). There were also significant changes in the overall antimicrobial resistance patterns observed, including the decrease of the clindamycin, erythromycin, levofloxacin and moxifloxacin multidrug resistance pattern, likely the result of t002/SCCmec II strains being displaced by t008/SCCmec IV strains. Rates of high-level mupirocin resistance did not change significantly from our past study (4.1% compared to 4.7%; P=0.758) but an increase in low-level resistance, particularly among t002/SCCmec II isolates, was observed. Copyright © 2017 Elsevier Inc. All rights reserved.

Systematic review of "filling" procedures for lip augmentation regarding types of material, outcomes and complications.

PubMed

San Miguel Moragas, Joan; Reddy, Rajgopal R; Hernández Alfaro, Federico; Mommaerts, Maurice Y

2015-07-01

The ideal lip augmentation technique provides the longest period of efficacy, lowest complication rate, and best aesthetic results. A myriad of techniques have been described for lip augmentation, but the optimal approach has not yet been established. This systematic review with meta-regression will focus on the various filling procedures for lip augmentation (FPLA), with the goal of determining the optimal approach. A systematic search for all English, French, Spanish, German, Italian, Portuguese and Dutch language studies involving FPLA was performed using these databases: Elsevier Science Direct, PubMed, Highwire Press, Springer Standard Collection, SAGE, DOAJ, Sweetswise, Free E-Journals, Ovid Lippincott Williams & Wilkins, Willey Online Library Journals, and Cochrane Plus. The reference section of every study selected through this database search was subsequently examined to identify additional relevant studies. The database search yielded 29 studies. Nine more studies were retrieved from the reference sections of these 29 studies. The level of evidence ratings of these 38 studies were as follows: level Ib, four studies; level IIb, four studies; level IIIb, one study; and level IV, 29 studies. Ten studies were prospective. This systematic review sought to highlight all the quality data currently available regarding FPLA. Because of the considerable diversity of procedures, no definitive comparisons or conclusions were possible. Additional prospective studies and clinical trials are required to more conclusively determine the most appropriate approach for this procedure. IV. Copyright © 2015 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

In search of mixed anxiety-depressive disorder: a primary care study.

PubMed

Means-Christensen, Adrienne J; Sherbourne, Cathy D; Roy-Byrne, Peter P; Schulman, Martin C; Wu, Jennifer; Dugdale, David C; Lessler, Daniel; Stein, Murray B

2006-01-01

The diagnosis of mixed anxiety-depressive disorder, as proposed in DSM-IV, is intended to be useful in settings such as primary care, where low-level anxiety and depressive symptoms may cause clinically significant impairment but are undiagnosable using current criteria. Evidence of the prevalence of this diagnosis is, however, lacking, particularly since the publication of the proposed diagnostic criteria in DSM-IV. Our study examined symptoms of anxiety and depression in 65 primary care patients screened for anxiety and depression while visiting their doctor. Results indicated that of the 37 patients without a diagnosable anxiety or depressive disorder, none had symptoms of depression and anxiety accompanied by interference that the patient deemed significant and attributable to his or her symptoms. These data dispute the need for a mixed anxiety-depression category (beyond mood and anxiety syndromes currently in DSM-IV) in future editions of the DSM.

A Meta-Analytic Review of the Relationships Between the Five-Factor Model and DSM-IV-TR Personality Disorders: A Facet Level Analysis

PubMed Central

Samuel, Douglas B.; Widiger, Thomas A.

2008-01-01

Theory and research have suggested that the personality disorders contained within the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR) can be understood as maladaptive variants of the personality traits included within the five-factor model (FFM). The current meta-analysis of FFM personality disorder research both replicated and extended the 2004 work of Saulsman and Page (The five-factor model and personality disorder empirical literature: A meta-analytic review. Clinical Psychology Review, 23, 1055-1085) through a facet-level analysis that provides a more specific and nuanced description of each DSM-IV-TR personality disorder. The empirical FFM profiles generated for each personality disorder were generally congruent at the facet level with hypothesized FFM translations of the DSM-IV-TR personality disorders. However, notable exceptions to the hypotheses did occur and even some findings that were consistent with FFM theory could be said to be instrument specific. PMID:18708274

A study of metabolic balance in crewmembers of Skylab IV

NASA Technical Reports Server (NTRS)

Rambaut, P. C.; Leach, C. S.; Whedon, G. D.

1979-01-01

A metabolic balance study was conducted on the three crewmembers of the 84-day Skylab IV earth orbital mission. Dietary intake was controlled, monitored, and kept very nearly constant for a period commencing 21 days prior to flight, throughout flight, and for a period of 18 days postflight. Within the first 30 days of flight urine calcium rose to a level approx. 100% above preflight levels and remained elevated for the remainder of the flight. Fecal calcium excretion increased more slowly but continued to accelerate throughout the flight and did not return to baseline levels during the postflight period. Urinary nitrogen increased to 25-30% above preflight levels within one month following launch and thereafter gradually subsided toward control values. The overall losses of calcium averaged approx. 200 mg per day throughout the mission while nitrogen losses averaged 590 mg. Various other indices of musculoskeletal deterioration are discussed and correlated. The parallelism between the effects of weightlessness and bed rest is reviewed. It is noted, that no evidence is yet available as to the identity of the initial biological response to the absence of gravity.

Equilibrium between Different Coordination Geometries in Oxidovanadium(IV) Complexes

ERIC Educational Resources Information Center

Ugone, Valeria; Garribba, Eugenio; Micera, Giovanni; Sanna, Daniele

2015-01-01

In this laboratory activity, the equilibrium between square pyramidal and octahedral V(IV)O[superscript 2+] complexes is described. We propose a set of experiments to synthesize and characterize two types of V(IV)O[superscript 2+] complexes. The experiment allows great flexibility and may be effectively used at a variety of levels and the activity…

Levels of heroin and its metabolites in blood and brain extracellular fluid after i.v. heroin administration to freely moving rats

PubMed Central

Gottås, A; Øiestad, E L; Boix, F; Vindenes, V; Ripel, Å; Thaulow, C H; Mørland, J

2013-01-01

BACKGROUND AND PURPOSE Heroin, with low affinity for μ-opioid receptors, has been considered to act as a prodrug. In order to study the pharmacokinetics of heroin and its active metabolites after i.v. administration, we gave a bolus injection of heroin to rats and measured the concentration of heroin and its metabolites in blood and brain extracellular fluid (ECF). EXPERIMENTAL APPROACH After an i.v. bolus injection of heroin to freely moving Sprague–Dawley rats, the concentrations of heroin and metabolites in blood samples from the vena jugularis and in microdialysis samples from striatal brain ECF were measured by ultraperformance LC-MS/MS. KEY RESULTS Heroin levels decreased very fast, both in blood and brain ECF, and could not be detected after 18 and 10 min respectively. 6-Monoacetylmorphine (6-MAM) increased very rapidly, reaching its maximal concentrations after 2.0 and 4.3 min, respectively, and falling thereafter. Morphine increased very slowly, reaching its maximal levels, which were six times lower than the highest 6-MAM concentrations, after 12.6 and 21.3 min, with a very slow decline during the rest of the experiment and only surpassing 6-MAM levels at least 30 min after injection. CONCLUSIONS AND IMPLICATIONS After an i.v. heroin injection, 6-MAM was the predominant opioid present shortly after injection and during the first 30 min, not only in the blood but also in rat brain ECF. 6-MAM might therefore mediate most of the effects observed shortly after heroin intake, and this finding questions the general assumption that morphine is the main and most important metabolite of heroin. PMID:23865556

A Population-Based Survival Assessment of Categorizing Level III and IV Rural Hospitals as Trauma Centers

ERIC Educational Resources Information Center

Arthur, Melanie; Newgard, Craig D.; Mullins, Richard J.; Diggs, Brian S.; Stone, Judith V.; Adams, Annette L.; Hedges, Jerris R.

2009-01-01

Context: Patients injured in rural areas are hypothesized to have improved outcomes if statewide trauma systems categorize rural hospitals as Level III and IV trauma centers, though evidence to support this belief is sparse. Purpose: To determine if there is improved survival among injured patients hospitalized in states that categorize rural…

Impact of dietary fat source and concentration and daily fatty acid intake on the composition of carcass fat and iodine value sampled in three regions of the pork carcass.

PubMed

Kellner, T A; Prusa, K J; Patience, J F

2014-12-01

The increased inclusion of unsaturated fats in pig diets has raised issues related to pork carcass fat quality. The objective of this experiment was to more precisely measure how differing levels of daily fatty acid intake alters the fatty acid composition in 3 different fat depots. A total of 42 gilts and 21 barrows (PIC 337×C22/29) with an average initial weight of 77.80±0.38 kg were allotted randomly based on sex and BW to 7 treatments: 3 and 6% of each of tallow (TAL; iodine value [IV]=41.9), choice white grease (CWG; IV=66.5), or corn oil (CO; IV=123.1) and a control (CNTR) corn-soybean meal-based diet with no added fat. Pigs were individually housed to allow accurate measurement of individual feed intake, in particular, daily dietary fatty acid and energy intake. Fat samples were collected from the jowl, belly, and loin at slaughter. Diet and carcass fat samples were analyzed for IV. Belly weights were recorded at slaughter along with a subjective belly firmness score (1=firmest to 3=least firm). Carcass lipid IV was increased (P<0.001) by increasing the degree of unsaturation of the dietary fat source (66.8, 70.3, and 76.3 for TAL, CWG, and CO, respectively). Carcass lipid IV for TAL and CWG was not affected (P>0.05) by inclusion levels; however, carcass lipid IV was greater (P<0.001) in pigs fed 6 than 3% CO (80.0 vs. 72.6), and carcasses of gilts had greater IV (P<0.001) than carcasses of barrows (71.5 vs. 69.1). Increasing the level of TAL and CO but not CWG from 3 to 6% decreased the apparent total tract digestibility of GE, resulting in a source×level interaction (P<0.05). Dietary fat source had no effect (P≥0.66) on apparent total tract digestibility of either DM or GE, but feeding 6% dietary fat increased G:F (P=0.006) over pigs fed 3% fat (0.358 vs. 0.337). Of all the fatty acids measured, only linoleic acid intake presented a reasonable coefficient of determination (R2=0.61). Overall, IV product (IVP) was approximately equal to linoleic acid intake as a predictor of carcass IV (R2=0.93 vs. R2=0.94). When inclusion of dietary fat and PUFA intake increased, IVP placed more emphasis on the dietary fat inclusion level rather than the dietary fat composition. Linoleic acid intake corrected the overemphasis placed on dietary fat inclusion by IVP. To conclude, linoleic acid intake showed a strong relationship with carcass IV and can be used as a predictor.

Use of tranexamic acid in total knee arthroplasty

PubMed Central

MARRA, FRANCESCO; ROSSO, FEDERICA; BRUZZONE, MATTEO; BONASIA, DAVIDE EDOARDO; DETTONI, FEDERICO; ROSSI, ROBERTO

2016-01-01

Purpose different strategies have been developed to reduce blood loss in total knee arthroplasty (TKA). The efficacy of both systemic and local tranexamic acid (TXA) administration is demonstrated in the literature. The aim of the present study was to compare the efficacy of systemic, local and combined (systemic + local) administration of TXA in reducing blood loss after TKA. Methods we enrolled all patients submitted to a primary TKA in our department between November 2014 and August 2015. They were divided into three groups corresponding to the method of TXA administration used: intravenous (IV), intra-articular (IA), and a combination of the two. Demographic data, as well as preoperative hemoglobin and platelet levels, were collected. The primary outcome was the maximum hemoglobin loss, while the secondary outcomes were the amount of blood in the drain (cc/hour) and the rate of transfusions; postoperative pain was also assessed. Student’s t-test or a χ2 test was used to evaluate between-group differences, using p<0.05 as the cut-off for statistically significant differences. Results the sample comprised 34 patients: IV, 10 cases; IA, 15 cases, and combined (IV + IA), 9 cases. The average age of the patients was 71.1±6.4 years. No significant differences in the outcome measures were found between the groups, with the exception of a significantly lower maximum hemoglobin loss in the combined versus the IV group (p=0.02). There were no differences between the groups in the amount of blood in the drain or the rate of transfusions. Conclusions the data from this preliminary study, as well as data from the literature, confirm that TXA administration is safe and effective in reducing total blood loss in TKA, and no administration protocol seems to be superior to the others. Level of evidence Level II, prospective comparative study. PMID:28217656

Comparing the influence of selenite (Se4+) and selenate (Se6+) on the inhibition of the mercury (Hg) phytotoxicity to pak choi.

PubMed

Tran, Thi Anh Thu; Dinh, Quang Toan; Cui, Zeiwei; Huang, Jie; Wang, Dan; Wei, Tianjiao; Liang, Dongli; Sun, Xin; Ning, Ping

2018-01-01

Selenite (Se (IV)) and selenate (Se (IV)) have recently been demonstrated to be equally effective in inhibiting mercury (Hg) phytotoxicity to plants. This assertion is still unclear. In this study, we aimed to explore the potential effects of Se species (Se 4+ and Se 6+ ) on the inhibition of the mercury (Hg) bioavailability to pak choi in dry land. Pot experiments with exposure to different dosages of mercuric chloride (HgCl 2 ) and selenite (Na 2 SeO 3 ) or selenate (Na 2 SeO 4 ) were treated. To compare the influence of Se (IV) and Se (VI) on the bioaccumulation and bioavailability of Hg, the levels of total Hg in different pak choi (Brassica chinensis L.) tissues (roots and shoots) and the distribution changes of Hg fractions in soil before planting and after harvest were determined as well as the Hg I R values in soils (relative binding intensity) were analyzed. Results showed that application Se (IV) reduced the concentrations of Hg in pak choi roots more than Se (VI). Hg concentrations were also decreased in pak choi shoots in Se (IV) treatments, while which notably increased in Se (VI) treatments. Thus, Se (IV) plays a more important role than Se (VI) in limiting the absorption and bioaccumulation of Hg in pak choi. Moreover, this inhibition may only significantly occur when Se (IV) is at an appropriate level (2.5mg/kg). In addition, the good correlations between the proportions of mobile Hg fractions (soluble and exchangeable fractions), I R values with the Hg concentrations in plants were observed. This affirmed the importance of the Hg fractions transformation and the I R indicator of Hg in the assessment of their bioavailability. Our findings regarding the importance of Se (IV) influence in reducing Hg bioaccumulation not only provided the correct appraisal about the effect of Se species on the inhibition of the Hg phytotoxicity to pak choi in dry land, but also be a good reference for selecting Se fertilizer forms (Se 4+ or Se 6+ ). Copyright © 2017 Elsevier Inc. All rights reserved.

Deep sequencing-based transcriptome analysis of Plutella xylostella larvae parasitized by Diadegma semiclausum

PubMed Central

2011-01-01

Background Parasitoid insects manipulate their hosts' physiology by injecting various factors into their host upon parasitization. Transcriptomic approaches provide a powerful approach to study insect host-parasitoid interactions at the molecular level. In order to investigate the effects of parasitization by an ichneumonid wasp (Diadegma semiclausum) on the host (Plutella xylostella), the larval transcriptome profile was analyzed using a short-read deep sequencing method (Illumina). Symbiotic polydnaviruses (PDVs) associated with ichneumonid parasitoids, known as ichnoviruses, play significant roles in host immune suppression and developmental regulation. In the current study, D. semiclausum ichnovirus (DsIV) genes expressed in P. xylostella were identified and their sequences compared with other reported PDVs. Five of these genes encode proteins of unknown identity, that have not previously been reported. Results De novo assembly of cDNA sequence data generated 172,660 contigs between 100 and 10000 bp in length; with 35% of > 200 bp in length. Parasitization had significant impacts on expression levels of 928 identified insect host transcripts. Gene ontology data illustrated that the majority of the differentially expressed genes are involved in binding, catalytic activity, and metabolic and cellular processes. In addition, the results show that transcription levels of antimicrobial peptides, such as gloverin, cecropin E and lysozyme, were up-regulated after parasitism. Expression of ichnovirus genes were detected in parasitized larvae with 19 unique sequences identified from five PDV gene families including vankyrin, viral innexin, repeat elements, a cysteine-rich motif, and polar residue rich protein. Vankyrin 1 and repeat element 1 genes showed the highest transcription levels among the DsIV genes. Conclusion This study provides detailed information on differential expression of P. xylostella larval genes following parasitization, DsIV genes expressed in the host and also improves our current understanding of this host-parasitoid interaction. PMID:21906285

Single treatment of VX poisoned guinea pigs with the phosphotriesterase mutant C23AL: Intraosseous versus intravenous injection.

PubMed

Wille, Timo; Neumaier, Katharina; Koller, Marianne; Ehinger, Christina; Aggarwal, Nidhi; Ashani, Yacov; Goldsmith, Moshe; Sussman, Joel L; Tawfik, Dan S; Thiermann, Horst; Worek, Franz

2016-09-06

The recent attacks with the nerve agent sarin in Syria reveal the necessity of effective countermeasures against highly toxic organophosphorus compounds. Multiple studies provide evidence that a rapid onset of antidotal therapy might be life-saving but current standard antidotal protocols comprising reactivators and competitive muscarinic antagonists show a limited efficacy for several nerve agents. We here set out to test the newly developed phosphotriesterase (PTE) mutant C23AL by intravenous (i.v.), intramuscular (i.m.; model for autoinjector) and intraosseous (i.o.; model for intraosseous insertion device) application in an in vivo guinea pig model after VX challenge (∼2LD50). C23AL showed a Cmax of 0.63μmolL(-1) after i.o. and i.v. administration of 2mgkg(-1) providing a stable plasma profile up to 180min experimental duration with 0.41 and 0.37μmolL(-1) respectively. The i.m. application of C23AL did not result in detectable plasma levels. All animals challenged with VX and subsequent i.o. or i.v. C23AL therapy survived although an in part substantial inhibition of erythrocyte, brain and diaphragm AChE was detected. Theoretical calculation of the time required to hydrolyze in vivo 96.75% of the toxic VX enantiomer is consistent with previous studies wherein similar activity of plasma containing catalytic scavengers of OPs resulted in non-lethal protection although accompanied with a variable severity of cholinergic symptoms. The relatively low C23AL plasma level observed immediately after its i.v. or i.o load, point at a possible volume of distribution greater than the guinea pig plasma content, and thus underlines the necessity of in vivo experiments in antidote research. In conclusion the i.o. application of PTE is efficient and resulted in comparable plasma levels to the i.v. application at a given time. Thus, i.o. vascular access systems could improve the post-exposure PTE therapy of nerve agent poisoning. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Randomized, controlled, cross-over clinical trial comparing intravenous midazolam sedation with nitrous oxide sedation in children undergoing dental extractions.

PubMed

Wilson, K E; Girdler, N M; Welbury, R R

2003-12-01

The use of benzodiazepines for paediatric dental sedation has received limited attention with regard to research into clinical effectiveness. A study was therefore designed to investigate the use of midazolam, for i.v. sedation in paediatric dental patients. The aim of the study was to assess the effectiveness of i.v. midazolam in a randomized, controlled, cross-over trial. Children aged 12-16 yr (ASA I and II), requiring two appointments for equivalent but contralateral dental extractions for orthodontic purposes, were recruited. Conscious sedation with either i.v. midazolam titrated at 0.5 mg x min(-1), to a maximum of 5 mg, or nitrous oxide/oxygen titrated to 30%/70% inhalation sedation was used at the first visit, the alternative being used at the second visit. Vital signs including blood pressure, arterial oxygen saturation and ventilatory frequency, as well as sedation levels and behavioural scores, were recorded every 2 min. Forty patients, mean age 13.2 yr (range 12-16 yr), participated in the trial. A mean dose of midazolam 2.8 mg was administered in the test group. The median time to the maximum level of sedation was 8 min for midazolam compared with 6 min for nitrous oxide (P<0.001). Vital signs for both treatments were comparable and within acceptable clinical limits and communication with the patient was maintained at all times. The median (range) lowest arterial oxygen saturation level recorded for midazolam was 97 (91-99)% compared with 97 (92-100)% for nitrous oxide. The mean (range) recovery time for midazolam was 51.6 (39-65) min and 23.3 (20-34) min for nitrous oxide (P<0.0001). Fifty-one per cent said they preferred i.v. midazolam, 38% preferred nitrous oxide, and 11% had no preference. I.V. midazolam sedation (0.5 mg x min(-1) to a maximum of 5 mg) appears to be as effective as nitrous oxide sedation in 12-16-yr-old healthy paediatric dental patients.

Temporal variations in dissolved selenium in Lake Kinneret (Israel)

USGS Publications Warehouse

Nishri, A.; Brenner, I.B.; Hall, G.E.M.; Taylor, Howard E.

1999-01-01

Selenium is an essential micronutrient for the growth of the dinoflagellate Peridinium gatunense that dominates the spring algal bloom in Lake Kinneret (LK). The relationship between the levels of dissolved selenium species and the occurance of algal blooms in this lake was studied. During algal blooms of P. gatunense in spring and of the blue-green Aphanizomenon ovalisporum in fall (in 1994) the concentration of epilimnetic dissolved organic Se (Se(org)) increased whereas that of selenite (SeIV) decreased, to levels below the limit of detection: 5 ng/l. The disappearance of SeIV during these blooms is attributed to algal uptake and it is suggested that the growth of both algae may have depended on Se(org) regeneration. A budget performed for selenate (SeVI) suggests that this species is also consumed by algae but to a lesser extent than SeIV (in 1994 ~40% of the epilimnetic load). During the stratification period the hypolimnion of Lake Kinneret becomes anoxic, with high levels of dissolved sulfide. The affects of this environment on the distribution of Se oxy-anions, selenite (SeIV) and selenate(SeVI), were also studied. At the onset of thermal stratification (March) about 35% of the lake inventory of both Se oxidized species are entrapped in the hypolimnion. During stages of oxygen depletion and H2S accumulation, SeIV is completely and SeVI partially removed from this layer. The removal is attributed to reduction followed by formation of particulate reduced products, such as elemental selenium Se(o). The ratio between SeVI to total dissolved selenium (SE(T)) in water sources to the lake is ~0.84, about twice the corresponding ratio in the lake (~0.44, during holomixis). In the lake about 75% of annual SeVI inflow from external sources undergoes reduction to selenide (Se-II) and Se(o) through epilimnetic algal assimilation and hypolimnetic anoxic reduction, respectively. It is suggested that the latter oxidation of the dissolved organic selenide released from biogenic particles and of Se(o) only to the tetravalent species is the cause for the lower ratio of SeVI/Se(T) in the lake.

A study of electrically active traps in AlGaN/GaN high electron mobility transistor

NASA Astrophysics Data System (ADS)

Yang, Jie; Cui, Sharon; Ma, T. P.; Hung, Ting-Hsiang; Nath, Digbijoy; Krishnamoorthy, Sriram; Rajan, Siddharth

2013-10-01

We have studied electron conduction mechanisms and the associated roles of the electrically active traps in the AlGaN layer of an AlGaN/GaN high electron mobility transistor structure. By fitting the temperature dependent I-V (Current-Voltage) curves to the Frenkel-Poole theory, we have identified two discrete trap energy levels. Multiple traces of I-V measurements and constant-current injection experiment all confirm that the main role of the traps in the AlGaN layer is to enhance the current flowing through the AlGaN barrier by trap-assisted electron conduction without causing electron trapping.

Mouse embryonic stem cells, but not somatic cells, predominantly use homologous recombination to repair double-strand DNA breaks.

PubMed

Tichy, Elisia D; Pillai, Resmi; Deng, Li; Liang, Li; Tischfield, Jay; Schwemberger, Sandy J; Babcock, George F; Stambrook, Peter J

2010-11-01

Embryonic stem (ES) cells give rise to all cell types of an organism. Since mutations at this embryonic stage would affect all cells and be detrimental to the overall health of an organism, robust mechanisms must exist to ensure that genomic integrity is maintained. To test this proposition, we compared the capacity of murine ES cells to repair DNA double-strand breaks with that of differentiated cells. Of the 2 major pathways that repair double-strand breaks, error-prone nonhomologous end joining (NHEJ) predominated in mouse embryonic fibroblasts, whereas the high fidelity homologous recombinational repair (HRR) predominated in ES cells. Microhomology-mediated end joining, an emerging repair pathway, persisted at low levels in all cell types examined. The levels of proteins involved in HRR and microhomology-mediated end joining were highly elevated in ES cells compared with mouse embryonic fibroblasts, whereas those for NHEJ were quite variable, with DNA Ligase IV expression low in ES cells. The half-life of DNA Ligase IV protein was also low in ES cells. Attempts to increase the abundance of DNA Ligase IV protein by overexpression or inhibition of its degradation, and thereby elevate NHEJ in ES cells, were unsuccessful. When ES cells were induced to differentiate, however, the level of DNA Ligase IV protein increased, as did the capacity to repair by NHEJ. The data suggest that preferential use of HRR rather than NHEJ may lend ES cells an additional layer of genomic protection and that the limited levels of DNA Ligase IV may account for the low level of NHEJ activity.

Career and Technical Education: States Have Broad Flexibility in Implementing Perkins IV. Report to Congressional Requesters. GAO-09-683

ERIC Educational Resources Information Center

Scott, George A.

2009-01-01

The Carl D. Perkins Career and Technical Education Act of 2006 (Perkins IV) supports career and technical education (CTE) in high schools and postsecondary institutions, such as community colleges. Perkins IV established student performance measures at the secondary and postsecondary levels for state agencies, such as state educational agencies,…

Weigh the pros and cons to ovarian reserve before stripping ovarian endometriomas prior to IVF/ICSI: A meta-analysis.

PubMed

Tao, Xin; Chen, Lei; Ge, Shuqi; Cai, Lisi

2017-01-01

To explore the effects of conservative surgery for endometriomas on ovarian responsiveness during assisted reproductive technology (ART) and provide reproductive and gynecological doctors with a more reliable reference program for the treatment of endometriomas. A literature search was performed by searching the PubMed, Embase, Cochrane Library, Web of Science and Science Direct databases. Studies with inter- and intra-patient comparisons of ovarian responses and oocyte quality between operated and unoperated ovaries and that met the inclusion criteria were retrieved, and the data from the outcome measures were extracted and pooled for this meta-analysis. Twenty-one published studies (2649 ART cycles) were included. The total amount of gonadotropin (Gn) used (inverse variance (IV):0.48; 95% confidence interval (CI): [0.13, 1.82], P = 0.0007) was significantly increased in the women with endometriomas who had a history of cystectomy. The estrogen (E) level on the day of hCG administration (IV: -0.29; 95% CI: [-0.41, -0.17], P<0.00001), the number of mature or dominant follicles (IV: -1.17; 95% CI: [-1.51, -0.82], P<0.00001) and the total number of oocytes retrieved (IV: -1.78; 95% CI: [-2.38, -1.17], P<0.00001) were significantly decreased in the women with endometriomas who had a history of cystectomy. The duration of stimulation (IV: 0.02; 95% CI: [-0.09, 0.13], P = 0.77), the total number of formed embryos (IV: -0.06; 95% CI: [-0.17, 0.04], P = 0.25), the pregnancy rate(IV:0.98;95%CI[0.82,1.18], P = 0.83) and the live birth rate(IV:0.93;95%CI[0.70,1.23], P = 0.61)were not statistically different between the two groups. Similar intra-patient results were found in the number of mature or dominant follicles (IV: -0.88; 95% CI: [-1.25, -0.52], P<0.00001) and the total number of oocytes retrieved (IV: -3.48; 95% CI: [-4.77, -2.19], P<0.00001). ART might be a better therapeutic method for ovarian endometrioma-related infertility than cystectomy.

An enhanced cerium(IV)-rhodamine 6G chemiluminescence system using guest-host interactions in a lab-on-a-chip platform for estimating the total phenolic content in food samples.

PubMed

Al Haddabi, Buthaina; Al Lawati, Haider A J; Suliman, FakhrEldin O

2016-04-01

Two chemiluminescence-microfluidic (CL-MF) systems, e.g., Ce(IV)-rhodamine B (RB) and Ce(IV)-rhodamine 6G (R6G), for the determination of the total phenolic content in teas and some sweeteners were evaluated. The results indicated that the Ce(IV)-R6G system was more sensitive in comparison to the Ce(IV)-RB CL system. Therefore, a simple (CL-MF) method based on the CL of Ce(IV)-R6G was developed, and the sensitivity, selectivity and stability of this system were evaluated. Selected phenolic compounds (PCs), such as quercetin (QRC), catechin (CAT), rutin (RUT), gallic acid (GA), caffeic acid (CA) and syringic acid (SA), produced analytically useful chemiluminescence signals with low detection limits ranging from 0.35 nmol L(-1) for QRC to 11.31 nmol L(-1) for SA. The mixing sequence and the chip design were crucial, as the sensitivity and reproducibility could be substantially affected by these two factors. In addition, the anionic surfactant (i.e., sodium dodecyl sulfate (SDS)) can significantly enhance the CL signal intensity by as much as 300% for the QRC solution. Spectroscopic studies indicated that the enhancement was due to a strong guest-host interaction between the cationic R6G molecules and the anionic amphiphilic environment. Other parameters that could affect the CL intensities of the PCs were carefully optimized. Finally, the method was successfully applied to tea and sweetener samples. Six different tea samples exhibited total phenolic/antioxidant levels from 7.32 to 13.5 g per 100g of sample with respect to GA. Four different sweetener samples were also analyzed and exhibited total phenolic/antioxidant levels from 500.9 to 3422.9 mg kg(-1) with respect to GA. The method was selective, rapid and sensitive when used to estimate the total phenolic/antioxidant level, and the results were in good agreement with those reported for honey and tea samples. Copyright © 2015 Elsevier B.V. All rights reserved.

Active phytochemicals of Pueraria tuberosa for DPP-IV inhibition: in silico and experimental approach.

PubMed

Srivastava, Shivani; Shree, Priya; Tripathi, Yamini Bhusan

2017-01-01

We had earlier reported that the extract of Pueraria tuberosa significantly inhibits DPP-IV enzyme, resulting in glucose tolerance response in rats. In this study, we have explored the active phytochemicals responsible for this potential. The results have been validated in both fasting and postprandial states in the plasma of normal rats and also in fasting blood and intestinal homogenates of diabetic models. Pueraria tuberosa water extract (PTWE) was administered to normal Charles Foster rats for 35 days and to diabetic model (65 mg/kg bw) for 10 days. After treatments, oral glucose tolerance test (OGTT) and insulin was done for 90 min, and the changes in the levels of GLP-1, GIP, and DPP-IV activities were monitored in fasting and postprandial states. In the case of the diabetic model, DPP-IV activity was measured in intestinal homogenate and basal insulin in plasma. The components of PTWE were analyzed via HPLC-MS based on their chemical formula, molecular mass, and retention time. Using the molecular docking study, we have selected the top five components having strong binding energy with DPP-IV. The increase in secretion of GLP-1 and GIP was significantly higher in the postprandial state when compared to fasting condition. GLP-1 plasma concentration increased by 5.8 and 2.9 folds and GIP increased by 8.7 and 2.4 folds in PTWE and control rats, respectively. In contrast, the postprandial decrease in DPP-IV specific activities was recorded at 2.3 and 1.4 folds. The response in OGTT and insulin was also consistent with these changes. In comparison to diabetic controls, PTWE-administered rats showed decreased DPP-IV activity in the intestine, leading to enhanced basal insulin concentration. Through molecular docking, we found Puerarone and Robinin to be the most potential phytochemicals of PTWE for DPP-IV inhibition. Binding energy (kcal/mol) and dissociation constant (pM) of Robinin with DPP-IV protein were found to be 7.543 and 2,957,383.75, respectively. For Puerarone, it was 7.376 and 3,920,309, respectively. Thus, this study provides the novel active components that contribute to the DPP-IV inhibitory property of PTWE.

The impact of magnesium on isometric twitch parameters and resting membrane potential of the skeletal muscle in diabetic rats.

PubMed

Pelit, Aykut; Emre, Mustafa; Dağli, Kenan; Tuli, Abdullah

2013-04-01

To present the relationship between oral magnesium supplementation, blood glucose, and changes in isometric twitch parameters, resting membrane potential (RMP), in the gastrocnemius muscle in diabetic rats. Sixty rats were used in this study. The rats were divided into four groups: control (drinking tap water, Group I, n = 15), control with treated with magnesium sulfate (10 g/L) (Group II, n = 15), diabetic (Group III, n = 15), and diabetic with treated with magnesium sulfate (10 g/L) (Group IV, n = 15). In Group II and IV, the level of plasma magnesium was increased comparing to those of the control group (p < 0.05). Isometric twitch tensions were decreased significantly in the Group III, but Group IV isometric twitch tensions were increased significantly. Group IV RMP values were close to the Group I. Hyperglycemia decreases gastrocnemius muscle isometric twitch tension and increases RMP in diabetic rats. Magnesium treatment can prevent these diabetic complications.

A review of somatoform disorders in DSM-IV and somatic symptom disorders in proposed DSM-V.

PubMed

Ghanizadeh, Ahmad; Firoozabadi, Ali

2012-12-01

Psychiatric care providers should be trained to use current changes in the somatoform disorders criteria. New diagnostic criteria for Somatic Symptom disorders in the proposed DSM-V is discussed and compared with its older counterpart in DSM-IV. A new category called Somatic Syndrome Disorders is suggested. It includes new subcategories such as "Complex Somatic Symptom Disorder" (CSSD) and "Simple Somatic Symptom Disorder" (SSSD). Some of the subcategories of DSM-IV derived disorders are included in CSSD. While there are some changes in diagnostic criteria, there are concerns and limitations about the new classification needed to be more discussed before implementation. Functional somatic disturbance, the counterpart of converion disorder in DSM-IV, can be highly dependet on the developmental level of children. However, the role of developmental level needs to be considered.

Inhibitory effect of collagen-derived tripeptides on dipeptidylpeptidase-IV activity.

PubMed

Hatanaka, Tadashi; Kawakami, Kayoko; Uraji, Misugi

2014-12-01

The collagen tripeptide fragments Gly-Ala-Hyp, Gly-Pro-Ala and Gly-Pro-Hyp were generated by hydrolyzing collagen from pig-skin, cattle-skin, fish-scales and chicken-feet, respectively, with Streptomyces collagenase. Collagenase treatment increased the concentration of tripeptides in the hydrolysates by 13-15% (w/w). Of the three peptides, Gly-Pro-Hyp was a true peptidic inhibitor of dipeptidylpeptidase-IV (DPP-IV), because DPP-IV could not hydrolyze the bond between Pro-Hyp. This tripeptide was a moderately competitive inhibitor (Ki=4.5 mM) of DPP-IV, and its level in the collagen hydrolysates could be greatly increased (4-9% [w/w]) using Streptomyces collagenase.

Astragaloside-IV Alleviates Heat-Induced Inflammation by Inhibiting Endoplasmic Reticulum Stress and Autophagy.

PubMed

Dong, Zhiwei; Zhou, Jian; Zhang, Ying; Chen, Yajie; Yang, Zichen; Huang, Guangtao; Chen, Yu; Yuan, Zhiqiang; Peng, Yizhi; Cao, Tongtong

2017-01-01

Thermal injury is the main cause of pulmonary disease in stroke after burn and can be life threatening. Heat-induced inflammation is an important factor that triggers a series of induces pathological changes. However, this mechanism underlying heat-induced inflammation in thermal inhalation injury remains unclear. Studies have revealed that astragaloside-IV (AS-IV), a natural compound extracted from Astragalus membranaceus, has protective effects in inflammatory diseases. Here, we investigated whether the protective effects of AS-IV occur because of the suppression of heat-induced endoplasmic reticulum (ER) stress and excessive autophagy Methods: AS-IV was administered to Wistar rats after thermal inhalation injury and 16HBE140-cells were treated with AS-IV. TNF-α, IL-6, and IL-8 levels were determined by ELISA and real-time PCR. ER stress and autophagy were determined by western blot. Autophagic flux was measured by recording the fluorescence emission of the fusion protein mRFP-GFP-LC3 by dynamic live-cell imaging. AS-IV had protective effects against heat-induced reactive oxygen species production and attenuated ER stress. AS IV alleviated heat-induced excessive autophagy in vitro and in vivo. Excessive autophagy was attenuated by the PERK inhibitor GSK2656157 and eIF2α siRNA, suggesting that heat stress-induced autophagy can activate the PERK-eIF2α pathway. Beclin 1 and Atg5 siRNAs inhibited the upregulation of the inflammatory cytokines TNF-α, IL-6, and IL-8 after heat exposure. Thus, AS-IV may attenuate inflammatory responses by disrupting the crosstalk between autophagy and the PERK-eIF2α pathway and may be an ideal agent for treating inflammatory pulmonary diseases. © 2017 The Author(s). Published by S. Karger AG, Basel.

Recurrent instability after revision anterior shoulder stabilization surgery.

PubMed

Friedman, Lisa Genevra Mandeville; Griesser, Michael J; Miniaci, Anthony A; Jones, Morgan H

2014-03-01

The purpose of this study was to perform a systematic review of the literature to compare outcomes of revision anterior stabilization surgeries based on technique. This study also sought to compare the impact of bone defects on outcomes. A systematic review of the electronic databases PubMed, Cochrane Central Register of Controlled Trials, and Scopus was performed in July 2012 and March 2013. Of 345 articles identified in the search, 17 studies with Level I to IV Evidence satisfied the inclusion criteria and were analyzed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Recurrent instability was defined as redislocation, resubluxation, or a positive apprehensive test after revision surgery. Procedures were categorized as arthroscopic Bankart repair, open Bankart repair, Bristow-Latarjet procedure, and other open procedures. In total, 388 shoulders were studied. Male patients comprised 74.1% of patients, 66.7% of cases involved the dominant shoulder, the mean age was 28.2 years, and the mean follow-up period was 44.2 months. The surgical procedures classified as "other open procedures" had the highest rate of recurrent instability (42.7%), followed by arthroscopic Bankart repair (14.7%), the Bristow-Latarjet procedure (14.3%), and open Bankart repair (5.5%). Inconsistent reporting of bone defects precluded drawing significant conclusions. A number of different procedures are used to address recurrent instability after a primary operation for anterior shoulder instability has failed. There is significant variability in the rate of recurrent instability after revision anterior shoulder stabilization surgery. Level IV, systematic review of Level I to IV studies. Copyright © 2014 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

The Impact of Development and Sensory Deprivation on Dendritic Protrusions in the Mouse Barrel Cortex

PubMed Central

Chen, Chia-Chien; Bajnath, Adesh; Brumberg, Joshua C.

2015-01-01

Dendritic protrusions (spines and filopodia) are structural indicators of synapses that have been linked to neuronal learning and memory through their morphological alterations induced by development and experienced-dependent activities. Although previous studies have demonstrated that depriving sensory experience leads to structural changes in neocortical organization, the more subtle effects on dendritic protrusions remain unclear, mostly due to focus on only one specific cell type and/or age of manipulation. Here, we show that sensory deprivation induced by whisker trimming influences the dendritic protrusions of basilar dendrites located in thalamocortical recipient lamina (IV and VI) of the mouse barrel cortex in a layer-specific manner. Following 1 month of whisker trimming after birth, the density of dendritic protrusions increased in layer IV, but decreased in layer VI. Whisker regrowth for 1 month returned protrusion densities to comparable level of age-matched controls in layer VI, but not in layer IV. In adults, chronic sensory deprivation led to an increase in protrusion densities in layer IV, but not in layer VI. In addition, chronic pharmacological blockade of N-methyl-d-aspartate receptors (NMDARs) increased protrusion density in both layers IV and VI, which returned to the control level after 1 month of drug withdrawal. Our data reveal that different cortical layers respond to chronic sensory deprivation in different ways, with more pronounced effects during developmental critical periods than adulthood. We also show that chronically blocking NMDARs activity during developmental critical period also influences the protrusion density and morphology in the cerebral cortex. PMID:24408954

Protective effect of gallic acid and Syzygium cumini extract against oxidative stress-induced cellular injury in human lymphocytes.

PubMed

De Bona, Karine Santos; Bonfanti, Gabriela; Bitencourt, Paula Eliete Rodrigues; da Silva, Thainan Paz; Borges, Raphaela Maleski; Boligon, Aline; Pigatto, Aline; Athayde, Margareth Lynde; Moretto, Maria Beatriz

2016-01-01

Syzygium cumini (Myrtaceae) presents antioxidant, anti-inflammatory, hypoglycemic and antibacterial effects; however, the cellular and molecular mechanisms of action in the immune system are not yet completely elucidated. This study evaluates the in vitro effect of gallic acid and aqueous S. cumini leaf extract (ASc) on adenosine deaminase (ADA) and dipeptidyl peptidase IV (DPP-IV) activities, cell viability and oxidative stress parameters in lymphocytes exposed to 2, 2'-azobis-2-amidinopropane dihydrochloride (AAPH). Lymphocytes were incubated with ASc (100 and 500 µg/ml) and gallic acid (50 and 200 µM) at 37 °C for 30 min followed by incubation with AAPH (1 mM) at 37 °C for 2 h. After the incubation time, the lymphocytes were used for determinations of ADA, DPP-IV and lactate dehydrogenase (LDH) activities, lipid peroxidation, protein thiol (P-SH) group levels and cellular viability by colorimetric methods. (i) HPLC fingerprinting of ASc revealed the presence of catechin, epicatechin, rutin, quercitrin, isoquercitrin, quercetin, kaempferol and chlorogenic, caffeic, gallic and ellagic acids; (ii) for the first time, ASc reduced the AAPH-induced increase in ADA activity, but no effect was observed on DPP-IV activity; (iii) ASc increased P-SH groups and cellular viability and decreased LDH activity, but was not able to reduce the AAPH-induced lipid peroxidation; (iv) gallic acid showed less protective effects than ASc. ASc affects the purinergic system and may modulate adenosine levels, indicating that the extract of this plant exhibits immunomodulatory properties. ASc also may potentially prevent the cellular injury induced by oxidative stress, highlighting its cytoprotective effects.

Preemptive carprofen for peri-operative analgesia in dogs undergoing Tibial Plateau Leveling Osteotomy (TPLO): a prospective, randomized, blinded, placebo controlled clinical trial.

PubMed

Bufalari, A; Maggio, C; Cerasoli, I; Morath, U; Adami, C

2012-03-01

Eighteen client-owned dogs undergoing Tibial Plateau Leveling Osteotomy (TPLO) were included in this blinded clinical study and randomly assigned to one of two treatment groups. Group C (carprofen) received intravenous (IV) carprofen, 4 mg/kg, prior to anesthesia, whereas group P (placebo) received IV saline. General anesthesia was maintained with isoflurane in oxygen and a constant rate infusion (CRI) of sufentanyl IV. Intra-operatively, assessment of nociception was based on changes in physiological parameters and on the analgesics requirement, whereas in the post-operative period evaluation of pain was performed by using a Hellyer and Gaynor pain score and by comparing the doses of rescue buprenorphine required by the two treatment groups. Although no statistically significant differences in intra-operative sufentanyl doses were found between treatment groups, group C had superior cardiovascular stability, and lower post-operative pain scores and rescue buprenorphine doses than group P. Our results indicate that administration of carprofen prior to surgery was effective in improving peri-operative analgesia in dogs undergoing TPLO.

Ethanol extract of Moringa oliefera prevents in vitro glucose induced cataract on isolated goat eye lens

PubMed Central

Kurmi, Raghvendra; Ganeshpurkar, Aditya; Bansal, Divya; Agnihotri, Abhishek; Dubey, Nazneen

2014-01-01

Aim of Study: The aim of current work was to evaluate in vitro anticataract potential of Moringa oliefera extract. Materials and Methods: Goat eye lenses were divided into 4 groups; Group served as control, Group II as toxic control, Group III and Group IV were incubated in extract (250 μg/ml and 500 μg/ml of extract of M. oliefera) Group II, III and IV were incubated in 55 mM glucose in artificial aqueous humor to induce lens opacification. Estimation of total, water soluble protein, catalase, glutathione and malondialdehyde along with photographic evaluation of lens was done. Results: Group II (toxic control) lenses showed high amount of MDA (Malondialdehyde), soluble, insoluble protein, decreased catalase and glutathione levels, while lenses treated with Moringa oliefera extract (Group III and Group IV) showed significant (* P < 0.05) reduction in MDA and increased level of catalase, glutathione, total and soluble protein. Conclusion: Results of present findings suggest protective effect of Moringa oliefera in prevention of in vitro glucose induced cataract. PMID:24008789

A newly developed solution enhances thirty-hour preservation in a canine lung transplantation model.

PubMed

Liu, C J; Ueda, M; Kosaka, S; Hirata, T; Yokomise, H; Inui, K; Hitomi, S; Wada, H

1996-09-01

Ischemia and reperfusion cause the production of oxygen free radicals. These damage grafts or disrupt normal vascular homeostatic mechanisms, with a parallel reduction in endothelial nitric oxide and adenosine 3',5'-cyclic monophosphate levels. We hypothesized that lung preservation failure may be related to these events. To improve lung preservation, we prepared a new ET-Kyoto solution, which contains N-acetylcysteine (a radical scavenger), nitroglycerin (to elevate the nitric oxide level), and dibutyryl adenosine 3',5'-cyclic monophosphate (to elevate the adenosine 3',5'-cyclic monophosphate level) and examined its efficacy in a canine single-lung transplantation model. Lungs were flushed with new ET-Kyoto solution (group I, n = 9), basal ET-Kyoto solution (group II, n = 6), basal ET-Kyoto solution plus ethanol and propylene glycol (solvents of nitroglycerin; group III, n = 6), or low-potassium dextran glucose solution (group IV, n = 6), and stored at 4 degrees C for 30 hours. After left single-lung transplantation, the right main bronchus and right pulmonary artery were ligated and the functions of the transplanted lung were assessed for 6 hours. Arterial oxygen tension was significantly higher in group I than in groups II, III, and IV (p < 0.05). Peak inspiratory pressure and wet-to-dry lung weight ratio were significantly lower in group I than in groups II and IV (p < 0.01). Histologic and ultrastructural studies showed better preservation in group I than in groups II, III, and IV. We conclude that the new ET-Kyoto solution provides enhanced 30-hour lung preservation.

BDNF expression in the hippocampus of maternally separated rats: does Bifidobacterium breve 6330 alter BDNF levels?

PubMed

O'Sullivan, E; Barrett, E; Grenham, S; Fitzgerald, P; Stanton, C; Ross, R P; Quigley, E M M; Cryan, J F; Dinan, T G

2011-09-01

Brain-derived neurotrophic factor (BDNF) is of interest because of its putative role in stress and psychiatric disorders. Maternal separation is used as an animal model of early-life stress and of irritable bowel syndrome (IBS). Animals exposed to the paradigm show altered gut function together with heightened levels of arousal and corticosterone. Some probiotic organisms have been shown to be of benefit in IBS and influence the brain-gut axis. Our objective was to investigate the effects of maternal separation on BDNF under basal conditions and in response to the probiotic Bifidobacterium breve 6330. The study implemented the maternal separation model which we have previously described. Polymerase chain reaction and in situ hybridisation were performed to measure the effect of maternal separation on both BDNF total variants and BDNF splice variant (exon) IV in the hippocampus. Maternally separated and non-separated rats were treated with B. breve 6330, to investigate the effect of this probiotic on BDNF total variant and BDNF exon IV expression. Maternal separation increased BDNF total variants (P<0.01), whilst having no effect on BDNF exon IV. B. breve 6330 increased BDNF total variants (P<0.01), and decreased BDNF splice variant IV, in non-separated rats (P<0.01). B. breve 6330 did not alter BDNF levels in the maternally separated rats. Maternal separation caused a marked increase in BDNF in the hippocampus. While B. breve 6330 influenced BDNF in normal animals, it had no significant effect on BDNF in those which were maternally separated. We have demonstrated that an orally administered probiotic can influence hippocampal BDNF.

Astragaloside IV attenuates injury caused by myocardial ischemia/reperfusion in rats via regulation of toll-like receptor 4/nuclear factor-κB signaling pathway.

PubMed

Lu, Meili; Tang, Futian; Zhang, Jing; Luan, Aina; Mei, Meng; Xu, Chonghua; Zhang, Suping; Wang, Hongxin; Maslov, Leonid N

2015-04-01

Myocardial ischemia/reperfusion (MI/R) injury, in which inflammatory response and cell apoptosis play a vital role, is frequently encountered in clinical practice. Astragaloside IV (AsIV), a small molecular saponin of Astragalus membranaceus, has been shown to confer protective effects against many cardiovascular diseases. The present study was aimed to investigate the antiinflammatory and antiapoptotic effects and the possible mechanism of AsIV on MI/R injury in rats. Rats were randomly divided into sham operation group, MI/R group and groups with combinations of MI/R and different doses of AsIV. The results showed that the expressions of myocardial toll-like receptor 4 (TLR4) and nuclear factor-κB (NF-κB) were significantly increased, and apoptosis of cardiomyocytes was induced in MI/R group compared with that in sham operation group. Administration of AsIV attenuated MI/R injury, downregulated the expressions of TLR4 and NF-κB and inhibited cell apoptosis as evidenced by decreased terminal deoxynucleotidyl transferase dUTP nick end labeling positive cells, B-cell lymphoma-2 associated X protein and caspase-3 expressions and increased B-cell lymphoma-2 expression compared with that in MI/R group. In addition, AsIV treatment reduced levels of inflammatory cytokines induced by MI/R injury. In conclusion, our results demonstrated that AsIV downregulates TLR4/NF-κB signaling pathway and inhibits cell apoptosis, subsequently attenuating MI/R injury in rats. Copyright © 2015 John Wiley & Sons, Ltd.

Sex and age differences in attention-deficit/hyperactivity disorder symptoms and diagnoses: implications for DSM-V and ICD-11.

PubMed

Ramtekkar, Ujjwal P; Reiersen, Angela M; Todorov, Alexandre A; Todd, Richard D

2010-03-01

To examine gender and age differences in attention-deficit/hyperactivity disorder (ADHD) symptom endorsement in a large community-based sample. Families with four or more full siblings ascertained from Missouri birth records completed telephone interviews regarding lifetime DSM-IV ADHD symptoms and the Strengths and Weaknesses of ADHD-Symptoms and Normal-behavior (SWAN) questionnaire for current ADHD symptoms. Complete data were available for 9,380 subjects aged 7 through 29 years. Lifetime and current DSM-IV-like ADHD diagnoses were assigned by the DSM-IV symptom criteria. Linear regression was used to examine sex and age effects on SWAN ADHD symptom scores. Logistic regression was used to examine sex and age effects on specific ADHD diagnoses. Fractional polynomial graphs were used to examine ADHD symptom count variations across age. Overall prevalence of current DSM-IV-like ADHD was 9.2% with a male:female ratio of 2.28:1. The prevalence of DSM-IV-like ADHD was highest in children. Gender differences in DSM-IV-like ADHD subtype prevalences were highest in adolescents. On average, individuals with lifetime DSM-IV-like ADHD diagnoses had elevated current ADHD symptoms even as adolescents or adults. Lower male:female ratios than reported in some clinic-based studies suggest that females are underdiagnosed in the community. Although they may no longer meet the full symptom criteria, young adults with a history of lifetime DSM-IV-like ADHD maintain higher levels of ADHD symptoms compared with the general population. The use of age-specific diagnostic criteria should be considered for DSM-V and ICD-11.

Is DSM-IV bereavement exclusion for major depressive episode relevant to severity and pattern of symptoms? A case-control, cross-sectional study.

PubMed

Corruble, Emmanuelle; Chouinard, Virginie-Anne; Letierce, Alexia; Gorwood, Philip A P M; Chouinard, Guy

2009-08-01

To assess the DSM-IV major depressive episode (MDE) bereavement exclusion criterion by comparing severity and pattern of symptoms in bereavement-excluded individuals satisfying all other DSM-IV MDE criteria to these same variables in MDE controls. A case-control, cross-sectional study of self-referred individuals seeking treatment for depressive symptoms was conducted. A total of 17,988 subjects met DSM-IV MDE symptom criteria. Of these, 1,521 individuals (8.5%) met all MDE criteria except the bereavement exclusion. They were matched by age, gender, marital status, and educational level with 1,521 MDE controls. Among the MDE controls, 292 had a recent bereavement and 1,229 did not. Severity of depression was measured by the number of MDE symptoms and the Montgomery-Asberg Depression Rating Scale (MADRS) score. Symptom cues of the bereavement-exclusion criterion were analyzed. The study was conducted between September 2003 and May 2004. Bereavement-excluded subjects were more severely depressed than MDE controls without bereavement and similar to MDE controls with bereavement. Two symptom cues, suicidal ideation and worthlessness, and the majority of other depressive symptoms were more pronounced in bereavement-excluded individuals than in MDE controls. Symptom cues of the DSM-IV MDE bereavement exclusion criterion should be modified since they could result in patients failing to be correctly diagnosed and treated. ©Copyright 2009 Physicians Postgraduate Press, Inc.

Evaluation of the Relationship between Brain-Derived Neurotropic Factor Levels and the Stroop Interference Effect in Children with Attention-Deficit Hyperactivity Disorder.

PubMed

Şimşek, Şeref; Gençoğlan, Salih; Yüksel, Tuğba; Kaplan, İbrahim; Aktaş, Hüseyin; Alaca, Rümeysa

2016-12-01

Brain-derived neurotropic factor (BDNF) has been suggested to play a role in the pathogenesis of attention-deficit hyperactivity disorder (ADHD). In addition, impairment in executive functions has been reported in children with ADHD. This study investigated the presence of a relationship between Stroop test scores and BDNF levels in children with ADHD. The study was conducted in the Department of Child Psychiatry at Dicle University. The study included 49 children between 6 and 15 years of age (M/F: 42/7), who were diagnosed with ADHD according to DSM-IV, and who did not receive previous therapy. Similar in terms of age and gender to the ADHD group, 40 children were selected in the control group. The Kiddie Schedule for Affective Disorders and Schizophrenia, Present and Lifetime version was administered to all participants. Parents and teachers were administered Turgay DSM-IV-based Child and Adolescent Behavior Disorders Screening and Rating Scale to measure symptom severity in children with ADHD. Children with ADHD underwent the Stroop test. BDNF levels were evaluated in serum by ELISA. The ADHD and control groups did not differ in terms of BDNF levels. BDNF levels did not differ between ADHD subtypes. There was also no relationship between the Stroop test interference scores and BDNF levels. The findings of the present study are in line with those in studies that demonstrated no significant role of BDNF in the pathogenesis of ADHD.

Bombesin-like peptides stimulate growth hormone secretion mediated by the gastrin-releasing peptide receptor in cattle.

PubMed

Zhao, Hongqiong; Matsuda, Seinosuke; Thanthan, Sint; Yannaing, Swe; Kuwayama, Hideto

2012-10-01

This study was designed to determine the effects of bombesin-like peptides (BLPs) on the secretion of growth hormone (GH) and to characterize the receptor subtypes mediating these effects in cattle. Four experiments were conducted: (1) six steers were randomly assigned to receive intravenous (IV) bolus injections of 0, 0.2, 1.0, 12.5 and 50.0 μg/kg neuromedin C (NMC); (2) seven pre-weaned calves were IV injected with 1.0 μg/kg NMC; (3) six steers were IV injected with 2.5μg/kg bovine gastrin-releasing peptide (GRP), 1.0 μg/kg NMC combined with 20.0 μg/kg [d-Lys(3)]-GHRP-6 (an antagonist for the GH secretagogue receptor type 1a [GHS-R1a]), 1.0 μg/kg NMC combined with 20.0 μg/kg N-acetyl-GRP(20-26)-OCH(2)CH(3) (N-GRP-EE, an antagonist for the GRP receptor), 20.0 μg/kg N-GRP-EE alone, 1.0 μg/kg neuromedin B (NMB); and (4) four rats were IV injected 1.0 μg/kg NMC. A serial blood sample was collected before and after injection. Plasma GH levels dose-dependently increased at 5 min after NMC injection and the minimal effective dose was 1.0 μg/kg. Plasma GH level was elevated by GRP, but not by NMB. The NMC-induced elevation of GH was completely blocked by N-GRP-EE. The administration of NMC elevated GH level in pre-weaned calves but not in rats. Ghrelin level was unaffected by any treatments; and [d-Lys(3)]-GHRP-6 did not block the NMC-induced elevation of GH. The results indicate BLP-induced elevation of GH levels is mediated by the GRP receptor but not through a ghrelin/GHS-R1a pathway in cattle. Copyright © 2012 Elsevier Inc. All rights reserved.

[Evolution of non-invasive ventilation in acute bronchiolitis].

PubMed

Toledo del Castillo, B; Fernández Lafever, S N; López Sanguos, C; Díaz-Chirón Sánchez, L; Sánchez da Silva, M; López-Herce Cid, J

2015-08-01

The aim of the study was to analyse the evolution, over a12-year period, of the use of non-invasive (NIV) and invasive ventilation (IV) in children admitted to a Paediatric Intensive Care Unit (PICU) due to acute bronchiolitis. A retrospective observational study was performed including all children who were admitted to the PICU requiring NIV or IV between 2001 and 2012. Demographic characteristics, ventilation assistance and clinical outcome were analysed. A comparison was made between the first six years and the last 6 years of the study. A total of 196 children were included; 30.1% of the subjects required IV and 93.3% required NIV. The median duration of IV was 9.5 days and NIV duration was 3 days. The median PICU length of stay was 7 days, and 2% of the patients died. The use of NIV increased from 79.4% in first period to 100% in the second period (P<.0001) and IV use decreased from 46% in first period to 22.6% in the last 6 years (P<.0001). Continuous positive airway pressure and nasopharyngeal tube were the most frequently used modality and interface, although the use of bi-level non-invasive ventilation (P<.001) and of nasal cannulas significantly increased (P<.0001) in the second period, and the PICU length of stay was shorter (P=.011). The increasing use of NIV in bronchiolitis in our PICU during the last 12 years was associated with a decrease in the use of IV and length of stay in the PICU. Copyright © 2014 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

Effects of lornoxicam and intravenous ibuprofen on erythrocyte deformability and hepatic and renal blood flow in rats.

PubMed

Arpacı, Hande; Çomu, Faruk Metin; Küçük, Ayşegül; Kösem, Bahadır; Kartal, Seyfi; Şıvgın, Volkan; Turgut, Hüseyin Cihad; Aydın, Muhammed Enes; Koç, Derya Sebile; Arslan, Mustafa

2016-01-01

Change in blood supply is held responsible for anesthesia-related abnormal tissue and organ perfusion. Decreased erythrocyte deformability and increased aggregation may be detected after surgery performed under general anesthesia. It was shown that nonsteroidal anti-inflammatory drugs decrease erythrocyte deformability. Lornoxicam and/or intravenous (iv) ibuprofen are commonly preferred analgesic agents for postoperative pain management. In this study, we aimed to investigate the effects of lornoxicam (2 mg/kg, iv) and ibuprofen (30 mg/kg, iv) on erythrocyte deformability, as well as hepatic and renal blood flows, in male rats. Eighteen male Wistar albino rats were randomly divided into three groups as follows: iv lornoxicam-treated group (Group L), iv ibuprofen-treated group (Group İ), and control group (Group C). Drug administration was carried out by the iv route in all groups except Group C. Hepatic and renal blood flows were studied by laser Doppler, and euthanasia was performed via intra-abdominal blood uptake. Erythrocyte deformability was measured using a constant-flow filtrometry system. Lornoxicam and ibuprofen increased the relative resistance, which is an indicator of erythrocyte deformability, of rats (P=0.016). Comparison of the results from Group L and Group I revealed no statistically significant differences (P=0.694), although the erythrocyte deformability levels in Group L and Group I were statistically higher than the results observed in Group C (P=0.018 and P=0.008, respectively). Hepatic and renal blood flows were significantly lower than the same in Group C. We believe that lornoxicam and ibuprofen may lead to functional disorders related to renal and liver tissue perfusion secondary to both decreased blood flow and erythrocyte deformability. Further studies regarding these issues are thought to be essential.

ACGME case logs: Surgery resident experience in operative trauma for two decades

PubMed Central

Drake, Frederick Thurston; Van Eaton, Erik G.; Huntington, Ciara R.; Jurkovich, Gregory J.; Aarabi, Shahram; Gow, Kenneth W.

2014-01-01

BACKGROUND Surgery resident education is based on experiential training, which is influenced by changes in clinical management strategies, technical and technologic advances, and administrative regulations. Trauma care has been exposed to each of these factors, prompting concerns about resident experience in operative trauma. The current study analyzed the reported volume of operative trauma for the last two decades; to our knowledge, this is the first evaluation of nationwide trends during such an extended time line. METHODS The Accreditation Council for Graduate Medical Education (ACGME) database of operative logs was queried from academic year (AY) 1989–1990 to 2009–2010 to identify shifts in trauma operative experience. Annual case log data for each cohort of graduating surgery residents were combined into approximately 5-year blocks, designated Period I (AY1989–1990 to AY1993–1994), Period II (AY1994–1995 to AY1998–1999), Period III (AY1999–2000 to AY2002–2003), and Period IV (AY2003–2004 to AY2009–2010). The latter two periods were delineated by the year in which duty hour restrictions were implemented. RESULTS Overall general surgery caseload increased from Period I to Period II (p < 0.001), remained stable from Period II to Period III, and decreased from Period III to Period IV (p < 0.001). However, for ACGME-designated trauma cases, there were significant declines from Period I to Period II (75.5 vs. 54.5 cases, p < 0.001) and Period II to Period III (54.5 vs. 39.3 cases, p < 0.001) but no difference between Period III and Period IV (39.3 vs. 39.4 cases). Graduating residents in Period I performed, on average, 31 intra-abdominal trauma operations, including approximately five spleen and four liver operations. Residents in Period IV performed 17 intra-abdominal trauma operations, including three spleen and approximately two liver operations. CONCLUSION Recent general surgery trainees perform fewer trauma operations than previous trainees. The majority of this decline occurred before implementation of work-hour restrictions. Although these changes reflect concurrent changes in management of trauma, surgical educators must meet the challenge of training residents in procedures less frequently performed. LEVEL OF EVIDENCE Epidemiologic study, level III; therapeutic study, level IV. PMID:23188243

Safety, pharmacokinetics, and immunological activities of multiple intravenous or subcutaneous doses of an anti-HIV monoclonal antibody, VRC01, administered to HIV-uninfected adults: Results of a phase 1 randomized trial.

PubMed

Mayer, Kenneth H; Seaton, Kelly E; Huang, Yunda; Grunenberg, Nicole; Isaacs, Abby; Allen, Mary; Ledgerwood, Julie E; Frank, Ian; Sobieszczyk, Magdalena E; Baden, Lindsey R; Rodriguez, Benigno; Van Tieu, Hong; Tomaras, Georgia D; Deal, Aaron; Goodman, Derrick; Bailer, Robert T; Ferrari, Guido; Jensen, Ryan; Hural, John; Graham, Barney S; Mascola, John R; Corey, Lawrence; Montefiori, David C

2017-11-01

VRC01 is an HIV-1 CD4 binding site broadly neutralizing antibody (bnAb) that is active against a broad range of HIV-1 primary isolates in vitro and protects against simian-human immunodeficiency virus (SHIV) when delivered parenterally to nonhuman primates. It has been shown to be safe and well tolerated after short-term administration in humans; however, its clinical and functional activity after longer-term administration has not been previously assessed. HIV Vaccine Trials Network (HVTN) 104 was designed to evaluate the safety and tolerability of multiple doses of VRC01 administered either subcutaneously or by intravenous (IV) infusion and to assess the pharmacokinetics and in vitro immunologic activity of the different dosing regimens. Additionally, this study aimed to assess the effect that the human body has on the functional activities of VRC01 as measured by several in vitro assays. Eighty-eight healthy, HIV-uninfected, low-risk participants were enrolled in 6 United States clinical research sites affiliated with the HVTN between September 9, 2014, and July 15, 2015. The median age of enrollees was 27 years (range, 18-50); 52% were White (non-Hispanic), 25% identified as Black (non-Hispanic), 11% were Hispanic, and 11% were non-Hispanic people of diverse origins. Participants were randomized to receive the following: a 40 mg/kg IV VRC01 loading dose followed by five 20 mg/kg IV VRC01 doses every 4 weeks (treatment group 1 [T1], n = 20); eleven 5 mg/kg subcutaneous (SC) VRC01 (treatment group 3 [T3], n = 20); placebo (placebo group 3 [P3], n = 4) doses every 2 weeks; or three 40 mg/kg IV VRC01 doses every 8 weeks (treatment group 2 [T2], n = 20). Treatment groups T4 and T5 (n = 12 each) received three 10 or 30 mg/kg IV VRC01 doses every 8 weeks, respectively. Participants were followed for 32 weeks after their first VRC01 administration and received a total of 249 IV infusions and 208 SC injections, with no serious adverse events, dose-limiting toxicities, nor evidence for anti-VRC01 antibodies observed. Serum VRC01 levels were detected through 12 weeks after final administration in all participants who received all scheduled doses. Mean peak serum VRC01 levels of 1,177 μg/ml (95% CI: 1,033, 1,340) and 420 μg/ml (95% CI: 356, 494) were achieved 1 hour after the IV infusion series of 30 mg/kg and 10 mg/kg doses, respectively. Mean trough levels at week 24 in the IV infusion series of 30 mg/kg and 10 mg/kg doses, respectively, were 16 μg/ml (95% CI: 10, 27) and 6 μg/ml (95% CI: 5, 9) levels, which neutralize a majority of circulating strains in vitro (50% inhibitory concentration [IC50] > 5 μg/ml). Post-infusion/injection serum VRC01 retained expected functional activity (virus neutralization, antibody-dependent cellular cytotoxicity, phagocytosis, and virion capture). The limitations of this study include the relatively small sample size of each VRC01 administration regimen and missing data from participants who were unable to complete all study visits. VRC01 administered as either an IV infusion (10-40 mg/kg) given monthly or bimonthly, or as an SC injection (5 mg/kg) every 2 weeks, was found to be safe and well tolerated. In addition to maintaining drug concentrations consistent with neutralization of the majority of tested HIV strains, VRC01 concentrations from participants' sera were found to avidly capture HIV virions and to mediate antibody-dependent cellular phagocytosis, suggesting a range of anti-HIV immunological activities, warranting further clinical trials. Clinical Trials Registration: NCT02165267.

Quality of research and level of evidence in foot and ankle publications.

PubMed

Barske, Heather L; Baumhauer, Judith

2012-01-01

The quality of research and evidence to support medical treatments is under scrutiny from the medical profession and the public. This study examined the current quality of research and level of evidence (LOE) of foot and ankle surgery papers published in orthopedic and podiatric medical journals. Two independent evaluators performed a blinded assessment of all foot and ankle clinical research articles (January 2010 to June 2010) from seven North American orthopedic and podiatric journals. JBJS-A grading system was used for LOE. Articles were assessed for indicators of study quality. The data was stratified by journal and medical credentials. A total of 245 articles were published, 128 were excluded based on study design, leaving 117 clinical research articles. Seven (6%) were Level I, 14 (12%) Level II, 18 (15%) Level III, and 78 (67%) Level IV. The orthopedic journals published 78 studies on foot and ankle topics. Of the podiatric journals, the Journal of the American Podiatric Medical Association (JAPMA) published 12 clinical studies and the Journal of Foot and Ankle Surgery (JFAS) published 27, 21 (78%) of which were Level IV studies. When the quality of research was examined, few therapeutic studies used validated outcome measures and only 38 of 96 (40%) gathered data prospectively. Thirty (31%) studies used a comparison group. Eighty-seven articles (74%) were authored by a MD and 22 (19%) by a DPM. Foot & Ankle International (FAI) published higher quality studies with a higher LOE as compared to podiatry journals. Regardless of the journal, MDs produced the majority of published clinical foot and ankle research. Although improvements have been made in the quality of some clinical research, this study highlights the need for continued improvement in methodology within foot and ankle literature.

A gargantuan acetaminophen level in an acidemic patient treated solely with intravenous N-acetylcysteine.

PubMed

Zell-Kanter, Michele; Coleman, Patrick; Whiteley, Patrick M; Leikin, Jerrold B

2013-01-01

The objective of this report is to describe an acidemic patient with one of the largest recorded acetaminophen ingestions in a patient with acidemia who was treated with supportive care and intravenous (IV) N-acetylcysteine. A 59-year-old female with a history of depression was found comatose. In the Emergency Department, she was obtunded with agonal respirations and immediately intubated. Activated charcoal was given through a nasogastric tube. An initial acetaminophen serum level was 1141 mg/L. The patient was started on IV N-acetylcysteine. The acetaminophen level peaked 2 hours later at 1193 mg/L. She was continued on the IV N-acetylcysteine protocol. The next day her aspartate aminotransferase was 3150 U/L, alanine aminotransferase was 2780 U/L, and creatinine phosphokinase was 16,197 U/L. There was no elevation in bilirubin or international normalized ratio (INR). Transaminase levels decreased on day 3 and normalized by day 4 when she was transferred to a psychiatric unit. Few cases have been reported of strikingly elevated acetaminophen levels in poisoned patients who did not receive hemodialysis. These patients did have increased lactate levels, and some had normal liver function tests. All of these patients received N-acetylcysteine and survived the poisoning without sequelae. This patient in this report was unique in that she had the highest reported serum acetaminophen level with acidosis and was treated successfully with only IV N-acetylcysteine and supportive care.

Hypochondriasis and somatization: two distinct aspects of somatoform disorders?

PubMed

Leibbrand, R; Hiller, W; Fichter, M M

2000-01-01

We investigated boundaries and overlap between somatization and hypochondriasis on different levels of psychopathology: (1) comorbidity between hypochondriasis and somatization on the level of diagnoses in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV; American Psychiatric Association, 1994): (2) comorbidity with other mental disorders; (3) differences in clinical characteristics: and (4) overlap on the level of psychometric measures. The sample consisted of 120 psycho somatic inpatients. Somatoform, hypochondriacal, and depressive symptomatology, cognitions about body and health, and further aspects of general symptomatology were investigated. Diagnoses of Axis I and II were based on DSM-IV Our results suggest a large overlap on the level of DSM-IV-diagnoses: only 3 of 31 hypochondriacal patients had no multiple somatoform symptoms, while 58 of 86 patients with multiple somatoform symptoms had no hypochondriasis. However, the overlap between hypochondriacal and somatization symptomatology on the level of psychometric measurement is only moderate, indicating that hypochondriasis is a markedly distinct aspect of somatoform disorders.

Primary healthcare worker knowledge related to prenatal and immediate newborn care: a cross sectional study in Masindi, Uganda

PubMed Central

2014-01-01

Background Global neonatal mortality remains unacceptably high. Health workers who attend to prenatal and postnatal mothers need to be knowledgeable in preventive and curative care for pregnant women and their newborn babies. This study aimed to determine the level of knowledge related to prenatal and immediate newborn care among primary healthcare workers in Masindi, Uganda. Methods A cross-sectional study was conducted. Interviews comprised of 25 multiple-choice questions were administered to health workers who were deployed to offer prenatal and postnatal care in Masindi in November 2011. Questions were related to four domains of knowledge: prenatal care, immediate newborn care, management of neonatal infections and identifying and stabilizing Low-Birth Weight (LBW) babies. Corresponding composite variables were derived; level of knowledge among health workers dichotomized as ‘adequate’ or ‘inadequate’. The chi-square statistic test was used to examine associations with independent variables including level of training (nursing assistant, general nurse or midwife), level of care (hospital/health centre level IV or health centre level III/II) and years of service (five years or less, six years or more). Results 183 health workers were interviewed: general nurses (39.3%), midwives (21.9%) and nursing assistants (38.8%). Respectively, 53.6%, 46.5%, 7.1% and 56.3% were considered to have adequate knowledge in prenatal care, newborn care, management of neonatal infections and identifying/stabilizing LBW babies. Being a general nurse was significantly associated with having adequate knowledge in identifying and stabilizing LBW babies (p < 0.001) compared to being a nursing assistant. Level of care being hospital/health centre level IV was not significantly associated with having adequate knowledge in prenatal or newborn care with reference to health centres of level III/II. Conclusion Knowledge regarding prenatal and newborn care among primary healthcare workers in Masindi was very low. The highest deficit of knowledge was in management of neonatal infections. Efforts are needed to orientate health workers regarding prenatal and newborn care especially the offer of infection management among newborns. Similar levels of knowledge between health workers deployed to hospital/health centre level IV and health centres of level III/II raise important implementation questions for the referral system which is crucial for maternal and newborn survival. PMID:24511880

Comparing personality disorder models: cross-method assessment of the FFM and DSM-IV-TR.

PubMed

Samuel, Douglas B; Widiger, Thomas W

2010-12-01

The current edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR; American Psychiatric Association, 2000) defines personality disorders as categorical entities that are distinct from each other and from normal personality traits. However, many scientists now believe that personality disorders are best conceptualized using a dimensional model of traits that span normal and abnormal personality, such as the Five-Factor Model (FFM). However, if the FFM or any dimensional model is to be considered as a credible alternative to the current model, it must first demonstrate an increment in the validity of the assessment offered within a clinical setting. Thus, the current study extended previous research by comparing the convergent and discriminant validity of the current DSM-IV-TR model to the FFM across four assessment methodologies. Eighty-eight individuals receiving ongoing psychotherapy were assessed for the FFM and the DSM-IV-TR personality disorders using self-report, informant report, structured interview, and therapist ratings. The results indicated that the FFM had an appreciable advantage over the DSM-IV-TR in terms of discriminant validity and, at the domain level, convergent validity. Implications of the findings and directions for future research are discussed.

Comparing Personality Disorder Models: Cross-Method Assessment of the FFM and DSM-IV-TR

PubMed Central

Samuel, Douglas B.; Widiger, Thomas A.

2010-01-01

The current edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR; American Psychiatric Association, 2000) defines personality disorders as categorical entities that are distinct from each other and from normal personality traits. However, many scientists now believe that personality disorders are best conceptualized using a dimensional model of traits that span normal and abnormal personality, such as the Five-Factor Model (FFM). However, if the FFM or any dimensional model is to be considered as a credible alternative to the current model, it must first demonstrate an increment in the validity of the assessment offered within a clinical setting. Thus, the current study extended previous research by comparing the convergent and discriminant validity of the current DSM-IV-TR model to the FFM across four assessment methodologies. Eighty-eight individuals receiving ongoing psychotherapy were assessed for the FFM and the DSM-IV-TR personality disorders using self-report, informant report, structured interview, and therapist ratings. The results indicated that the FFM had an appreciable advantage over the DSM-IV-TR in terms of discriminant validity and, at the domain level, convergent validity. Implications of the findings and directions for future research are discussed. PMID:21158596

Somatoform disorders and rheumatic diseases: from DSM-IV to DSM-V.

PubMed

Alciati, A; Atzeni, F; Sgiarovello, P; Sarzi-Puttini, P

2014-06-06

Medically unexplained symptoms are considered 'somatoform disorders' in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV). The introduction of this nosographic category has been helpful in drawing attention to a previously neglected area, but has not been successful in promoting an understanding of the disorders' biological basis and treatment implications, probably because of a series of diagnostic shortcomings. The newly proposed DSM-V diagnostic criteria try to overcome the limitations of the DSM-IV definition, which was organised centrally around the concept of medically unexplained symptoms, by emphasising the extent to which a patient's thoughts, feelings and behaviours concerning their somatic symptoms are disproportionate or excessive. This change is supported by a growing body of evidence showing that psychological and behavioural features play a major role in causing patient disability and maintaining high level of health care use. Pain disorders is the sub-category of DSM-IV somatoform disorders that most closely resembles fibromyalgia. Regardless of the diagnostic changes recently brought about by DSM-V, neuroimaging studies have identified important components of the mental processes associated with a DSM- IV diagnosis of pain disorder.

Evaluation of a Hyperlinked Consumer Health Dictionary for reading EHR notes.

PubMed

Slaughter, Laura; Oyri, Karl; Fosse, Erik

2011-01-01

In this paper, we report on a pilot study conducted to test the usefulness and understandability of definitions in a Consumer Health Dictionary (IVS-CHD). Our two main goals for this study were to evaluate functionality of the dictionary when embedded in electronic health records (EHR) and determine the methodology for our larger-scale project to iteratively develop the IVS-CHD. The hyperlinked IVS-CHD was made available to thoracic surgery patients reading their own EHR. We asked patients to rate definitions on two 5-level Likert items measuring perceived usefulness and understandability. We also captured the terms that patients wanted defined, but that were not included in the IVS-CHD. Preliminary results indicate the types of problems that must be avoided when creating definitions, for example, that patients prefer detailed explanations that include medical outcomes, and that do not use "unfamiliar" terms they must also look up. We also have gained insight into the types of terms that patients want defined from their EHR notes, especially certain abbreviations. Patients further commented on the experience of reading EHR notes directly from the same system used by healthcare personnel and the help strategy of linking the contents to a hyperlinked dictionary.

The DSM-IV nosology of chronic pain: a comparison of pain disorder and multiple somatization syndrome.

PubMed

Hiller, W; Heuser, J; Fichter, M M

2000-01-01

This study evaluates the classification of pain from the perspective of the DSM-IV system. Of 60 in-patients with long-standing and disabling pain syndromes, 29 with pain disorder (PD) and 31 with pain as part of a multiple somatization syndrome (MSS) were compared before and after a structured cognitive-behavioral treatment. It was hypothesized that MSS patients show more psychological distress, are more severely disabled, and respond less to the treatment. Both groups were similar with respect to sociodemographic status, history of pain symptomatology and comorbidity with DSM-IV mental disorders. The results show that MSS patients had higher levels of affective and sensoric pain sensations as well as more pain-related disabilities. They were also less successful during treatment to reduce their pain-related depression and anxiety. Psychosocial functioning was improved only by PD patients, but remained almost unchanged in the MSS group. However, there were no group differences concerning general depression and hypochondriasis, dysfunctional attitudes towards body and health, and use of pain coping strategies. It is concluded that the DSM-IV distinction between 'pure' pain disorder and syndromes involving pain plus multiple somatoform symptoms cannot generally be confirmed, but further studies of validation are needed. Copyright 2000 European Federation of Chapters of the International Association for the Study of Pain.

Alcohol-Use Disorders and Nonmedical Use of Prescription Drugs Among U.S. College Students*

PubMed Central

McCABE, SEAN ESTEBAN; WEST, BRADY T.; WECHSLER, HENRY

2008-01-01

Objective The purpose of this study was to examine the association between Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), alcohol-use disorders (AUDs) and nonmedical use of prescription drugs (NMPD) among U.S. college students. A secondary aim of this study was to identify individual-level and college-level characteristics associated with the co-occurrence of AUDs and NMPD. Method Data were collected from self-administered mail surveys, sent to a random sample of approximately 14,000 college students from a nationally representative sample of 119 U.S. colleges and universities. Results Among U.S. college students, those with AUDs represented approximately 75% of nonmedical users of prescription drugs. Multivariate logistic regression analyses indicated that college students with past-year DSM-IV alcohol abuse only (adjusted odds ratio [AOR] = 4.46, 95% confidence interval [CI] = 3.59-5.55) and students with past-year DSM-IV alcohol dependence (AOR = 9.17, 95% CI = 7.05-11.93) had significantly increased odds of NMPD in the past year compared with students without AUDs. The co-occurrence of AUDs and NMPD was more likely among college students who were male, white, earned lower grade point averages, and attended co-ed colleges and institutions located in Southern or Northeastern U.S. regions. Conclusions The findings provide evidence that NMPD is more prevalent among those college students with AUDs, especially individuals with past-year DSM-IV alcohol dependence. The assessment and treatment of AUDs among college students should account for other forms of drug use such as NMPD. PMID:17568959

Revised and extended analysis of Br IV

NASA Astrophysics Data System (ADS)

Riyaz, A.; Rahimullah, K.; Tauheed, A.

2014-01-01

The spectrum of three-times ionized bromine Br IV has been studied in the 319-2350 Å wavelength region. The spectrum was recorded on a 3-m normal incidence vacuum spectrograph at the St. Francis Xavier University, Antigonish (Canada) and 6.65-m grazing incidence spectrograph at the Zeeman laboratory (Amsterdam). The light sources used were a triggered spark and sliding spark, respectively. The ground configuration of Br IV 3d104s24p2, the excited configurations 3d104s4p3+3d104s24p (4d+5d+6d+5s+6s+7s) in the odd parity system and 3d104s24p (5p+4f+5f)+3d104s4p2 (4d+5s)+3d104p4 in the even parity system have been studied. Relativistic Hartree-Fock (HFR) and least squares fitted (LSF) parametric calculations were used to interpret the observed spectrum. 120 Levels of Br IV have now been established, 58 being new. Among 424 spectral lines, 277 are newly classified. The levels 4s4p35S2, 4s24p4d 3F4 and 4p5p (3P0, 1, 3D1, 2, 3S1) are revised. We estimate the accuracy of our measured wavelength for sharp and unblended lines to be ±0.005 Å. The ionization limit is determined as 385,390±100 cm-1 (47.782±0.012 eV).

Sonographic Features of Cervical Lymph Nodes in Patients With Hashimoto Thyroiditis and the Impacts From the Levothyroxine With Prednisone Therapy.

PubMed

Lyu, Guo-Rong; Zheng, Wei-Kun; Lin, Wan-Ling; Zheng, Li-Ping; Guo, Hai-Xin; Li, Li-Ya

2017-11-06

This study aimed to evaluate the ultrasonographic pattern of cervical lymph nodes (CLNs) and whether levothyroxine with prednisone therapy is effective for lymphadenopathy in patients with Hashimoto thyroiditis (HT). This retrospective study was looking at patients with confirmed diagnosis of HT who underwent comprehensive neck ultrasound examination. We reviewed sonographic findings in 127 patients with HT, 234 euthyroid patients with goiter, and 122 healthy subjects. In addition, 30 untreated HT patients with cervical lymphadenopathy were recruited for the levothyroxine with prednisone therapy. We rescanned the patients 9 months after treatment with levothyroxine and prednisone. Patients with HT had a higher rate of CLN detection on ultrasound than euthyroid patients with goiter and healthy subjects at cervical levels III, IV, and VI (P < 0.01). In addition, patients with HT had a higher rate of detection of CLNs with abnormal sonographic features than the other 2 groups, most notably at cervical levels III, IV, and VI (P < 0.01). After the treatment, the mean thyroid volume, thyroid nodule volume, CLN volume, symptom score, and cosmetic grade of 30 HT patients were remarkably decreased (P < 0.01 or P < 0.001). Hashimoto thyroiditis seems to be associated with an increased rate of detection of CLNs with abnormal sonographic features, particularly at cervical levels III, IV, and VI. Therapy with levothyroxine with prednisone is effective for cervical lymphadenopathy in patients with HT.

Impact of Renin-Angiotensin Aldosterone System Inhibition on Serum Potassium Levels among Peritoneal Dialysis Patients.

PubMed

Ribeiro, Silvia Carreira; Figueiredo, Ana Elizabeth; Barretti, Pasqual; Pecoits-Filho, Roberto; de Moraes, Thyago Proença

2017-01-01

The chronic use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blocker has been associated with hyperkalemia in patients with reduced renal function even after the initiation of hemodialysis. Whether such medications may cause a similar effect in peritoneal dialysis patients is not well established. So, the aim of our study was to analyze the impact of renin-angiotensin-aldosterone inhibitors on the serum levels of potassium in a national cohort of peritoneal dialysis patients. A prospective, observational, nationwide cohort study was conducted. We identified all incident patients on peritoneal dialysis that had angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB) prescribed for at least 3 months and a similar period of time without these medications. Patients were divided into 4 groups: Groups I and III correspond to patients using, respectively, an ACEi or ARB and then got the drug suspended; Groups II and IV started peritoneal dialysis without the use of any renin-angiotensin aldosterone system inhibitor and then got, respectively, an ACEi or ARB introduced. Changes in potassium serum levels were compared using 2 statistical approaches: (1) the non-parametric Wilcoxon test for repeated measures and (2) a crossover analysis. Mean potassium serum levels at the first phase of the study for Groups I, II, III, and IV were, respectively, 4.46 ± 0.79, 4.33 ± 0.78, 4.41 ± 0.63, and 4.44 ± 0.56. Changes in mean potassium serum levels for Groups I, II, III, and IV were -0.10 ± 0.60, 0.02 ± 0.56, -0.06 ± 0.46, and 0.03 ± 0.50, respectively. The use of ACEi and ARB was not associated with a greater risk for hyperkalemia in stable peritoneal dialysis patients independently of residual renal function. © 2017 S. Karger AG, Basel.

Arthroscopic repair of lateral ankle ligament complex by suture anchor.

PubMed

Wang, Jingwei; Hua, Yinghui; Chen, Shiyi; Li, Hongyun; Zhang, Jian; Li, Yunxia

2014-06-01

Arthroscopic repair of the lateral ligament complex with suture anchors is increasingly used to treat chronic ankle instability (CAI). Our aims are (1) to analyze and evaluate the literature on arthroscopic suture anchor repair of the anterior talofibular ligament and (2) to conduct a systematic review of the clinical evidence on the reported outcomes and complications of treating CAI with this technique. We performed a systematic review of the literature using PubMed, Ovid, Elsevier ScienceDirect, Web of Science-Conference Proceedings Citation Index, and the Cochrane Database of Systematic Reviews from 1987 to September 2013. Clinical studies using the arthroscopic suture anchor technique to treat CAI were included. Outcome measures consisted of clinical assessment of postoperative ligament stability and complications. In addition, the methodologic quality of the included studies was assessed by use of the modified Coleman Methodology Score. After reviewing 371 studies, we identified 6 studies (5 retrospective case series and 1 prospective case series, all Level IV) that met the inclusion criteria, with a mean Coleman Methodology Score of 71.8 ± 7.52 (range, 63 to 82). In these studies 178 patients (179 ankles) underwent arthroscopic suture anchor repair of the anterior talofibular ligament with a mean follow-up period of 38.9 months (range, 6 to 117.6 months). All patients were reported to have subjective improvement of their ankle instability, with complications in 31 cases. Studies of arthroscopic suture anchor technique to treat CAI are sparse, with moderate mean methodologic quality. The included studies suggest that the arthroscopic technique is a feasible procedure to restore ankle stability; however, on the basis of our review, this technique seems to be associated with a relatively high complication rate. Extensive cadaveric studies, clinical trials, and comparative studies comparing arthroscopic and open repair should be performed in the future. Level IV, systematic review of Level IV studies. Copyright © 2014 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

One-Step Cartilage Repair Technique as a Next Generation of Cell Therapy for Cartilage Defects: Biological Characteristics, Preclinical Application, Surgical Techniques, and Clinical Developments.

PubMed

Zhang, Chi; Cai, You-Zhi; Lin, Xiang-Jin

2016-07-01

To provide a comprehensive overview of the basic science rationale, surgical technique, and clinical outcomes of 1-step cartilage repair technique used as a treatment strategy for cartilage defects. A systematic review was performed in the main medical databases to evaluate the several studies concerning 1-step procedures for cartilage repair. The characteristics of cell-seed scaffolds, behavior of cells seeded into scaffolds, and surgical techniques were also discussed. Clinical outcomes and quality of repaired tissue were assessed using several standardized outcome assessment tools, magnetic resonance imaging scans, and biopsy histology. One-step cartilage repair could be divided into 2 types: chondrocyte-matrix complex (CMC) and autologous matrix-induced chondrogenesis (AMIC), both of which allow a simplified surgical approach. Studies with Level IV evidence have shown that 1-step cartilage repair techniques could significantly relieve symptoms and improve functional assessment (P < .05, compared with preoperative evaluation) at short-term follow-up. Furthermore, magnetic resonance imaging showed that 76% cases in all included case series showed at least 75% defect coverage in each lesion, and 3 studies clearly showed hyaline-like cartilage tissue in biopsy tissues by second-look arthroscopy. The 1-step cartilage repair technique, with its potential for effective, homogeneous distribution of chondrocytes and multipotent stem cells on the surface of the cartilage defect, is able to regenerate hyaline-like cartilage tissue, and it could be applied to cartilage repair by arthroscopy. Level IV, systematic review of Level II and IV studies. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Multiparametric in situ mRNA hybridization analysis to predict disease recurrence in patients with colon carcinoma.

PubMed Central

Kitadai, Y.; Ellis, L. M.; Tucker, S. L.; Greene, G. F.; Bucana, C. D.; Cleary, K. R.; Takahashi, Y.; Tahara, E.; Fidler, I. J.

1996-01-01

We examined the expression level of several genes that regulate different steps of metastasis in formalin-fixed, paraffin-embedded archival specimens of primary human colon carcinomas from patients with at least 5 years of follow-up. The expression of epidermal growth factor receptor, basic fibroblast growth factor, type IV collagenase, E-cadherin, and multidrug resistance (mdr-1) was examined by a colorimetric in situ mRNA hybridization technique concentrating on reactivity at the periphery of the neoplasms. The in situ hybridization technique revealed inter- and intratumor heterogeneity for expression of the metastasis-related genes. The expression of basic fibroblast growth factor, collagenase type IV, epidermal growth factor receptor, and mdr-1 mRNA was higher in Dukes's stage D than in Dukes' stage B tumors. Among the 22 Dukes' stage B neoplasms, 5 specimens exhibited a high expression level of epidermal growth factor receptor, basic fibroblast growth factor, and collagenase type IV. Clinical outcome data (5-year follow-up) revealed that all 5 patients with Dukes' stage B tumors developed distant metastasis (recurrent disease), whereas the other 17 patients with Dukes' stage B tumors expressing low levels of the metastasis-related genes were disease-free. Multivariate analysis identified high levels of expression of collagenase type IV and low levels of expression of E-cadherin as independent factors significantly associated with metastasis or recurrent disease. More specifically, metastatic or recurrent disease was associated with a high ratio (> 1.35) of expression of collagenase type IV to E-cadherin (specificity of 95%). Collectively, the data show that multiparametric in situ hybridization analysis for several metastasis-related genes may predict the metastatic potential, and hence the clinical outcome, of individual lymph-node-negative human colon cancers. Images Figure 1 Figure 2 PMID:8909244

Delayed Enhancement of Ascites After IV Contrast Material Administration at CT: Time Course and Clinical Correlation

PubMed Central

Benedetti, Nancy; Aslam, Rizwan; Wang, Zhen J.; Joe, Bonnie N.; Fu, Yanjun; Yee, Judy; Yeh, Benjamin M.

2010-01-01

OBJECTIVE The objective of our study was to determine the prevalence and clinical predictors of delayed contrast enhancement of ascites. MATERIALS AND METHODS In this retrospective study, 132 consecutive patients with ascites who underwent repeated abdominopelvic CT examinations performed within 7 days of each other were identified. These patients included 112 patients who received and 20 who did not receive IV contrast material at the initial CT examination. For each examination, we recorded the CT attenuation of the ascites. For the follow-up scan, the presence of delayed enhancement of ascites was defined as an increase in CT attenuation > 10 HU over baseline. The Fisher’s exact test, unpaired Student’s t test, and logistic regression were used to determine predictors of delayed enhancement of ascites. RESULTS A threshold increase in the attenuation of ascites by > 10 HU or more between the initial and follow-up CT examinations occurred only when IV contrast material was given with the initial examination. The increased attenuation was due to delayed contrast enhancement of ascites and occurred in 15 of the 112 patients (13%). Of the 16 patients scanned less than 1 day apart, 10 (63%) showed delayed enhancement of ascites. Delayed enhancement was not observed 3 or more days after IV contrast material administration. For each 1 mg/dL increase in serum creatinine level, the likelihood of delayed enhancement of ascites increased (odds ratio, 2.02; 95% CI, 1.11–3.69). Multivariate logistic regression showed that a short time interval between examinations (p < 0.001), increased serum creatinine level (p < 0.001), and presence of loculated ascites (p = < 0.01) were independent predictors of the magnitude of delayed enhancement of ascites. CONCLUSION Delayed contrast enhancement of ascites occurs commonly after recent prior IV contrast material administration and should not be mistaken for hemoperitoneum or proteinaceous fluid such as pus. PMID:19696286

Stable self-serving personality traits in recreational and dependent cocaine users

PubMed Central

Quednow, Boris B.; Hulka, Lea M.; Preller, Katrin H.; Baumgartner, Markus R.; Eisenegger, Christoph; Vonmoos, Matthias

2017-01-01

Chronic cocaine use has been associated with impairments in social cognition, self-serving and antisocial behavior, and socially relevant personality disorders (PD). Despite the apparent relationship between Machiavellianism and stimulant use, no study has explicitly examined this personality concept in cocaine users so far. In the frame of the longitudinal Zurich Cocaine Cognition Study, the Machiavellianism Questionnaire (MACH-IV) was assessed in 68 recreational and 30 dependent cocaine users as well as in 68 psychostimulant-naïve controls at baseline. Additionally, three closely related personality dimensions from the Temperament and Character Inventory (TCI)–cooperativeness, (social) reward dependence, and self-directedness–and the screening questionnaire of the Structured Clinical Interview for DSM-IV Axis II Personality Disorders (SCID-II) were acquired. At the one-year follow-up, 57 cocaine users and 48 controls were reassessed with the MACH-IV. Finally, MACH-IV scores were correlated with measures of social cognition and interaction (cognitive/emotional empathy, Theory-of-Mind, prosocial behavior) and with SCID-II PD scores assessed at baseline. Both recreational and dependent cocaine users showed significantly higher Machiavellianism than controls, while dependent cocaine users additionally displayed significantly lower levels of TCI cooperativeness and self-directedness. During the one-year interval, MACH-IV scores showed high test-retest reliability and also the significant gap between cocaine users and controls remained. Moreover, in cocaine users, higher Machiavellianism correlated significantly with lower levels of cooperativeness and self-directedness, with less prosocial behavior, and with higher cluster B PD scores. However, Machiavellianism was not correlated with measures of cocaine use severity (r<-.15). Both recreational and dependent cocaine users display pronounced and stable Machiavellian personality traits. The lack of correlations with severity of cocaine use and its temporal stability indicates that a Machiavellian personality trait might represent a predisposition for cocaine use that potentially serves as a predictor for stimulant addiction. PMID:28253291

Efficacy of anidulafungin in 539 patients with invasive candidiasis: a patient-level pooled analysis of six clinical trials

PubMed Central

Kullberg, Bart Jan; Vasquez, José; Mootsikapun, Piroon; Nucci, Marcio; Paiva, José-Artur; Garbino, Jorge; Yan, Jean Li; Aram, Jalal; Capparella, Maria Rita; Conte, Umberto; Schlamm, Haran; Swanson, Robert; Herbrecht, Raoul

2017-01-01

Abstract Objectives: To evaluate the efficacy of anidulafungin for the treatment of candidaemia and invasive candidiasis in a large dataset, including patients with deep-seated tissue candidiasis, neutropenia and infection due to non-albicans Candida species. Methods: Data were pooled from six prospective, multicentre, multinational studies: four open-label, non-comparative studies of anidulafungin and two double-blind, double-dummy, randomized studies of anidulafungin versus caspofungin (clinical trial registrations: NCT00496197, NCT00548262, NCT00537329, NCT00689338, NCT00806351 and NCT00805740; ClinicalTrials.gov). In all studies, patients with culture-confirmed invasive candidiasis received a single intravenous (iv) loading dose of anidulafungin 200 mg on day 1, followed by 100 mg once-daily. Switch to oral fluconazole or voriconazole was permitted after 5–10 days of iv treatment in all studies except one. Antifungal treatment (iv plus oral therapy if applicable) was maintained for ≥14 days after the last positive Candida culture. The primary endpoint was successful global response at end of iv therapy (EOivT) in the modified ITT (mITT) population. Results: In total, 539 patients were included (mITT population). The most common baseline Candida species were Candida albicans (47.9%), Candida glabrata (21.0%), Candida tropicalis (13.7%), Candida parapsilosis (13.2%) and Candida krusei (3.5%). Median duration of anidulafungin iv treatment was 10.0 days. The global response success rate at EOivT was 76.4% (95% CI 72.9%–80.0%). All-cause mortality was 13.0% on day 14 and 19.1% on day 28. Adverse events (AEs) were consistent with the known AE profile for anidulafungin. Conclusions: These data demonstrate that anidulafungin is effective for treatment of candidaemia and invasive candidiasis in a broad patient population. PMID:28459966

What is the Ideal Route of Administration of Tranexamic Acid in TKA? A Randomized Controlled Trial.

PubMed

Lee, Sung Yup; Chong, Suri; Balasubramanian, Dhanasekaraprabu; Na, Young Gon; Kim, Tae Kyun

2017-08-01

TKA commonly involves substantial blood loss and tranexamic acid has been used to reduce blood loss after TKA. Numerous clinical trials have documented the efficacy and safety of intravenous (IV) or intraarticular (IA) use of tranexamic acid. Combined administration of tranexamic acid also has been suggested; however, there is no consensus regarding the ideal route of tranexamic acid administration. (1) To compare the efficacy of tranexamic acid in terms of total blood loss and the allogeneic transfusion rate among three routes of administration: IV alone, IA alone, and combined IV and IA. (2) To compare these regimens in terms of venous thromboembolism (VTE) and the frequency of wound complications. In total, 376 patients undergoing TKA between March 2014 and March 2015 were randomized to four groups by the route of tranexamic acid administration: IV only, IA only, low-dose combined (IV + IA injection of 1 g), and high-dose combined (IV + IA injection of 2 g). The calculated total blood loss, allogeneic transfusion rate, decrease in hemoglobin, the frequency of symptomatic deep vein thrombosis and pulmonary embolism, wound complications, and periprosthetic joint infection were compared among the groups. Total blood loss was calculated using estimated total body blood volume and hemoglobin loss. The decision regarding when to transfuse was determined based on preset criteria. The high- and low-dose combined groups and the IA-only group had lower total blood loss (564 ± 242 mL, 642 ± 242 mL, and 633 ± 205 mL, respectively) than the IV-only group (764 ± 217 mL; mean differences = 199 mL [95% CI, 116-283 mL], p < 0.001; 121 mL [95% CI, 38-205 mL], p = 0.001; 131 mL [95% CI, 47-214 mL], p < 0.001); no differences were found among the other three groups. No patients in any study group received an allogeneic transfusion. One patient in the IV-only group had a symptomatic pulmonary embolism develop, but no other symptomatic VTE events occurred in any group. In addition, no differences were observed in wound complications, such as superficial wound necrosis (one patient in the IV-only and the high-dose combined group, respectively) and oozing (IV-only, IA-only, low-dose combined, high-dose combined = 3%, 4%, 4%, and 7%; p = 0.572) between the groups. No patients had a periprosthetic joint infection. IA tranexamic acid administration further reduces blood loss after TKA in comparison to IV use alone; no additional effect in further reducing blood loss was found in combination with IV tranexamic acid. Appropriately powered studies are needed to confirm the safety of this route of administration as the preferred route of administration in TKA. Level I, therapeutic study.

Mitogen-activated protein kinases (MAPKs) regulate IL-6 over-production during concomitant influenza virus and Staphylococcus aureus infection.

PubMed

Klemm, Carolin; Bruchhagen, Christin; van Krüchten, Andre; Niemann, Silke; Löffler, Bettina; Peters, Georg; Ludwig, Stephan; Ehrhardt, Christina

2017-02-14

Bacterial super-infections are a major complication of influenza virus (IV) infections and often lead to severe pneumonia. One hallmark of IV-associated Staphylococcus aureus (S. aureus) infection is rapid progression to a serious disease outcome. Changes in immune and inflammatory host responses increase morbidity and complicate efficient therapy. A key player during inflammation is the multifunctional cytokine IL-6. Although increased IL-6 levels have been observed after severe disease upon IV and/or bacterial super-infection, the underlying molecular mechanisms still remain to be elucidated. In the present study, we focused on cellular signalling pathways regulating IL-6 production upon IV/S. aureus super-infection. Additionally, infection with viable bacteria was mimicked by lipoteichoic acid stimulation in this model. Analyses of cellular signalling mechanisms revealed synergistically increased activation of the MAPK p38 as well as enhanced phosphorylation of the MAPKs ERK1/2 and JNK in the presence of super-infecting bacteria. Interestingly, inhibition of MAPK activity indicated a strong dependence of IL-6 expression on p38 and ERK1/2, while the MAPK JNK seems not to be involved. Thus, our results provide new molecular insights into the regulation of IL-6, a marker of severe disease, which might contribute to the lethal synergism of IV and S. aureus.

Effect of soil humic and fulvic acids, pH and ionic strength on Th(IV) sorption to TiO2 nanoparticles.

PubMed

Tan, Xiaoli; Wang, Xiangke; Chen, Changlun; Sun, Aihua

2007-04-01

Thorium is considered as a chemical analog of other tetravalent actinides. Herein, the sorption of Th(IV) on TiO(2) in the presence or absence of soil fulvic acid (FA)/humic acid (HA) as a function of pH, ionic strength and FA/HA concentration has been studied by a batch method. The morphology was characterized by scanning electron microscopy (SEM). The results indicate that sorption of Th(IV) on TiO(2) increases from 0% to approximately 94% at pH 1 approximately 4, and then maintains level with increasing pH values. Both FA and HA have a positive effect on Th(IV) sorption at low pH values and the contribution of FA on Th(IV) sorption is rather higher than that of HA at pH<4. The sorption is weakly dependent on the concentration of KNO(3) in solution, but the cations K(+), Na(+) and Li(+) influence Th(IV) sorption more obviously. The batch results indicate that the inner sphere complex formation is formed at bare surfaces or FA/HA-bound TiO(2) particle surfaces. Results of SEM analysis show that the particle sizes of TiO(2), Th-TiO(2) and Th-HA-TiO(2) colloids are quite different. Surface complexation may be considered as the main sorption mechanism.

Comparison of variance estimators for meta-analysis of instrumental variable estimates

PubMed Central

Schmidt, AF; Hingorani, AD; Jefferis, BJ; White, J; Groenwold, RHH; Dudbridge, F

2016-01-01

Abstract Background: Mendelian randomization studies perform instrumental variable (IV) analysis using genetic IVs. Results of individual Mendelian randomization studies can be pooled through meta-analysis. We explored how different variance estimators influence the meta-analysed IV estimate. Methods: Two versions of the delta method (IV before or after pooling), four bootstrap estimators, a jack-knife estimator and a heteroscedasticity-consistent (HC) variance estimator were compared using simulation. Two types of meta-analyses were compared, a two-stage meta-analysis pooling results, and a one-stage meta-analysis pooling datasets. Results: Using a two-stage meta-analysis, coverage of the point estimate using bootstrapped estimators deviated from nominal levels at weak instrument settings and/or outcome probabilities ≤ 0.10. The jack-knife estimator was the least biased resampling method, the HC estimator often failed at outcome probabilities ≤ 0.50 and overall the delta method estimators were the least biased. In the presence of between-study heterogeneity, the delta method before meta-analysis performed best. Using a one-stage meta-analysis all methods performed equally well and better than two-stage meta-analysis of greater or equal size. Conclusions: In the presence of between-study heterogeneity, two-stage meta-analyses should preferentially use the delta method before meta-analysis. Weak instrument bias can be reduced by performing a one-stage meta-analysis. PMID:27591262

Resonant tunneling via a Ru-dye complex using a nanoparticle bridge junction.

PubMed

Nishijima, Satoshi; Otsuka, Yoichi; Ohoyama, Hiroshi; Kajimoto, Kentaro; Araki, Kento; Matsumoto, Takuya

2018-06-15

Nonlinear current-voltage (I-V) characteristics is an important property for the realization of information processing in molecular electronics. We studied the electrical conduction through a Ru-dye complex (N-719) on a 2-aminoethanethiol (2-AET) monolayer in a nanoparticle bridge junction system. The nonlinear I-V characteristics exhibited a threshold voltage at around 1.2 V and little temperature dependence. From the calculation of the molecular states using density functional theory and the energy alignment between the electrodes and molecules, the conduction mechanism in this system was considered to be resonant tunneling via the HOMO level of N-719. Our results indicate that the weak electronic coupling of electrodes and molecules is essential for obtaining nonlinear I-V characteristics with a clear threshold voltage that reflect the intrinsic molecular state.

7 CFR 1463.106 - Base quota levels for eligible tobacco producers.

Code of Federal Regulations, 2012 CFR

2012-01-01

...)—.952381 (iv) Virginia Sun-cured (type 37) 1.0000 3 Multiply the sum from Step 2 times the farm's average... (35-36)—.952381 (iv) Virginia Sun-cured (type 37) 1.0000 6 Multiply the sum from Step 5 times the farm... (35-36)—.94264 (iv) Virginia Sun-cured (type 37) 1.0000 3 Multiply the sum from Step 2 times the farm...

7 CFR 1463.106 - Base quota levels for eligible tobacco producers.

Code of Federal Regulations, 2013 CFR

2013-01-01

...)—.952381 (iv) Virginia Sun-cured (type 37) 1.0000 3 Multiply the sum from Step 2 times the farm's average... (35-36)—.952381 (iv) Virginia Sun-cured (type 37) 1.0000 6 Multiply the sum from Step 5 times the farm... (35-36)—.94264 (iv) Virginia Sun-cured (type 37) 1.0000 3 Multiply the sum from Step 2 times the farm...

7 CFR 1463.106 - Base quota levels for eligible tobacco producers.

Code of Federal Regulations, 2014 CFR

2014-01-01

...)—.952381 (iv) Virginia Sun-cured (type 37) 1.0000 3 Multiply the sum from Step 2 times the farm's average... (35-36)—.952381 (iv) Virginia Sun-cured (type 37) 1.0000 6 Multiply the sum from Step 5 times the farm... (35-36)—.94264 (iv) Virginia Sun-cured (type 37) 1.0000 3 Multiply the sum from Step 2 times the farm...

7 CFR 1463.106 - Base quota levels for eligible tobacco producers.

Code of Federal Regulations, 2011 CFR

2011-01-01

...)—.952381 (iv) Virginia Sun-cured (type 37) 1.0000 3 Multiply the sum from Step 2 times the farm's average... (35-36)—.952381 (iv) Virginia Sun-cured (type 37) 1.0000 6 Multiply the sum from Step 5 times the farm... (35-36)—.94264 (iv) Virginia Sun-cured (type 37) 1.0000 3 Multiply the sum from Step 2 times the farm...

Long-Term Outcomes of Elagolix in Women With Endometriosis: Results From Two Extension Studies.

PubMed

Surrey, Eric; Taylor, Hugh S; Giudice, Linda; Lessey, Bruce A; Abrao, Mauricio S; Archer, David F; Diamond, Michael P; Johnson, Neil P; Watts, Nelson B; Gallagher, J Chris; Simon, James A; Carr, Bruce R; Dmowski, W Paul; Leyland, Nicholas; Singh, Sukhbir S; Rechberger, Tomasz; Agarwal, Sanjay K; Duan, W Rachel; Schwefel, Brittany; Thomas, James W; Peloso, Paul M; Ng, Juki; Soliman, Ahmed M; Chwalisz, Kristof

2018-06-06

To evaluate the efficacy and safety of elagolix, an oral, nonpeptide gonadotropin-releasing hormone antagonist, over 12 months in women with endometriosis-associated pain. Elaris Endometriosis (EM)-III and -IV were extension studies that evaluated an additional 6 months of treatment after two 6-month, double-blind, placebo-controlled phase 3 trials (12 continuous treatment months) with two elagolix doses (150 mg once daily and 200 mg twice daily). Coprimary efficacy endpoints were the proportion of responders (clinically meaningful pain reduction and stable or decreased rescue analgesic use) based on average monthly dysmenorrhea and nonmenstrual pelvic pain scores. Safety assessments included adverse events, clinical laboratory tests, and endometrial and bone mineral density assessments. The power of Elaris EM-III and -IV was based on the comparison to placebo in Elaris EM-I and -II with an expected 25% dropout rate. Between December 28, 2012, and October 31, 2014 (Elaris EM-III), and between May 27, 2014, and January 6, 2016 (Elaris EM-IV), 569 participants were enrolled. After 12 months of treatment, Elaris EM-III responder rates for dysmenorrhea were 52.1% at 150 mg once daily (Elaris EM-IV=50.8%) and 78.1% at 200 mg twice daily (Elaris EM-IV=75.9%). Elaris EM-III nonmenstrual pelvic pain responder rates were 67.8% at 150 mg once daily (Elaris EM-IV=66.4%) and 69.1% at 200 mg twice daily (Elaris EM-IV=67.2%). After 12 months of treatment, Elaris EM-III dyspareunia responder rates were 45.2% at 150 mg once daily (Elaris EM-IV=45.9%) and 60.0% at 200 mg twice daily (Elaris EM-IV=58.1%). Hot flush was the most common adverse event. Decreases from baseline in bone mineral density and increases from baseline in lipids were observed after 12 months of treatment. There were no adverse endometrial findings. Long-term elagolix treatment provided sustained reductions in dysmenorrhea, nonmenstrual pelvic pain, and dyspareunia. The safety was consistent with reduced estrogen levels and no new safety concerns were associated with long-term elagolix use. ClinicalTrials.gov, NCT01760954 and NCT02143713.

Prophylactic vitamin K for the prevention of vitamin K deficiency bleeding in preterm neonates.

PubMed

Ardell, Stephanie; Offringa, Martin; Ovelman, Colleen; Soll, Roger

2018-02-05

Vitamin K is necessary for the synthesis of coagulation factors. Term infants, especially those who are exclusively breast fed, are deficient in vitamin K and consequently may have vitamin K deficiency bleeding (VKDB). Preterm infants are potentially at greater risk for VKDB because of delayed feeding and subsequent delay in the colonization of their gastrointestinal system with vitamin K producing microflora, as well as immature hepatic and hemostatic function.  OBJECTIVES: To determine the effect of vitamin K prophylaxis in the prevention of vitamin K deficiency bleeding (VKDB) in preterm infants. We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2016, Issue 11), MEDLINE via PubMed (1966 to 5 December 2016), Embase (1980 to 5 December 2016), and CINAHL (1982 to 5 December 2016). We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles. Randomized controlled trials (RCTs) or quasi-RCTs of any preparation of vitamin K given to preterm infants. We evaluated potential studies and extracted data in accordance with the recommendations of Cochrane Neonatal. We did not identify any eligible studies that compared vitamin K to no treatment.One study compared intravenous (IV) to intramuscular (IM) administration of vitamin K and compared various dosages of vitamin K. Three different prophylactic regimes of vitamin K (0.5 mg IM, 0.2 mg vitamin K 1 , or 0.2 mg IV) were given to infants less than 32 weeks' gestation. Given that only one small study met the inclusion criteria, we assessed the quality of the evidence for the outcomes evaluated as low.Intramuscular versus intravenousThere was no statistically significant difference in vitamin K levels in the 0.2 mg IV group when compared to the infants that received either 0.2 or 0.5 mg vitamin K IM (control) on day 5. By day 25, vitamin K 1 levels had declined in all of the groups, but infants who received 0.5 mg vitamin K IM had higher levels of vitamin K 1 than either the 0.2 mg IV group or the 0.2 mg IM group.Vitamin K 1 2,3-epoxide (vitamin K 1 O) levels in the infants that received 0.2 mg IV were not statistically different from those in the control group on day 5 or 25 of the study. All of the infants had normal or supraphysiologic levels of vitamin K 1 concentrations and either no detectable or insignificant amounts of prothrombin induced by vitamin K absence-II (PIVKA II).Dosage comparisonsDay 5 vitamin K 1 levels and vitamin K 1 O levels were significantly lower in the 0.2 mg IM group when compared to the 0.5 mg IM group. On day 25, vitamin K 1 O levels and vitamin K 1 levels in the 0.2 mg IM group and the 0.5 mg IM group were not significantly different. Presence of PIVKA II proteins in the 0.2 mg IM group versus the 0.5 mg IM group was not significantly different at day 5 or 25 of the study. Preterm infants have low levels of vitamin K and develop detectable PIVKA proteins during the first week of life. Despite being at risk for VKDB, there are no studies comparing vitamin K versus non-treatment and few studies that address potential dosing strategies for effective treatment. Dosage studies suggest that we are currently giving doses of vitamin K to preterm infants that lead to supraphysiologic levels. Because of current uncertainty, clinicians will have to extrapolate data from term infants to preterm infants. Since there is no available evidence that vitamin K is harmful or ineffective and since vitamin K is an inexpensive drug, it seems prudent to follow the recommendations of expert bodies and give vitamin K to preterm infants. However, further research on appropriate dose and route of administration is warranted.

Safety and activity of temsirolimus and bevacizumab in patients with advanced renal cell carcinoma previously treated with tyrosine kinase inhibitors: a phase 2 consortium study.

PubMed

Merchan, Jaime R; Qin, Rui; Pitot, Henry; Picus, Joel; Liu, Glenn; Fitch, Tom; Maples, William J; Flynn, Patrick J; Fruth, Briant F; Erlichman, Charles

2015-03-01

Bevacizumab or temsirolimus regimens have clinical activity in the first-line treatment of advanced renal cell carcinoma (RCC). This phase I/II trial was conducted to determine the safety of combining both agents and its efficacy in RCC patients who progressed on at least one prior anti-VEGF receptor tyrosine kinase inhibitor (RTKI) agent. In the phase I portion, eligible patients were treated with temsirolimus (25 mg IV weekly) and escalating doses of IV bevacizumab (level 1 = 5 mg/kg; level 2 = 10 mg/kg) every other week. The primary endpoint for the phase II portion (RTKI resistant patients) was the 6-month progression-free rate. Secondary endpoints were response rate, toxicity evaluation, and PFS and OS. Maximum tolerated dose was not reached at the maximum dose administered in 12 phase I patients. Forty evaluable patients were treated with the phase II recommended dose (temsirolimus 25 mg IV weekly and bevacizumab 10 mg/kg IV every 2 weeks). The 6-month progression-free rate was 40 % (16/40 pts). Median PFS was 5.9 (4-7.8) months, and median OS was 20.6 (11.5-23.7) months. Partial response, stable disease, and progressive disease were seen in 23, 63, and 14 % of patients, respectively. Most common grade 3-4 AEs included fatigue (17.8 %), hypertriglyceridemia (11.1 %), stomatitis (8.9 %), proteinuria (8.9 %), abdominal pain (6.7 %), and anemia (6.7 %). Baseline levels of serum sFLT-1 and VEGF-A were inversely correlated with PFS and OS, respectively. Temsirolimus and bevacizumab is a feasible combination in patients with advanced RCC previously exposed to oral anti-VEGF agents. The safety and efficacy results warrant further confirmatory studies in this patient population.

Current-voltage characteristics of dendrimer light-emitting diodes

NASA Astrophysics Data System (ADS)

Stevenson, S. G.; Samuel, I. D. W.; Staton, S. V.; Knights, K. A.; Burn, P. L.; Williams, J. H. T.; Walker, Alison B.

2010-09-01

We have investigated current-voltage (I-V) characteristics of unipolar and bipolar organic diodes that use phosphorescent dendrimers as the emissive organic layer. Through simulation of the measured I-V characteristics we were able to determine the device parameters for each device structure studied, leading to a better understanding of injection and transport behaviour in these devices. It was found that the common practice of assuming injection barriers are equal to the difference between bare electrode work functions and molecular orbital levels is unsuitable for the devices considered here, particularly for gold contacts. The studies confirm that different aromatic units in the dendrons can give significant differences in the charge transporting properties of the dendrimers.

Phase I study of intravenous (IV) docetaxel and intraperitoneal (IP) oxaliplatin in recurrent ovarian and fallopian tube cancer.

PubMed

Taylor, Sarah E; Li, Ruosha; Petschauer, Jennifer S; Donovan, Heidi; O'Neal, Sara; Keeler, Amanda W; Zamboni, William C; Edwards, Robert P; Zorn, Kristin K

2015-09-01

The primary objective was to define the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of IV docetaxel and IP oxaliplatin in women with recurrent ovarian (OV), fallopian tube (FT) or peritoneal (PP) cancer. Secondary objectives included response rate, time to progression, pharmacokinetics (PK) and quality of life (QoL). Patients received docetaxel 75mg/m(2) IV day (d) 1 and oxaliplatin escalating from 50mg/m(2) IP d2 every 3weeks using a 3+3 design. Treatment continued until disease progression, remission, or intolerable toxicity. Plasma and IP samples were taken to determine drug concentrations. MD Anderson Symptom Inventory and symptom interference scale were completed weekly. Thirteen patients were included. Median number of cycles was 6 (range 1-10). Ten patients had measureable disease. Best response was partial response (PR-2), stable disease (SD-7), and progressive disease (PD-1). Twenty-one Grades 3-4 toxicities were noted, commonly hematologic. Two patients had DLTs: prolonged neutropenia (1) and abdominal pain (1). MTD was d1 docetaxel 75mg/m(2) IV and d2 oxaliplatin 50mg/m(2) IP. Symptom burden peaked week one and returned to baseline by week two of each cycle on dose level 1. Dose level 2 had persistently high symptom burden and interference. At IP oxaliplatin doses of 50mg/m(2), total unbound drug exposure (AUC) averaged 8 times larger and Cmax reached concentrations 50-fold greater in IP fluid compared to plasma. Docetaxel 75mg/m(2) IV d1 and oxaliplatin 50mg/m(2) IP d2 is the MTD. Most patients had PR or SD. Patient-reported outcomes demonstrate temporary but tolerable decrements in QoL. IP oxaliplatin provides PK advantages over IV administration. Copyright © 2015 Elsevier Inc. All rights reserved.

The DAPP-SF as a screener for personality disorder in a forensic setting.

PubMed

Spaans, Marleen; Rinne, Thomas; de Beurs, Edwin; Spinhoven, Philip

2015-01-01

Studies on the Dimensional Assessment of Personality Pathology-Short Form (DAPP-SF) have shown its ability to identify treatment-seeking patients with personality disorders. This study focuses on its screening potential for personality disorder in 89 criminal suspects (77 men, 12 women; M age = 37.0 years) undergoing residential pretrial psychological assessments in a high-security setting. It was expected that Structured Interview for DSM-IV Personality (SIDP-IV) criteria met for personality disorder(s) would be associated with higher DAPP-SF scores. A floor effect was found in DAPP-SF scores: The forensic population reported less personality pathology than the general population. Only moderate associations between DAPP-SF and SIDP-IV outcome were found. Receiver operating characteristic analysis showed that some DAPP-SF subscales did not exceed chance level in their ability to screen for personality disorders. It is concluded that the DAPP-SF has limited usefulness as a screener for personality disorders in a forensic pretrial setting. Alternative forensic screening instruments are presented.

Effect of microwave disinfection on compressive and tensile strengths of dental stones.

PubMed

Robati Anaraki, Mahmood; Moslehifard, Elnaz; Aminifar, Soran; Ghanati, Hamed

2013-01-01

Although microwave irradiation has been used for disinfection of dental stone casts, there are concerns regarding mechanical damage to casts during the process. The aim of this study was to evaluate the effect of microwave irradiation on the compressive strength (CS) and diametral tensile strength (DTS) of stone casts. In this in vitro study, 80 cylindrical type III and IV stone models (20 × 40 mm) were prepared and divided into 8 groups of 10. The DTS and CS of the specimens were measured by a mechanical testing machine at a crosshead speed of 0.5 cm/min after 7 times of frequent wetting, irradiating at an energy level of 600 W for 3 minutes and cooling. Data were analyzed by Student's t-test. Microwave irradiation significantly increased DTS of type III and IV to 5.23 ± 0.64 and 8.17 ± 0.94, respectively (P < 0.01). According to the results, microwave disinfection increases DTS of type III and IV stone casts without any effects on their CS.

Genetic and environmental structure of DSM-IV criteria for Antisocial Personality Disorder: a twin study

PubMed Central

Rosenström, Tom; Ystrom, Eivind; Torvik, Fartein Ask; Czajkowski, Nikolai Olavi; Gillespie, Nathan A.; Aggen, Steven H.; Krueger, Robert F.; Kendler, Kenneth S; Reichborn-Kjennerud, Ted

2017-01-01

Results from previous studies on DSM-IV and DSM-5 Antisocial Personality Disorder (ASPD) have suggested that the construct is etiologically multidimensional. To our knowledge, however, the structure of genetic and environmental influences in ASPD has not been examined using an appropriate range of biometric models and diagnostic interviews. The 7 ASPD criteria (section A) were assessed in a population-based sample of 2794 Norwegian twins by a structured interview for DSM-IV personality disorders. Exploratory analyses were conducted at the phenotypic level. Multivariate biometric models, including both independent and common pathways, were compared. A single phenotypic factor was found, and the best-fitting biometric model was a single-factor common pathway model, with common-factor heritability of 51% (95% CI = 40–67%). In other words, both genetic and environmental correlations between the ASPD criteria could be accounted for by a single common latent variable. The findings support the validity of ASPD as a unidimensional diagnostic construct. PMID:28108863

Genetic and Environmental Structure of DSM-IV Criteria for Antisocial Personality Disorder: A Twin Study.

PubMed

Rosenström, Tom; Ystrom, Eivind; Torvik, Fartein Ask; Czajkowski, Nikolai Olavi; Gillespie, Nathan A; Aggen, Steven H; Krueger, Robert F; Kendler, Kenneth S; Reichborn-Kjennerud, Ted

2017-05-01

Results from previous studies on DSM-IV and DSM-5 Antisocial Personality Disorder (ASPD) have suggested that the construct is etiologically multidimensional. To our knowledge, however, the structure of genetic and environmental influences in ASPD has not been examined using an appropriate range of biometric models and diagnostic interviews. The 7 ASPD criteria (section A) were assessed in a population-based sample of 2794 Norwegian twins by a structured interview for DSM-IV personality disorders. Exploratory analyses were conducted at the phenotypic level. Multivariate biometric models, including both independent and common pathways, were compared. A single phenotypic factor was found, and the best-fitting biometric model was a single-factor common pathway model, with common-factor heritability of 51% (95% CI 40-67%). In other words, both genetic and environmental correlations between the ASPD criteria could be accounted for by a single common latent variable. The findings support the validity of ASPD as a unidimensional diagnostic construct.

Circuit analysis method for thin-film solar cell modules

NASA Technical Reports Server (NTRS)

Burger, D. R.

1985-01-01

The design of a thin-film solar cell module is dependent on the probability of occurrence of pinhole shunt defects. Using known or assumed defect density data, dichotomous population statistics can be used to calculate the number of defects expected in a module. Probability theory is then used to assign the defective cells to individual strings in a selected series-parallel circuit design. Iterative numerical calculation is used to calcuate I-V curves using cell test values or assumed defective cell values as inputs. Good and shunted cell I-V curves are added to determine the module output power and I-V curve. Different levels of shunt resistance can be selected to model different defect levels.

Contribution of alpha3(IV)alpha4(IV)alpha5(IV) Collagen IV to the Mechanical Properties of the Glomerular Basement Membrane

NASA Astrophysics Data System (ADS)

Gyoneva, Lazarina

The glomerular basement membrane (GBM) is a vital part of the blood-urine filtration barrier in the kidneys. In healthy GBMs, the main tension-resisting component is alpha3(IV)alpha4(IV)alpha5(IV) type IV collagen, but in some diseases it is replaced by other collagen IV isoforms. As a result, the GBM becomes leaky and disorganized, ultimately resulting in kidney failure. Our goal is to understanding the biomechanical aspects of the alpha3(IV)alpha4(IV)alpha5(IV) chains and how their absence could be responsible for (1) the initial injury to the GBM and (2) progression to kidney failure. A combination of experiments and computational models were designed for that purpose. A model basement membrane was used to compare experimentally the distensibility of tissues with the alpha3(IV)alpha4(IV)alpha5(IV) chains present and missing. The experiments showed basement membranes containing alpha3(IV)alpha4(IV)alpha5(IV) chains were less distensible. It has been postulated that the higher level of lateral cross-linking (supercoiling) in the alpha3(IV)alpha4(IV)alpha5(IV) networks contributes additional strength/stability to basement membranes. In a computational model of supercoiled networks, we found that supercoiling greatly increased the stiffness of collagen IV networks but only minimally decreased the permeability, which is well suited for the needs of the GBM. It is also known that the alpha3(IV)alpha4(IV)alpha5(IV) networks are more protected from enzymatic degradation, and we explored their significance in GBM remodeling. Our simulations showed that the more protected network was needed to prevent the system from entering a dangerous feedback cycle due to autoregulation mechanisms in the kidneys. Overall, the work adds to the evidence of biomechanical differences between the alpha3(IV)alpha4(IV)alpha5(IV) networks and other collagen IV networks, points to supercoiling as the main source of biomechanical differences, discusses the suitability of alpha3(IV)alpha4(IV)alpha5(IV) networks to meet the mechanics and permeability needs of the GBM, and explores the role of biomechanics and enzymatic digestion in GBM remodeling.

Urinary type IV collagen is related to left ventricular diastolic function and brain natriuretic peptide in hypertensive patients with prediabetes.

PubMed

Iida, Masato; Yamamoto, Mitsuru; Ishiguro, Yuko S; Yamazaki, Masatoshi; Ueda, Norihiro; Honjo, Haruo; Kamiya, Kaichirou

2014-01-01

Urinary type IV collagen is an early biomarker of diabetic nephropathy. Concomitant prediabetes (the early stage of diabetes) was associated with left ventricular (LV) diastolic dysfunction and increased brain natriuretic peptide (BNP) in hypertensive patients. We hypothesized that urinary type IV collagen may be related to these cardiac dysfunctions. We studied hypertensive patients with early prediabetes (HbA1c <5.7% and fasting glucose >110, n=18), those with prediabetes (HbA1c 5.7-6.4, n=98), and those with diabetes (HbA1c>6.5 or on diabetes medications, n=92). The participants underwent echocardiography to assess left atrial volume/body surface area (BSA) and the ratio of early mitral flow velocity to mitral annular velocity (E/e'). Left ventricular diastolic dysfunction (LVDD) was defined if patients had E/e'≥15, or E/e'=9-14 accompanied by left atrial volume/BSA≥32ml/mm(2). Urinary samples were collected for type IV collagen and albumin, and blood samples were taken for BNP and HbA1c. Urinary type IV collagen and albumin increased in parallel with the deterioration of glycemic status. In hypertensive patients with prediabetes, subjects with LVDD had higher levels of BNP and urinary type IV collagen than those without LVDD. In contrast, in hypertensive patients with diabetes, subjects with LVDD had higher urinary albumin and BNP than those without LVDD. Urinary type IV collagen correlated positively with BNP in hypertensive patients with prediabetes, whereas it correlated with HbA1c in those with diabetes. In hypertensive patients with prediabetes, urinary type IV collagen was associated with LV diastolic dysfunction and BNP. Copyright © 2014 Elsevier Inc. All rights reserved.

Comparing the Effects of Combined General/Epidural Anaesthesia and General Anaesthesia on Serum Cytokine Levels in Radical Cystectomy

PubMed Central

Karadeniz, Meltem Savran; Mammadov, Orkhan; Çiftci, Hayriye Şentürk; Usta, Sebahat Akgül; Pembeci, Kamil

2017-01-01

Objective Surgical stress combined with general anaesthesia (GA) suppresses the immune system and leads to cancer cell growth and premature metastasis in major oncological interventions. Epidural analgesia decreases the need for inhalation agents and opioids during surgery by suppressing sympathetic and neuroendocrine responses in the postoperative period. This study aimed to compare the effects of combined general/epidural anaesthesia (GEA)+patient-controlled epidural analgesia (PCEA) and GA+IV patient-controlled analgesia (PCA) on serum tumour necrosis factor-alpha TNF-α), interleukin-1 beta (IL-1β) and interferon-gamma (IFN-γ) levels in patients undergoing radical cystectomy. Methods Sixty-five patients were enrolled in this prospective study. Patients were randomly enrolled to the GEA group, i.e., combined GEA+ PCEA (0.1% bupivacaine+1 μg mL−1 fentanyl), and the GA group, namely combined GA+IV PCA (0.03 mg mL−1 morphine). To evaluate the cytokine response, blood samples were collected at preoperative, postoperative 1st and 24th hours. Results There was no statistically significant difference in serum TNF-α, IL-1β and IFN-γ levels between groups GA and GEA at preoperative and postoperative 1st hour and 24th hour. Total remifentanil consumption was significantly lower and length of hospital stay was significantly shorter in the GEA group than in the GA group (p<0.05). Conclusion There is no difference between two anaesthesia methods in terms of serum cytokine levels; however, combined GEA+PCEA technique appeared to be superior to GA+IV PCA because of lower intraoperative narcotic analgesic consumption and shorter hospital stay. PMID:28868167

Assessment of oral and dental health status in children with cerebral palsy: An exploratory study

PubMed Central

Sedky, Nabila A

2018-01-01

Objectives: Evaluating oral and dental health status in Egyptian children with cerebral palsy (CP) in relation to gross motor skills and types of CP. Methods: A Cross-sectional study was conducted at el-Shatby Hospital for Children, Alexandria-Egypt. Oral examination for 62 children with CP between the age ranges 3–12 years was performed and decay missing filling-tooth/decay filling-tooth (DMFT/dft), simplified oral hygiene index (OHI-S), and modified gingival index (MGI) indices were charted. Maxillofacial defects, dental problems and drooling of saliva were assessed. Children’s CP type, motor milestone, and gross motor skills were determined. All statistical analyses were performed at P < 0.05 and 0.01. Results: About 84.0% of children had spastic quadriplegia, 41.9% were sit supported, 32.3% had Level IV gross motor function classification system (GMFCS), and 29.0% had Level V. No maxillofacial defects, 14.5% had dentine exposure >1/3 of the surface, and 22.6% had frequent/severe drooling saliva. Caries prevalence comprised 54.8%, 53.2% had poor oral hygiene (OHI-S index), and 43.6% had severe gingival inflammation (MGI index). The first best predictor variable for dft was “Motor Milestone.” GMFCS (Level IV and V) was the first best predictor variable for DMFT, OHI-S, and MGI indices. Conclusion: The majority of children had dental caries, poor oral hygiene, and severe gingival inflammation. Children who were sit supported had no neck support and stand supported were suffering from dental caries (dft) more than children who were sitting and walking alone. Children with Levels IV/V GMFCS were prone to have dental caries (DMFT), susceptible to suffer from bad oral hygiene, and older children experiencing severe gingivitis more than younger ones. PMID:29623011

Plasma progesterone levels and luteal activity during gestation and prolonged oviductal egg retention in a tropical lizard, Calotes versicolor.

PubMed

Shanbhag, B A; Radder, R S; Saidapur, S K

2001-07-01

Plasma progesterone (P) levels and luteal and adrenal activities were studied during normal gestation and unusual prolonged period of oviductal egg retention in a polyautochronic, multiclutched lizard, Calotes versicolor. The normal gestation period (approximately 15 days) was categorized into four stages: stage I--a few hours following ovulation, stage II--eggs with shell and embryo at primitive streak, stage III--embryonic stages 16-20, and stage IV--prior to ovipostion (stages 26-27). The gravid lizards maintained in captivity retained eggs in their oviducts for 45 days. Plasma P levels were low in stage I, increased significantly during stage II, declined in stage III, and reached their lowest in stage IV of gestation. 3Beta-hydroxysteroid dehydrogenase (3beta-HSDH) activity was greater in lutein cells at stage II and was present in traces in stage IV gestation. Interestingly, plasma P titers that were high in lizards with eggs retained longer though the corpora lutea (CL) showed a trace 3beta-HSDH activity. However, 3beta-HSDH activity was greater in the adrenocortical cells in these lizards than that in lizards during a normal gestation period. The present study on C. versicolor shows that the CL remains active and secretes P only during the early part of the gestation. The drop in P level during the later part of gestation might facilitate growth of a second set of vitellogenic follicles. During unfavorable conditions when the lizards are forced to retain eggs in the oviduct, the adrenal glands seem to secrete progesterone to help in egg retention and in inhibition of oviposition.

Intravenous Acetaminophen May Be Associated with Reduced Odds of 30-Day Readmission after Total Knee Arthroplasty.

PubMed

Mont, Michael A; Lovelace, Belinda; Pham, An T; Hansen, Ryan N; Chughtai, Morad; Gwam, Chukwuweike U; Khlopas, Anton; Barrington, John W

2018-05-07

The purpose of this study was (1) to evaluate 30-day readmission rates in total knee arthroplasty (TKA) patients who either received intravenous (IV) or oral (PO) acetaminophen (APAP) perioperatively and (2) to extrapolate the potential annual cost savings on the national level. This was a review of 190,691 TKA recipients between the years 2012 and 2015 who received either IV ( n  = 56,475) or PO APAP ( n  = 134,216). All-cause readmissions that occurred between patient discharge and 30 days postdischarge were recorded. Continuous and categorical variables were evaluated using t -test and chi-square test, respectively. A logistic regression analysis was conducted to assess the effect of IV APAP on 30-day readmission. We also performed a literature review on 30-day readmission rates and risk prediction tools for TKA and correlated these with our findings. In addition, we extrapolated potential cost savings on the national level. The readmission rate was 0.04% in the IV and 0.14% in the PO APAP cohort (69% decreased risk; odds ratio = 0.31; 95% confidence interval = 0.20-0.47; p  < 0.001). The readmission rate in this patient population appears to be markedly lower, when compared with previous reports. This reduction in readmissions may potentially result in $160 million savings per year. The use of IV APAP in TKA patients resulted in lower readmission rates, which may be valuable in clinical decision making by surgeons and health care administrators looking to lower costs of care. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Multidisciplinary approach for the management of complex hepatic injuries AAST-OIS grades IV-V: a prospective study.

PubMed

Asensio, J A; Petrone, P; García-Núñez, L; Kimbrell, B; Kuncir, E

2007-01-01

Complex hepatic injuries grades IV-V are highly lethal. The objective of this study is to assess the multidisciplinary approach for their management and to evaluate if survival could be improved with this approach. Prospective 54-month study of all patients sustaining hepatic injuries grades IV-V managed operatively at a Level I Trauma Center. survival. univariate and stepwise logistic regression. Seventy-five patients sustained penetrating (47/63%) and blunt (28/37%) injuries. Seven (9%) patients underwent emergency department thoracotomy with a mortality of 100%. Out of the 75 patients, 52 (69%) sustained grade IV, and 23 (31%) grade V. The estimated blood loss was 3,539+/-3,040 ml. The overall survival was 69%, adjusted survival excluding patients requiring emergency department thoracotomy was 76%. Survival stratified to injury grade: grade IV 42/52-81%, grade V 10/23-43%. Mortality grade IV versus V injuries (p < 0.002; RR 2.94; 95% CI 1.52-5.70). Risk factors for mortality: packed red blood cells transfused in operating room (p=0.024), estimated blood loss (p < 0.001), dysryhthmia (p < 0.0001), acidosis (p = 0.051), hypothermia (p = 0.04). The benefit of angiography and angioembolization indicated: 12% mortality (2/17) among those that received it versus a 36% mortality (21/58) among those that did not (p = 0.074; RR 0.32; 95% CI 0.08-1.25). Stepwise logistic regression identified as significant independent predictors of outcome: estimated blood loss (p= 0.0017; RR 1.24; 95% CI 1.08-1.41) and number of packed red blood cells transfused in the operating room (p = 0.0358; RR 1.16; 95% CI 1.01-1.34). The multidisciplinary approach to the management of these severe grades of injuries appears to improve survival in these highly lethal injuries. A prospective multi-institutional study is needed to validate this approach.

Protective Effects of Caffeic Acid Phenethyl Ester on Fluoxetine-Induced Hepatotoxicity: An Experimental Study.

PubMed

Yılmaz, Ahmet; Elbey, Bilal; Yazgan, Ümit Can; Dönder, Ahmet; Arslan, Necmi; Arslan, Serkan; Alabalık, Ulaş; Aslanhan, Hamza

2016-01-01

Background. The aim of the study was to analyse the effect of caffeic acid phenethyl ester (CAPE) on fluoxetine-induced hepatotoxicity in rats. Materials and Methods. Group I served as control. Group II received CAPE intraperitoneally. Group III received fluoxetine per orally. Group IV received fluoxetine and CAPE. The total antioxidant capacity (TAC), total oxidant status (TOS), oxidative stress index (OSI), and liver enzymes including paraoxonase-1 (PON-1), aspartate transaminase, and alanine transaminase levels were measured. Liver tissues were processed histopathologically for evaluation of liver injury and to validate the serum enzyme levels. Results. An increase in TOS and OSI and a decrease in TAC and PON-1 levels in serum and liver tissues of Group III were observed compared to Groups I and II. After treatment with CAPE, the level of TOS and OSI decreased while TAC and PON-1 increased in serum and liver in Group IV. Histopathological examination of the liver revealed hepatic injury after fluoxetine treatment and reduction of injury with CAPE treatment. Conclusion. Our results suggested that CAPE treatment provided protection against fluoxetine toxicity. Following CAPE treatment with fluoxetine-induced hepatotoxicity, TOS and OSI levels decreased, whereas PON-1 and TAC increased in the serum and liver.

The acute effect of a mineralocorticoid receptor agonist on corticotrope secretion in Addison's disease.

PubMed

Berardelli, R; Karamouzis, I; D'Angelo, V; Fussotto, B; Minetto, M A; Ghigo, E; Giordano, R; Arvat, E

2016-05-01

Mineralocorticoid receptors (MR) in the hippocampus display an important role in the control of hypothalamic-pituitary-adrenal (HPA) axis, mediating the ''proactive'' feedback of glucocorticoids (GC). Fludrocortisone (FC), a potent MR agonist, has been shown to decrease HPA activity through a hippocampal mechanism. Since it has been demonstrated that FC shows a significant inhibition of the HPA axis response to hCRH stimulus in normal subjects, also at doses usually administered as replacement therapy in patients with Addison's disease, an FC effect at MRs in human pituitary or a GR-pituitary agonism stronger than believed until now has been postulated. Ten patients affected by autoimmune Addison's disease received: (1) placebo p.o. + placebo i.v., (2) hydrocortisone (H) 10 mg p.o. + placebo i.v., (3) FC 0.1 mg p.o. + placebo i.v., (4) FC 0.1 mg and H 10 mg p.o. + placebo i.v. to verify a possible GR FC-mediated effect that might display a repercussion on the GC-replacement therapy. H reduced ACTH (p < 0.01) and increased cortisol levels (p < 0.01) with respect to the placebo session, while FC did not affect either ACTH or cortisol levels compared to placebo, and higher ACTH and lower cortisol levels (p < 0.03 and p < 0.01) were observed compared with the H session; furthermore the co-administration of FC + H showed ACTH and cortisol profiles similar to that observed during H alone. Our study showed a lack of FC effect on corticotrope secretion in Addison's disease, thus making unlikely the hypothesis of its GR pituitary agonism and the risk of glucocorticoid excess in primary adrenal insufficiency.

Assessing the role of insulin-like growth factors and binding proteins in prostate cancer using Mendelian randomization: Genetic variants as instruments for circulating levels.

PubMed

Bonilla, Carolina; Lewis, Sarah J; Rowlands, Mari-Anne; Gaunt, Tom R; Davey Smith, George; Gunnell, David; Palmer, Tom; Donovan, Jenny L; Hamdy, Freddie C; Neal, David E; Eeles, Rosalind; Easton, Doug; Kote-Jarai, Zsofia; Al Olama, Ali Amin; Benlloch, Sara; Muir, Kenneth; Giles, Graham G; Wiklund, Fredrik; Grönberg, Henrik; Haiman, Christopher A; Schleutker, Johanna; Nordestgaard, Børge G; Travis, Ruth C; Pashayan, Nora; Khaw, Kay-Tee; Stanford, Janet L; Blot, William J; Thibodeau, Stephen; Maier, Christiane; Kibel, Adam S; Cybulski, Cezary; Cannon-Albright, Lisa; Brenner, Hermann; Park, Jong; Kaneva, Radka; Batra, Jyotsna; Teixeira, Manuel R; Pandha, Hardev; Lathrop, Mark; Martin, Richard M; Holly, Jeff M P

2016-10-01

Circulating insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are associated with prostate cancer. Using genetic variants as instruments for IGF peptides, we investigated whether these associations are likely to be causal. We identified from the literature 56 single nucleotide polymorphisms (SNPs) in the IGF axis previously associated with biomarker levels (8 from a genome-wide association study [GWAS] and 48 in reported candidate genes). In ∼700 men without prostate cancer and two replication cohorts (N ∼ 900 and ∼9,000), we examined the properties of these SNPS as instrumental variables (IVs) for IGF-I, IGF-II, IGFBP-2 and IGFBP-3. Those confirmed as strong IVs were tested for association with prostate cancer risk, low (< 7) vs. high (≥ 7) Gleason grade, localised vs. advanced stage, and mortality, in 22,936 controls and 22,992 cases. IV analysis was used in an attempt to estimate the causal effect of circulating IGF peptides on prostate cancer. Published SNPs in the IGFBP1/IGFBP3 gene region, particularly rs11977526, were strong instruments for IGF-II and IGFBP-3, less so for IGF-I. Rs11977526 was associated with high (vs. low) Gleason grade (OR per IGF-II/IGFBP-3 level-raising allele 1.05; 95% CI: 1.00, 1.10). Using rs11977526 as an IV we estimated the causal effect of a one SD increase in IGF-II (∼265 ng/mL) on risk of high vs. low grade disease as 1.14 (95% CI: 1.00, 1.31). Because of the potential for pleiotropy of the genetic instruments, these findings can only causally implicate the IGF pathway in general, not any one specific biomarker. © 2016 UICC.

Stark broadening of several Bi IV spectral lines of astrophysical interest

NASA Astrophysics Data System (ADS)

Colón, C.; Moreno-Díaz, C.; de Andrés-García, I.; Alonso-Medina, A.

2017-09-01

The presence of spectral lines of bismuth in stellar atmospheres has been reported in different stars. The anomalous values of the spectral intensities of Bi II and Bi III, compared to the theoretical Local Termodinamic Equilibrium (LTE) standards of Bi I/Bi II/Bi III, have been reported in the spectra obtained with the High Resolution Spectrograph of the Hubble/Goddard Space Telescope in the chemically peculiar stars HgMn stars χ Lupi and HR 7775. Spectral lines of 1436.8, 1902.3, 2630.9 and 2936.7 Å of Bi II and 1423.4 Å of Bi III were reported and their relative intensities were measured in these studies Litzén & Wahlgren 2002. These lines are overlapped with spectral lines of 1437.65, 2630.1 and 2937.1 Å of Bi IV. A study of the Stark broadening parameters of Bi IV spectral lines can help to study these overlaps. In this paper, using the Griem semi-empirical approach, we report calculated values of the Stark parameters for 64 spectral lines of Bi IV. The matrix elements used in these calculations have been determined from 17 configurations of Bi IV. They were calculated using the cowan code including core polarization effects. Data are displayed for an electron density of 1017 cm-3 and temperatures T = 10 000-160 000 K. Also calculated radiative lifetimes for 12 levels with experimental lifetime are presented, in order to test the goodness of our calculations. Theoretical trends of the Stark width and shift parameters versus the temperature for spectral lines of astrophysical interest are displayed.

27-Hydroxycholesterol impairs neuronal glucose uptake through an IRAP/GLUT4 system dysregulation

PubMed Central

Mateos, Laura; Maioli, Silvia; Ali, Zeina; Gulyás, Balázs; Winblad, Bengt; Savitcheva, Irina

2017-01-01

Hypercholesterolemia is associated with cognitively deteriorated states. Here, we show that excess 27-hydroxycholesterol (27-OH), a cholesterol metabolite passing from the circulation into the brain, reduced in vivo brain glucose uptake, GLUT4 expression, and spatial memory. Furthermore, patients exhibiting higher 27-OH levels had reduced 18F-fluorodeoxyglucose uptake. This interplay between 27-OH and glucose uptake revealed the engagement of the insulin-regulated aminopeptidase (IRAP). 27-OH increased the levels and activity of IRAP, countered the IRAP antagonist angiotensin IV (AngIV)–mediated glucose uptake, and enhanced the levels of the AngIV-degrading enzyme aminopeptidase N (AP-N). These effects were mediated by liver X receptors. Our results reveal a molecular link between cholesterol, brain glucose, and the brain renin-angiotensin system, all of which are affected in some neurodegenerative diseases. Thus, reducing 27-OH levels or inhibiting AP-N maybe a useful strategy in the prevention of the altered glucose metabolism and memory decline in these disorders. PMID:28213512

Direct spectrophotometric measurement of supra-physiological levels of ascorbate in plasma.

PubMed

Witmer, Jordan R; Wetherell, Bailey J; Wagner, Brett A; Du, Juan; Cullen, Joseph J; Buettner, Garry R

2016-08-01

Supra-physiological concentrations of ascorbate, vitamin C, in blood, greater than 1mM, achieved through intravenous administration (IV), are being tested in clinical trials to treat human disease, e.g. cancer. These trials need information on the high levels of ascorbate achieved in blood upon IV administration of pharmacological ascorbate so appropriate clinical decisions can be made. Here we demonstrate that in the complex matrix of human blood plasma supra-physiological levels of ascorbate can be quantified by direct UV spectroscopy with use of a microvolume UV-vis spectrophotometer. Direct quantitation of ascorbate in plasma in the range of 2.9mM, lower limit of detection, up to at least 35mM can be achieved without any sample processing, other than centrifugation. This approach is rapid, economical, and can be used to quantify supraphysiological blood levels of ascorbate associated with the use of IV administration of pharmacological ascorbate to treat disease. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

Growth hormone secretory pattern and response to treatment in children with short stature followed to adult height.

PubMed

Radetti, Giorgio; Buzi, Fabio; Cassar, Walburga; Paganini, Claudio; Stacul, Elisabetta; Maghnie, Mohamad

2003-07-01

To compare the relative utility of GH stimulation tests and assays of spontaneous GH secretion as predictors of change in height standard deviation score at the end of GH treatment in children with short stature. We retrospectively studied 116 children (67 boys and 49 girls) with subnormal growth rates and short stature, defined as a height of more than 2SD below the mean for age and sex. The patients were classified according to their pattern of findings on baseline pharmacological GH stimulation tests and a 12-h assay of nocturnal spontaneous GH secretion. Twenty-eight patients (24%) had normal hormone levels by both methods (group I); 14 (12%) had normal levels by stimulation tests but subnormal levels by the physiological assay (group II); 48 (41%) had subnormal levels on pharmacological stimulation, with normal physiologic levels (group III); and 26 (22%) had subnormal levels by both methods (group IV). All children in groups II and IV, and 27 in group III, designated IIIb, were treated with recombinant GH at 0.7 U (0.23 mg/kg) of body weight per week. GH secretory patterns were related to final height SD scores and other growth parameters, after the patients had attained their adult stature 6.7 +/- 2.2 years (SD) after GH evaluation. The five groups were similar with respect to mean baseline height SD scores for chronological as well as bone age. Whether assessed as absolute or parentally adjusted (relative) values, mean gains in height SD scores were significantly greater in treated patients with physiological hormone deficiency (groups II and IV) than in those with normal hormone levels (group I, untreated controls). Relative height gains were 1.03 +/- 1.45 cm (6.6 +/- 9.28 cm) and 1.85 +/- 1.21 cm (SDS; 11.8 +/- 7.74 cm) in groups II and IV respectively, compared with only 0.11 +/- 0.42 cm (0.7 +/- 2.68 cm) in group I (P < 0.01 and P < 0.001). GH treatment failed to improve either the absolute or parentally adjusted final height of patients with GH deficiency by stimulation tests but normal levels by physiological assay. Long-term administration of GH to short children with normal spontaneous GH secretion is not associated with an appreciable increase in adult height.

Usefulness of the brain natriuretic peptide to atrial natriuretic peptide ratio in determining the severity of mitral regurgitation.

PubMed

Shimamoto, Ken; Kusumoto, Miyako; Sakai, Rieko; Watanabe, Hirota; Ihara, Syunichi; Koike, Natsuka; Kawana, Masatoshi

2007-03-15

Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) levels were characterized in subjects with mitral regurgitation (MR). Sixty-two cases of moderate or severe chronic MR were studied. The blood levels of neurohormonal factors were stratified by the known MR prognostic factors of New York Heart Association (NYHA) functional class, left ventricular end-diastolic diameters, left ventricular end-systolic diameter (LVDs), ejection fraction (EF), left atrial diameter and presence of atrial fibrillation (AF). ANP levels were higher in NYHA class II and lower in classes I and III/IV (P=0.0206). BNP levels were higher in NYHA class II than class I (P=0.0355). The BNP/ANP ratio was significantly higher in NYHA classes II and III/IV than in class I (P=0.0007). To differentiate between NYHA classes I/II and III/IV, a cut-off BNP/ANP ratio of 2.97 produced a sensitivity of 78% and specificity of 87%. Compared with subjects in sinus rhythm, patients with AF had an enlarged left atrium and lower ANP levels. The BNP/ANP ratio correlated significantly with left atrial diameter, LVDs and EF (r=0.429, P=0.0017; r=0.351, P=0.0117; and r=-0.349, P=0.0122; respectively), and was significantly higher among all the known operative indications for MR tested (LVDs 45 mm or more, EF 60% or less, NYHA class II or greater and AF; P=0.0073, P=0.003, P=0.0102 and P=0.0149, respectively). In chronic MR, levels of ANP and BNP, and the BNP/ANP ratio are potential indicators of disease severity.

Increased Incretin But Not Insulin Response after Oral versus Intravenous Branched Chain Amino Acids.

PubMed

Gojda, Jan; Straková, Radka; Plíhalová, Andrea; Tůma, Petr; Potočková, Jana; Polák, Jan; Anděl, Michal

2017-01-01

Branched chain amino acids (BCAAs) are known to exert an insulinotropic effect. Whether this effect is mediated by incretins (glucagon like peptide 1 [GLP-1] or glucose-dependent insulinotropic peptide [GIP]) is not known. The aim of this study was to show whether an equivalent dose of BCAA elicits a greater insulin and incretin response when administered orally than intravenously (IV). Eighteen healthy, male subjects participated in 3 tests: IV application of BCAA solution, oral ingestion of BCAA and placebo in an equivalent dose (30.7 ± 1.1 g). Glucose, insulin, C-peptide, glucagon, GLP-1, GIP, valine, leucine and isoleucine concentrations were measured. Rise in serum BCAA was achieved in both BCAA tests, with incremental areas under the curve (iAUC) being 2.1 times greater for IV BCAA compared with those of the oral BCAA test (p < 0.0001). Oral and IV BCAA induced comparable insulin response greater than placebo (240 min insulin iAUC: oral 3,411 ± 577 vs. IV 2,361 ± 384 vs. placebo 961.2 ± 175 pmol/L, p = 0.0006). Oral BCAA induced higher GLP-1 (p < 0.0001) and GIP response (p < 0.0001) compared with the IV or placebo. Glucose levels declined significantly (p < 0.001) in the same pattern during both BCAA tests with no change in the placebo group. An equivalent dose of BCAA elicited a comparable insulin and greater incretin response when administered orally and not when administered through IV. We conclude that insulinotropic effects of BCAA are partially incretin dependent. © 2017 S. Karger AG, Basel.

Presence of anti-phosphatidylserine-prothrombin complex antibodies and anti-moesin antibodies in patients with polyarteritis nodosa.

PubMed

Okano, Tatsuro; Takeuchi, Sora; Soma, Yoshinao; Suzuki, Koya; Tsukita, Sachiko; Ishizu, Akihiro; Suzuki, Kazuo; Kawakami, Tamihiro

2017-01-01

We measured both serum anti-phosphatidylserine-prothrombin complex (anti-PSPT) antibodies and anti-moesin antibodies, as well as various cytokines (interleukin [IL]-2, IL-4, IL-5, IL-10, IL-13, IL-17, granulocyte macrophage colony-stimulating factor, γ-interferon, tumor necrosis factor-α) levels in polyarteritis nodosa (PAN) patients with cutaneous manifestations. All patients showed the presence of a histological necrotizing vasculitis in the skin specimen. They were treated with i.v. cyclophosphamide pulse therapy (IV-CY) and prednisolone therapy or steroid pulse therapy. The immunological assessments were performed on sera collected prior to and after treatment with IV-CY or steroid pulse therapy. We found a significant positive correlation between serum anti-moesin antibodies and both clinical Birmingham Vasculitis Activity Scores and Vasculitis Damage Index. Anti-PSPT antibody and IL-2 levels after treatment in PAN patients were significantly lower than before treatment. In contrast, anti-moesin antibody levels were higher following IV-CY or steroid pulse therapy compared with the pretreatment levels. In the treatment-resistant PAN patients (n = 8), anti-PSPT antibody levels after treatment were significantly lower than before treatment. In contrast, anti-moesin antibody levels after treatment in the patients were significantly higher compared with the pretreatment levels. Immunohistochemical staining revealed moesin overexpression in mainly fibrinoid necrosis of the affected arteries in the PAN patients. We suggest that measurement of serum anti-PSPT antibody levels could serve as a marker for PAN and aid in earlier diagnosis of PAN. We also propose that elevated serum anti-moesin antibodies could play some role of the exacerbation in patients with PAN. © 2016 Japanese Dermatological Association.

Collagen type IV at the fetal-maternal interface.

PubMed

Oefner, C M; Sharkey, A; Gardner, L; Critchley, H; Oyen, M; Moffett, A

2015-01-01

Extracellular matrix proteins play a crucial role in influencing the invasion of trophoblast cells. However the role of collagens and collagen type IV (col-IV) in particular at the implantation site is not clear. Immunohistochemistry was used to determine the distribution of collagen types I, III, IV and VI in endometrium and decidua during the menstrual cycle and the first trimester of pregnancy. Expression of col-IV alpha chains during the reproductive cycle was determined by qPCR and protein localisation by immunohistochemistry. The structure of col-IV in placenta was examined using transmission electron microscopy. Finally, the expression of col-IV alpha chain NC1 domains and collagen receptors was localised by immunohistochemistry. Col-IV alpha chains were selectively up-regulated during the menstrual cycle and decidualisation. Primary extravillous trophoblast cells express collagen receptors and secrete col-IV in vitro and in vivo, resulting in the increased levels found in decidua basalis compared to decidua parietalis. A novel expression pattern of col-IV in the mesenchyme of placental villi, as a three-dimensional network, was found. NC1 domains of col-IV alpha chains are known to regulate tumour cell migration and the selective expression of these domains in decidua basalis compared to decidua parietalis was determined. Col-IV is expressed as novel forms in the placenta. These findings suggest that col-IV not only represents a structural protein providing tissue integrity but also influences the invasive behaviour of trophoblast cells at the implantation site. Copyright © 2014 Elsevier Ltd. All rights reserved.

In vivo imaging of human retinal microvasculature using adaptive optics scanning light ophthalmoscope fluorescein angiography

PubMed Central

Pinhas, Alexander; Dubow, Michael; Shah, Nishit; Chui, Toco Y.; Scoles, Drew; Sulai, Yusufu N.; Weitz, Rishard; Walsh, Joseph B.; Carroll, Joseph; Dubra, Alfredo; Rosen, Richard B.

2013-01-01

The adaptive optics scanning light ophthalmoscope (AOSLO) allows visualization of microscopic structures of the human retina in vivo. In this work, we demonstrate its application in combination with oral and intravenous (IV) fluorescein angiography (FA) to the in vivo visualization of the human retinal microvasculature. Ten healthy subjects ages 20 to 38 years were imaged using oral (7 and/or 20 mg/kg) and/or IV (500 mg) fluorescein. In agreement with current literature, there were no adverse effects among the patients receiving oral fluorescein while one patient receiving IV fluorescein experienced some nausea and heaving. We determined that all retinal capillary beds can be imaged using clinically accepted fluorescein dosages and safe light levels according to the ANSI Z136.1-2000 maximum permissible exposure. As expected, the 20 mg/kg oral dose showed higher image intensity for a longer period of time than did the 7 mg/kg oral and the 500 mg IV doses. The increased resolution of AOSLO FA, compared to conventional FA, offers great opportunity for studying physiological and pathological vascular processes. PMID:24009994

Locally Advanced Stage IV Squamous Cell Carcinoma of the Head and Neck: Impact of Pre-Radiotherapy Hemoglobin Level and Interruptions During Radiotherapy

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

Rades, Dirk; Department of Radiation Oncology, University Medical Center Hamburg-Eppendorf, Hamburg; Stoehr, Monika

2008-03-15

Purpose: Stage IV head and neck cancer patients carry a poor prognosis. Clear understanding of prognostic factors can help to optimize care for the individual patient. This study investigated 11 potential prognostic factors including pre-radiotherapy hemoglobin level and interruptions during radiotherapy for overall survival (OS), metastases-free survival (MFS), and locoregional control (LC) after radiochemotherapy. Methods and Materials: Eleven factors were investigated in 153 patients receiving radiochemotherapy for Stage IV squamous cell head and neck cancer: age, gender, Karnofsky performance score (KPS), tumor site, grading, T stage, N stage, pre-radiotherapy hemoglobin level, surgery, chemotherapy type, and interruptions during radiotherapy >1 week.more » Results: On multivariate analysis, improved OS was associated with KPS 90-100 (relative risk [RR], 2.36; 95% confidence interval [CI], 1.20-4.93; p = .012), hemoglobin {>=}12 g/dL (RR, 1.88; 95% CI, 1.01-3.53; p = .048), and no radiotherapy interruptions (RR, 2.59; 95% CI, 1.15-5.78; p = .021). Improved LC was significantly associated with lower T stage (RR, 2.17; 95% CI, 1.16-4.63; p = .013), hemoglobin {>=}12 g/dL (RR, 4.12; 95% CI, 1.92-9.09; p < .001), surgery (RR, 2.67; 95% CI, 1.28-5.88; p = .008), and no radiotherapy interruptions (RR, 3.32; 95% CI, 1.26-8.79; p = .015). Improved MFS was associated with KPS 90-100 (RR, 3.41; 95% CI, 1.46-8.85; p = .012). Conclusions: Significant predictors for outcome in Stage IV head and neck cancer were performance status, stage, surgery, pre-radiotherapy hemoglobin level, and interruptions during radiotherapy >1 week. It appears important to avoid anemia and radiotherapy interruptions to achieve the best treatment results.« less

Integrative analysis of differentially expressed microRNAs of pulmonary alveolar macrophages from piglets during H1N1 swine influenza A virus infection

PubMed Central

Jiang, Pengfei; Zhou, Na; Chen, Xinyu; Zhao, Xing; Li, Dengyun; Wang, Fen; Bi, Lijun; Zhang, Deli

2015-01-01

H1N1 swine influenza A virus (H1N1 SwIV) is one key subtype of influenza viruses with pandemic potential. MicroRNAs (miRNAs) are endogenous small RNA molecules that regulate gene expression. MiRNAs relevant with H1N1 SwIV have rarely been reported. To understand the biological functions of miRNAs during H1N1 SwIV infection, this study profiled differentially expressed (DE) miRNAs in pulmonary alveolar macrophages from piglets during the H1N1 SwIV infection using a deep sequencing approach, which was validated by quantitative real-time PCR. Compared to control group, 70 and 16 DE miRNAs were respectively identified on post-infection day (PID) 4 and PID 7. 56 DE miRNAs were identified between PID 4 and PID 7. Our results suggest that most host miRNAs are down-regulated to defend the H1N1 SwIV infection during the acute phase of swine influenza whereas their expression levels gradually return to normal during the recovery phase to avoid the occurrence of too severe porcine lung damage. In addition, targets of DE miRNAs were also obtained, for which bioinformatics analyses were performed. Our results would be useful for investigating the functions and regulatory mechanisms of miRNAs in human influenza because pig serves as an excellent animal model to study the pathogenesis of human influenza. PMID:25639204

Circulating Vascular Basement Membrane Fragments are Associated with the Diameter of the Abdominal Aorta and Their Expression Pattern is Altered in AAA Tissue.

PubMed

Holsti, Mari; Wanhainen, Anders; Lundin, Christina; Björck, Martin; Tegler, Gustaf; Svensson, Johan; Sund, Malin

2018-04-12

Abdominal aortic aneurysm (AAA) is characterised by enhanced proteolytic activity, and extracellular matrix (ECM) remodelling in the vascular wall. Type IV and XVIII collagen/endostatin are structural proteins in vascular basement membrane (VBM), a specialised ECM structure. Here the association between plasma levels of these collagens with the aortic diameter and expansion rate is studied, and their expression in aortic tissue characterised. This was a retrospective population based cohort study. Type IV and XVIII collagen/endostatin were analysed in plasma by ELISA assay in 615 men, divided into three groups based on the aortic diameter: 1) normal aorta ≤ 25 mm, 2) sub-aneurysmal aorta (SAA) 26-29 mm, and 3) AAA ≥ 30 mm. Follow up data were available for 159 men. The association between collagen levels and aortic diameter at baseline, and with the expansion rate at follow up were analysed in ordinal logistic regression and linear regression models, controlling for common confounding factors. Tissue expression of the collagens was analysed in normal aorta (n = 6) and AAA (n = 6) by immunofluorescence. Plasma levels of type XVIII collagen/endostatin (136 ng/mL [SD 29] in individuals with a normal aorta diameter, 154 ng/ml [SD 45] in SAA, and 162 ng/ml [SD 46] in AAA; p = .001) and type IV collagen (105 ng/mL [SD 42] normal aorta, 124 ng/ml [SD 46] SAA, and 127 ng/ml [SD 47] AAA; p = .037) were associated with a larger aortic diameter. A significant association was found between the baseline levels of type XVIII/endostatin and the aortic expansion rate (p = .035), but in the multivariable model, only the initial aortic diameter remained significantly associated with expansion (p = .005). Altered expression patterns of both collagens were observed in AAA tissue. Plasma levels of circulating type IV and XVIII collagen/endostatin increase with AAA diameter. The expression pattern of VBM proteins is altered in the aneurysm wall. Copyright © 2018 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.

Inflammatory mediators in chronic heart failure in North India.

PubMed

Fedacko, Jan; Singh, Ram B; Gupta, Aditya; Hristova, Krasimira; Toda, Eri; Kumar, Adarsh; Saxena, Manoj; Baby, Anjum; Singh, Ranjana; Toru, Takahashi; Wilson, Douglas W

2014-08-01

Recent evidence shows that pro-inflammatory cytokines may be important in the assessment of severity and prognosis in congestive heart failure (CHF). In the present study, we examine the association of cytokines with causes, grade and prognosis of CHF patients. Of 127 patients with CHF, 11 were excluded and the remaining 116 patients with different aetiologies of CHF, and 250 age- and sex-matched control subjects, were evaluated in this case study. Severity of disease based on the New York Heart Association (NYHA) standards, fell within functional classes II to IV. The diagnosis of HF was based on clinical manifestations as well as on echocardiographic heart enlargement. Cytokines were measured by chemiluminescence. Causes of death were assessed based on death certificates. Multivariate logistic regression analysis was used to determine the risk factors of heart failure. Echocardiographic ejection fraction was 39.1 +/- 8.2% (mean +/- SD) in the study group indicating class II-IV heart failure. Laboratory data showed increase in biomarkers of oxidative stress, among HF patients compared to healthy subjects. Pro-inflammatory cytokines; IL-6 and TNF-alpha were significantly higher among HF patients compared to healthy subjects. TNF-alpha and IL-6, showed significant increase among patients with CHF due to ischaemic heart disease and cardiomyopathy compared to levels among CHF patients with valvular heart disease and hypertensive heart diseases. The levels of the cytokines were significantly higher among patients with class III and IV heart failure and those who died, compared to patients with class II heart failure. Multivariate logistic regression analysis revealed that CAD, cardiomyopathy, and IL-6 were strongly associated--and low ejection fraction and TNF-alpha--weakly associated with HF. Of 116 patients, 20 (17.2%) died during a follow-up of two years, and the deaths were mainly among NYHA class III and IV patients in whom the cause of CHF was CAD (10.9%) and cardiomyopathy (6.9%) which had greater levels of cytokines. The findings indicated that pro-inflammatory cytokines may be important indicators of causes, severity of CHF and prognosis among these patients.

A cross-sectional study of water arsenic exposure and intellectual function in adolescence in Araihazar, Bangladesh.

PubMed

Wasserman, Gail A; Liu, Xinhua; Parvez, Faruque; Chen, Yu; Factor-Litvak, Pam; LoIacono, Nancy J; Levy, Diane; Shahriar, Hasan; Uddin, Mohammed Nasir; Islam, Tariqul; Lomax, Angela; Saxena, Roheeni; Gibson, Elizabeth A; Kioumourtzoglou, Marianthi-Anna; Balac, Olgica; Sanchez, Tiffany; Kline, Jennie K; Santiago, David; Ellis, Tyler; van Geen, Alexander; Graziano, Joseph H

2018-06-19

Exposure to inorganic arsenic (As) from drinking water is associated with modest deficits in intellectual function in young children; it is unclear whether deficits occur during adolescence, when key brain functions are more fully developed. We sought to determine the degree to which As exposure is associated with adolescent intelligence, and the contributory roles of lead, cadmium, manganese and selenium. We recruited a cross-section of 726 14-16 year olds (mean age = 14.8 years) whose mothers are participants in the Bangladesh Health Effects of Arsenic Longitudinal Study (HEALS), and whose household well water As levels, which varied widely, were well characterized. Using a culturally modified version of the WISC-IV, we examined raw Full Scale scores, and Verbal Comprehension, Perceptual Reasoning, Working Memory and Processing Speed Indices. Blood levels of As (BAs), Mn, Pb, Cd and Se were assessed at the time of the visit, as was creatinine-adjusted urinary As (UAs/Cr). Linear regression analyses revealed that BAs was significantly negatively associated with all WISC-IV scores except for Perceptual Reasoning. With UAs/Cr as the exposure variable, we observed significantly negative associations for all WISC-IV scores. Except for Se, blood levels of other metals, were also associated with lower WISC-IV scores. Controlling for covariates, doubling BAs, or UAs/Cr, was associated with a mean decrement (95% CI) of 3.3 (1.1, 5.5), or 3.0 (1.2, 4.5) points, respectively, in raw Full scale scores with a sample mean of 177.6 (SD = 36.8). Confirmatory analyses using Bayesian Kernel Machine Regression, which identifies important mixture members, supported these findings; the primary contributor of the mixture was BAs, followed by BCd. Our data indicate that the adverse consequences of As exposure on neurodevelopment observed in other cross-sectional studies of younger children are also apparent during adolescence. They also implicate Cd as a neurotoxic element that deserves more attention. Copyright © 2018 Elsevier Ltd. All rights reserved.

Lithium chloride protects retinal neurocytes from nutrient deprivation by promoting DNA non-homologous end-joining

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

Zhuang Jing; Li Fan; Liu Xuan

2009-03-13

Lithium chloride is a therapeutic agent for treatment of bipolar affective disorders. Increasing numbers of studies have indicated that lithium has neuroprotective effects. However, the molecular mechanisms underlying the actions of lithium have not been fully elucidated. This study aimed to investigate whether lithium chloride produces neuroprotective function by improving DNA repair pathway in retinal neurocyte. In vitro, the primary cultured retinal neurocytes (85.7% are MAP-2 positive cells) were treated with lithium chloride, then cultured with serum-free media to simulate the nutrient deprived state resulting from ischemic insult. The neurite outgrowth of the cultured cells increased significantly in a dose-dependentmore » manner when exposed to different levels of lithium chloride. Genomic DNA electrophoresis demonstrated greater DNA integrity of retinal neurocytes when treated with lithium chloride as compared to the control. Moreover, mRNA and protein levels of Ligase IV (involved in DNA non-homologous end-joining (NHEJ) pathway) in retinal neurocytes increased with lithium chloride. The end joining activity assay was performed to determine the role of lithium on NHEJ in the presence of extract from retinal neurocytes. The rejoining levels in retinal neurocytes treated with lithium were significantly increased as compared to the control. Furthermore, XRCC4, the Ligase IV partner, and the transcriptional factor, CREB and CTCF, were up-regulated in retinal cells after treating with 1.0 mM lithium chloride. Therefore, our data suggest that lithium chloride protects the retinal neural cells from nutrient deprivation in vitro, which may be similar to the mechanism of cell death in glaucoma. The improvement in DNA repair pathway involving in Ligase IV might have an important role in lithium neuroprotection. This study provides new insights into the neural protective mechanisms of lithium chloride.« less

Adiponectin has a pivotal role in the cardioprotective effect of CP-3(iv), a selective CD36 azapeptide ligand, after transient coronary artery occlusion in mice.

PubMed

Huynh, David N; Bessi, Valérie L; Ménard, Liliane; Piquereau, Jérôme; Proulx, Caroline; Febbraio, Maria; Lubell, William D; Carpentier, André C; Burelle, Yan; Ong, Huy; Marleau, Sylvie

2018-02-01

CD36 is a multiligand receptor involved in lipid metabolism. We investigated the mechanisms underlying the cardioprotective effect of CP-3(iv), an azapeptide belonging to a new class of selective CD36 ligands. The role of CP-3(iv) in mediating cardioprotection was investigated because CD36 signaling leads to activation of peroxisome proliferator-activated receptor-γ, a transcriptional regulator of adiponectin. CP-3(iv) pretreatment reduced infarct size by 54% and preserved hemodynamics in C57BL/6 mice subjected to 30 min coronary ligation and reperfusion but had no effect in CD36-deficient mice. The effects of CP-3(iv) were associated with an increase in circulating adiponectin levels, epididymal fat adiponectin gene expression, and adiponectin transcriptional regulators ( Pparg, Cebpb, Sirt1) after 6 h of reperfusion. Reduced myocardial oxidative stress and apoptosis were observed along with an increase in expression of myocardial adiponectin target proteins, including cyclooxygenase-2, phospho-AMPK, and phospho-Akt. Moreover, CP-3(iv) increased myocardial performance in isolated hearts, whereas blockade of adiponectin with an anti-adiponectin antibody abrogated it. CP-3(iv) exerts cardioprotection against myocardial ischemia and reperfusion (MI/R) injury and dysfunction, at least in part, by increasing circulating and myocardial adiponectin levels. Hence, both paracrine and endocrine effects of adiponectin may contribute to reduced reactive oxygen species generation and apoptosis after MI/R, in a CD36-dependent manner.-Huynh, D. N., Bessi, V. L., Ménard, L., Piquereau, J., Proulx, C., Febbraio, M., Lubell, W. D., Carpentier, A. C., Burelle, Y., Ong, H., Marleau, S. Adiponectin has a pivotal role in the cardioprotective effect of CP-3(iv), a selective CD36 azapeptide ligand, after transient coronary artery occlusion in mice.

Norelgestromin/ethinyl estradiol intravenous infusion formulation optimization, stability and compatibility testing: A case study to overcome polysorbate 80 interference in chromatographic analysis.

PubMed

Abdallah, Inas A; Hammell, Dana C; Hassan, Hazem E; Stinchcomb, Audra L

2016-06-05

Norelgestromin/ethinyl estradiol is a progestin/estrogen combination hormonal contraceptive indicated for the prevention of pregnancy in women. The very poor solubility and wettability of these drugs, along with their high potency (adsorption issues), give rise to difficulties in designing intravenous (IV) formulations to assess absolute bioavailability of products containing both drugs. The purpose of this study was to develop an IV formulation, evaluate its stability under different conditions and evaluate its compatibility with IV sets for potential use in absolute bioavailability studies in humans. Also, a selective high-performance liquid chromatography (HPLC) method for quantification of ethinyl estradiol and norelgestromin in polysorbate 80 matrix was developed and validated. Norelgestromin/ethinyl estradiol IV solution was prepared using sterile water for injection with 2.5% ethanol and 2.5% polysorbate 80 as a cosolvent/surfactant system to obtain a final drug solution of 25μg ethinyl estradiol and 252μg norelgestromin from a concentrated stock drug solution. The stabilities of the concentrated stock and IV solutions were assessed after storing them in the refrigerator (3.7±0.6°C) and at room temperature (19.5±0.5°C), respectively. Additional studies were conducted to examine the stability of the IV solution using an Alarias(®) low sorbing IV administration set with and without an inline filter. The solution was allowed to drip at 1mL/min over a 60min period. Samples were obtained at the beginning, middle and end of the 60min duration. The chemical stability was evaluated for up to 10 days. Norelgestromin and ethinyl estradiol concentration, purity, and degradant levels were determined using the HPLC method. The norelgestromin/ethinyl estradiol IV formulation met the chemical stability criteria when tested on day 1 through day 9 (216h). Norelgestromin concentrations assayed in stock and IV solutions were in the range of 90.0-98.5% and 90.9-98.8% after 9 days, respectively. As for ethinyl estradiol, the assayed concentrations were in the range of 91.8-100.9% and 92.7-100.8% for the stock and IV solutions, respectively. The administration set was found to be compatible with both drugs; the assayed concentrations were in the range of 99.2-100.3% for norelgestromin and 96.3-102.7% for ethinyl estradiol, but the inline filter showed some adsorption of ethinyl estradiol; where the assayed concentrations were in the range of 98.1-99.8% for norelgestromin and 95.9-97.4% for ethinyl estradiol. The present study provided evidence supporting the suitability of an intravenous formulation for norelgestromin/ethinyl estradiol using ethanol/polysorbate 80 as a cosolvent/surfactant system. Both IV and concentrated stock solutions when stored at room temperature and refrigeration, respectively, were found to be chemically stable up to 9 days. These results indicated that this formulation is chemically stable and can be used over the time period tested. This IV formulation can be used to evaluate the absolute bioavailability of products containing norelgestromin and ethinyl estradiol provided that microbial testing of the IV formulation is performed. Copyright © 2016. Published by Elsevier B.V.

Effect of Sea buckthorn on liver fibrosis: A clinical study

PubMed Central

Gao, Ze-Li; Gu, Xiao-Hong; Cheng, Feng-Tao; Jiang, Fo-Hu

2003-01-01

AIM: To appraise the effect of sea buckthorn (Hippophae rhamnoides) on cirrhotic patients. METHODS: Fifty cirrhotic patients of Child-Pugh grade A and B were randomly divided into two groups: Group A as the treated group (n = 30), taking orally the sea buckthorn extract, 15 g 3 times a day for 6 mo. Group B as the control group (n = 18), taking vitamin B complex one tablet, 3 times a day for 6 mo. The following tests were performed before and after the treatment in both groups to determine LN, HA, collagens types III and IV, cytokines IL-6 and TNFα, liver serum albumin, total bile acid, ALT, AST and prothrombin time. RESULTS: The serum levels of TNFα, IL-6, laminin and type IV collagen in group A were significantly higher than those in the control group. After a course of sea buckthorn treatment, the serum levels of LN, HA, collagen types III and IV, total bile acid (TBA) decreased significantly as compared with those before and after treatment in the control group. The sea buckthorn notably shortened the duration for normalization of aminotransferases. CONCLUSION: Sea buckthorn may be a hopeful drug for prevention and treatment of liver fibrosis. PMID:12854177

Metastatic volume: an old oncologic concept and a new prognostic factor for stage IV melanoma patients.

PubMed

Panasiti, V; Curzio, M; Roberti, V; Lieto, P; Devirgiliis, V; Gobbi, S; Naspi, A; Coppola, R; Lopez, T; di Meo, N; Gatti, A; Trevisan, G; Londei, P; Calvieri, S

2013-01-01

The last melanoma staging system of the 2009 American Joint Committee on Cancer takes into account, for stage IV disease, the serum levels of lactate dehydrogenase (LDH) and the site of distant metastases. Our aim was to compare the significance of metastatic volume, as evaluated at the time of stage IV melanoma diagnosis, with other clinical predictors of prognosis. We conducted a retrospective multicentric study. To establish which variables were statistically correlated both with death and survival time, contingency tables were evaluated. The overall survival curves were compared using the Kaplan-Meier method. Metastatic volume and number of affected organs were statistically related to death. In detail, patients with a metastatic volume >15 cm(3) had a worse prognosis than those with a volume lower than this value (survival probability at 60 months: 6.8 vs. 40.9%, respectively). The Kaplan-Meier method confirmed that survival time was significantly related to the site(s) of metastases, to elevated LDH serum levels and to melanoma stage according to the latest system. Our results suggest that metastatic volume may be considered as a useful prognostic factor for survival among melanoma patients.

Catalase-loaded cisplatin-prodrug-constructed liposomes to overcome tumor hypoxia for enhanced chemo-radiotherapy of cancer.

PubMed

Zhang, Rui; Song, Xuejiao; Liang, Chao; Yi, Xuan; Song, Guosheng; Chao, Yu; Yang, Yu; Yang, Kai; Feng, Liangzhu; Liu, Zhuang

2017-09-01

Aiming at improved therapeutic efficacies, the combination of chemotherapy and radiotherapy (chemo-radiotherapy) has been widely studied and applied in clinic. However, the hostile characteristics of tumor microenvironment such as hypoxia often limit the efficacies in both types of cancer therapies. Herein, catalase (CAT), an antioxidant enzyme, is encapsulated inside liposomes constituted by cisplatin (IV)-prodrug-conjugated phospholipid, forming CAT@Pt (IV)-liposome for enhanced chemo-radiotherapy of cancer. After being loaded inside liposomes, CAT within CAT@Pt (IV)-liposome shows retained and well-protected enzyme activity, and is able to trigger decomposition of H 2 O 2 produced by tumor cells, so as to produce additional oxygen for hypoxia relief. As the result, treatment of CAT@Pt (IV)-liposome induces the highest level of DNA damage in cancer cells after X-ray radiation compared to the control groups. In vivo tumor treatment further demonstrates a remarkably improved therapeutic outcome in chemo-radiotherapy with such CAT@Pt (IV)-liposome nanoparticles. Hence, an exquisite type of liposome-based nanoparticles is developed in this work by integrating cisplatin-based chemotherapy and catalase-induced tumor hypoxia relief together for combined chemo-radiotherapy with great synergistic efficacy, promising for clinical translation in cancer treatment. Copyright © 2017. Published by Elsevier Ltd.

Relationship between the antidiarrhoeal effects of Hange-Shashin-To and its active components.

PubMed

Kase, Y; Saitoh, K; Makino, B; Hashimoto, K; Ishige, A; Komatsu, Y

1999-09-01

This study was designed to examine the relationship between the antidiarrhoeal effects of Hange-Shashin-To (TJ-14) and its active components. Oral treatment with TJ-14 at 1000 mg/kg significantly inhibited castor oil-induced diarrhoea. Both the 50% methanol eluate fraction (fraction III) and the methanol eluate fraction (fraction IV) showed antidiarrhoeal effects at oral doses of 68 mg/kg and 63 mg/kg, respectively, corresponding to 1000 mg/kg of TJ-14. TJ-14 (1000 mg/kg, p.o.) showed a significant increase in blood corticosterone levels. Increased blood corticosterone was noted after the oral administration of 63 mg/kg of fraction IV. The inhibitory activity of TJ-14 on cyclooxygenase-2 (COX-2) was also observed in fractions III and IV. The main component of fraction III was Scutellariae Radix-derived baicalin. Fraction IV contained Glycyrrhizae Radix-derived glycyrrhizin and isoliquiritin, Coptidis Rhizoma-derived berberine, coptisine and palmitine. Ginseng Radix-derived saponins were also present in fraction IV. These compounds inhibited castor-oil induced diarrhoea at oral doses of 10 or 30 mg/kg. Thus, the present results indicate that Scutellariae Radix, Glycyrrhizae Radix, Ginseng radix and Coptidis Rhizoma-derived components are involved in the antidiarrhoeal action of TJ-14. Copyright 1999 John Wiley & Sons, Ltd.

Comparison of DNA decatenation by Escherichia coli topoisomerase IV and topoisomerase III: implications for non-equilibrium topology simplification

PubMed Central

Seol, Yeonee; Hardin, Ashley H.; Strub, Marie-Paule; Charvin, Gilles; Neuman, Keir C.

2013-01-01

Type II topoisomerases are essential enzymes that regulate DNA topology through a strand-passage mechanism. Some type II topoisomerases relax supercoils, unknot and decatenate DNA to below thermodynamic equilibrium. Several models of this non-equilibrium topology simplification phenomenon have been proposed. The kinetic proofreading (KPR) model postulates that strand passage requires a DNA-bound topoisomerase to collide twice in rapid succession with a second DNA segment, implying a quadratic relationship between DNA collision frequency and relaxation rate. To test this model, we used a single-molecule assay to measure the unlinking rate as a function of DNA collision frequency for Escherichia coli topoisomerase IV (topo IV) that displays efficient non-equilibrium topology simplification activity, and for E. coli topoisomerase III (topo III), a type IA topoisomerase that unlinks and unknots DNA to equilibrium levels. Contrary to the predictions of the KPR model, topo IV and topo III unlinking rates were linearly related to the DNA collision frequency. Furthermore, topo III exhibited decatenation activity comparable with that of topo IV, supporting proposed roles for topo III in DNA segregation. This study enables us to rule out the KPR model for non-equilibrium topology simplification. More generally, we establish an experimental approach to systematically control DNA collision frequency. PMID:23460205

Personality Disorders, Impulsiveness, and Novelty Seeking in Persons with DSM-IV Pathological Gambling and Their First-Degree Relatives.

PubMed

Black, Donald W; Coryell, William H; Crowe, Raymond R; Shaw, Martha; McCormick, Brett; Allen, Jeff

2015-12-01

This study investigates the presence of personality disorders, impulsiveness, and novelty seeking in probands with DSM-IV pathological gambling (PG), controls, and their respective first-degree relatives using a blind family study methodology. Ninety-three probands with DSM-IV PG, 91 controls, and their 395 first-degree relatives were evaluated for the presence of personality disorder with the Structured Interview for DSM-IV Personality. Impulsiveness was assessed with the Barratt Impulsiveness Scale (BIS). Novelty seeking was evaluated using questions from Cloninger's Temperament and Character Inventory. Results were analyzed using logistic regression by the method of generalized estimating equations to account for within family correlations. PG probands had a significantly higher prevalence of personality disorders than controls (41 vs. 7 %, OR = 9.0, P < 0.001), along with higher levels of impulsiveness and novelty seeking. PG probands with a personality disorder had more severe gambling symptoms; earlier age at PG onset; more suicide attempts; greater psychiatric comorbidity; and a greater family history of psychiatric illness than PG probands without a personality disorder. PG relatives had a significantly higher prevalence of personality disorder than relatives of controls (24 vs. 9%, OR = 3.2, P < 0.001) and higher levels of impulsiveness. Risk for PG in relatives is associated with the presence of personality disorder and increases along with rising BIS Non-Planning and Total scale scores. Personality disorders, impulsiveness, and novelty seeking are common in people with PG and their first-degree relatives. The presence of a personality disorder appears to be a marker of PG severity and earlier age of onset. Risk for PG in relatives is associated with the presence of personality disorder and trait impulsiveness. These findings suggest that personality disorder and impulsiveness may contribute to a familial diathesis for PG.

Systemic Correction of Murine Glycogen Storage Disease Type IV by an AAV-Mediated Gene Therapy.

PubMed

Yi, Haiqing; Zhang, Quan; Brooks, Elizabeth D; Yang, Chunyu; Thurberg, Beth L; Kishnani, Priya S; Sun, Baodong

2017-03-01

Deficiency of glycogen branching enzyme (GBE) causes glycogen storage disease type IV (GSD IV), which is characterized by the accumulation of a less branched, poorly soluble form of glycogen called polyglucosan (PG) in multiple tissues. This study evaluates the efficacy of gene therapy with an adeno-associated viral (AAV) vector in a mouse model of adult form of GSD IV (Gbe1 ys/ys ). An AAV serotype 9 (AAV9) vector containing a human GBE expression cassette (AAV-GBE) was intravenously injected into 14-day-old Gbe1 ys/ys mice at a dose of 5 × 10 11 vector genomes per mouse. Mice were euthanized at 3 and 9 months of age. In the AAV-treated mice at 3 months of age, GBE enzyme activity was highly elevated in heart, which is consistent with the high copy number of the viral vector genome detected. GBE activity also increased significantly in skeletal muscles and the brain, but not in the liver. The glycogen content was reduced to wild-type levels in muscles and significantly reduced in the liver and brain. At 9 months of age, though GBE activity was only significantly elevated in the heart, glycogen levels were significantly reduced in the liver, brain, and skeletal muscles of the AAV-treated mice. In addition, the AAV treatment resulted in an overall decrease in plasma activities of alanine transaminase, aspartate transaminase, and creatine kinase, and a significant increase in fasting plasma glucose concentration at 9 months of age. This suggests an alleviation of damage and improvement of function in the liver and muscles by the AAV treatment. This study demonstrated a long-term benefit of a systemic injection of an AAV-GBE vector in Gbe1 ys/ys mice.

Normal plasma levels of cardiac troponin I measured by the high-sensitivity cardiac troponin I access prototype assay and the impact on the diagnosis of myocardial ischemia.

PubMed

Venge, Per; Johnston, Nina; Lindahl, Bertil; James, Stefan

2009-09-22

This study sought to evaluate the analytical and clinical performance of the novel hypersensitive cardiac troponin I (cTnI) prototype assay from Beckman Coulter (Fullerton, California). Studies on patients with acute coronary syndromes and on seemingly healthy subjects have shown that even very minor elevations of cardiac troponins are associated with an increased risk of death. However, the normal plasma levels of cardiac troponins are still not known. cTnI plasma levels were measured in 542 healthy subjects, 319 men (age 59.9 +/- 11.8 years) and 213 women (age 59.8 +/- 13.1 years), and in 1,503 randomly selected patients of the GUSTO IV (Global Utilization of Strategies To open Occluded arteries IV) cohort with unstable angina and non-ST-segment elevation myocardial infarctions (MIs). The cTnI levels at 10% coefficient of variation and 20% coefficient of variation imprecision were 0.0033 and 0.0016 microg/l, respectively. The cTnI levels were measurable in >95% of the healthy subjects. The median level of healthy subjects <60 years of age was 0.0032 microg/l (range 0.0011 to 0.0079 microg/l) with the 99th percentile being 0.010 microg/l. No sex differences were observed. A receiver-operator characteristic curve analysis showed an optimal discrimination between healthy subjects and patients at 0.0064 microg/l with a sensitivity of 84.8% (95% confidence interval: 82.8% to 86.6%) and specificity of 89.7% (95% confidence interval: 86.8% to 92.2%). Outcomes as to death and/or MI were significantly different at this level (p < 0.01) in the GUSTO IV cohort. The novel high-sensitivity cTnI prototype assay from Beckman Coulter allows for the first time the measurement of cTnI levels in almost all healthy subjects. Our data indicate that the assay may be a powerful aid in the diagnosis and outcome prediction of patients with suspected myocardial ischemia and question any definition of myocardial infarction.

An exploratory study on equity in funding allocation for essential medicines and health supplies in Uganda's public sector.

PubMed

Kusemererwa, Donna; Alban, Anita; Obua, Ocwa Thomas; Trap, Birna

2016-08-30

To ascertain equity in financing for essential medicines and health supplies (EMHS) in Uganda, this paper explores the relationships among government funding allocations for EMHS, patient load, and medicines availability across facilities at different levels of care. We collected data on EMHS allocations and availability of selected vital medicines from 43 purposively sampled hospitals and the highest level health centers (HC IV), 44 randomly selected lower-level health facilities (HC II, III), and from over 400 facility health information system records and National Medical Stores records. The data were analyzed to determine allocations per patient within and across levels of care and the effects of allocations on product availability. EMHS funding allocations per patient varied widely within facilities at the same level, and allocations per patient between levels overlapped considerably. For example, HC IV allocations per patient ranged from US$0.25 to US$2.14 (1:9 ratio of lowest to highest allocation), and over 75 % of HC IV facilities had the same or lower average allocation per patient than HC III facilities. Overall, 43 % of all the facilities had optimal stock levels, 27 % were understocked, and 30 % were overstocked. Using simulations, we reduced the ratio between the highest and lowest allocations per patient within a level of care to less than two and eliminated the overlap in allocation per patient between levels. Inequity in EMHS allocation is demonstrated by the wide range of funding allocations per patient and the corresponding disparities in medicines availability. We show that using patient load to calculate EMHS allocations has the potential to improve equity significantly. However, more research in this area is urgently needed. The article does not report any results of human participants. It is implemented in collaboration with the Uganda's Ministry of Health, Pharmacy Division.

Acute cocaine induced deficits in cognitive performance in rhesus macaque monkeys treated with baclofen

PubMed Central

Porrino, Linda J.; Hampson, Robert E.; Opris, Ioan; Deadwyler, Samuel A.

2013-01-01

Rationale Acute and/or chronic exposure to cocaine can affect cognitive performance, which may influence rate of recovery during treatment. Objective Effects of the GABA-B receptor agonist baclofen were assessed for potency to reverse the negative influence of acute, pre-session, intravenous (IV) injection of cocaine on cognitive performance in Macaca mulatta nonhuman primates. Methods Animals were trained to perform a modified delayed match to sample (DMS) task incorporating two types of trials with varying degrees of cognitive load that had different decision requirements in order to correctly utilize information retained over the delay interval. The effects of cocaine (0.2, 0.4, and 0.6 mg/kg, IV) alone and in combination with baclofen (0.29 and 0.40 mg/kg, IV) were examined with respect to sustained performance levels. Brain metabolic activity during performance of the task was assessed using PET imaged uptake of [18F]-fluorodeoxyglucose. Results Acute cocaine injections produced a dose-dependent decline in DMS performance selective for trials of high cognitive load. The GABA-receptor agonist baclofen, co-administered with cocaine, reversed task performance back to nondrug (saline IV) control levels. Simultaneous assessment of PET-imaged brain metabolic activity in prefrontal cortex (PFC) showed alterations by cocaine compared to PFC metabolic activation in nondrug (saline, IV) control DMS sessions, but like performance, PFC activation was returned to control levels by baclofen (0.40 mg/kg, IV) injected with cocaine. Conclusions The results show that baclofen, administered at a relatively high dose, reversed the cognitive deficits produced by acute cocaine intoxication that may have implications for use in chronic drug exposure. PMID:22836369

Sex Differences in DSM-IV Posttraumatic Stress Disorder Symptoms Expression Using Item Response Theory: a Population-based Study

PubMed Central

Rivollier, Fabrice; Peyre, Hugo; Hoertel, Nicolas; Blanco, Carlos; Limosin, Frédéric; Delorme, Richard

2015-01-01

Background Whether there are systematic sex differences in posttraumatic stress disorder (PTSD) symptom expression remains debated. Using methods based on item response theory (IRT), we aimed at examining differences in the likelihood of reporting DSM-IV symptoms of PTSD between women and men, while stratifying for major trauma type and equating for PTSD severity. Method We compared data from women and men in a large nationally representative adult sample, the National Epidemiologic Survey on Alcohol and Related Conditions. Analyses were conducted in the full population sample of individuals who met the DSM-IV criterion A (n = 23,860) and in subsamples according to trauma types. Results The clinical presentation of the 17 DSM-IV PTSD symptoms in the general population did not substantially differ in women and men in the full population and by trauma type after equating for levels of PTSD severity. The only exception was the symptom “foreshortened future”, which was more likely endorsed by men at equivalent levels of PTSD severity. Limitations The retrospective nature of the assessment of PTSD symptoms could have led to recall bias. Our sample size was too small to draw conclusions among individuals who experienced war-related traumas. Conclusions Our findings suggest that the clinical presentation of PTSD does not differ substantially between women and men. We also provide additional psychometric support to the exclusion of the symptom “foreshortened future” from the diagnostic criteria for PTSD in the DSM-5. PMID:26342916

Sex differences in DSM-IV posttraumatic stress disorder symptoms expression using item response theory: A population-based study.

PubMed

Rivollier, Fabrice; Peyre, Hugo; Hoertel, Nicolas; Blanco, Carlos; Limosin, Frédéric; Delorme, Richard

2015-11-15

Whether there are systematic sex differences in posttraumatic stress disorder (PTSD) symptom expression remains debated. Using methods based on item response theory (IRT), we aimed at examining differences in the likelihood of reporting DSM-IV symptoms of PTSD between women and men, while stratifying for major trauma type and equating for PTSD severity. We compared data from women and men in a large nationally representative adult sample, the National Epidemiologic Survey on Alcohol and Related Conditions. Analyses were conducted in the full population sample of individuals who met the DSM-IV criterion A (n=23,860) and in subsamples according to trauma types. The clinical presentation of the 17 DSM-IV PTSD symptoms in the general population did not substantially differ in women and men in the full population and by trauma type after equating for levels of PTSD severity. The only exception was the symptom "foreshortened future", which was more likely endorsed by men at equivalent levels of PTSD severity. The retrospective nature of the assessment of PTSD symptoms could have led to recall bias. Our sample size was too small to draw conclusions among individuals who experienced war-related traumas. Our findings suggest that the clinical presentation of PTSD does not differ substantially between women and men. We also provide additional psychometric support to the exclusion of the symptom "foreshortened future" from the diagnostic criteria for PTSD in the DSM-5. Copyright © 2015 Elsevier B.V. All rights reserved.

Subcutaneous infusion of human C1 inhibitor in swine.

PubMed

Jiang, Haixiang; Zhang, Hua-Mei; Frank, Michael M

2010-09-01

Hereditary angioedema afflicts patients with unpredictable episodes of swelling that can be life threatening. Treatments approved by the Food and Drug Administration for routine prophylaxis include danazol given orally and the nanofiltered human C1 esterase inhibitor, CINRYZE, which is approved for intravenous administration. Approved for the treatment of acute attacks are the C1 esterase inhibitor, Berinert, given intravenously, and the kallikrein inhibitor, KALBITOR, given subcutaneously. C1 inhibitor has generally been non-toxic and neither pro-inflammatory nor pro-fibrotic, suggesting that it may be suitable for subcutaneous infusion. The current study used a swine model to compare blood levels of human C1 inhibitor following intravenous and subcutaneous infusion, and the effect of infusion route on heart and skin pathology. Levels of C1 inhibitor achieved with SC infusion compared favorably with levels achieved after IV infusion and were relatively more stable than those after IV infusion. Neither cardiac nor skin toxicity was observed. Copyright 2010 Elsevier Inc. All rights reserved.

Glycated hemoglobin level is an independent predictor of major adverse cardiac events after nonfatal acute myocardial infarction in nondiabetic patients: A retrospective observational study.

PubMed

Chen, Chin-Lan; Yen, David H-T; Lin, Chin-Sheng; Tsai, Shih-Hung; Chen, Sy-Jou; Sheu, Wayne H-H; Hsu, Chin-Wang

2017-05-01

The effect of glycemic control on the prognosis of nondiabetic patients after acute myocardial infarction (AMI) remains uncertain. We investigated whether glycated hemoglobin (HbA1c) is associated with adverse outcomes after AMI in nondiabetic patients. In this observational study, we enrolled nondiabetic patients with AMI in the emergency department of 2 medical centers from January 2011 to September 2014. All patients received primary percutaneous coronary intervention and were divided into 4 groups according to the interquartile range of average HbA1c level (Group I, ≤5.6%; Group II, 5.6%-5.8%; Group III, 5.8%-6.0%; and Group IV, >6.0%). Multivariate logistic analysis was performed to estimate the correlation of HbA1c with major adverse cardiac events (MACEs) after AMI. In total, 267 eligible patients were enrolled; 48 patients (18%) developed MACEs within a median follow-up of 178 days. Univariate analysis showed HbA1c > 6.0%, with a higher risk of MACEs in Group IV than in Group I (odds ratio [OR]: 2.733; 95% confidence interval [CI]: 1.123-6.651 vs OR: 1.511; 95% CI: 0.595-3.835). Multivariate analysis revealed an approximately 3.8 times higher risk of MACEs in Group IV than in Group I (OR: 3.769; 95% CI: 1.30-10.86). The HbA1 level is a significant predictor of MACEs after AMI in nondiabetic patients.

Clinical and pharmacokinetic study of cefotetan in biliary tract infections: preliminary report.

PubMed

Cristiano, P; Lobello, R; Iovene, M R; De Ascentis, G; Altucci, P; Paradisi, F; Manguso, L

1988-08-01

Twelve hospitalised patients, affected by biliary tract infections, were treated with cefotetan at dosages ranging between 4 and 6 g daily i.v. In only 11 patients was the aetiological agent identified. Eleven patients (91.67%) completely recovered from their infections and the pathogens were eradicated; the treatment failed in only 1 patient (8.33%). Furthermore, determinations were made of cefotetan concentrations in serum, gallbladder bile, gallbladder wall and gallstones of 14 patients undergoing cholecystectomy: in 7 patients after only 1 injection i.v. of 2 g and in 7 patients after 7 injections i.v. of 2 g at intervals of 12 h. The levels recorded were several times higher than the minimum inhibitory concentrations against bacteria that are most often responsible for biliary infections. Cefotetan is a promising and effective antimicrobial agent in the therapy of biliary tract infections.

Predisposing factors to phlebitis in patients with peripheral intravenous catheters: a descriptive study.

PubMed

Uslusoy, Esin; Mete, Samiye

2008-04-01

The purpose of this study was to investigate the predisposing factors in the development of phlebitis in peripheral intravenous (IV) catheterization sites in patients treated with a variety of IV infusion solutions and drugs. Systematic observation of 568 IV sites inserted for fluid infusion and drug administration in 355 patients in the Department of General Surgery of a University Hospital in Turkey. A data collection tool was based on standards established by the Infusion Nurses Society. Patients' infusion sites were monitored every 24 h during treatment and for 48 h after discontinuation of the IV. In contrast to the usual findings in the literature, the authors found that infusion through an infusion pump and insertion of catheters in the veins around the elbow increased the risk of phlebitis. Also, the number of times infusions were started led to an increased rate of phlebitis. However, conflicting results were obtained about the relation between phlebitis, gender, and catheter size. Phlebitis causes sepsis, pain, additional diagnostic investigations, and treatments, and may lead to increased duration of hospitalization, patient's stress level, and financial burden, as well as increasing staff workload. Advanced practice nurses need to be aware of the factors that increase the likelihood of phlebitis and take appropriate measures to prevent it.

Spinal mechanism of micturition reflex inhibition by naftopidil in rats.

PubMed

Sugaya, Kimio; Nishijima, Saori; Kadekawa, Katsumi; Ashitomi, Katsuhiro; Ueda, Tomoyuki; Yamamoto, Hideyuki

2014-10-29

We investigated the spinal mechanism through which naftopidil inhibits the micturition reflex by comparing the effects of noradrenaline and naftopidil in rats. The following were investigated: the influence of oral naftopidil on plasma monoamine and amino acid levels, the distribution of oral 14C-naftopidil, the effects of intravenous (IV) or intrathecal (IT) injection of noradrenaline or naftopidil on isovolumetric bladder contractions, amino acid levels in the lumbosacral spinal cord after IT noradrenaline or naftopidil, and the effects of IT naftopidil and strychnine and/or bicuculline on isovolumetric bladder contractions. Oral naftopidil decreased the plasma adrenaline level, while it increased the serotonin and glycine levels. After oral administration, 14C-naftopidil was detected in the spinal cord and cerebrum, as well as in plasma and the prostate gland. When the bladder volume was below the threshold for isovolumetric reflex contractions, IV (0.1mg) or IT (0.1μg) noradrenaline evoked bladder contractions, but IV (1mg) or IT (0.01-1μg) naftopidil did not. When the bladder volume was above the threshold for isovolumetric reflex contractions, IV or IT noradrenaline transiently abolished bladder contractions. IT noradrenaline decreased the levels of glycine and gamma-aminobutyric acid (GABA) in the lumbosacral cord, while IT naftopidil increased the GABA level. IT strychnine and/or bicuculline blocked the inhibitory effect of IT naftopidil on bladder contractions. Naftopidil inhibits the micturition reflex by blocking α1 receptors, as well as by the activation of serotonergic, glycinergic, and GABAergic neurons in the central nervous system. Copyright © 2014 Elsevier Inc. All rights reserved.

Non-effect of hexamethonium, a ganglionic blocker, on the response of ileal apolipoprotein A-IV mRNA following a massive small bowel resection in rats.

PubMed

Sonoyama, K; Fujiwara, R; Kasai, T

2000-06-01

An intravenous infusion of hexamethonium, a ganglionic blocker, did not affect the increase in the apolipoprotein A-IV mRNA level in the residual ileum following a massive small bowel resection in unrestrained conscious rats. The result suggests that upregulation of the apolipoprotein A-IV gene in the residual ileum is not mediated by a neural pathway, including the nicotinic synapse route.

Estimation and application of indicator values for common macroinvertebrate genera and families of the United States

USGS Publications Warehouse

Carlisle, D.M.; Meador, M.R.; Moulton, S.R.; Ruhl, P.M.

2007-01-01

Tolerance of macroinvertebrate taxa to chemical and physical stressors is widely used in the analysis and interpretation of bioassessment data, but many estimates lack empirical bases. Our main objective was to estimate genus- and family-level indicator values (IVs) from a data set of macroinvertebrate communities, chemical, and physical stressors collected in a consistent manner throughout the United States. We then demonstrated an application of these IVs to detect alterations in benthic macroinvertebrate assemblages along gradients of urbanization in New England and Alabama. Principal components analysis (PCA) was used to create synthetic gradients of chemical stressors, for which genus- and family-level weighted averages (WAs) were calculated. Based on results of PCA, WAs were calculated for three synthetic gradients (ionic concentration, nutrient concentration, and dissolved oxygen/water temperature) and two uncorrelated physical variables (suspended sediment concentration and percent fines). Indicator values for each stress gradient were subsequently created by transforming WAs into ten ordinal ranks based on percentiles of values across all taxa. Mean IVs of genera and families were highly correlated to road density in Alabama and New England, and supported the conclusions of independent assessments of the chemical and physical stressors acting in each geographic area. Family IVs were nearly as responsive to urbanization as genus IVs. The limitations of widespread use of these IVs are discussed.

Mass motions in the solar chromosphere and transition zone

NASA Technical Reports Server (NTRS)

Mein, P.; Simon, G.; Vial, J. C.; Shine, R. A.

1982-01-01

A comparison is made between H-alpha and C IV observations of Active Region 2717 on October 9, 1980. On the basis of this comparison, it is found that upward velocities are present above sunspots in the chromosphere-corona transition zone (20 km/s). The downward velocities are found to be well correlated in both lines. Doppler-shift ratios between C IV and H-alpha levels (approximately 10) are seen to be much smaller than expected from density ratio estimates. The comparison is seen as suggesting that flow lines are probably far from vertical in the transition zone. It is pointed out, however, that this depends on model densities that may not be correct. A simple method for comparing matter flows is presented. The best fit between H-alpha and C IV levels is obtained when C IV Doppler shifts are multiplied by the line intensity to the power 0.5 (approximately) in order to make allowance for density fluctuations.

Which Route of Tranexamic Acid Administration is More Effective to Reduce Blood Loss Following Total Knee Arthroplasty?

PubMed

Keyhani, Sohrab; Esmailiejah, Ali Akbar; Abbasian, Mohammad Reza; Safdari, Farshad

2016-01-01

The most appropriate route of tranexamic acid administration is controversial. In the current study, we compared the efficacy of intravenous (IV) and topical intra-articular tranexamic acid in reducing blood loss and transfusion rate in patients who underwent primary total knee arthroplasty. One hundred twenty 120 patients were scheduled to undergo primary total knee arthroplasty. Patients were randomly allocated to three equal groups: IV tranexamic acid (500 mg), topical tranexamic acid (3 g in 100 mL normal saline) and the control. In the topical group, half of the volume was used to irrigate the joint and the other half was injected intra-articularly. The volume of blood loss, hemoglobin (Hb) level at 24 hours postoperative, and rate of transfusion was compared between groups. The blood loss and Hb level were significantly greater and lower in the control group, respectively (P=0.031). Also, the rate of transfusion was significantly greater in the control group (P=0.013). However, IV and topical groups did not differ significantly in terms of measured variables. No patient experienced a thromboembolic event in our study. Tranexamic acid is a useful antifibrinolytic drug to reduce postoperative blood loss, Hb drop, and rate of blood transfusion in patients undergoing total knee arthroplasty. The route of tranexamic acid administration did not affect the efficacy and safety.

Astragaloside IV attenuates inflammatory cytokines by inhibiting TLR4/NF-кB signaling pathway in isoproterenol-induced myocardial hypertrophy.

PubMed

Yang, Juan; Wang, Hong-Xin; Zhang, Ying-Jie; Yang, Yu-Hong; Lu, Mei-Li; Zhang, Jing; Li, Sheng-Tao; Zhang, Su-Ping; Li, Guang

2013-10-25

Astragaloside IV(As IV) is one of the main effective components isolated from the traditional Chinese medical herb Astragalus membranaceus. The protective effect of Astragalus membranaceus on myocardial hypertrophy has been extensively proved. To test the hypothesis that Astragaloside IV can ameliorate the myocardial hypertrophy and inflammatory effect induced by β-adrenergic hyperactivity, we carried out in vivo and in vitro experiments. In in vivo study, the isoproterenol(Iso) (5mg.kg -1 .d -1 ) was used as a model of myocardial hypertrophy by intraperitoneal injection. SD rats were randomly assigned to following six groups: A:the control；B: Iso group；C: Iso plus As IV 20mg.kg -1 .d -1 ；D: Iso plus As IV 40mg.kg -1 .d -1 ；E: Iso plus As IV 80mg.kg -1 .d -1 ；F: Iso plus Propranolol 40mg.kg -1 .d -1 . In in vitro study, cultured neonatal rat cardiomyocytes were pretreated with As IV(3, 10, 30μmol.L -1 ), Propranolol(2μmol.L -1 ) and BAY11-7082(5μmol.L -1 ) for 30minutes, and then incubated with Iso(10μmol.L -1 ) for 48 hours. For the rats in each group, the heart mass index (HMI) and the left ventricular mass index (LVMI) were measured. To measure the transverse diameter of left ventricular myocardial cells (TDM), the hematoxylin-eosin (HE) staining method was applied. In addition, the volume and the total protein content of cardiomyocytes were measured, the mRNA expression of ANP and TLR4 were quantified by RT-PCR, the protein expression of TLR4, IκBα and p65 were quantified by Western blot, and the level of TNF-α and IL-6 were measured by ELISA. In vivo: Comparing the Iso group to the control, the HMI, LVMI, TDM were significantly increased; the protein expression of TLR4 and p65 were increased, while the IκBα were decreased; the expression of ANP, TLR4 mRNA, and TNF-α, IL-6 in serum were significantly increased. These changes could be partly prevented by As IV and Pro. In vitro: the over-expression of the cell size, total protein content could remarkably down-regulated by As IV and Pro, and the results of RT-PCR, Western blot and ELISA were similar to those of in vivo. The results of these studies indicate that Astragaloside IV has good protective effect on myocardial hypertrophy induced by isoproterenol. More specifically, the cardioprotection is related to inhibiting the TLR4/NF-кB signaling pathway and the attenuating inflammatory effect. Astragaloside IV (PubChem CID:122690); BAY 11-7082 (PubChem CID:5353431); Propranolol (PubChem CID:62882); Isoproterenol (PubChem CID: 5806). © 2013 The Authors. Published by Elsevier Ireland Ltd All rights reserved.

A High Serum Iron Level Causes Mouse Retinal Iron Accumulation Despite an Intact Blood-Retinal Barrier

PubMed Central

Zhao, Liangliang; Li, Yafeng; Song, Delu; Song, Ying; Theurl, Milan; Wang, Chenguang; Cwanger, Alyssa; Su, Guanfang; Dunaief, Joshua L.

2015-01-01

The retina can be shielded by the blood-retinal barrier. Because photoreceptors are damaged by excess iron, it is important to understand whether the blood-retinal barrier protects against high serum iron levels. Bone morphogenic protein 6 (Bmp6) knockout mice have serum iron overload. Herein, we tested whether the previously documented retinal iron accumulation in Bmp6 knockout mice might result from the high serum iron levels or, alternatively, low levels of retinal hepcidin, an iron regulatory hormone whose transcription can be up-regulated by Bmp6. Furthermore, to determine whether increases in serum iron can elevate retinal iron levels, we i.v. injected iron into wild-type mice. Retinas were analyzed by real-time quantitative PCR and immunofluorescence to assess the levels of iron-regulated genes/proteins and oxidative stress. Retinal hepcidin mRNA levels in Bmp6 knockout retinas were the same as, or greater than, those in age-matched wild-type retinas, indicating that Bmp6 knockout does not cause retinal hepcidin deficiency. Changes in mRNA levels of L ferritin and transferrin receptor indicated increased retinal iron levels in i.v. iron-injected wild-type mice. Oxidative stress markers were elevated in photoreceptors of mice receiving i.v. iron. These findings suggest that elevated serum iron levels can overwhelm local retinal iron regulatory mechanisms. PMID:25174877

Engagement of groups in family medicine board maintenance of certification.

PubMed

Fisher, Dena M; Brenner, Christopher J; Cheren, Mark; Stange, Kurt C

2013-01-01

The American Board of Medical Specialties' Performance in Practice ("Part IV") portion of Maintenance of Certification (MOC) requirement provides an opportunity for practicing physicians to demonstrate quality improvement (QI) competence. However, specialty boards' certification of one physician at a time does not tap into the potential of collective effort. This article shares learning from a project to help family physicians work in groups to meet their Part IV MOC requirement. A year-long implementation and evaluation project was conducted. Initially, 348 members of a regional family physician organization were invited to participate. A second path was established through 3 health care systems and a county-wide learning collaborative. Participants were offered (1) a basic introduction to QI methods, (2) the option of an alternative Part IV MOC module using a patient experience survey to guide QI efforts, (3) practice-level improvement coaching, (4) support for collaboration and co-learning, and (5) provision of QI resources. More physicians participated through group (66) than individual (12) recruitment, for a total of 78 physicians in 20 practices. Participation occurred at 3 levels: individual, intrapractice, and interpractice. Within the 1-year time frame, intrapractice collaboration occurred most frequently. Interpractice and system-level collaboration has begun and continues to evolve. Physicians felt that they benefited from access to a practice coach and group process. Practice-level collaboration, access to a practice coach, flexibility in choosing and focusing improvement projects, tailored support, and involvement with professional affiliations can enhance the Part IV MOC process. Specialty boards are likely to discover productive opportunities from working with practices, professional organizations, and health care systems to support intra- and interpractice collaborative QI work that uses Part IV MOC requirements to motivate practice improvement.

Exercise prescription for overhead athletes with shoulder pathology: a systematic review with best evidence synthesis.

PubMed

Wright, Alexis A; Hegedus, Eric J; Tarara, Daniel T; Ray, Samantha C; Dischiavi, Steven L

2018-02-01

To produce a best evidence synthesis of exercise prescription used when treating shoulder pathology in the overhead athlete. A systematic review of exercises used in overhead athletes including case studies and clinical commentaries. MEDLINE, PubMed, SPORTDiscus and CINAHL from database inception through July 8, 2016. We examined data from randomised controlled trials and prospective cohort (level I-IV evidence) studies that addressed exercise intervention in the rehabilitation of the overhead athlete with shoulder pathology. Case studies and clinical commentaries (level V evidence) were examined to account for expert opinion-based research. Data were combined using best evidence synthesis and graded (A-F) recommendations (Centre for Evidence-Based Medicine). There were 33 unique exercises in six level I-IV studies that met our inclusion criteria. Most exercises were single-plane, upper extremity exercises performed below 90 o of elevation. There were 102 unique exercises in 33 level V studies that met our inclusion criteria. These exercises emphasised plyometrics, kinetic chain and sport-specific training. Overall, evidence for exercise interventions in overhead athletes with shoulder pathology is dominated by expert opinion (grade D). There is great variability between exercise approaches suggested by experts and those investigated in research studies and the overall level of evidence is low. The strongest available evidence (level B) supports the use of single-plane, open chain upper extremity exercises performed below 90° of elevation and closed chain upper extremity exercises. Clinical expert pieces support a more advanced, global treatment approach consistent with the complex, multidimensional nature of sport. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

The contextual effects of social capital on health: a cross-national instrumental variable analysis

PubMed Central

Kim, Daniel; Baum, Christopher F; Ganz, Michael; Subramanian, S V; Kawachi, Ichiro

2011-01-01

Past observational studies of the associations of area-level/contextual social capital with health have revealed conflicting findings. However, interpreting this rapidly growing literature is difficult because estimates using conventional regression are prone to major sources of bias including residual confounding and reverse causation. Instrumental variable (IV) analysis can reduce such bias. Using data on up to 167 344 adults in 64 nations in the European and World Values Surveys and applying IV and ordinary least squares (OLS) regression, we estimated the contextual effects of country-level social trust on individual self-rated health. We further explored whether these associations varied by gender and individual levels of trust. Using OLS regression, we found higher average country-level trust to be associated with better self-rated health in both women and men. Instrumental variable analysis yielded qualitatively similar results, although the estimates were more than double in size in women and men using country population density and corruption as instruments. The estimated health effects of raising the percentage of a country's population that trusts others by 10 percentage points were at least as large as the estimated health effects of an individual developing trust in others. These findings were robust to alternative model specifications and instruments. Conventional regression and to a lesser extent IV analysis suggested that these associations are more salient in women and in women reporting social trust. In a large cross-national study, our findings, including those using instrumental variables, support the presence of beneficial effects of higher country-level trust on self-rated health. Past findings for contextual social capital using traditional regression may have underestimated the true associations. Given the close linkages between self-rated health and all-cause mortality, the public health gains from raising social capital within countries may be large. PMID:22078106

Comparative pathogenicity in Swiss mice of Trypanosoma cruzi IV from northern Brazil and Trypanosoma cruzi II from southern Brazil.

PubMed

Meza, Sheila Karina Lüders; Kaneshima, Edilson Nobuyoshi; Silva, Sueli de Oliveira; Gabriel, Maristela; de Araújo, Silvana Marques; Gomes, Mônica Lúcia; Monteiro, Wuelton Marcelo; Barbosa, Maria das Graças Vale; Toledo, Max Jean de Ornelas

2014-11-01

The geographical heterogeneity of Chagas disease (ChD) is mainly caused by genetic variability of the etiological agent Trypanosoma cruzi. Our hypothesis was that the pathogenicity for mice may vary with the genetic lineage (or Discrete Typing Unit - DTU) of the parasite. To test this hypothesis, parasitological and histopathological evaluations were performed in mice inoculated with strains belonging to the DTU T. cruzi IV (TcIV) from the State of Amazonas (northern Brazil), or the DTU T. cruzi II (TcII) from the State of Paraná (southern Brazil). Groups of 10 Swiss mice were inoculated with eight strains of TcIV obtained from acute cases (7) from two outbreaks of orally acquired ChD, and from the triatomine Rhodnius robustus (1) from Amazonas; and three strains of TcII obtained from chronic patients in Paraná. We evaluated the pre-patent period, patent period, maximum peak of parasitemia, day of maximum peak of parasitemia, area under the parasitemia curve, inflammatory process, and tissue parasitism in the acute phase. TcIV was less virulent than TcII, and showed significantly (p < 0.005) lower parasitemia levels. Although the levels of tissue parasitism did not differ statistically, mice infected with TcIV displayed significantly (p < 0.001) fewer inflammatory processes than mice infected with TcII. This supported the working hypothesis, since TcIV from Amazonas was less pathogenic than TcII from Paraná; and agreed with the lower severity of human cases of ChD in the Amazon region. Copyright © 2014 Elsevier Inc. All rights reserved.

Practice patterns for the use of iodinated i.v. contrast media for pediatric CT studies: a survey of the Society for Pediatric Radiology.

PubMed

Callahan, Michael J; Servaes, Sabah; Lee, Edward Y; Towbin, Alexander J; Westra, Sjirk J; Frush, Donald P

2014-04-01

There are limited data available on the use of i.v. contrast media for CT studies in the pediatric population. The purpose of this study is to determine the practice patterns of i.v. contrast media usage for pediatric CT by members of the Society for Pediatric Radiology (SPR). SPR members were surveyed regarding the use of i.v. contrast media for pediatric CT studies. Questions pertained to information required before administering i.v. contrast media, types of central catheters for injecting i.v. contrast media, injection rates based on angiocatheter size and study type, and management of i.v. contrast media extravasation. The response rate of 6% (88/1545) represented practice patterns of 26% (401/1545) of the SPR membership. Most respondents thought the following clinical information was mandatory before i.v. contrast media administration: allergy to i.v. contrast media (97%), renal insufficiency (97%), current metformin use (72%), significant allergies (61%), diabetes (54%), and asthma (52%). Most administered i.v. contrast media through nonimplanted central venous catheters (78%), implanted venous ports (78%), and peripherally inserted central catheters (72%). The most common maximum i.v. contrast media injection rates were 5.0 mL/s or greater for a 16-gauge angiocatheter, 4.0 mL/s for an 18-gauge angiocatheter, 3.0 mL/s for a 20-gauge angiocatheter, and 2.0 mL/s for a 22-gauge angiocatheter. For soft-tissue extravasation of i.v. contrast media, 95% elevate the affected extremity, 76% use ice, and 45% use heat. The results of this survey illustrate the collective opinion of a subset of SPR members relating to the use of i.v. contrast media in pediatric CT, providing guidelines for clinical histories needed before i.v. contrast media, maximum i.v. contrast injection rates for standard angiocatheters, contrast media injection rates for specific CT studies, and management of i.v. contrast media soft-tissue extravasation.

Prevalence of dementia in Latin America, India, and China: a population-based cross-sectional survey.

PubMed

Llibre Rodriguez, Juan J; Ferri, Cleusa P; Acosta, Daisy; Guerra, Mariella; Huang, Yueqin; Jacob, K S; Krishnamoorthy, E S; Salas, Aquiles; Sosa, Ana Luisa; Acosta, Isaac; Dewey, Michael E; Gaona, Ciro; Jotheeswaran, A T; Li, Shuran; Rodriguez, Diana; Rodriguez, Guillermina; Kumar, P Senthil; Valhuerdi, Adolfo; Prince, Martin

2008-08-09

Studies have suggested that the prevalence of dementia is lower in developing than in developed regions. We investigated the prevalence and severity of dementia in sites in low-income and middle-income countries according to two definitions of dementia diagnosis. We undertook one-phase cross-sectional surveys of all residents aged 65 years and older (n=14 960) in 11 sites in seven low-income and middle-income countries (China, India, Cuba, Dominican Republic, Venezuela, Mexico, and Peru). Dementia diagnosis was made according to the culturally and educationally sensitive 10/66 dementia diagnostic algorithm, which had been prevalidated in 25 Latin American, Asian, and African centres; and by computerised application of the dementia criterion from the Diagnostic and Statistical Manual of Mental Disorders (DSM IV). We also compared prevalence of DSM-IV dementia in each of the study sites with that from estimates in European studies. The prevalence of DSM-IV dementia varied widely, from 0.3% (95% CI 0.1-0.5) in rural India to 6.3% (5.0-7.7) in Cuba. After standardisation for age and sex, DSM-IV prevalence in urban Latin American sites was four-fifths of that in Europe (standardised morbidity ratio 80 [95% CI 70-91]), but in China the prevalence was only half (56 [32-91] in rural China), and in India and rural Latin America a quarter or less of the European prevalence (18 [5-34] in rural India). 10/66 dementia prevalence was higher than that of DSM-IV dementia, and more consistent across sites, varying between 5.6% (95% CI 4.2-7.0) in rural China and 11.7% (10.3-13.1) in the Dominican Republic. The validity of the 847 of 1345 cases of 10/66 dementia not confirmed by DSM-IV was supported by high levels of associated disability (mean WHO Disability Assessment Schedule II score 33.7 [SD 28.6]). As compared with the 10/66 dementia algorithm, the DSM-IV dementia criterion might underestimate dementia prevalence, especially in regions with low awareness of this emerging public-health problem.

Notes on the uwainat oil rim development, Maydan Mahzam and Bul Hanine Fields, offshore Qatar

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

Hamam, K.A.

As a result of reservoir simulation studies of the Uwainat reservoirs (Maydan Mahzam and Bul Hanine Fields), drilling to the Uwainat oil rim target became very ''tight'' with a very limited vertical tolerance. To achieve drilling to the tight target requires a precise position of the well at the top of the Lower Arab IV reservoir (a reliable marker) and an accurate isochore of the Lower Arab IV - Uwainat. The discussion shows that the level of accuracy needed in determining both the actual subsea well position and in constructing the depth contours of the reservoirs is extremely high.

Networks consolidation program: Maintenance and Operations (M&O) staffing estimates

NASA Technical Reports Server (NTRS)

Goodwin, J. P.

1981-01-01

The Mark IV-A consolidate deep space and high elliptical Earth orbiter (HEEO) missions tracking and implements centralized control and monitoring at the deep space communications complexes (DSCC). One of the objectives of the network design is to reduce maintenance and operations (M&O) costs. To determine if the system design meets this objective an M&O staffing model for Goldstone was developed which was used to estimate the staffing levels required to support the Mark IV-A configuration. The study was performed for the Goldstone complex and the program office translated these estimates for the overseas complexes to derive the network estimates.

Acoustic stimulation promotes DNA fragmentation in the Guinea pig cochlea.

PubMed

Kamio, Tomonobu; Watanabe, Ken-Ichi; Okubo, Kimihiro

2012-01-01

Apoptosis can be described as programmed cell death. Apoptosis regulates cell turnover and is involved in various pathological conditions. The characteristic features of apoptosis are shrinkage of the cell body, chromatin condensation, and nucleic acid fragmentation. During apoptosis, double-stranded DNA is broken down into single-stranded DNA (ssDNA) by proteases. Acoustic trauma is commonly encountered in otorhinolaryngology clinics. Intense noise can cause inner ear damage, such as hearing disturbance, tinnitus, ear fullness, and decreased speech discrimination. In this study, we used immunohistochemical and electrophysiological methods to examine the fragmentation of DNA in the cochleas of guinea pigs that had been exposed to intense noise. Twenty-four guinea pigs weighing 250 to 350 g were used. The animals were divided into 4 groups: (I) a control group (n=6), (II) a group that was exposed to noise for 2 hours (n=6), (III) a group that was exposed to noise for 5 hours (n=6), and (IV) a group that was exposed to noise for 20 hours. The stimulus was a pure tone delivered at a frequency of 2 kHz. The sound pressure level was 120 dBSPL. No threshold shifts were apparent in group I. Group II showed a significant elevation of the hearing threshold (ANOVA, p<0.05(*)). The ABR threshold level was also significantly elevated immediately after the acoustic stimulation in groups III and IV (ANOVA, p<0.01(**)). In groups I, II, and IV, the lateral wall of the ear did not show immunoreactivity to ssDNA but did in group III. No immunoreactivity was apparent in the organ of Corti in group I or II. However, the supporting cells and outer hair cells in groups III and IV showed reactions for ssDNA. The fine structure of the organ of Corti had been destroyed in group IV. The lateral wall showed immunoreactivity for ssDNA only in group III, whereas the organ of Corti showed reactions for ssDNA in groups III and IV. Our study suggests that apoptotic changes occur in patients that suffer acoustic trauma. Once the apoptotic pathway has started, it is irreversible. Thus, early diagnosis and treatment are necessary. Earplugs should also be worn at rock concerts.

A Pilot Study for Gainful Employment in Home Economics. Final Report. Volume IV, A Suggested Curriculum Guide for Preparing Food Service Workers for Entry Level Jobs.

ERIC Educational Resources Information Center

Cozine, June; And Others

Curriculum guidelines for teacher use in organizing and teaching a course to prepare 11th and 12th grade students for entry level food service occupations were developed as part of a pilot study which is reported in VT 006 870. The 1-year program requires 2 hours daily plus 10 hours per week on-the-job work experience. Content areas are: (1)…

Relationship between gross motor and intellectual function in children with cerebral palsy: a cross-sectional study.

PubMed

Dalvand, Hamid; Dehghan, Leila; Hadian, Mohammad Reza; Feizy, Awat; Hosseini, Seyed Ali

2012-03-01

To explore the relationship between gross motor and intellectual function in children with cerebral palsy (CP). A cross-sectional study. Occupational therapy clinic. Children with CP (N=662; 281 girls, 381 boys; age range, 3-14y). Not applicable. Intelligence testing was carried out by means of the Wechsler Preschool and Primary Scale of Intelligence and the Wechsler Intelligence Scale for Children-Revised. Gross motor function level was determined by the Gross Motor Function Classification System Expanded and Revised (GMFCS E&R). Of the children, 10.4% were at level I of the GMFCS E&R, 38% at levels II and III, and 51.5% at levels IV and V. The lowest level of intelligence or profound intellectual disability was found in children with spastic quadriplegia (n=28, 62.2%). Children at the lowest levels (I-IV, GMFCS E&R) obtained higher ratings in terms of intelligence in comparison with children at level V. Based on the present results, the diagnosis was statistically related to the intellectual level as dependent variable (P<.01); accordingly, hypotonic, quadriplegic, and hemiplegic patients had the highest odds to assign higher ratings in abnormal intelligence, respectively. Sex and age were not statistically related to the dependent variable. The study results demonstrated a significant association between GMFCS E&R and intellectual function. Therefore, we suggest that particular attention should be paid to the intellectual level in terms of evaluations of gross motor function. These results, in respect, might be interested for occupational and physical therapists who are involved in rehabilitation programs for these children. Copyright © 2012 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

The Chemical Chaperone, PBA, Reduces ER Stress and Autophagy and Increases Collagen IV α5 Expression in Cultured Fibroblasts From Men With X-Linked Alport Syndrome and Missense Mutations.

PubMed

Wang, Dongmao; Mohammad, Mardhiah; Wang, Yanyan; Tan, Rachel; Murray, Lydia S; Ricardo, Sharon; Dagher, Hayat; van Agtmael, Tom; Savige, Judy

2017-07-01

X-linked Alport syndrome (OMIM 301050) is caused by COL4A5 missense variants in 40% of families. This study examined the effects of chemical chaperone treatment (sodium 4-phenylbutyrate) on fibroblast cell lines derived from men with missense mutations. Dermal fibroblast cultures were established from 2 affected men and 3 normals. Proliferation rates were examined, the collagen IV α5 chain localized with immunostaining, and levels of the intra- and extracellular chains quantitated with an in-house enzyme-linked immunosorbent assay. COL4A5 mRNA was measured using quantitative reverse transcriptase polymerase chain reaction. Endoplasmic reticulum (ER) size was measured on electron micrographs and after HSP47 immunostaining. Markers of ER stress (ATF6, HSPA5, DDIT3), autophagy (ATG5, BECN1, ATG7), and apoptosis (CASP3, BAD, BCL 2 ) were also quantitated by quantitative reverse transcriptase polymerase chain reaction. Measurements were repeated after 48 hours of incubation with 10 mM sodium 4-phenylbutyrate acid. Both COL4A5 missense variants were associated with reduced proliferation rates on day 6 ( P  = 0.01 and P  = 0.03), ER enlargement, and increased mRNA for ER stress and autophagy (all P values < 0.05) when compared with normal. Sodium 4-phenylbutyrate treatment increased COL4A5 transcript levels ( P  < 0.01), and reduced ER size ( P  < 0.01 by EM and P  < 0.001 by immunostaining), ER stress (p HSPA5 and DDIT3, all P values < 0.01) and autophagy (ATG7, P  < 0.01). Extracellular collagen IV α5 chain was increased in the M1 line only ( P  = 0.06). Sodium 4-phenylbutyrate increases collagen IV α5 mRNA levels, reduces ER stress and autophagy, and possibly facilitates collagen IV α5 extracellular transport. Whether these actions delay end-stage renal failure in men with X-linked Alport syndrome and missense mutations will only be determined with clinical trials.

Pathological mechanisms underlying single large‐scale mitochondrial DNA deletions

PubMed Central

Rocha, Mariana C.; Rosa, Hannah S.; Grady, John P.; Blakely, Emma L.; He, Langping; Romain, Nadine; Haller, Ronald G.; Newman, Jane; McFarland, Robert; Ng, Yi Shiau; Gorman, Grainne S.; Schaefer, Andrew M.; Tuppen, Helen A.; Taylor, Robert W.

2018-01-01

Objective Single, large‐scale deletions in mitochondrial DNA (mtDNA) are a common cause of mitochondrial disease. This study aimed to investigate the relationship between the genetic defect and molecular phenotype to improve understanding of pathogenic mechanisms associated with single, large‐scale mtDNA deletions in skeletal muscle. Methods We investigated 23 muscle biopsies taken from adult patients (6 males/17 females with a mean age of 43 years) with characterized single, large‐scale mtDNA deletions. Mitochondrial respiratory chain deficiency in skeletal muscle biopsies was quantified by immunoreactivity levels for complex I and complex IV proteins. Single muscle fibers with varying degrees of deficiency were selected from 6 patient biopsies for determination of mtDNA deletion level and copy number by quantitative polymerase chain reaction. Results We have defined 3 “classes” of single, large‐scale deletion with distinct patterns of mitochondrial deficiency, determined by the size and location of the deletion. Single fiber analyses showed that fibers with greater respiratory chain deficiency harbored higher levels of mtDNA deletion with an increase in total mtDNA copy number. For the first time, we have demonstrated that threshold levels for complex I and complex IV deficiency differ based on deletion class. Interpretation Combining genetic and immunofluorescent assays, we conclude that thresholds for complex I and complex IV deficiency are modulated by the deletion of complex‐specific protein‐encoding genes. Furthermore, removal of mt‐tRNA genes impacts specific complexes only at high deletion levels, when complex‐specific protein‐encoding genes remain. These novel findings provide valuable insight into the pathogenic mechanisms associated with these mutations. Ann Neurol 2018;83:115–130 PMID:29283441

A Double-Blind Placebo-Controlled Comparison of a Novel Formulation of Intravenous Diclofenac and Ketorolac for Postoperative Third Molar Extraction Pain

PubMed Central

Christensen, Kyle; Daniels, Stephen; Bandy, Donald; Ernst, Cynthia C.; Hamilton, Douglas A.; Mermelstein, Fred H.; Wang, Jianyuan; Carr, Daniel B.

2011-01-01

Dyloject is a novel formulation of diclofenac intended for intravenous (IV) administration. This formulation employs the solubilizing agent hydroxypropyl-β-cyclodextrin to permit bolus IV administration. The efficacy and safety of 5 dose levels of IV diclofenac were compared with IV ketorolac and placebo following third molar extraction. This was a single-dose, randomized, double-blind, placebo- and comparator-controlled, parallel-group study. A total of 353 subjects with moderate to severe pain received placebo; ketorolac 30 mg; or IV diclofenac 3.75, 9.4, 18.75, 37.5, or 75 mg (N  =  51 for all groups, except N  =  47 for ketorolac). The primary endpoint was total pain relief over 6 hours (TOTPAR6) as measured by the visual analog scale (VAS). Secondary endpoints included multiple measures of pain intensity and relief; patient global evaluation; and times to pain relief and rescue medication. Dropouts and adverse effects (AEs) were also monitored. IV diclofenac was superior to placebo as measured by TOTPAR6 (P < .0001 for all doses except 3.75 mg, for which P  =  .0341). IV diclofenac 3.75 mg was statistically superior to placebo for TOTPAR2 and TOTPAR4. IV diclofenac at both 37.5 and 75 mg was superior to placebo (P < .05) at the earliest (5 minute) assessments of pain intensity and pain relief, but ketorolac was not. The proportion of patients reporting 30% or greater pain relief at 5 minutes was significantly greater after IV diclofenac 37.5 and 75 mg than after ketorolac 30 mg or placebo. Secondary endpoints confirmed the primary findings. Treatment-related AEs were generally mild to moderate and were typical for nonsteroidal anti-inflammatory drugs (NSAIDs). The more rapid onset of action of IV diclofenac compared with the reference injectable NSAID ketorolac suggests additional clinical benefit. If confirmed in larger series, these findings may improve the safety and efficacy of postoperative NSAID analgesia. PMID:21679043

Focused Feasibility Study Final Field Sampling Plan

DTIC Science & Technology

1993-10-01

baseline of groundwater chemistry prior to commencing additional environmental investigations of the area. Work for Phase I of the FFS is designed lo...investigations and remedial feasibility investigations at Beach Point. The groundwater data will also be used to aid in the design of any groundwater extraction...approved laboratories. The analytical data will be the equivalent of EPA Level IV data. This level of data quality has been established for environmental

Induction chemotherapy followed by alternating chemo-radiotherapy in non-endemic undifferentiated carcinoma of the nasopharynx: optimal compliance and promising 4-year results.

PubMed

Ponzanelli, Anna; Vigo, Viviana; Marcenaro, Michela; Bacigalupo, Almalina; Gatteschi, Beatrice; Ravetti, Jean-Luis; Corvò, Renzo; Benasso, Marco

2008-08-01

Concomitant chemo-radiotherapy is the standard treatment for advanced nasopharyngeal carcinoma (NPC). Induction chemotherapy may improve the results further by enhancing both loco-regional and distant control. Fifty patients with untreated, stage IV (UICC 1992) undifferentiated NPC were initially treated with three courses of epidoxorubicin, 90 mg/m(2), day 1 and cisplatin, 40 mg/m(2), days 1 and 2, every three weeks and then underwent three courses of cisplatin, 20 mg/m(2)/day, days 1-4 and fluorouracil, 200mg/m(2)/day, days 1-4 (weeks 1, 4, 7), alternated to three splits of radiation (week 2-3, 5-6, 8-9-10) up to 70 Gy. All patients but one received 3 cycles of induction chemotherapy. Toxicities from induction chemotherapy were grade III or IV mucositis (2%), grade III or IV nausea/vomiting (22%), grade III or IV hematological toxicity (6%). At the end of induction phase 12% of CRs, 84% of PRs were recorded. Toxicities from alternating chemo-radiotherapy were grade III or IV mucositis (30%), grade III or IV nausea/vomiting (8%), grade III or IV hematological toxicity (24%). Overall, 86% of CRs and 14% of PRs were observed. Four-year progression free survival and overall survival rates are 71% and 81%, respectively. In a small number of patients studied, no correlation between the level of EGFR overexpression and outcomes was detected. In locally advanced UNPC our combined program including induction chemotherapy followed by alternating chemo-radiotherapy is active and gives promising long-term outcomes with acceptable toxicity and optimal patients' compliance. This program merits to be tested in a phase III trial.

Rapid metabolism of exogenous angiotensin II by catecholaminergic neuronal cells in culture media.

PubMed

Basu, Urmi; Seravalli, Javier; Madayiputhiya, Nandakumar; Adamec, Jiri; Case, Adam J; Zimmerman, Matthew C

2015-02-01

Angiotensin II (AngII) acts on central neurons to increase neuronal firing and induce sympathoexcitation, which contribute to the pathogenesis of cardiovascular diseases including hypertension and heart failure. Numerous studies have examined the precise AngII-induced intraneuronal signaling mechanism in an attempt to identify new therapeutic targets for these diseases. Considering the technical challenges in studying specific intraneuronal signaling pathways in vivo, especially in the cardiovascular control brain regions, most studies have relied on neuronal cell culture models. However, there are numerous limitations in using cell culture models to study AngII intraneuronal signaling, including the lack of evidence indicating the stability of AngII in culture media. Herein, we tested the hypothesis that exogenous AngII is rapidly metabolized in neuronal cell culture media. Using liquid chromatography-tandem mass spectrometry, we measured levels of AngII and its metabolites, Ang III, Ang IV, and Ang-1-7, in neuronal cell culture media after administration of exogenous AngII (100 nmol/L) to a neuronal cell culture model (CATH.a neurons). AngII levels rapidly declined in the media, returning to near baseline levels within 3 h of administration. Additionally, levels of Ang III and Ang-1-7 acutely increased, while levels of Ang IV remained unchanged. Replenishing the media with exogenous AngII every 3 h for 24 h resulted in a consistent and significant increase in AngII levels for the duration of the treatment period. These data indicate that AngII is rapidly metabolized in neuronal cell culture media, and replenishing the media at least every 3 h is needed to sustain chronically elevated levels. © 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Proangiogenic and Profibrotic Markers in Pulmonary Sarcoidosis.

PubMed

Tuleta, I; Biener, L; Pizarro, C; Nickenig, G; Skowasch, D

2018-04-21

The aim of our study was to determine the blood levels of vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-β1, fibroblast growth factor (FGF)-2, and platelet-derived growth factor (PDGF)-AB in different stages of pulmonary sarcoidosis. There were 92 patients in sarcoidosis stages I + II, III, and IV enrolled into the study. All the patients underwent lung diffusing capacity and blood sampling. We found that VEGF levels differed significantly between the stage groups with the peak VEGF concentrations in stage III. TGF-β1 levels were similar in stages I + II and III, and tended to be lower in stage IV. The analysis of the subgroups showed increased VEGF and FGF-2, and reduced TGF-β1 concentration in stages I + II patients with relevantly reduced lung diffusing capacity or increased sarcoidosis activity compared to patients with normal lung diffusing capacity or inactive sarcoidosis. A tendency towards increased VEGF, PDGF-AB and TGF-β1 levels was observed in the analogical subgroup analysis within the stage III. We conclude that proangiogenic VEGF, and profibrotic FGF-2 and PDGF-AB may contribute to the progression of sarcoidosis, whereas TGF-β1, with its dual anti-inflammatory and profibrotic actions, may play a dichotomous protective or deleterious role. Reduced diffusing capacity and active sarcoidosis are associated with an unfavorable constellation of the markers studied, which predicts a progressive disease course.

Effects of zinc oxide nanoparticles on Kupffer cell phagosomal motility, bacterial clearance, and liver function

PubMed Central

Watson, Christa Y; Molina, Ramon M; Louzada, Andressa; Murdaugh, Kimberly M; Donaghey, Thomas C; Brain, Joseph D

2015-01-01

Background Zinc oxide engineered nanoparticles (ZnO ENPs) have potential as nanomedicines due to their inherent properties. Studies have described their pulmonary impact, but less is known about the consequences of ZnO ENP interactions with the liver. This study was designed to describe the effects of ZnO ENPs on the liver and Kupffer cells after intravenous (IV) administration. Materials and methods First, pharmacokinetic studies were conducted to determine the tissue distribution of neutron-activated 65ZnO ENPs post-IV injection in Wistar Han rats. Then, a noninvasive in vivo method to assess Kupffer cell phagosomal motility was employed using ferromagnetic iron particles and magnetometry. We also examined whether prior IV injection of ZnO ENPs altered Kupffer cell bactericidal activity on circulating Pseudomonas aeruginosa. Serum and liver tissues were collected to assess liver-injury biomarkers and histological changes, respectively. Results We found that the liver was the major site of initial uptake of 65ZnO ENPs. There was a time-dependent decrease in tissue levels of 65Zn in all organs examined, refecting particle dissolution. In vivo magnetometry showed a time-dependent and transient reduction in Kupffer cell phagosomal motility. Animals challenged with P. aeruginosa 24 hours post-ZnO ENP injection showed an initial (30 minutes) delay in vascular bacterial clearance. However, by 4 hours, IV-injected bacteria were cleared from the blood, liver, spleen, lungs, and kidneys. Seven days post-ZnO ENP injection, creatine phosphokinase and aspartate aminotransferase levels in serum were significantly increased. Histological evidence of hepatocyte damage and marginated neutrophils were observed in the liver. Conclusion Administration of ZnO ENPs transiently inhibited Kupffer cell phagosomal motility and later induced hepatocyte injury, but did not alter bacterial clearance from the blood or killing in the liver, spleen, lungs, or kidneys. Our data show that diminished Kupffer cell organelle motion correlated with ZnO ENP-induced liver injury. PMID:26170657

Psychiatric Symptom Clusters as Risk Factors for Alcohol Use Disorders in Adolescence: A National Study

PubMed Central

Harford, Thomas C.; Yi, Hsiao-ye; Chen, Chiung M.; Grant, Bridget F.

2015-01-01

Background Few epidemiologic studies have examined a full range of adolescent psychiatric disorders in the general population. The association between psychiatric symptom clusters (PSCs) and DSM-IV alcohol use disorders (AUDs) among adolescents is not well understood. Methods This study draws upon the public-use data from the 2000 National Household Survey on Drug Abuse, including a study sample of 19,430 respondents ages 12 to 17. Logistic regression and exploratory structural equation modeling assess the associations between PSCs and DSM-IV AUDs by gender. The PSCs are based on brief screening scales devised from the Diagnostic Interview Schedule for Children Predictive Scales. Results Several PSCs were found to be significantly associated with DSM-IV AUDs, including separation anxiety, generalized anxiety, depression, oppositional defiant disorder, and conduct disorder among both genders, and panic disorder and obsessive compulsive disorder among females. Consistent with the literature, the analysis of PSCs yields three factors identical for both genders—two internalizing factors (fear and anxiety–misery) and one externalizing factor. Adolescents who scored higher on the externalizing factor tended to have higher levels of the AUD factor. Female adolescents who scored higher on the internalizing misery factor and lower on the internalizing fear factor also tended to have higher levels of the AUD factor. Conclusion The associations that we found between PSCs and AUDs among adolescents in this study are consistent with those found among adults in other studies, although gender may moderate associations between internalizing PSCs and AUDs. Our findings lend support to previous findings on the developmentally stable associations between disruptive behaviors and AUDs among adolescents as well as adults in the general population. PMID:26110378

Gene expression profile of collagen types, osteopontin in the tympanic membrane of patients with tympanosclerosis.

PubMed

Sakowicz-Burkiewicz, Monika; Kuczkowski, Jerzy; Przybyła, Tomasz; Grdeń, Marzena; Starzyńska, Anna; Pawełczyk, Tadeusz

2017-09-01

Tympanosclerosis is a pathological process involving the middle ear. The hallmark of this disease is the formation of calcium deposits. In the submucosal layer, as well as in the right layer of the tympanic membrane, the calcium deposits result in a significant increase in the activity of fibroblasts and deposition of collagen fibers. The aim of our study was to examine the expression level of genes encoding collagen type I, II, III and IV (COL1A1, COL2A1, COL3A1, COL4A1) and osteopontin (SPP1) in the tympanic membrane of patients with tympanosclerosis. The total RNA was isolated from middle ear tissues with tympanosclerosis, received from 25 patients and from 19 normal tympanic membranes. The gene expression level was determined by real-time RT-PCR. The gene expression levels were correlated with clinical Tos classification of tympanosclerosis. We observed that in the tympanic membrane of patients with tympanosclerosis, the expression of type I collagen is decreased, while the expression of type II and IV collagen and osteopontin is increased. Moreover, mRNA levels of the investigated genes strongly correlated with the clinical stages of tympanosclerosis. The strong correlations between the expression of type I, II, IV collagen and osteopontin and the clinical stage of tympanosclerosis indicate the involvement of these proteins in excessive fibrosis and pathological remodeling of the tympanic membrane. In the future, a treatment aiming to modulate these gene expressions and/or regulation of the degradation of their protein products could be used as a new medical approach for patients with tympanosclerosis.

Circulating filarial antigen in the hydrocele fluid from individuals living in a bancroftian filariasis area - Recife, Brazil: detected by the monoclonal antibody Og4C3-assay.

PubMed

Rocha, Abraham; Lima, Guilherme; Medeiros, Zulma; Aguiar-Santos, Ana; Alves, Sandra; Montarroyos, Ulisses; Oliveira, Paula; Béliz, Fátima; Netto, Maria José; Furtado, André

2004-02-01

The purpose of this study was to examine the circulating filarial antigen (CFA) detected by the monoclonal antibody (mAb) Og4C3-ELISA in paired samples of serum and hydrocele fluid from 104 men with hydrocele, living in an endemic area of Wuchereria bancrofti. Nocturnal blood specimens were filtered and examined for microfilariae (MF) and ultrasound was used in order to identify the presence of adult worms (the filaria dance sign - FDS) in the lymphatic vessels of the scrotal area. Four groups were selected according to their parasitological status: group I - 71 MF- and FDS-; group II - 21 MF+ and FDS+; group III - 10 MF- and FDS+ and group IV- 2 MF+ and FDS-. CFA was identified simultaneously (fluid and serum) in 11 (15.5%), 21 (100%), 3 (30%), and 1 (50%) in groups I, II, III, and IV, respectively. In despite of high CFA+ level (antigen Og4C3) units/ml, the Geometrical Mean (GM) = 2696) in the sera of these 36/104 paired samples, when compared to the hydrocele fluid, (GM = 1079), showed a very good correlation between the CFA level in the serum and CFA level in the fluid (r = 0.731). CFA level in the serum of the 23 microfilaremics (groups II and IV) was extremely high (GM = 4189) and was correlated with MF density (r = 0.442). These findings report for the first time the potential alternative use of the hydrocele fluid to investigate CFA using the mAb Og4C3-ELISA.

Protective effect of hydroxytyrosol in arsenic-induced mitochondrial dysfunction in rat brain.

PubMed

Soni, Manisha; Prakash, Chandra; Sehwag, Sfurti; Kumar, Vijay

2017-07-01

The present study was planned to investigate the protective effect of hydroxytyrosol (HT) against arsenic (As)-induced mitochondrial dysfunction in rat brain. Rats exposed to sodium arsenite (25 ppm for 8 weeks) showed decreased mitochondrial complexes (I, II, IV) activities, mitochondrial superoxide dismutase (MnSOD), and catalase activities in brain mitochondria. As-treated rats showed reduced mRNA expression of complex I (ND-1, ND-2), IV (COX-1, COX-4) subunits, and uncoupling protein-2 (UCP-2). In addition to this, As exposure downregulated the protein expression of MnSOD. Administration of HT with As restored the enzymatic activities of mitochondrial complexes, MnSOD and catalase, increased the mRNA levels of complexes subunits and UCP-2 as well as proteins level of MnSOD. These results suggest that HT efficiently restores mitochondrial dysfunction in As neurotoxicity and might be used as potential mitoprotective agent in future. © 2017 Wiley Periodicals, Inc.

The O IV and S IV intercombination lines in solar and stellar ultraviolet spectra

NASA Technical Reports Server (NTRS)

Cook, J. W.; Keenan, F. P.; Dufton, P. L.; Kingston, A. E.; Pradhan, A. K.; Zhang, H. L.; Doyle, J. G.; Hayes, M. A.

1995-01-01

New calculations of O IV electron density diagnostic emission-line ratios involving the 1399.8, 1401.2, 1404.8, and 14076.4 A transitions are presented. A comparison of these calculations with observational data from a quiet solar region, a sunspot, and an active region obtained with the High Resolution Telescope and Spectrograph (HRTS), two flares observed with the SO82B spectrograph on board Skylab, and Hubble Space Telescope (HST) observations by the Goddard High Resolution Spectrograph (GHRS) of Capella, gives good results using the ratio R(sub 1) = I(1407.4 A)/I(1401.2 A). However, the electron density obtained using the ratio R(sub 2) = I(1407.4 A)/I(1404.8 A) is often an order of magnitude smaller. The O IV 1404.8 A line is blended with the S IV 1404.8 A line, and we investigate whether this ratio may still be used as a density diagnostic if the S IV 1406.1 A line intensity is used to correct for the presence of S IV 1404.8 A, using previous S IV calculations by Dufton et al. We still find systematic differences compared to density determinations from line ratios that do not involve the O IV 1404.8 A line, which we suggest are due to errors in earlier theoretical calculations of the S IV atomic data, and also possibly to previously unconsidered fluorescent pumping of the upper level of the S IV 1404.8 A transition.

A Prototype Model for Automating Nursing Diagnosis, Nurse Care Planning and Patient Classification.

DTIC Science & Technology

1986-03-01

Each diagnosis has an assessment level. Assessment levels are defining characteristics observed by the nurse or subjectively stated by the patient... characteristics of this order line. Select IV Order (Figure 4.l.1.le] is the first screen of a series of three. Select IV Order has up to 10 selections...For I F Upatient orders. Input Files Used: IVC.Scr and Procfile.Prg * Output Files Used: None Calling Routine: IUB.Prg * Routine Called: None

[THE PRINCIPLES OF ORGANIZATION AND TREATMENT FOR SORTING OF WOUNDED PERSONS WITH A COMBAT SURGICAL TRAUMA OF EXTREMITIES ON THE IV LEVEL OF THE MEDICAL CARE PROVISION].

PubMed

Korohl, S O; Zherdev, I I; Domanskiy, A M

2015-12-01

Experience of medical sorting of 434 injured persons with a gun-shot woundings of extremities in 2014-2015 yrs is adduced. The principles of organization and treatment for medical sorting of wounded persons were elaborated. Prognostic intrahospital, diagnostic and evacuation--transport sorting was introduced in wounded persons in the IV level hospital, concerning severity of traumatic shock and prognosis of their survival.

Foot and ankle tendoscopies: current concepts review

PubMed Central

Monteagudo, Manuel; Maceira, Ernesto; Martinez de Albornoz, Pilar

2016-01-01

Tendoscopy is an apparently safe and reliable procedure to manage some foot and ankle disorders. The most common foot and ankle tendoscopies are: Achilles; peroneal; and posterior tibial tendon. Tendoscopy may be used as an adjacent procedure to other techniques. Caution is recommended to avoid neurovascular injuries. Predominantly level IV and V studies are found in the literature, with no level I studies still available. There are many promising and evolving endoscopic techniques for tendinopathies around the foot and ankle, but studies of higher levels of evidence are needed to strongly recommend these procedures. Cite this article: EFORT Open Rev 2016;1:440-447. DOI: 10.1302/2058-5241.160028 PMID:28461923

Instrumental variable methods in comparative safety and effectiveness research.

PubMed

Brookhart, M Alan; Rassen, Jeremy A; Schneeweiss, Sebastian

2010-06-01

Instrumental variable (IV) methods have been proposed as a potential approach to the common problem of uncontrolled confounding in comparative studies of medical interventions, but IV methods are unfamiliar to many researchers. The goal of this article is to provide a non-technical, practical introduction to IV methods for comparative safety and effectiveness research. We outline the principles and basic assumptions necessary for valid IV estimation, discuss how to interpret the results of an IV study, provide a review of instruments that have been used in comparative effectiveness research, and suggest some minimal reporting standards for an IV analysis. Finally, we offer our perspective of the role of IV estimation vis-à-vis more traditional approaches based on statistical modeling of the exposure or outcome. We anticipate that IV methods will be often underpowered for drug safety studies of very rare outcomes, but may be potentially useful in studies of intended effects where uncontrolled confounding may be substantial.

"Let's get down to business: a validation study of the Psychopathic Personality Inventory among a sample of MBA students.".

PubMed

Heinze, Peter; Allen, Rhianon; Magai, Carol; Ritzler, Barry

2010-08-01

While the Psychopathic Personality Inventory (PPI) has gained increasing attention as a measure of noncriminal psychopathy, absent has been research involving samples including business people. This study investigated the validity of the PPI with such a population by examining the association between psychopathic traits and moral decision-making among MBA students. Sixty-six MBA students were assessed using the PPI, the MACH-IV (a measure of Machiavellianism), the Ethical Position Questionnaire (EPQ), and the Defining Issues Test (DIT-2). Only PPI Machiavellian Egocentricity was associated with level of post-conventional moral reasoning. MACH-IV Machiavellianism was a stronger predictor of the Subjectivist ethical position than were PPI subscales. However, a combination of MACH-IV Machiavellianism and four PPI scales accounted for 46% of the variance in Subjectivism. Results suggested that Machiavellian Egocentricity and Machiavellianism are distinct constructs. Benning, Patrick, Hicks, Blonigen, & Krueger (2003)'s two factor model of the PPI was also supported. In general, the findings provided further validation for the PPI as a tool for assessing psychopathic traits among "mainstream" individuals, including business people.

Use of Serum Infliximab Level Prior to Cyclosporine Salvage Therapy in Severe Ulcerative Colitis

PubMed Central

Bochenek, Ashley; Stein, Adam C.; Rubin, David T.

2014-01-01

Medical treatment options for severe, steroid refractory ulcerative colitis (UC) include infliximab (IFX) or cyclosporine (CSA), but general consensus has been that both agents should not be used together or even successively. We report a case of a 17-year-old male with severe UC refractory to IV steroids with successful sequential salvage therapy guided by serum IFX level. After primary lack of response to IFX, an undetectable serum IFX level and elevated IFX antibodies were followed by immediate transition to IV CSA. This case demonstrates the possibility of therapeutic drug monitoring of IFX levels when calculating the risk/benefit ratio for patients with steroid-refractory UC failing primary salvage therapy. PMID:26157857

Mutation in GNE Downregulates Peroxiredoxin IV Altering ER Redox Homeostasis.

PubMed

Chanana, Pratibha; Padhy, Gayatri; Bhargava, Kalpana; Arya, Ranjana

2017-12-01

GNE myopathy is a rare neuromuscular genetic disorder characterized by early adult onset and muscle weakness due to mutation in sialic acid biosynthetic enzyme, UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE). More than 180 different GNE mutations are known all over the world with unclear pathomechanism. Although hyposialylation of glycoproteins is speculated to be the major cause, but cellular mechanism leading to loss of muscle mass has not yet been deciphered. Besides sialic acid biosynthesis, GNE affects other cellular functions such as cell adhesion and apoptosis. In order to understand the effect of mutant GNE protein on cellular functions, differential proteome profile of HEK293 cells overexpressing pathologically relevant recombinant mutant GNE protein (D207V and V603L) was analyzed. These cells, along with vector control and wild-type GNE-overexpressing cells, were subjected to two-dimensional gel electrophoresis coupled with mass spectrometry (MALDI-TOF/TOF MS/MS). In the study, 10 differentially expressed proteins were identified. Progenesis same spots software revealed downregulation of peroxiredoxin IV (PrdxIV), an ER-resident H 2 O 2 sensor that regulates neurogenesis. Significant reduction in mRNA and protein levels of PrdxIV was observed in GNE mutant cell lines compared with vector control. However, neither total reactive oxygen species was altered nor H 2 O 2 accumulation was observed in GNE mutant cell lines. Interestingly, ER redox state was significantly affected due to reduced normal GNE enzyme activity. Our study indicates that downregulation of PrdxIV affects ER redox state that may contribute to misfolding and aggregation of proteins in GNE myopathy.

Determinants of quality of life of patients with heart failure and iron deficiency treated with ferric carboxymaltose: FAIR-HF sub-analysis.

PubMed

Gutzwiller, Florian S; Pfeil, Alena M; Comin-Colet, Josep; Ponikowski, Piotr; Filippatos, Gerasimos; Mori, Claudio; Braunhofer, Peter G; Szucs, Thomas D; Schwenkglenks, Matthias; Anker, Stefan D

2013-10-09

Heart failure (HF) is a burden to patients and health care systems. The objectives of HF treatment are to improve health related quality of life (HRQoL) and reduce mortality and morbidity. We aimed to evaluate determinants of health-related quality of life (HRQoL) in patients with iron deficiency and HF treated with intravenous (i.v.) iron substitution or placebo. A randomised, double-blind, placebo-controlled trial (n = 459) in iron-deficient chronic heart failure (CHF) patients with or without anaemia studied clinical and HRQoL benefits of i.v. iron substitution using ferric carboxymaltose (FCM) over a 24-week trial period. Multivariate analysis was carried out with various clinical variables as independent variables and HRQoL measures as dependent variables. Mean change from baseline of European Quality of Life - 5 Dimensions (EQ-5D) (value set-based) utilities (on a 0 to 100 scale) at week 24 was 8.91 (i.v. iron) and 0.68 (placebo; p < 0.01). In a multivariate analysis excluding baseline HRQoL, a higher exercise tolerance and i.v. iron substitution positively influenced HRQoL, whereas impaired renal function and a history of stroke had a negative effect. The level of HRQoL was also influenced by country of residence. When baseline HRQoL was factored in, the multivariate model remained stable. In this study, i.v. iron substitution, exercise tolerance, stroke, country of residence and renal function influenced measures of HRQoL in patients with heart failure and iron deficiency. © 2013.

Examining the Role of Perioperative Nerve Blocks in Hip Arthroscopy: A Systematic Review.

PubMed

Kay, Jeffrey; de Sa, Darren; Memon, Muzammil; Simunovic, Nicole; Paul, James; Ayeni, Olufemi R

2016-04-01

This systematic review examined the efficacy of perioperative nerve blocks for pain control after hip arthroscopy. The databases Embase, PubMed, and Medline were searched on June 2, 2015, for English-language studies that reported on the use of perioperative nerve blocks for hip arthroscopy. The studies were systematically screened and data abstracted in duplicate. Nine eligible studies were included in this review (2 case reports, 2 case series, 3 non-randomized comparative studies, and 2 randomized controlled trials). In total, 534 patients (534 hips), with a mean age of 37.2 years, who underwent hip arthroscopy procedures were administered nerve blocks for pain management. Specifically, femoral (2 studies), fascia iliaca (2 studies), lumbar plexus (3 studies), and L1 and L2 paravertebral (2 studies) nerve blocks were used. All studies reported acceptable pain scores after the use of nerve blocks, and 4 studies showed significantly lower postoperative pain scores acutely with the use of nerve blocks over general anesthesia alone. The use of nerve blocks also resulted in a decrease in opioid consumption in 4 studies and provided a higher level of patient satisfaction in 2 studies. No serious acute complications were reported in any study, and long-term complications from lumbar plexus blocks, such as local anesthetic system toxicity (0.9%) and long-term neuropathy (2.8%), were low in incidence. The use of perioperative nerve blocks provides effective pain management after hip arthroscopy and may be more effective in decreasing acute postoperative pain and supplemental opioid consumption than other analgesic techniques. Level IV, systematic review of Level I to Level IV studies. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

The Combination of IV and Perineural Dexamethasone Prolongs the Analgesic Duration of Intercostal Nerve Blocks Compared with IV Dexamethasone Alone.

PubMed

Maher, Dermot P; Serna-Gallegos, Derek; Mardirosian, Rodney; Thomas, Otto J; Zhang, Xiao; McKenna, Robert; Yumul, Roya; Zhang, Vida

2017-06-01

 The use of multiple-level, single-injection intercostal nerve blocks for pain control following video-assisted thorascopic surgery (VATS) is limited by the analgesic duration of local anesthetics. This study examines whether the combination of perineural and intravenous (IV) dexamethasone will prolong the duration of intraoperatively placed intercostal nerve blocks following VATS compared with IV dexamethasone and a perineural saline placebo.  Prospective, double-blind, randomized placebo-controlled trial.  Single level-1 academic trauma center.  Forty patients undergoing a unilateral VATS under the care of a single surgeon.  Patients were randomly assigned to two groups and received an intercostal nerve block containing 1) 0.5% bupivacaine with epinephrine and 1 ml of 0.9% saline or 2) 0.5% bupivacaine with epinephrine and 1 ml of a 4 mg/ml dexamethasone solution. All patients received 8 mg of IV dexamethasone.  Group 2 had lower NRS-11 scores at post-operative hours 8 (5.05, SD = 2.13 vs 3.50, SD = 2.50; p  = 0.04), 20 (4.30, SD = 2.96 vs 2.26, SD = 2.31; p  = 0.02), and 24 (4.53, SD = 1.95 vs 2.26, SD = 2.31; p  = 0.02). Equianalgesic opioid requirement was decreased in group 2 at 32 hours (5.78 mg, SD = 5.77 vs 1.67 mg, SD = 3.49; p  = 0.02). Group 2 also had greater FEV1 measured at 8, 12, 24, and 44 hours; greater FVC at 24 hours; greater PEF at 28 through 48 hours; and greater FEV1/FVC at 8 and 36 hours.  The combination of IV and perineural dexamethasone prolonged the duration of a single-injection bupivacaine intercostal nerve block as measured by NRS-11 compared with IV dexamethasone alone at 24 hours. Reduced NRS-11 at other times, reduced opioid requirements, and increased PFTs were observed in group 2. © 2016 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

Complications of wrist arthroscopy.

PubMed

Ahsan, Zahab S; Yao, Jeffrey

2012-06-01

The purpose of this systematic review was to address the incidence of complications associated with wrist arthroscopy. Given the paucity of information published on this topic, an all-inclusive review of published wrist arthroscopy complications was sought. Two independent reviewers performed a literature search using PubMed, Google Scholar, EBSCO, and Academic Megasearch using the terms "wrist arthroscopy complications," "complications of wrist arthroscopy," "wrist arthroscopy injury," and "wrist arthroscopy." Inclusion criteria were (1) Levels I to V evidence, (2) "complication" defined as an adverse outcome directly related to the operative procedure, and (3) explicit description of operative complications in the study. Eleven multiple-patient studies addressing complications of wrist arthroscopy from 1994 to 2010 were identified, with 42 complications reported from 895 wrist arthroscopy procedures, a 4.7% complication rate. Four case reports were also found, identifying injury to the dorsal sensory branch of the ulnar nerve, injury to the posterior interosseous nerve, and extensor tendon sheath fistula formation. This systematic review suggests that the previously documented rate of wrist arthroscopy complications may be underestimating the true incidence. The report of various complications provides insight to surgeons for improving future surgical techniques. Level IV, systematic review of Levels I-V studies. Copyright © 2012 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Extracellular chloride signals collagen IV network assembly during basement membrane formation

PubMed Central

Cummings, Christopher F.; Pedchenko, Vadim; Brown, Kyle L.; Colon, Selene; Rafi, Mohamed; Jones-Paris, Celestial; Pokydeshava, Elena; Liu, Min; Pastor-Pareja, Jose C.; Stothers, Cody; Ero-Tolliver, Isi A.; McCall, A. Scott; Vanacore, Roberto; Bhave, Gautam; Santoro, Samuel; Blackwell, Timothy S.; Zent, Roy; Pozzi, Ambra

2016-01-01

Basement membranes are defining features of the cellular microenvironment; however, little is known regarding their assembly outside cells. We report that extracellular Cl− ions signal the assembly of collagen IV networks outside cells by triggering a conformational switch within collagen IV noncollagenous 1 (NC1) domains. Depletion of Cl− in cell culture perturbed collagen IV networks, disrupted matrix architecture, and repositioned basement membrane proteins. Phylogenetic evidence indicates this conformational switch is a fundamental mechanism of collagen IV network assembly throughout Metazoa. Using recombinant triple helical protomers, we prove that NC1 domains direct both protomer and network assembly and show in Drosophila that NC1 architecture is critical for incorporation into basement membranes. These discoveries provide an atomic-level understanding of the dynamic interactions between extracellular Cl− and collagen IV assembly outside cells, a critical step in the assembly and organization of basement membranes that enable tissue architecture and function. Moreover, this provides a mechanistic framework for understanding the molecular pathobiology of NC1 domains. PMID:27216258

Physiochemical Characteristics and Molecular Structures for Digestible Carbohydrates of Silages.

PubMed

Refat, Basim; Prates, Luciana L; Khan, Nazir A; Lei, Yaogeng; Christensen, David A; McKinnon, John J; Yu, Peiqiang

2017-10-18

The main objectives of this study were (1) to assess the magnitude of differences among new barley silage varieties (BS) selected for varying rates of in vitro neutral detergent fiber (NDF) digestibility (ivNDFD; Cowboy BS with higher ivNDFD, Copeland BS with intermediate ivNDFD, and Xena BS with lower ivNDFD) with regard to their carbohydrate (CHO) molecular makeup, CHO chemical fractions, and rumen degradability in dairy cows in comparison with a new corn silage hybrid (Pioneer 7213R) and (2) to quantify the strength and pattern of association between the molecular structures and digestibility of carbohydrates. The carbohydrate-related molecular structure spectral data was measured using advanced vibrational molecular spectroscopy (FT/IR). In comparison to BS, corn silage showed a significantly (P < 0.05) higher level of starch and energy content and higher degradation of dry matter (DM). Cowboy BS had lower feeding value (higher indigestible fiber content and lower starch content) and lower DM degradation in the rumen compared to other BS varieties (P < 0.05). The spectral intensities of carbohydrates were significantly (P < 0.05) correlated with digestible carbohydrate content of the silages. In conclusion, the univariate approach with only one-factor consideration (ivNDFD) might not be a satisfactory method for evaluating and ranking BS quality. FT/IR molecular spectroscopy can be used to evaluate silage quality rapidly, particularly the digestible fiber content.

Perioperative haemostatic management of haemophilic mice using normal mouse plasma.

PubMed

Tatsumi, K; Ohashi, K; Kanegae, K; Shim, I K; Okano, T

2013-11-01

Intense haemostatic interventions are required to avoid bleeding complications when surgical procedures are performed on haemophilia patients. The objective of this study was to establish an appropriate protocol for perioperative haemostatic management of haemophilic mice. We assessed the prophylactic haemostatic effects of normal mouse plasma (NMP) on haemophilia B (HB) mice for both a skin flap procedure and a laparotomy. When 500 μL of NMP was administered to the mice, plasma factor IX (FIX:C) levels peaked at 15.1% immediately after intravenous (IV) administration, at 6.1% 2 h after intraperitoneal (IP) administration and at 2.7% 6 h after subcutaneous administration. Administering 500 μL of NMP via IP or IV 30 min in advance enabled the skin flap procedure to be performed safely without any complications. After the laparotomy procedure, several mice in the IP administration group exhibited lethal bleeding, but all mice survived in the IV administration group. Anti-mouse FIX inhibitors did not develop, even after repetitive administrations of NMP. However, human FIX concentrates, especially plasma-derived concentrates, elicited the anti-human FIX inhibitors. The results show that administering 500 μL of NMP via IV or IP 30 min in advance enables surgical procedures to be safely performed on HB mice, and that IV administration is more desirable than IP if the procedure requires opening of the abdominal wall. © 2013 John Wiley & Sons Ltd.

Alterations in IgG subclasses in acquired immune deficiency syndrome.

PubMed

Outschoorn, I M; Lluberes, R; Natta, C L

1989-01-01

Decreased IgG subclass levels in pyogenic infections and immunocompromised situations have been described. A study was made to determine IgG subclass levels in four groups of 68 Hispanic patients. The first group consisted of 25 terminal patients with AIDS, the second group of 20 i.v. drug abusers, and the third group of eight hospital patients with neither a diagnosis of AIDS/ARC nor a history of i.v. drug abuse. IgG subclass levels of these 53 cases were compared with those of a fourth group of 15 normal controls. The total IgG, IgA, and IgM levels as well as the four IgG subclass concentrations were measured by radial immunodiffusion using appropriate standards and specific antisera. The first two groups had similar values, with an average IgG level of 10.37 g/liter; IgA, 2.68; and IgM, 1.78; subclass levels were IgG1, 6.68 g/liter; IgG2, 2.77; IgG3, 0.34; and IgG4, 0.68. These were significantly lower than those of controls, except for IgG4. Determination of minor subclasses may offer some possibilities for immunomodulation and therapy and could be useful in terms of prognosis.

Changes in the serum lipid profile in man during 24 months of arctic residence.

PubMed

Bojko, E R; Larsen, T S

1999-07-01

The influence of the severe climate and geographical conditions at the Svalbard archipelago (78-79 degrees N) on serum lipid levels were measured in Caucasian miners who had arrived from the southern part of Ukraine and Russia (48 degrees N). The persons included in the study were randomly divided in five groups according to their time of living (1, 3, 6, 12 and 24 months) at Svalbard. Blood sampling took place during a two week period in January, when the Svalbard archipelago is into its polar night. General elevated levels of triglycerides were found in group I-III (1, 3 and 6 months stay), whereas the values measured in group IV and V (12 and 24 months stay) were somewhat lower. This apparent decline in triglycerides was paralelled by generally elevated levels of HDL cholesterol. The serum level of phospholipids was similar in all groups. All the level of free fatty acids was apparently higher in groups IV and V, particularly 18:3 and 16:1. These results may be indicative of a rise in triglyceride consumption after about a 12 month stay in the archipelago. Besides, the elevated levels of 18:3 and 16:1 fatty acids imply dietary modifications of the serum fatty acids.

High-Performance Reaction Wheel Optimization for Fine-Pointing Space Platforms: Minimizing Induced Vibration Effects on Jitter Performance plus Lessons Learned from Hubble Space Telescope for Current and Future Spacecraft Applications

NASA Technical Reports Server (NTRS)

Hasha, Martin D.

2016-01-01

The Hubble Space Telescope (HST) applies large-diameter optics (2.5-m primary mirror) for diffraction-limited resolution spanning an extended wavelength range (approx. 100-2500 nm). Its Pointing Control System (PCS) Reaction Wheel Assemblies (RWAs), in the Support Systems Module (SSM), acquired an unprecedented set of high-sensitivity Induced Vibration (IV) data for 5 flight-certified RWAs: dwelling at set rotation rates. Focused on 4 key ratios, force and moment harmonic values (in 3 local principal directions) are extracted in the RWA operating range (0-3000 RPM). The IV test data, obtained under ambient lab conditions, are investigated in detail, evaluated, compiled, and curve-fitted; variational trends, core causes, and unforeseen anomalies are addressed. In aggregate, these values constitute a statistically-valid basis to quantify ground test-to-test variations and facilitate extrapolations to on-orbit conditions. Accumulated knowledge of bearing-rotor vibrational sources, corresponding harmonic contributions, and salient elements of IV key variability factors are discussed. An evolved methodology is presented for absolute assessments and relative comparisons of macro-level IV signal magnitude due to micro-level construction-assembly geometric details/imperfections stemming from both electrical drive and primary bearing design parameters. Based upon studies of same-size/similar-design momentum wheels' IV changes, upper estimates due to transitions from ground tests to orbital conditions are derived. Recommended HST RWA choices are discussed relative to system optimization/tradeoffs of Line-Of-Sight (LOS) vector-pointing focal-plane error driven by higher IV transmissibilities through low-damped structural dynamics that stimulate optical elements. Unique analytical disturbance results for orbital HST accelerations are described applicable to microgravity efforts. Conclusions, lessons learned, historical context/insights, and perspectives on future applications are given; these previously unpublished data and findings represents a valuable resource for fine-pointing spacecraft or space-based platforms using RWAs, Control Moment Gyros (CMGs), Momentum Wheels, or other ball-bearing-based rotational units.

Very low density lipoprotein triglyceride transport in type IV hyperlipoproteinemia and the effects of carbohydrate-rich diets.

PubMed

Quarfordt, S H; Frank, A; Shames, D M; Berman, M; Steinberg, D

1970-12-01

Transport of plasma-free fatty acids (FFA) and of fatty acids in triglycerides of plasma very low density lipoproteins (VLDL-TGFA) was studied in two normal subjects, five patients with type IV hyperlipoproteinemia, and two patients with type I hyperlipoproteinemia. After intravenous pulse-labeling with albumin-bound 1-palmitate-(14)C, specific radioactivity of plasma FFA and VLDL-TGFA were determined at intervals up to 24 hr. The results were analyzed using several different multicompartmental models each compatible with the experimental data. Fractional transport of VLDL-TGFA was distinctly lower (no overlap) in the type IV patients than in the control subjects, both on a usual balanced diet (40% of calories from carbohydrate) and on a high-carbohydrate diet (80% of calories). However, net or total transport of VLDL-TGFA in the type IV patients was not clearly distinguishable from that in the control subjects, there being considerable overlap on either diet. The results suggest that in this group of type IV patients the underlying defect leading to the increased pool size of VLDL-TGFA is not overproduction but a relative defect in mechanisms for removal of VLDL-TGFA. Since some of these type IV patients had only a moderate degree of hypertriglyceridemia at the time they were studied, and since it is not established that patients with the type IV phenotype constitute a biochemically homogeneous population, the present results should not be generalized. Four studies were done (in two control subjects and two type IV patients) in which the kinetic parameters in the same individual were determined on the balanced diet and on the high-carbohydrate diet. All subjects showed an increase in VLDL-TGFA pool size. Using two of the models for analysis, all showed an increase in net transport of VLDL-TGFA; using the third model, three of the four studies showed an increase in VLDL-TGFA transport. The results are compatible with the interpretation that the carbohydrate-induced increase in VLDL-TGFA, both in controls and type IV patients, is at least in part due to an increased rate of production of VLDL-TGFA. The magnitude of the increase was approximately the same in controls and patients. Thus, metabolic adjustment to a high-carbohydrate regimen in these type IV patients may not be basically different from that in normal controls; the higher levels of VLDL-TGFA reached may simply be another reflection of a defective removal mechanism. An alternative interpretation, compatible with the data, would involve both a carbohydrate-induced increase in fractional rate of release of VLDL-TGFA from liver to plasma and a decrease in fractional removal of VLDL-TGFA from plasma without increase in net production rate. The simpler hypothesis of a single primary effect on net VLDL-TGFA production from FFA seems more likely.

Electromagnetic field enhancement effects in group IV semiconductor nanowires. A Raman spectroscopy approach

NASA Astrophysics Data System (ADS)

Pura, J. L.; Anaya, J.; Souto, J.; Prieto, A. C.; Rodríguez, A.; Rodríguez, T.; Periwal, P.; Baron, T.; Jiménez, J.

2018-03-01

Semiconductor nanowires (NWs) are the building blocks of future nanoelectronic devices. Furthermore, their large refractive index and reduced dimension make them suitable for nanophotonics. The study of the interaction between nanowires and visible light reveals resonances that promise light absorption/scattering engineering for photonic applications. Micro-Raman spectroscopy has been used as a characterization tool for semiconductor nanowires. The light/nanowire interaction can be experimentally assessed through the micro-Raman spectra of individual nanowires. As compared to both metallic and dielectric nanowires, semiconductor nanowires add additional tools for photon engineering. In particular, one can grow heterostructured nanowires, both axial and radial, and also one could modulate the doping level and the surface condition among other factors than can affect the light/NW interaction. We present herein a study of the optical response of group IV semiconductor nanowires to visible photons. The study is experimentally carried out through micro-Raman spectroscopy of different group IV nanowires, both homogeneous and axially heterostructured (SiGe/Si). The results are analyzed in terms of the electromagnetic modelling of the light/nanowire interaction using finite element methods. The presence of axial heterostructures is shown to produce electromagnetic resonances promising new photon engineering capabilities of semiconductor nanowires.

(2S,4S)-4-Fluoro-1-{[(2-hydroxy-1,1-dimethylethyl)amino]acetyl}-pyrrolidine-2-carbonitrile monobenzenesulfonate (TS-021) is a selective and reversible dipeptidyl peptidase IV inhibitor.

PubMed

Tajima, Atsushi; Yamamoto, Koji; Kozakai, Akinori; Okumura-Kitajima, Lisa; Mita, Yasuo; Kitano, Kiyokazu; Jingu, Shigeji; Nakaike, Shiro

2011-03-25

The incretin hormone glucagon-like peptide-1 (GLP-1) has significant roles in the regulation of postprandial glucose metabolism, and the active form of GLP-1 is rapidly degraded by dipeptidyl peptidase (DPP)-IV. Therefore, DPP-IV inhibition is a promising approach for the treatment of type 2 diabetes. In the present study, we investigated the character of a DPP-IV inhibitor, TS-021, (2S, 4S)-4-fluoro-1-{[(2-hydroxy-1,1-dimethylethyl)amino]acetyl}-pyrrolidine-2-carbonitrile monobenzenesulfonate both in vitro and in vivo. TS-021 inhibits DPP-IV activity in human plasma with an IC(50) value of 5.34nM. In kinetics experiments, TS-021 had a relatively higher dissociation rate constant, with a k(off) value of 1.09×10(-3)s, despite exhibiting a potent human plasma DPP-IV inhibition activity with a K(i) value of 4.96nM. TS-021 exhibited significant inhibition selectivity against DPP-8 (>600 fold), DPP-9 (>1200 fold) and other peptidases examined (>15,000 fold). In normal rats, dogs and monkeys, a single oral dose of TS-021 exhibited favorable pharmacokinetic profiles. In Zucker fatty (fa/fa) rats, a rat model of obesity and impaired glucose tolerance, the oral administration of TS-021 resulted in the suppression of plasma DPP-IV activity and an increase in the active form of GLP-1. Furthermore, TS-021 exhibited a significant improvement in glucose tolerance by increasing the plasma insulin level during oral glucose tolerance tests at doses of 0.02-0.5mg/kg. These results suggest that TS-021 is a selective and reversible dipeptidyl peptidase IV inhibitor and has excellent characteristics as an oral anti-diabetic agent for postprandial hyperglycemia in patients with impaired glucose tolerance or type 2 diabetes. Copyright © 2011 Elsevier B.V. All rights reserved.

Childhood trauma in the lives of substance-dependent patients: The relationship between depression, anxiety and self-esteem.

PubMed

Ekinci, Suat; Kandemir, Hasan

2015-05-01

High levels of childhood traumatic experiences have been observed among substance abusers. There has been insufficient study of the effects of childhood trauma in adulthood. The aim of this study is to research the relationship between childhood trauma, self-esteem, and levels of depression and anxiety in substance-dependent (SD) people. This study took place between March 2012 and April 2013, at Balıklı Rum Hospital (Istanbul) substance dependency clinic. It included 50 patients diagnosed as substance dependent according to the criteria of DSM-IV as compared with 45 healthy controls. The Structured Clinical Interview for DSM-IV Diagnosis (SCID-I) was used to identify Axis I disorders. All other data was collected using a semi-structured socio-demographic questionnaire, the Childhood Trauma Questionnaire (CTQ), the Rosenberg Self Esteem Scale (RSES), the Beck Depression Inventory (BDI) and the Beck Anxiety Inventory (BAI). The total scores of the SD group on the CTQ and on its Emotional Abuse/Emotional Neglect (EA/EN), Physical Abuse (PA) and Sexual Abuse (SA) subscales were statistically significant. In relation to the healthy controls, the SD group scored higher on the RSES, BDI and BAI. A correlation was observed between the total scores of SD individuals on the CTQ and their scores on the RSES, BDI and BAI. This study showed high levels of childhood traumatic experiences for SD people and indicates that there may be a relationship between these experiences and their levels of self-esteem, depression and anxiety.

Factors affecting response and tolerability to ferumoxytol in nondialysis chronic kidney disease patients.

PubMed

Fishbane, Steven; Bolton, W Kline; Winkelmayer, Wolfgang C; Strauss, William; Li, Zhu; Pereira, Brian J G

2012-09-01

Ferumoxytol is a unique intravenous (i.v.) iron therapy. This report examines factors affecting hemoglobin response to i.v. ferumoxytol, and the relationship between hematologic parameters, concomitant erythropoiesis-stimulating agents (ESA), and adverse events (AEs) in nondialysis CKD patients. A series of post-hoc efficacy and safety analyses were performed using pooled data from two identically designed Phase III studies in 608 nondialysis CKD patients randomized to receive two 510 mg i.v. injections of ferumoxytol within 5 ± 3 days versus oral iron. Ferumoxytol resulted in a significant increase in hemoglobin in the presence and absence of ESA, and across a range of baseline hemoglobin, transferrin saturation, ferritin, and reticulocyte hemoglobin content levels. Adverse event rates with ferumoxytol were similar across quartiles of change in hemoglobin; there were no trends suggesting an increased rate of cardiovascular AEs with higher maximum achieved hemoglobin or faster rate of hemoglobin rise. There was no meaningful difference in the rate of AEs, serious AEs, and cardiovascular AEs between patients receiving or not receiving ESA. These analyses add to the knowledge of predictors of response and safety outcomes associated with i.v. iron therapy in nondialysis CKD patients.

The pharmacokinetics of intraosseous atropine in hypovolemic swine.

PubMed

Yost, Jonathan; Baldwin, Phillip; Bellenger, Sarah; Bradshaw, Freida; Causapin, Edna; Demotica, Richelle; Livingston, Michael; Lee, Cynthia; Gegel, Brian; Burgert, James; Claessens, Adam; Johnson, Don; Loughren, Michael

2015-01-01

Compare the pharmacokinetics of atropine administered via the intravenous (IV), intramuscular (IM), and intraosseous (IO) routes in a normovolemic and hypovolemic swine model. Prospective, between subjects, experimental study. Vivarium. Yorkshire-cross swine (N = 36). Atropine was administered via IV, IM, or IO routes to normovolemic and hypovolemic swine. Blood samples were drawn at regular intervals after atropine administration and analyzed for plasma atropine concentration. Pharmacokinetic parameters were obtained from modeling the plasma concentrations. Pharmacokinetic parameters, maximum concentration (Cmax) and time to maximum concentration (Tmax). The IV and IO groups in both the normovolemic and hypovolemic models reached peak plasma concentration immediately and had a very rapid distribution phase with no apparent absorption phase for the IO groups. Peak plasma concentration and time to reach peak concentration were both significantly lower for the IM groups. There was a significant increase in absorption time with IM administration in the hypovolemic model compared to the normovolemic model. The IO route is an effective method of administering atropine and is comparable to the IV route even under conditions of significant hemorrhage. Therapeutic levels of atropine may be delayed and possibly difficult to obtain via IM injection in the presence of hypovolemic shock.

Contrary melanoma-associated antigen-A expression at the tumor front and center: A comparative analysis of stage I and IV head and neck squamous cell carcinoma

PubMed Central

Hartmann, Stefan; Brisam, Muna; Rauthe, Stephan; Driemel, Oliver; Brands, Roman C.; Rosenwald, Andreas; Kübler, Alexander C.; Müller-Richter, Urs D. A.

2016-01-01

There is a growing body of evidence indicating that several melanoma-associated antigen-A (MAGE-A) subgroups contribute to the malignancy of head and neck cancer. The present study retrospectively analyzed the expression of all known MAGE-A subgroups in the tumor front and center of 38 head and neck cancer patients (Union for International Cancer Control stage I or IV) by immunohistochemistry. MAGE-A1, -A6, -A8, -A9 and -A11 were expressed at significantly higher levels at the tumor front of stage IV specimens compared with the tumor front of stage I specimens. In stage I cancer, the tumor center and front ratio (C/F ratio) for each subgroup was >1.0. In stage IV cancer, the C/F ratio was <1.0 in 9/11 subgroups. The most significant change in the expression pattern was observed for MAGE-A11. These results indicated that there is a marked alteration and shift to the invasive front of almost all MAGE-A subgroups, but particularly MAGE-A11, during the progression of head and neck squamous cell carcinoma. PMID:27703530

Peer deviance, social support, and symptoms of internalizing disorders among youth exposed to Hurricane Georges.

PubMed

Rubens, Sonia L; Vernberg, Eric M; Felix, Erika D; Canino, Glorisa

2013-01-01

This study examined the influence of peers in meeting DSM-IV symptom criteria for an internalizing disorder in adolescents exposed to Hurricane Georges. Participants included a representative community sample of 905 youth (n = 476 boys) ages 11-17, residing in Puerto Rico. Data were gathered on hurricane exposure, symptoms of internalizing disorders, peer social support, peer violence, and peer substance use through in-person structured interviews with adolescents and caretakers from 1999 to 2000 in Puerto Rico, 12-27 months after Hurricane Georges. Hurricane exposure, peer violence, and peer substance use predicted whether adolescents met DSM-IV symptom criteria for a measured internalizing disorder. An interaction was found between hurricane exposure and peer violence, which indicated that hurricane exposure was significantly related to meeting DSM-IV symptom criteria for an internalizing disorder among adolescents who do not report associating with violent peers. However, for participants who reported high levels of peer violence, hurricane exposure did not convey additional risk for meeting DSM-IV symptom criteria for an internalizing disorder. With the increasing role peers play in adolescents' lives, understanding the influence of peers on the development of internalizing symptoms following hurricane exposure may assist in planning developmentally sensitive response plans.

Assessing the clinical utility of agoraphobia in the context of panic disorder.

PubMed

Schmidt, Norman B; Cromer, Kiara R

2008-01-01

In the DSM-IV, a panic disorder (PD) diagnosis includes specification of agoraphobia, which is primarily an index of situational avoidance due to fear of panic. No other anxiety diagnosis requires specification of level of avoidance. This raises the question as to whether agoraphobia provides unique information beyond the core features of PD (i.e., panic attacks and panic-related worry). The incremental validity of agoraphobia, defined using DSM-IV specifiers versus level of situational avoidance, was examined in relation to the expression and treatment of PD (N=146). Analyses indicate that agoraphobia status adds uniquely to the prediction of PD symptoms, impairment, and response to treatment. However, level of situational avoidance, defined either as a continuous or dichotomous variable, appears to have greater utility compared to the DSM-IV method of classifying agoraphobia. In summary, the agoraphobia specifier seems to have clinical utility but this could be improved by focusing on a dimensional assessment of situational avoidance.

Distribution of Flunixin Residues in Muscles of Dairy Cattle Dosed with Lipopolysaccharide or Saline and Treated with Flunixin by Intravenous or Intramuscular Injection.

PubMed

Shelver, Weilin L; Schneider, Marilyn J; Smith, David J

2016-12-28

Twenty dairy cows received flunixin meglumine at 2.2 mg/kg bw, administered once daily by either the intravenous (IV) or intramuscular (IM) route for three consecutive days with either intravenous normal saline (NS) or lipopolysaccharide (LPS) providing a balanced design with five animals per group. Cows were sacrificed after a 4 day withdrawal period, and 13 muscle types were collected and assayed for flunixin by LC-MS/MS. After elimination of sample outliers, the main effects of route of administration (IV or IM), treatment (NS or LPS), and tissue type significantly (P < 0.05) affected flunixin residues, with no interaction (P > 0.05). Intramuscular (nonlabel) flunixin administration produced greater (P < 0.05) flunixin residues in muscle than the IV (label) administration, whereas LPS resulted in lower flunixin levels. Differences among the tissue levels indicate it is necessary to specify the tissue to be used for any monitoring of drug levels for consumer protection.

Revision Hip Arthroscopy: A Systematic Review of Diagnoses, Operative Findings, and Outcomes.

PubMed

Cvetanovich, Gregory L; Harris, Joshua D; Erickson, Brandon J; Bach, Bernard R; Bush-Joseph, Charles A; Nho, Shane J

2015-07-01

To determine indications for, operative findings of, and outcomes of revision hip arthroscopy. A systematic review was registered with PROSPERO and performed based on PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Therapeutic clinical outcome studies reporting the indications for, operative findings of, and outcomes of revision hip arthroscopy were eligible for inclusion. All study-, patient-, and hip-specific data were extracted and analyzed. The Modified Coleman Methodology Score was used to assess study quality. Five studies were included (348 revision hip arthroscopies; 333 patients; mean age, 31.4 ± 4.2 years; 60% female patients). All 5 studies were either Level III or IV evidence. The surgeon performing revision hip arthroscopy was the same as the primary hip surgeon in only 25% of cases. The mean time between primary and revision hip arthroscopy was 27.8 ± 7.0 months (range, 2 to 193 months). Residual femoroacetabular impingement was the most common indication for and operative finding of revision hip arthroscopy (81% of cases). The most commonly reported revision procedures were femoral osteochondroplasty (24%) and acetabuloplasty (18%). The modified Harris Hip Score was used in all 5 analyzed studies, with significant (P < .05) improvements observed in all 5 studies (weighted mean, 56.8 ± 3.6 preoperatively v 72.0 ± 8.3 at final follow-up [22.4 ± 9.8 months]; P = .01). Other patient-reported outcomes (Non-Arthritic Hip Score, Hip Outcome Score, 33-item International Hip Outcome Tool, Short Form 12) showed significant improvements but were not used in all 5 analyzed studies. After revision hip arthroscopy, subsequent reported operations were hip arthroplasty in 11 patients and re-revision hip arthroscopy in 8 patients (5% total reoperation rate). Revision hip arthroscopy is most commonly performed for residual femoroacetabular impingement, with statistically significant and clinically relevant improvements shown in multiple patient-reported clinical outcome scores at short-term follow-up. The reoperation rate after revision hip arthroscopy is 5% within 2 years, including further arthroscopy or conversion to hip arthroplasty. Level IV, systematic review of Level III and IV studies. Copyright © 2015 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

A Prospective Randomized Controlled Trial of Nonpharmacological Pain Management During Intravenous Cannulation in a Pediatric Emergency Department.

PubMed

Miller, Kate; Tan, Xianghong; Hobson, Andrew Dillon; Khan, Asaduzzaman; Ziviani, Jenny; OʼBrien, Eavan; Barua, Kim; McBride, Craig A; Kimble, Roy M

2016-07-01

Intravenous (IV) cannulation is commonly performed in pediatric emergency departments (EDs). The busy ED environment is often not conducive to conventional nonpharmacological pain management. This study assessed the use of Ditto (Diversionary Therapy Technologies, Brisbane, Australia), a handheld electronic device which provides procedural preparation and distraction, as a means of managing pain and distress during IV cannulation performed in the pediatric ED. A randomized controlled trial with 98 participants, aged 3 to 12 years, was conducted in a pediatric ED. Participants were recruited and randomized into 5 intervention groups as follows: (1) Standard Distraction, (2) PlayStation Portable Distraction, (3) Ditto Distraction, (4) Ditto Procedural Preparation, and (5) Ditto Preparation and Distraction. Children's pain and distress levels were assessed via self-reports and observational reports by caregivers and nursing staff across the following 3 time points: (1) before, (2) during, and (3) after IV cannulation. Caregivers and nursing staff reported significantly reduced pain and distress levels in children accessing the combined preparation and distraction Ditto protocol, as compared to standard distraction (P ≤ 0.01). This intervention also saw the greatest reduction in pain and distress as reported by the child. Caregiver reports indicate that using the combined Ditto protocol was most effective in reducing children's pain experiences while undergoing IV cannulation in the ED. The use of Ditto offers a promising opportunity to negotiate barriers to the provision of nonpharmacological approaches encountered in the busy ED environment, and provide nonpharmacological pain-management interventions in pediatric EDs.

Does Prop-2-ynylideneamine, HC≡CCH=NH, Exist in Space? A Theoretical and Computational Investigation

PubMed Central

Osman, Osman I.; Elroby, Shaaban A.; Aziz, Saadullah G.; Hilal, Rifaat H.

2014-01-01

MP2, DFT and CCSD methods with 6-311++G** and aug-cc-pvdz basis sets have been used to probe the structural changes and relative energies of E-prop-2-ynylideneamine (I), Z-prop-2-ynylideneamine (II), prop-1,2-diene-1-imine (III) and vinyl cyanide (IV). The energy near-equivalence and provenance of preference of isomers and tautomers were investigated by NBO calculations using HF and B3LYP methods with 6-311++G** and aug-cc-pvdz basis sets. All substrates have Cs symmetry. The optimized geometries were found to be mainly theoretical method dependent. All elected levels of theory have computed I/II total energy of isomerization (ΔE) of 1.707 to 3.707 kJ/mol in favour of II at 298.15 K. MP2 and CCSD methods have indicated clearly the preference of II over III; while the B3LYP functional predicted nearly similar total energies. All tested levels of theory yielded a global II/IV tautomerization total energy (ΔE) of 137.3–148.4 kJ/mol in support of IV at 298.15 K. The negative values of ΔS indicated that IV is favoured at low temperature. At high temperature, a reverse tautomerization becomes spontaneous and II is preferred. The existence of II in space was debated through the interpretation and analysis of the thermodynamic and kinetic studies of this tautomerization reaction and the presence of similar compounds in the Interstellar Medium (ISM). PMID:24950178

The transport systems of Ventricaria ventricosa: hypotonic and hypertonic turgor regulation.

PubMed

Bisson, M A; Beilby, M J

2002-11-01

The time course of hypertonic and hypotonic turgor regulation was studied in Ventricaria (Valonia) using pressure probe and I/V(current-voltage) analysis. Of 11 cells, 9 exhibited hypertonic turgor regulation, ranging from 100% regulation in 150 min to 14% regulation (14% recovery of the decrease in turgor) in 314 min. Some cells began regulating immediately, others took up to 90 min to begin. The resting PD (potential difference) became more positive in most cells. The I/V characteristics became more nonlinear with high resistance between -150 and -20 mV and negative conductance region near -70 mV. Prolonged (16 sec) voltage clamps to negative levels (-100 to -150 mV) showed progressively more rapid current turn-off, but subsequent I/V characteristics were not affected. Clamping to +150 mV, however, abolished the high conductance between -50 and +100 mV to yield a uniform high resistance I/V characteristic, similar to that in high [K+]o. Decreasing illumination from 2.02 micromol sec(-1) m(-2) to 0.5 micromol sec(-1)1 m(-2) had a similar effect. Two out of a total of three cells exhibited hypotonic turgor regulation. Both cells started regulating within minutes and achieved near 50% regulation within 50 min. The PD became more negative. The I/V curves exhibited high resistance between +50 and +150 mV. The characteristics were similar to those in cells exposed to low [K+]o. Prolonged voltage clamps to both negative and positive levels showed slow current increase. Decreased illumination increased the membrane resistance.

Validity of a simpler definition of major depressive disorder.

PubMed

Zimmerman, Mark; Galione, Janine N; Chelminski, Iwona; Young, Diane; Dalrymple, Kristy; Witt, Caren Francione

2010-10-01

In previous reports from the Rhode Island Methods to Improve Diagnostic Assessment and Services project, we developed a briefer definition of major depressive disorder (MDD), and found high levels of agreement between the simplified and DSM-IV definitions of MDD. The goal of the present study was to examine the validity of the simpler definition of MDD. We hypothesized that compared to patients with adjustment disorder, patients with MDD would be more severely depressed, have poorer psychosocial functioning, have greater suicidal ideation at the time of the intake evaluation, and have an increased morbid risk for depression in their first-degree family members. We compared 1,486 patients who met the symptom criteria for current MDD according to either DSM-IV or the simpler definition to 145 patients with a current diagnosis of adjustment disorder with depressed mood or depressed and anxious mood. The patients with MDD were more severely depressed, more likely to have missed time from work due to psychiatric reasons, reported higher levels of suicidal ideation, and had a significantly higher morbid risk for depression in their first-degree family members. Both definitions of MDD were valid. The simpler definition of MDD was as valid as the DSM-IV definition. This new definition offers two advantages over the DSM-IV definition-it is briefer and therefore more likely to be recalled and applied in clinical practice, and it is free of somatic symptoms thereby making it easier to apply with medically ill patients. Depression and Anxiety, 2010. © 2010 Wiley-Liss, Inc.

Demethylation regulation of BDNF gene expression in dorsal root ganglion neurons is implicated in opioid-induced pain hypersensitivity in rats.

PubMed

Chao, Yu-Chieh; Xie, Fang; Li, Xueyang; Guo, Ruijuan; Yang, Ning; Zhang, Chen; Shi, Rong; Guan, Yun; Yue, Yun; Wang, Yun

2016-07-01

Repeated administration of morphine may result in opioid-induced hypersensitivity (OIH), which involves altered expression of numerous genes, including brain-derived neurotrophic factor (BDNF) in dorsal root ganglion (DRG) neurons. Yet, it remains unclear how BDNF expression is increased in DRG neurons after repeated morphine treatment. DNA methylation is an important mechanism of epigenetic control of gene expression. In the current study, we hypothesized that the demethylation regulation of certain BDNF gene promoters in DRG neurons may contribute to the development of OIH. Real-time RT-PCR was used to assess changes in the mRNA transcription levels of major BDNF exons including exon I, II, IV, VI, as well as total BDNF mRNA in DRGs from rats after repeated morphine administration. The levels of exon IV and total BDNF mRNA were significantly upregulated by repeated morphine administration, as compared to that in saline control group. Further, ELISA array and immunocytochemistry study revealed a robust upregulation of BDNF protein expression in DRG neurons after repeated morphine exposure. Correspondingly, the methylation levels of BDNF exon IV promoter showed a significant downregulation by morphine treatment. Importantly, intrathecal administration of a BDNF antibody, but not control IgG, significantly inhibited mechanical hypersensitivity that developed in rats after repeated morphine treatment. Conversely, intrathecal administration of an inhibitor of DNA methylation, 5-aza-2'-deoxycytidine (5-aza-dC) markedly upregulated the BDNF protein expression in DRG neurons and enhanced the mechanical allodynia after repeated morphine exposure. Together, our findings suggest that demethylation regulation of BDNF gene promoter may be implicated in the development of OIH through epigenetic control of BDNF expression in DRG neurons. Copyright © 2016 Elsevier Ltd. All rights reserved.

Lipoprotein(a) levels are associated with aortic valve calcification in asymptomatic patients with familial hypercholesterolaemia.

PubMed

Vongpromek, R; Bos, S; Ten Kate, G-J R; Yahya, R; Verhoeven, A J M; de Feyter, P J; Kronenberg, F; Roeters van Lennep, J E; Sijbrands, E J G; Mulder, M T

2015-08-01

Lipoprotein(a) [Lp(a)] is an independent risk factor for aortic valve stenosis and aortic valve calcification (AVC) in the general population. In this study, we determined the association between AVC and both plasma Lp(a) levels and apolipoprotein(a) [apo(a)] kringle IV repeat polymorphisms in asymptomatic statin-treated patients with heterozygous familial hypercholesterolaemia (FH). A total of 129 asymptomatic heterozygous FH patients (age 40-69 years) were included in this study. AVC was detected using computed tomography scanning. Lp(a) concentration and apo(a) kringle IV repeat number were measured using immunoturbidimetry and immunoblotting, respectively. Univariate and multivariate logistic regression were used to assess the association between Lp(a) concentration and the presence of AVC. Aortic valve calcification was present in 38.2% of patients, including three with extensive AVC (>400 Agatston units). Lp(a) concentration was significantly correlated with gender, number of apo(a) kringle IV repeats and the presence and severity of AVC, but not with coronary artery calcification (CAC). AVC was significantly associated with plasma Lp(a) level, age, body mass index, blood pressure, duration of statin use, cholesterol-year score and CAC score. After adjustment for all significant covariables, plasma Lp(a) concentration remained a significant predictor of AVC, with an odds ratio per 10-mg dL(-1) increase in Lp(a) concentration of 1.11 (95% confidence interval 1.01-1.20, P = 0.03). In asymptomatic statin-treated FH patients, plasma Lp(a) concentration is an independent risk indicator for AVC. © 2014 The Association for the Publication of the Journal of Internal Medicine.

Development of alternate paragraphs for the Logical Memory subtest of the Wechsler Memory Scale-IV.

PubMed

Morris, Jeri; Swier-Vosnos, Amy; Woodworth, Craig; Umfleet, Laura Glass; Czipri, Sheena; Kopald, Brandon

2014-01-01

The purpose of the two studies included in this article was to validate an alternate form, the Morris Revision-Fourth Edition (MR-IV), to the Logical Memory paragraphs of the Wechsler Memory Scale-Fourth Edition (LM-IV) for use when retesting of individuals is desired. Study I demonstrated high correlation with the LM-IV paragraphs. Study II was a replication that again demonstrated high correlation between the original LM-IV and the new MR-IV paragraphs. High interrater reliability also was demonstrated. Consequently, the MR-IV paragraphs can be considered an alternate form to the LM-IV paragraphs. Although other attempts have been made to develop alternate stories, these new paragraphs are the only ones that are equivalent in structure, affective tone, and number of scorable units. They have considerable clinical utility and research potential.

Characterization of SNF472 pharmacokinetics and efficacy in uremic and non-uremic rats models of cardiovascular calcification

PubMed Central

Ferrer, Miguel D.; Ketteler, Markus; Tur, Fernando; Tur, Eva; Isern, Bernat; Salcedo, Carolina; Joubert, Pieter H.; Behets, Geert J.; Neven, Ellen; D’Haese, Patrick C.

2018-01-01

End-stage renal disease is strongly associated with progressive cardiovascular calcification (CVC) and there is currently no therapy targeted to treat CVC. SNF472 is an experimental formulation under development for treatment of soft tissue calcification. We have investigated the pharmacokinetics of SNF472 administration in rats and its inhibitory effects on CVC. SNF472 was studied in three rat models: (1) prevention of vitamin D3-induced CVC with an intravenous SNF472 bolus of 1 mg/kg SNF472, (2) inhibition of progression of vitamin D3-induced CVC with a subcutaneous SNF472 bolus of 10 or 60 mg/kg SNF472, starting after calcification induction, (3) CVC in adenine-induced uremic rats treated with 50 mg/kg SNF472 via i.v. 4h -infusion. Uremic rats presented lower plasma levels of SNF472 than control animals after i.v. infusion. CVC in non-uremic rats was inhibited by 60–70% after treatment with SNF472 and progression of cardiac calcification completely blocked. Development of CVC in uremic rats was inhibited by up to 80% following i.v. infusion of SNF472. SNF472 inhibits the development and progression of CVC in uremic and non-uremic rats in the same range of SNF472 plasma levels but using in each case the required dose to obtain those levels. These results collectively support the development of SNF472 as a novel therapeutic option for treatment of CVC in humans. PMID:29742152

Perceived preparedness for physiatric specialization and future career goals of graduating postgraduate year IV residents during the 2004-2005 academic year.

PubMed

Raj, Vishwa S; Rintala, Diana H

2007-12-01

The purpose of this study was to evaluate trends among postgraduate year (PGY) IV physiatry residents, at the time of graduation from residency, in terms of their perceived experiences in the core clinical areas, confidence with procedural subspecialization, choice in career specialization, and desire to pursue clinical fellowship. Surveys were distributed to 386 PGY IV residents in physiatry at the end of the 2004-2005 academic year. Ninety-three residents (24%) completed responses in a confidential manner. Residents who were generally more confident in core clinical areas, as defined by the Self-Assessment Examination, and specialty prescription writing also believed themselves to be more prepared to practice these topics in their careers. Overall levels of confidence and perceived preparedness correlated positively with months of training and negatively with the belief in the need for postresidency fellowship training to incorporate these areas into clinical practice. Positive correlations also existed among perceived levels of preparedness in performing various physiatric procedures. Statistically significant differences in levels of confidence and preparedness existed among geographic regions when evaluating core physiatric subject matter. Fifty-six percent of residents who responded planned to pursue fellowship training, and a majority of residents intended to perform interventional procedures and musculoskeletal medicine in their practices. These results provide insight into how trainees perceive their current clinical education. With validation of measures for confidence and preparedness, this survey may be useful as an adjunct resource for residency programs to evaluate their trainees.

Correlation of serum IgE levels and clinical manifestations in patients with actinic prurigo*

PubMed Central

Cuevas-Gonzalez, Juan Carlos; Lievanos-Estrada, Zahide; Vega-Memije, Maria Elisa; Hojyo-Tomoka, Maria Teresa; Dominguez-Soto, Luciano

2016-01-01

BACKGROUND: Actinic prurigo is an idiopathic photodermatosis, the pathophysiology of which has been hypothesized to involve subtype IV type b (Th2) hypersensitive response, whereby IL4, IL5, and IL13 are secreted and mediate the production of B cells, IgE, and IgG4. OBJECTIVES: To examine the association of serum IgE levels and the clinical severity of injuries. METHODS: This case-control study comprised patients with a clinical and histopathological diagnosis of actinic prurigo, as well as clinically healthy subjects, from whom 3cc of peripheral blood was taken for immunoassay. Cases were classified by lesion severity as mild, moderate, and severe. Descriptive statistics were analyzed, and chi-square test was performed. RESULTS: We included 21 actinic prurigo patients and 21 subjects without disease; 11 patients with actinic prurigo had elevated serum IgE levels, and 10 had low serum levels. Six actinic prurigo (AP) patients with elevated serum levels of IgE had moderate injuries, 4 had severe injuries, and 1 had minor injuries. Eight out of 10 patients with normal IgE levels presented with minor injuries in the clinical evaluation. The 21 controls did not have increased serum IgE levels. CONCLUSIONS: Elevated IgE levels are associated with moderate to severe clinical lesions, suggesting that actinic prurigo entails a type IV subtype b hypersensitivity response in which Th2 cells predominate. PMID:26982774

Cardiorespiratory parameters and their relation with gestational age and level of oral feeding skills in preterm infants.

PubMed

Yamamoto, Raquel Coube de Carvalho; Prade, Leila Sauer; Berwig, Luana Cristina; Weinmann, Angela Regina Maciel; Keske-Soares, Márcia

2016-01-01

To correlate cardiorespiratory parameters with gestational age and level of oral feeding skills in the first oral feeding in preterm infants. Study participants were 37 clinically stable preterm infants. Cardiorespiratory rate was assessed before and after introduction of oral feeding. The newborns were divided into three strata according to gestational age at birth. Oral skill was classified into four levels: I - low oral skill and low resistance to feeding; II - low oral skill and high resistance to feeding; III - high oral skill and low resistance to feeding; IV - high oral skill and high resistance to feeding. No difference was observed in heart and respiratory rate between the strata of gestational age at birth and between the levels of oral skill. Comparison between pre- and post-cardiorespiratory rates within each level of oral skill and stratum of gestational age showed difference between heart rate in the strata of gestational ages of 30 to 33 weeks and of 34 to 36 weeks, as well as between oral skill of levels I, II, and IV. With regard to the comparison between pre- and post- respiratory rates, difference was found in the oral skill of level I. Differences were observed between pre- and post-prandial cardiorespiratory rates regarding the first oral feeding, as well as between strata of gestational age at birth and levels of oral feeding skills.

Pharmacokinetics of aniracetam and its metabolites in rats.

PubMed

Ogiso, T; Iwaki, M; Tanino, T; Ikeda, K; Paku, T; Horibe, Y; Suzuki, H

1998-05-01

The pharmacokinetics of aniracetam (AP), a new cognitive performance enhancer, and its main metabolites was investigated after intravenous (iv) and oral administrations to rat. The plasma levels of AP, 4-p-anisamidobutyric acid (ABA), and p-anisic acid (AA) were determined simultaneously by the HPLC method. The plasma concentrations of the parent drug and ABA quickly declined in a biexponential manner, with rapid terminal decay and a small mean residence time. However, AA yielded nonlinearly high levels at the initial times and the plasma concentrations of 2-pyrrolidinone (PD) were sustained over a relatively long time. When AA was administered intravenously, nonlinearity of the plasma concentrations was also found at higher doses. To describe the time course of the plasma levels of AP and its metabolites after iv administration, a pharmacokinetic model with seven compartments was applied, which included 10 first-order rate constants and one Michaelis-Menten constant. An approximate fit was obtained between the observed and calculated curves based on the model, except for the plasma concentrations of ABA. The plasma concentration-time profiles of AP and its metabolites following oral administration of AP (50 and 100 mg/kg) were similar to those after iv dosing, with the exception of PD, which showed much lower plasma levels than those after iv administration. Elimination of AP and ABA was rapid after oral dosing, and the bioavailability of AP was extremely small (11.4 and 8.6%). As a result, AP was largely metabolized to ABA, AA, and PD in rat.

Jejunal wall triglyceride concentration of morbidly obese persons is lower in those with type 2 diabetes mellitus

PubMed Central

Soriguer, F.; García-Serrano, S.; Garrido-Sánchez, L.; Gutierrez-Repiso, C.; Rojo-Martínez, G.; Garcia-Escobar, E.; García-Arnés, J.; Gallego-Perales, J. L.; Delgado, V.; García-Fuentes, Eduardo

2010-01-01

The overproduction of intestinal lipoproteins may contribute to the dyslipidemia found in diabetes. We studied the influence of diabetes on the fasting jejunal lipid content and its association with plasma lipids and the expression of genes involved in the synthesis and secretion of these lipoproteins. The study was undertaken in 27 morbidly obese persons, 12 of whom had type 2 diabetes mellitus (T2DM). The morbidly obese persons with diabetes had higher levels of chylomicron (CM) triglycerides (P < 0.001) and apolipoprotein (apo)B48 (P = 0.012). The jejunum samples obtained from the subjects with diabetes had a lower jejunal triglyceride content (P = 0.012) and angiopoietin-like protein 4 (ANGPTL4) mRNA expression (P = 0.043). However, the apoA-IV mRNA expression was significantly greater (P = 0.036). The jejunal triglyceride content correlated negatively with apoA-IV mRNA expression (r = −0.587, P = 0.027). The variables that explained the jejunal triglyceride content in a multiple linear regression model were the insulin resistance state and the apoA-IV mRNA expression. Our results show that the morbidly obese subjects with diabetes had lower jejunal lipid content and that this correlated negatively with apoA-IV mRNA expression. These findings show that the jejunum appears to play an active role in lipid homeostasis in the fasting state. PMID:20855567

Residence time effects on technetium reduction in slag-based cementitious materials.

PubMed

Arai, Yuji; Powell, Brian A; Kaplan, D I

2018-01-15

A long-term disposal of technetium-99 ( 99 Tc) has been considered in a type of cementitious formulation, slag-based grout, at the U.S. Department of Energy, Savannah River Site, Aiken SC, U.S.A. Blast furnace slag, which contains S and Fe electron donors, has been used in a mixture with fly ash, and Portland cement to immobilize 99 Tc(VII)O 4 - (aq) in low level radioactive waste via reductive precipitation reaction. However the long-term stability of Tc(IV) species is not clearly understood as oxygen gradually diffuses into the solid structure. In this study, aging effects of Tc speciation were investigated as a function of depth (<2.5cm) in slag-based grout using X-ray absorption spectroscopy. All of Fe(II) in solids was oxidized to Fe(III) after 117d. However, elemental S, sulfide, and sulfoxide persists at the 0-8mm depths even after 485d, suggesting the presence of a reduced zone below the surface few millimeters. Pertechnetate was successfully reduced to Tc(IV) after 29d. Distorted hydrolyzed Tc(IV) octahedral molecules were partially sulfidized and or polymerized at all depths (0-8mm) and were stable in 485d aged sample. The results of this study suggest that variable S species contribute to stabilize the partially sulfidized Tc(IV) species in aged slag-based grout. Copyright © 2017 Elsevier B.V. All rights reserved.

The Development of Concepts of Handicap in Adolescence: A Cross-Cultural Study. IV. The Rehabilitation of the Handicapped.

ERIC Educational Resources Information Center

Obani, Tim; Doherty, Jim

1987-01-01

Reports study examining the way in which age, sex, nationality, and attitude to the disabled affected the level of understanding achieved by a group of British and Nigerian adolescents about the rehabilitation of disabled individuals. Finds that age is the most important factor, sex somewhat important, and attitude not important. (Author/AEM)

Robust Requirements Tracing via Internet Search Technology: Improving an IV and V Technique. Phase 2

NASA Technical Reports Server (NTRS)

Hayes, Jane; Dekhtyar, Alex

2004-01-01

There are three major objectives to this phase of the work. (1) Improvement of Information Retrieval (IR) methods for Independent Verification and Validation (IV&V) requirements tracing. Information Retrieval methods are typically developed for very large (order of millions - tens of millions and more documents) document collections and therefore, most successfully used methods somewhat sacrifice precision and recall in order to achieve efficiency. At the same time typical IR systems treat all user queries as independent of each other and assume that relevance of documents to queries is subjective for each user. The IV&V requirements tracing problem has a much smaller data set to operate on, even for large software development projects; the set of queries is predetermined by the high-level specification document and individual requirements considered as query input to IR methods are not necessarily independent from each other. Namely, knowledge about the links for one requirement may be helpful in determining the links of another requirement. Finally, while the final decision on the exact form of the traceability matrix still belongs to the IV&V analyst, his/her decisions are much less arbitrary than those of an Internet search engine user. All this suggests that the information available to us in the framework of the IV&V tracing problem can be successfully leveraged to enhance standard IR techniques, which in turn would lead to increased recall and precision. We developed several new methods during Phase II; (2) IV&V requirements tracing IR toolkit. Based on the methods developed in Phase I and their improvements developed in Phase II, we built a toolkit of IR methods for IV&V requirements tracing. The toolkit has been integrated, at the data level, with SAIC's SuperTracePlus (STP) tool; (3) Toolkit testing. We tested the methods included in the IV&V requirements tracing IR toolkit on a number of projects.

Prospective Cohort Study Depending on the Use of Palliative Care for Advanced Stage of Cancer Patients

ClinicalTrials.gov

2017-09-05

Stage IV Breast Cancer; Stage IV Pancreatic Cancer; Stage IV Colon Cancer; Stage IV Gastric Cancer; Stage IV Lung Cancer; Stage IV Liver Cancer; Malignant Hematologic Neoplasm; Biliary Cancer Metastatic; Pediatric Leukemia; Pediatric Lymphoma; Pediatric Brain Tumor; Pediatric Solid Tumor

Fundamentals of Title IV Administration: From Applying to Creating Reports, 2003-2004.

ERIC Educational Resources Information Center

Office of Federal Student Aid (ED), Washington, DC.

This document provides a Fundamentals of Title IV Administration Workshop Agenda. The agenda includes an introduction and high level overview: the process in general; history of the programs; laws and regulations; and overview of the programs. Following this is a section on applying to participate and understand your school's responsibilities…

NARDAC Civilian DP Training: A Need for Management Attention.

DTIC Science & Technology

1982-12-01

POSITION DESCRIPTIONS ------------------------ 28 D. TRAINING ------------------------------------- 31 IV. NARDAC ORGANIZATIONAL DIAGNOSIS ------------------ 32...the production schedule. 31 IV. NARDAC ORGANIZATIONAL DIAGNOSIS The upper level manager of a highly sophisticated, production oriented ADP facility...14 September 1982. 22. Preziosi, R.C., " Organizational Diagnosis Questicnnaire", The 1990 Annual Handbook for Group Facilitators, p. 112, University

The Role of Dipeptidyl Peptidase IV in Lung Metastasis of Breast Cancer Cells

DTIC Science & Technology

1999-05-01

Our studies focused on (1) cloning and sequencing of wild-type endothelial DPP IV (wtDPP IV) and preparation of truncated DPP IV ( tDPP IV); (2...that was identical to hepatic DPP IV. Acid extraction of rat lung yielded a tDPP IV, which was an effective inhibitor of breast cancer cell adhesion to

Impaired complex IV activity in response to loss of LRPPRC function can be compensated by mitochondrial hyperfusion

PubMed Central

Rolland, Stéphane G.; Motori, Elisa; Memar, Nadin; Hench, Jürgen; Frank, Stephan; Winklhofer, Konstanze F.; Conradt, Barbara

2013-01-01

Mitochondrial morphology changes in response to various stimuli but the significance of this is unclear. In a screen for mutants with abnormal mitochondrial morphology, we identified MMA-1, the Caenorhabditis elegans homolog of the French Canadian Leigh Syndrome protein LRPPRC (leucine-rich pentatricopeptide repeat containing). We demonstrate that reducing mma-1 or LRPPRC function causes mitochondrial hyperfusion. Reducing mma-1/LRPPRC function also decreases the activity of complex IV of the electron transport chain, however without affecting cellular ATP levels. Preventing mitochondrial hyperfusion in mma-1 animals causes larval arrest and embryonic lethality. Furthermore, prolonged LRPPRC knock-down in mammalian cells leads to mitochondrial fragmentation and decreased levels of ATP. These findings indicate that in a mma-1/LRPPRC–deficient background, hyperfusion allows mitochondria to maintain their functions despite a reduction in complex IV activity. Our data reveal an evolutionary conserved mechanism that is triggered by reduced complex IV function and that induces mitochondrial hyperfusion to transiently compensate for a drop in the activity of the electron transport chain. PMID:23878239

[MK-801 or DNQX reduces electroconvulsive shock-induced impairment of learning-memory and hyperphosphorylation of Tau in rats].

PubMed

Liu, Chao; Min, Su; Wei, Ke; Liu, Dong; Dong, Jun; Luo, Jie; Liu, Xiao-Bin

2012-08-25

This study explored the effect of the excitatory amino acid receptor antagonists on the impairment of learning-memory and the hyperphosphorylation of Tau protein induced by electroconvulsive shock (ECT) in depressed rats, in order to provide experimental evidence for the study on neuropsychological mechanisms improving learning and memory impairment and the clinical intervention treatment. The analysis of variance of factorial design set up two intervention factors which were the electroconvulsive shock (two level: no disposition; a course of ECT) and the excitatory amino acid receptor antagonists (three level: iv saline; iv NMDA receptor antagonist MK-801; iv AMPA receptor antagonist DNQX). Forty-eight adult Wistar-Kyoto (WKY) rats (an animal model for depressive behavior) were randomly divided into six experimental groups (n = 8 in each group): saline (iv 2 mL saline through the tail veins of WKY rats ); MK-801 (iv 2 mL 5 mg/kg MK-801 through the tail veins of WKY rats) ; DNQX (iv 2 mL 5 mg/kg DNQX through the tail veins of WKY rats ); saline + ECT (iv 2 mL saline through the tail veins of WKY rats and giving a course of ECT); MK-801 + ECT (iv 2 mL 5 mg/kg MK-801 through the tail veins of WKY rats and giving a course of ECT); DNQX + ECT (iv 2 mL 5 mg/kg DNQX through the tail veins of WKY rats and giving a course of ECT). The Morris water maze test started within 1 day after the finish of the course of ECT to evaluate learning and memory. The hippocampus was removed from rats within 1 day after the finish of Morris water maze test. The content of glutamate in the hippocampus of rats was detected by high performance liquid chromatography. The contents of Tau protein which included Tau5 (total Tau protein), p-PHF1(Ser396/404), p-AT8(Ser199/202) and p-12E8(Ser262) in the hippocampus of rats were detected by immunohistochemistry staining (SP) and Western blot. The results showed that ECT and the glutamate ionic receptor blockers (NMDA receptor antagonist MK-801 and AMPA receptor antagonist DNQX) induced the impairment of learning and memory in depressed rats with extended evasive latency time and shortened space exploration time. And the two factors presented a subtractive effect. ECT significantly up-regulated the content of glutamate in the hippocampus of depressed rats which were not affected by the glutamate ionic receptor blockers. ECT and the glutamate ionic receptor blockers did not affect the total Tau protein in the hippocampus of rats. ECT up-regulated the hyperphosphorylation of Tau protein in the hippocampus of depressed rats, while the glutamate ionic receptor blockers down-regulated it, and combination of the two factors presented a subtractive effect. Our results indicate that ECT up-regulates the content of glutamate in the hippocampus of depressed rats, which up-regulates the hyperphosphorylation of Tau protein resulting in the impairment of learning and memory in depressed rats.

The effect of curcumin and its nanoformulation on adjuvant-induced arthritis in rats.

PubMed

Zheng, Zhaoling; Sun, YanHua; Liu, Ziliang; Zhang, Mingqin; Li, Chunqing; Cai, Hui

2015-01-01

Rheumatoid arthritis (RA), induced by the prolonged inappropriate inflammatory responses, is one of the most prevalent of all chronic inflammatory joint diseases. Curcumin (CM), a yellow hydrophobic polyphenol derived from the herb turmeric, has various pharmacological activities against many chronic diseases and acts by inhibiting cell proliferation and metastasis and downregulating various factors, including nuclear factor kappa B, interleukin-1β and TNF-α. Given the pathogenesis of RA, we hypothesized that the drug also has antiarthritic effects. The aims of the present study included the following: 1) examining the therapeutic effect of CM administered via intravenous (iv) injection on RA and 2) formulating the drug into oil-water nanoemulsions (Ns) to overcome the low oral bioavailability of CM and achieve oral delivery of the drug. The effect of CM administered through iv injection on adjuvant-induced arthritis in rats was studied in terms of paw swelling, weight indices of the thymus and spleen, and pathological changes in nuclear factor kappa B expression and inflammatory cytokines. Methotrexate was used as a positive control. The CM-Ns were prepared using a high-pressure homogenizing method and characterized with respect to the particle size and morphology. The stability of the CM-Ns in simulated gastrointestinal (GI) fluids and in vitro release were also investigated. A pharmacokinetic study of the CM-Ns and suspensions in which the plasma levels were determined using an high performance liquid chromatography method and the pharmacokinetic parameters were calculated based on a statistical moment theory was also performed in rats. CM administered via iv injection had a therapeutic effect on RA similar to methotrexate. CM-Ns with a diameter of approximately 150 nm were successfully prepared, and the drug was well encapsulated into the Ns without degradation in simulated GI conditions. The area under the curve (AUC) and Cmax for the CM-Ns were more than threefold greater than those for the suspensions; moreover, similar decreases in the levels of TNF-α and interleukin-1β in both synovial fluid and blood serum were obtained from oral administration of CM-Ns and iv injection. CM was an effective antiarthritic agent, and the present N formulation appeared to be a promising system that allowed RA therapy with CM to be converted from iv to oral administration.

Enzymatic and microstructural changes in the liver of experimental rats fed with fatty diet and fresh or heated soy oil concurrently.

PubMed

Jaarin, K; Hwa, Tay Chin; Umar, Nor Aini; Siti Aishah, M A; Das, S

2010-01-01

Consumption of heated edible oils may be harmful. The present study aimed to observe the histological changes due to concurrent consumption of soy oil (either fresh or heated) and fatty diet and the changes in the level of alanine transaminase (ALT) and alkaline phosphatase (ALP). Forty female Spraque-Dawley rats were equally divided into four groups (I to IV). All the rats n groups II, III and IV were ovariectomised. Rats in group I (control) were fed with 2% cholesterol diet, whereas the rats in groups II, III and IV were fed with 2% cholesterol diet fortified with 15% weight/weight (w/w) fresh soy oil (FSO), once heated soy oil (1HSO) and five times heated soy oil (5HSO) respectively, for 16 weeks. Blood was taken for liver enzymes and analysed before and after 16 weeks of study. At the end of the study the animals were sacrificed, and the liver was examined histologically. The specimens were weighed, formalin fixed and the sections were stained with hematoxylin and eosin. Fresh, 1HSO and 5HSO soy oil caused significant increase in serum ALT and ALP compared to their base line values. Fresh, 1HSO and 5HSO soy oil caused microsteatosis, inflammation and necrosis of the liver tissues. However, there was no significant difference in the ALT and ALP enzyme levels amongst the oil fed groups. It is concluded that the effect of both fresh and heated soy oil on these parameters was not affected by repeated heating except for the inflammation.

Arthroscopic management of suprascapular neuropathy of the shoulder improves pain and functional outcomes with minimal complication rates.

PubMed

Memon, M; Kay, J; Ginsberg, L; Simunovic, N; Bak, K; Lapner, P; Ayeni, O R

2018-01-01

The purpose of this study was to systematically assess the arthroscopic management of suprascapular neuropathy, including the aetiology, surgical decision-making, clinical outcomes, and complications associated with the procedure. Three databases [PubMed, Ovid (Medline), and Embase] were searched. Systematic literature screening and data abstraction was performed in duplicate to present a review of studies reporting on arthroscopic management of suprascapular neuropathy. The quality of the included studies was assessed using level of evidence and the MINORS (Methodological Index for Nonrandomized Studies) checklist. In total, 40 studies (17 case reports, 20 case series, 2 retrospective comparative studies, and 1 prospective comparative study) were identified, including 259 patients (261 shoulders) treated arthroscopically for suprascapular neuropathy. The most common aetiology of suprascapular neuropathy was suprascapular nerve compression by a cyst at the spinoglenoid notch (42%), and the decision to pursue arthroscopic surgery was most commonly based on the results of clinical findings and investigations (47%). Overall, 97% of patients reported significant improvement in or complete resolution of their pre-operative symptoms (including pain, strength, and subjective function of the shoulder) over a mean follow-up period of 23.7 months. Further, there was a low overall complication rate (4%) associated with the arthroscopic procedures. While most studies evaluating arthroscopic management of suprascapular neuropathy are uncontrolled studies with lower levels of evidence, results indicate that such management provides patients with significant improvements in pain, strength, and subjective function of the shoulder, and has a low incidence of complications. Patients managed arthroscopically for suprascapular neuropathy may expect significant improvements in pain, strength, and subjective function of the shoulder. Level IV, systematic review of level II to IV studies.

Evaluation of who oral rehydration solution (ORS) and salt tablets in resuscitating adult patients with burns covering more than 15% of total body surface area (TBSA).

PubMed

Moghazy, A M; Adly, O A; Elbadawy, M A; Hashem, R E

2016-03-31

Intra-venous (IV) burn resuscitation is effective; nevertheless it has its disadvantages. WHO Oral Rehydration Solution (ORS) has shown high effectiveness in treating dehydration. WHO-ORS, with salt supplement, seems to be suitable for burn resuscitation, where IV resuscitation is not available, feasible or possible. The objective of the study was to evaluate acute phase efficacy and safety, as well as limitations and complications of burn resuscitation using WHO-ORS and salt tablets. This randomized controlled clinical trial was conducted in the Burn Unit, Suez Canal University Hospital, Ismailia, Egypt. The study group was given WHO-ORS (15% of body weight/day) with one salt tablet (5gm) per liter according to Sørensen's formula. The control group was given IV fluids according to the Parkland formula. Patients' vital signs and urine output were monitored for 72 hours after starting resuscitation. Both groups were comparable regarding age, sex, and percentage, etiology and degree of burns. For all assessed parameters, there were no major significant differences between the study group (10 cases) and control group (20 cases). Even where there was a significant difference, apart from blood pressure in the first hour of the first day, the study group never crossed safe limits for pulse, systolic blood pressure, urine output, respiratory rate and conscious level. WHO-ORS with 5gm salt tablets, given according to Sørenson's formula, is a safe and efficient alternative for IV resuscitation. It could even be a substitute, particularly in low resource settings and fire disasters.

Valine/isoleucine variants drive selective pressure in the VP1 sequence of EV-A71 enteroviruses.

PubMed

Duy, Nghia Ngu; Huong, Le Thi Thanh; Ravel, Patrice; Huong, Le Thi Song; Dwivedi, Ankit; Sessions, October Michael; Hou, Yan'An; Chua, Robert; Kister, Guilhem; Afelt, Aneta; Moulia, Catherine; Gubler, Duane J; Thiem, Vu Dinh; Thanh, Nguyen Thi Hien; Devaux, Christian; Duong, Tran Nhu; Hien, Nguyen Tran; Cornillot, Emmanuel; Gavotte, Laurent; Frutos, Roger

2017-05-08

In 2011-2012, Northern Vietnam experienced its first large scale hand foot and mouth disease (HFMD) epidemic. In 2011, a major HFMD epidemic was also reported in South Vietnam with fatal cases. This 2011-2012 outbreak was the first one to occur in North Vietnam providing grounds to study the etiology, origin and dynamic of the disease. We report here the analysis of the VP1 gene of strains isolated throughout North Vietnam during the 2011-2012 outbreak and before. The VP1 gene of 106 EV-A71 isolates from North Vietnam and 2 from Central Vietnam were sequenced. Sequence alignments were analyzed at the nucleic acid and protein level. Gene polymorphism was also analyzed. A Factorial Correspondence Analysis was performed to correlate amino acid mutations with clinical parameters. The sequences were distributed into four phylogenetic clusters. Three clusters corresponded to the subgenogroup C4 and the last one corresponded to the subgenogroup C5. Each cluster displayed different polymorphism characteristics. Proteins were highly conserved but three sites bearing only Isoleucine (I) or Valine (V) were characterized. The isoleucine/valine variability matched the clusters. Spatiotemporal analysis of the I/V variants showed that all variants which emerged in 2011 and then in 2012 were not the same but were all present in the region prior to the 2011-2012 outbreak. Some correlation was found between certain I/V variants and ethnicity and severity. The 2011-2012 outbreak was not caused by an exogenous strain coming from South Vietnam or elsewhere but by strains already present and circulating at low level in North Vietnam. However, what triggered the outbreak remains unclear. A selective pressure is applied on I/V variants which matches the genetic clusters. I/V variants were shown on other viruses to correlate with pathogenicity. This should be investigated in EV-A71. I/V variants are an easy and efficient way to survey and identify circulating EV-A71 strains.

Selective angiographic embolization of blunt splenic traumatic injuries in adults decreases failure rate of nonoperative management.

PubMed

Bhullar, Indermeet S; Frykberg, Eric R; Siragusa, Daniel; Chesire, David; Paul, Julia; Tepas, Joseph J; Kerwin, Andrew J

2012-05-01

To determine whether angioembolization (AE) in hemodynamically stable adult patients with blunt splenic trauma (BST) at high risk for failure of nonoperative management (NOM) (contrast blush [CB] on computed tomography, high-grade IV-V injuries, or decreasing hemoglobin) results in lower failure rates than reported. The records of patients with BST from July 2000 to December 2010 at a Level I trauma center were retrospectively reviewed using National Trauma Registry of the American College of Surgeons. Failure of NOM (FNOM) occurred if splenic surgery was required after attempted NOM. Logistic regression analysis was used to identify factors associated with FNOM. A total of 1,039 patients with BST were found. Pediatric patients (age <17 years), those who died in the emergency department, and those requiring immediate surgery for hemodynamic instability were excluded. Of the 539 (64% of all BST) hemodynamically stable patients who underwent NOM, 104 (19%) underwent AE and 435 (81%) were observed without AE (NO-AE). FNOM for the various groups were as follows: overall NOM (4%), NO-AE (4%), and AE (4%). There was no significant difference in FNOM for NO-AE versus AE for grades I to III: grade I (1% vs. 0%, p = 1), grade II (2% vs. 0%, p = 0.318), and grade III (5% vs. 0%, p = 0.562); however, a significant decrease in FNOM was noted with the addition of AE for grades IV to V: grade IV (23% vs. 3%, p = 0.04) and grade V (63% vs. 9%, p = 0.03). Statistically significant independent risk factors for FNOM were grade IV to V injuries and CB. Application of strictly defined selection criteria for NOM and AE in patients with BST resulted in one of the lowest overall FNOM rates (4%). Hemodynamically stable BST patients are candidates for NOM with selective AE for high-risk patients with grade IV to V injuries, CB on initial computed tomography, and/or decreasing hemoglobin levels. III, therapeutic study.

Multidrug resistance in epilepsy and polymorphisms in the voltage-gated sodium channel genes SCN1A, SCN2A, and SCN3A: correlation among phenotype, genotype, and mRNA expression.

PubMed

Kwan, Patrick; Poon, Wai Sang; Ng, Ho-Keung; Kang, David E; Wong, Virginia; Ng, Ping Wing; Lui, Colin H T; Sin, Ngai Chuen; Wong, Ka S; Baum, Larry

2008-11-01

Many antiepileptic drugs (AEDs) prevent seizures by blocking voltage-gated brain sodium channels. However, treatment is ineffective in 30% of epilepsy patients, which might, at least in part, result from polymorphisms of the sodium channel genes. We investigated the association of AED responsiveness with genetic polymorphisms and correlated any association with mRNA expression of the neuronal sodium channels. We performed genotyping of tagging and candidate single nucleotide polymorphisms (SNPs) of SCN1A, 2A, and 3A in 471 Chinese epilepsy patients (272 drug responsive and 199 drug resistant). A total of 27 SNPs were selected based on the HapMap database. Genotype distributions in drug-responsive and drug-resistant patients were compared. SCN2A mRNA was quantified by real-time PCR in 24 brain and 57 blood samples. Its level was compared between patients with different genotypes of an SCN2A SNP found to be associated with drug responsiveness. SCN2A IVS7-32A>G (rs2304016) A alleles were associated with drug resistance (odds ratio = 2.1, 95% confidence interval: 1.2-3.7, P=0.007). Haplotypes containing the IVS7-32A>G allele A were also associated with drug resistance. IVS7-32A>G is located within the putative splicing branch site for splicing exons 7 and 9. PCR of reverse-transcribed RNA from blood or brain of patients with different IVS7-32A>G genotypes using primers in exons 7 and 9 showed no skipping of exon 8, and real-time PCR showed no difference in SCN2A mRNA levels among genotypes. Results of this study suggest an association between SCN2A IVS7-32A>G and AED responsiveness, without evidence of an effect on splicing or mRNA expression.

Psychopathological characteristics of patients seeking for bariatric surgery, either affected or not by binge eating disorder following the criteria of the DSM IV TR and of the DSM 5.

PubMed

Vinai, Piergiuseppe; Da Ros, Annalisa; Speciale, Maurizio; Gentile, Nicola; Tagliabue, Anna; Vinai, Paolo; Bruno, Cecilia; Vinai, Luisa; Studt, Stacia; Cardetti, Silvia

2015-01-01

We evaluate whether there are any significant differences in psychopathology between severe obese patients affected by Binge Eating Disorder diagnosed following both the DSM IV TR and the DSM5 criteria, and severe obese patients not having an eating disorder. 118 severe obese patients seeking treatment at a center for bariatric surgery in northern Italy were asked to take part in the current study for a period of six months. Average participant age was 44.27 years, SD 12.42. Age ranged from 18 to 67 years. Average patient BMI was 45.03, SD 7.11, ranging from 32.14 to 66.16 kg/m(2). Seventy seven of the patients (65.3%) were females and 41 (34.7%) were males. BED diagnosis was determined following the diagnostic criteria of both the DSM IV TR and the DSM 5. The presence of other eating disorders was excluded through a clinical screening using the Eating Disorder Inventory (EDI). Patient eating habits and the presence of emotional eating were appraised using the Three-Factor Eating Questionnaire. Levels of depression and anxiety were evaluated using the Beck Depression Inventory and the State Trait Anxiety Inventory. 57 out of 118 patients were found to be affected by BED following the DSM 5 criteria; among them 24 followed those of the DSM IV TR. BED patients scored higher on four subscales of the Eating Disorders Inventory: Drive for thinness (DT), Bulimia (B), Body dissatisfaction (BD) and Interoceptive awareness (IA) on the STAI and on the Disinhibition and Hunger subscales of the TFEQ. The results confirm the presence of high levels of psychopathology among patients diagnosed with BED, even if they have been diagnosed following the criteria of the DSM 5. There is a great overlap in psychopathology between BED patients diagnosed following the DSM IV TR and the DSM 5 criteria. Copyright © 2014 Elsevier Ltd. All rights reserved.

Instrumental variable methods in comparative safety and effectiveness research†

PubMed Central

Brookhart, M. Alan; Rassen, Jeremy A.; Schneeweiss, Sebastian

2010-01-01

Summary Instrumental variable (IV) methods have been proposed as a potential approach to the common problem of uncontrolled confounding in comparative studies of medical interventions, but IV methods are unfamiliar to many researchers. The goal of this article is to provide a non-technical, practical introduction to IV methods for comparative safety and effectiveness research. We outline the principles and basic assumptions necessary for valid IV estimation, discuss how to interpret the results of an IV study, provide a review of instruments that have been used in comparative effectiveness research, and suggest some minimal reporting standards for an IV analysis. Finally, we offer our perspective of the role of IV estimation vis-à-vis more traditional approaches based on statistical modeling of the exposure or outcome. We anticipate that IV methods will be often underpowered for drug safety studies of very rare outcomes, but may be potentially useful in studies of intended effects where uncontrolled confounding may be substantial. PMID:20354968

Should Level V Be Routinely Dissected in N1b Papillary Thyroid Carcinoma?

PubMed

Kim, Seo Ki; Park, Inhye; Hur, Nayoon; Lee, Jun Ho; Choe, Jun-Ho; Kim, Jung-Han; Kim, Jee Soo

2017-02-01

For N1b papillary thyroid carcinoma (PTC) patients, modified radical neck dissection (MRND) encompassing levels II-V is generally recommended. However, routine level V dissection is controversial because of the low incidence of metastasis/recurrence in level V and the increased morbidities associated with level V dissection. This study retrospectively reviewed 646 N1b PTC patients who underwent unilateral MRND between January 1997 and June 2015. Specifically, to assess surgery-related outcomes of level V dissection, outcomes from N1b PTC patients who underwent unilateral MRND (levels II-V) were compared with those who underwent unilateral selective neck dissection (SND; levels II-IV) using propensity score matching. Overall and occult level V metastases were observed in 13.9% and 8.6% of patients, respectively. Level V recurrences were observed in only 2.26 (7.7%) recurred N1b PTC patients who underwent unilateral MRND. In multivariate analysis, three-level (II, III, and IV) simultaneous metastasis (adjusted odds ratio = 3.079, p = 0.003) was an independent predictor for level V metastasis. Under a matched condition, "shoulder syndrome" encompassing shoulder dysfunction and pain (9.1% vs. 2.7%, p = 0.002) was significantly more frequent in the MRND group than it was in the SND group. Because of the low incidence of metastasis/recurrence in level V and the clear evidence of increased morbidities, level V dissection in N1b PTC patients may be reserved for those with three-level simultaneous metastasis or clinically/radiologically evident level V metastasis.

Drosophila Neurexin IV Interacts with Roundabout and is Required for Repulsive Midline Axon Guidance

PubMed Central

Banerjee, Swati; Blauth, Kevin; Peters, Kimberly; Rogers, Stephen L.; Fanning, Alan S.; Bhat, Manzoor A.

2010-01-01

Slit/Roundabout (Robo) signaling controls midline repulsive axon guidance. However, proteins that interact with Slit/Robo at the cell surface remain largely uncharacterized. Here, we report that the Drosophila transmembrane septate junction-specific protein, Neurexin IV (Nrx IV), functions in midline repulsive axon guidance. Nrx IV is expressed in the neurons of the developing ventral nerve cord and nrx IV mutants show crossing and circling of ipsilateral axons and fused commissures. Interestingly, the axon guidance defects observed in nrx IV mutants seem independent of its other binding partners such as Contactin and Neuroglian and the midline glia protein Wrapper that interacts in trans with Nrx IV. nrx IV mutants show diffuse Robo localization and dose-dependent genetic interactions between nrx IV/robo and nrx IV/slit indicate that they function in a common pathway. In vivo biochemical studies reveal that Nrx IV associates with Robo, Slit and Syndecan, and interactions between Robo and Slit, or Nrx IV and Slit, are affected in nrx IV and robo mutants, respectively. Coexpression of Nrx IV and Robo in mammalian cells confirms that these proteins retain the ability to interact in a heterologous system. Furthermore, we demonstrate that the extracellular region of Nrx IV is sufficient to rescue Robo localization and axon guidance phenotypes in nrx IV mutants. Together our studies establish that Nrx IV is essential for proper Robo localization, and identify Nrx IV as a novel interacting partner of the Slit/Robo signaling pathway. PMID:20410118

Drosophila neurexin IV interacts with Roundabout and is required for repulsive midline axon guidance.

PubMed

Banerjee, Swati; Blauth, Kevin; Peters, Kimberly; Rogers, Stephen L; Fanning, Alan S; Bhat, Manzoor A

2010-04-21

Slit/Roundabout (Robo) signaling controls midline repulsive axon guidance. However, proteins that interact with Slit/Robo at the cell surface remain largely uncharacterized. Here, we report that the Drosophila transmembrane septate junction-specific protein Neurexin IV (Nrx IV) functions in midline repulsive axon guidance. Nrx IV is expressed in the neurons of the developing ventral nerve cord, and nrx IV mutants show crossing and circling of ipsilateral axons and fused commissures. Interestingly, the axon guidance defects observed in nrx IV mutants seem independent of its other binding partners, such as Contactin and Neuroglian and the midline glia protein Wrapper, which interacts in trans with Nrx IV. nrx IV mutants show diffuse Robo localization, and dose-dependent genetic interactions between nrx IV/robo and nrx IV/slit indicate that they function in a common pathway. In vivo biochemical studies reveal that Nrx IV associates with Robo, Slit, and Syndecan, and interactions between Robo and Slit, or Nrx IV and Slit, are affected in nrx IV and robo mutants, respectively. Coexpression of Nrx IV and Robo in mammalian cells confirms that these proteins retain the ability to interact in a heterologous system. Furthermore, we demonstrate that the extracellular region of Nrx IV is sufficient to rescue Robo localization and axon guidance phenotypes in nrx IV mutants. Together, our studies establish that Nrx IV is essential for proper Robo localization and identify Nrx IV as a novel interacting partner of the Slit/Robo signaling pathway.

Metal oxidation states in biological water splitting.

PubMed

Krewald, Vera; Retegan, Marius; Cox, Nicholas; Messinger, Johannes; Lubitz, Wolfgang; DeBeer, Serena; Neese, Frank; Pantazis, Dimitrios A

2015-03-01

A central question in biological water splitting concerns the oxidation states of the manganese ions that comprise the oxygen-evolving complex of photosystem II. Understanding the nature and order of oxidation events that occur during the catalytic cycle of five S i states ( i = 0-4) is of fundamental importance both for the natural system and for artificial water oxidation catalysts. Despite the widespread adoption of the so-called "high-valent scheme"-where, for example, the Mn oxidation states in the S 2 state are assigned as III, IV, IV, IV-the competing "low-valent scheme" that differs by a total of two metal unpaired electrons ( i.e. III, III, III, IV in the S 2 state) is favored by several recent studies for the biological catalyst. The question of the correct oxidation state assignment is addressed here by a detailed computational comparison of the two schemes using a common structural platform and theoretical approach. Models based on crystallographic constraints were constructed for all conceivable oxidation state assignments in the four (semi)stable S states of the oxygen evolving complex, sampling various protonation levels and patterns to ensure comprehensive coverage. The models are evaluated with respect to their geometric, energetic, electronic, and spectroscopic properties against available experimental EXAFS, XFEL-XRD, EPR, ENDOR and Mn K pre-edge XANES data. New 2.5 K 55 Mn ENDOR data of the S 2 state are also reported. Our results conclusively show that the entire S state phenomenology can only be accommodated within the high-valent scheme by adopting a single motif and protonation pattern that progresses smoothly from S 0 (III, III, III, IV) to S 3 (IV, IV, IV, IV), satisfying all experimental constraints and reproducing all observables. By contrast, it was impossible to construct a consistent cycle based on the low-valent scheme for all S states. Instead, the low-valent models developed here may provide new insight into the over-reduced S states and the states involved in the assembly of the catalytically active water oxidizing cluster.

Astragaloside IV inhibits pathological functions of gastric cancer-associated fibroblasts.

PubMed

Wang, Zhen-Fei; Ma, Da-Guang; Zhu, Zhe; Mu, Yong-Ping; Yang, Yong-Yan; Feng, Li; Yang, Hao; Liang, Jun-Qing; Liu, Yong-Yan; Liu, Li; Lu, Hai-Wen

2017-12-28

To investigate the inhibitory effect of astragaloside IV on the pathological functions of cancer-associated fibroblasts, and to explore the underlying mechanism. Paired gastric normal fibroblast (GNF) and gastric cancer-associated fibroblast (GCAF) cultures were established from resected tissues. GCAFs were treated with vehicle control or different concentrations of astragaloside IV. Conditioned media were prepared from GNFs, GCAFs, control-treated GCAFs, and astragaloside IV-treated GCAFs, and used to culture BGC-823 human gastric cancer cells. Proliferation, migration and invasion capacities of BGC-823 cells were determined by MTT, wound healing, and Transwell invasion assays, respectively. The action mechanism of astragaloside IV was investigated by detecting the expression of microRNAs and the expression and secretion of the oncogenic factor, macrophage colony-stimulating factor (M-CSF), and the tumor suppressive factor, tissue inhibitor of metalloproteinase 2 (TIMP2), in different groups of GCAFs. The expression of the oncogenic pluripotency factors SOX2 and NANOG in BGC-823 cells cultured with different conditioned media was also examined. GCAFs displayed higher capacities to induce BGC-823 cell proliferation, migration, and invasion than GNFs ( P < 0.01). Astragaloside IV treatment strongly inhibited the proliferation-, migration- and invasion-promoting capacities of GCAFs ( P < 0.05 for 10 μmol/L, P < 0.01 for 20 μmol/L and 40 μmol/L). Compared with GNFs, GCAFs expressed a lower level of microRNA-214 ( P < 0.01) and a higher level of microRNA-301a ( P < 0.01). Astragaloside IV treatment significantly up-regulated microRNA-214 expression ( P < 0.01) and down-regulated microRNA-301a expression ( P < 0.01) in GCAFs. Reestablishing the microRNA expression balance subsequently suppressed M-CSF production ( P < 0.01) and secretion ( P < 0.05), and elevated TIMP2 production ( P < 0.01) and secretion ( P < 0.05). Consequently, the ability of GCAFs to increase SOX2 and NANOG expression in BGC-823 cells was abolished by astragaloside IV. Astragaloside IV can inhibit the pathological functions of GCAFs by correcting their dysregulation of microRNA expression, and it is promisingly a potent therapeutic agent regulating tumor microenvironment.

Astragaloside IV inhibits pathological functions of gastric cancer-associated fibroblasts

PubMed Central

Wang, Zhen-Fei; Ma, Da-Guang; Zhu, Zhe; Mu, Yong-Ping; Yang, Yong-Yan; Feng, Li; Yang, Hao; Liang, Jun-Qing; Liu, Yong-Yan; Liu, Li; Lu, Hai-Wen

2017-01-01

AIM To investigate the inhibitory effect of astragaloside IV on the pathological functions of cancer-associated fibroblasts, and to explore the underlying mechanism. METHODS Paired gastric normal fibroblast (GNF) and gastric cancer-associated fibroblast (GCAF) cultures were established from resected tissues. GCAFs were treated with vehicle control or different concentrations of astragaloside IV. Conditioned media were prepared from GNFs, GCAFs, control-treated GCAFs, and astragaloside IV-treated GCAFs, and used to culture BGC-823 human gastric cancer cells. Proliferation, migration and invasion capacities of BGC-823 cells were determined by MTT, wound healing, and Transwell invasion assays, respectively. The action mechanism of astragaloside IV was investigated by detecting the expression of microRNAs and the expression and secretion of the oncogenic factor, macrophage colony-stimulating factor (M-CSF), and the tumor suppressive factor, tissue inhibitor of metalloproteinase 2 (TIMP2), in different groups of GCAFs. The expression of the oncogenic pluripotency factors SOX2 and NANOG in BGC-823 cells cultured with different conditioned media was also examined. RESULTS GCAFs displayed higher capacities to induce BGC-823 cell proliferation, migration, and invasion than GNFs (P < 0.01). Astragaloside IV treatment strongly inhibited the proliferation-, migration- and invasion-promoting capacities of GCAFs (P < 0.05 for 10 μmol/L, P < 0.01 for 20 μmol/L and 40 μmol/L). Compared with GNFs, GCAFs expressed a lower level of microRNA-214 (P < 0.01) and a higher level of microRNA-301a (P < 0.01). Astragaloside IV treatment significantly up-regulated microRNA-214 expression (P < 0.01) and down-regulated microRNA-301a expression (P < 0.01) in GCAFs. Reestablishing the microRNA expression balance subsequently suppressed M-CSF production (P < 0.01) and secretion (P < 0.05), and elevated TIMP2 production (P < 0.01) and secretion (P < 0.05). Consequently, the ability of GCAFs to increase SOX2 and NANOG expression in BGC-823 cells was abolished by astragaloside IV. CONCLUSION Astragaloside IV can inhibit the pathological functions of GCAFs by correcting their dysregulation of microRNA expression, and it is promisingly a potent therapeutic agent regulating tumor microenvironment. PMID:29358859

Low-Level Laser Irradiation Improves Depression-Like Behaviors in Mice.

PubMed

Xu, Zhiqiang; Guo, Xiaobo; Yang, Yong; Tucker, Donovan; Lu, Yujiao; Xin, Ning; Zhang, Gaocai; Yang, Lingli; Li, Jizhen; Du, Xiangdong; Zhang, Quanguang; Xu, Xingshun

2017-08-01

Major depressive disorder (MDD) is one of the leading forms of psychiatric disorders, characterized by aversion to mobility, neurotransmitter deficiency, and energy metabolic decline. Low-level laser therapy (LLLT) has been investigated in a variety of neurodegenerative disorders associated with mitochondrial dysfunction and functional impairments. The goal of this study was to examine the effect of LLLT on depression-like behaviors and to explore the potential mechanism by detecting mitochondrial function following LLLT. Depression models in space restriction mice and Abelson helper integration site-1 (Ahi1) knockout (KO) mice were employed in this work. Our results revealed that LLLT effectively improved depression-like behaviors, in the two depression mice models, by decreasing immobility duration in behavioral despair tests. In addition, ATP biosynthesis and the level of mitochondrial complex IV expression and activity were significantly elevated in prefrontal cortex (PFC) following LLLT. Intriguingly, LLLT has no effects on ATP content and mitochondrial complex I-IV levels in other tested brain regions, hippocampus and hypothalamus. As a whole, these findings shed light on a novel strategy of transcranial LLLT on depression improvement by ameliorating neurotransmitter abnormalities and promoting mitochondrial function in PFC. The present work provides concrete groundwork for further investigation of LLLT for depression treatment.

Transferable tight-binding model for strained group IV and III-V materials and heterostructures

NASA Astrophysics Data System (ADS)

Tan, Yaohua; Povolotskyi, Michael; Kubis, Tillmann; Boykin, Timothy B.; Klimeck, Gerhard

2016-07-01

It is critical to capture the effect due to strain and material interface for device level transistor modeling. We introduce a transferable s p3d5s* tight-binding model with nearest-neighbor interactions for arbitrarily strained group IV and III-V materials. The tight-binding model is parametrized with respect to hybrid functional (HSE06) calculations for varieties of strained systems. The tight-binding calculations of ultrasmall superlattices formed by group IV and group III-V materials show good agreement with the corresponding HSE06 calculations. The application of the tight-binding model to superlattices demonstrates that the transferable tight-binding model with nearest-neighbor interactions can be obtained for group IV and III-V materials.

NMA Analysis Center

NASA Technical Reports Server (NTRS)

Kierulf, Halfdan Pascal; Andersen, Per Helge

2013-01-01

The Norwegian Mapping Authority (NMA) has during the last few years had a close cooperation with Norwegian Defence Research Establishment (FFI) in the analysis of space geodetic data using the GEOSAT software. In 2012 NMA has taken over the full responsibility for the GEOSAT software. This implies that FFI stopped being an IVS Associate Analysis Center in 2012. NMA has been an IVS Associate Analysis Center since 28 October 2010. NMA's contributions to the IVS as an Analysis Centers focus primarily on routine production of session-by-session unconstrained and consistent normal equations by GEOSAT as input to the IVS combined solution. After the recent improvements, we expect that VLBI results produced with GEOSAT will be consistent with results from the other VLBI Analysis Centers to a satisfactory level.

Arthroscopy Up to Date: Hip Femoroacetabular Impingement.

PubMed

Khan, Moin; Habib, Anthony; de Sa, Darren; Larson, Christopher M; Kelly, Bryan T; Bhandari, Mohit; Ayeni, Olufemi R; Bedi, Asheesh

2016-01-01

To provide a comprehensive review and summary of the research published in Arthroscopy: The Journal of Arthroscopic and Related Surgery and The American Journal of Sports Medicine (AJSM) related to hip arthroscopy for femoroacetabular impingement (FAI). A comprehensive review was conducted in duplicate of Arthroscopy and AJSM from February 2012 to February 2015 for all articles related to FAI, and a quality assessment was completed for all included studies. Clinical outcomes were dichotomized into short-term (<6 months) and midterm (<24 months) outcomes, and values were pooled when possible. We identified 60 studies in Arthroscopy and 44 studies in AJSM, primarily from North America (78.8%), that predominantly assessed clinical outcomes after arthroscopic hip surgery (46.1%). Seventy-one percent of Arthroscopy studies and 20.5% of AJSM studies were Level IV evidence. The modified Harris Hip Score (mHHS) was used by 81.5% of included studies. Pooled weighted mean mHHS values after arthroscopic surgery for FAI showed improvements at the midterm from 60.5 points (range, 56.6 to 83.6 points) to 80.5 points (range, 72.1 to 98.0 points) out of a possible 100 points. Pooled weighted outcomes for labral repair showed mean mHHS improvements from 63.8 points (range, 62.5 to 69.0 points) preoperatively to 86.9 points (range, 85.5 to 89.9 points) up to 24 months postoperatively. This comprehensive review of research published in Arthroscopy and AJSM over the past 3 years identified a number of key findings. Arthroscopic intervention results in improvements in functional outcomes at both the short-term and midterm for patients with symptomatic FAI in the absence of significant existing degenerative changes. Labral repair may result in improvements over labral debridement. The most commonly used outcome score was the mHHS for objective assessment of surgical success. There is a need for continued focus on improvement of methodologic quality and reporting of research pertaining to FAI. Level IV, systematic review of Level IV studies. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Comparison of the Effect of Thiopental Sodium with Midazolam-ketamine on Post-tonsillectomy Agitation in Children.

PubMed

Toliyat, Maryam; Zangoee, Maliheh; Ahrari, Shahnaz; Zangoee, Reza

2015-10-01

The aim of this study was to determine the effect of thiopental sodium with that of midazolam-ketamine on relieving agitation after tonsillectomy in children. In a clinical trial, 50 children aged 5-10 years, candidates for tonsillectomy, were randomly divided into two 25-member groups. In the first group, thiopental sodium 5mg/kg/IV, and in the second group combination of midazolam 0.01 mg/kg/IV and ketamine 1 mg/kg/IV were used to induce anesthesia. The level of sedation was assessed after surgery with the Ramsay scale. There were no significant differences between the two groups in terms of heart rate, arterial oxygen pressure (PO2), and duration of anesthesia. The Ramsay sedation score was significantly higher in the thiopental sodium group than in the midazolam-ketamine group (P=0.01). Thiopental sodium can be more effective than the combination of midazolam-ketamine for controlling agitation after tonsillectomy in children.

Inelastic cotunneling with energy-dependent contact transmission

NASA Astrophysics Data System (ADS)

Blok, S.; Agundez Mojarro, R. R.; Maduro, L. A.; Blaauboer, M.; Van Der Molen, S. J.

2017-03-01

We investigate inelastic cotunneling in a model system where the charging island is connected to the leads through molecules with energy-dependent transmission functions. To study this problem, we propose two different approaches. The first is a pragmatic approach that assumes Lorentzian-like transmission functions that determine the transmission probability to the island. Using this model, we calculate current versus voltage (IV) curves for increasing resonance level positions of the molecule. We find that shifting the resonance energy of the molecule away from the Fermi energy of the contacts leads to a decreased current at low bias, but as bias increases, this difference decreases and eventually inverses. This is markedly different from IV behavior outside the cotunneling regime. The second approach involves multiple cotunneling where also the molecules are considered to be in the Coulomb blockade regime. We find here that when Ec≫eV ,kBT , the IV behavior approaches the original cotunneling behavior proposed by Averin and Nazarov [Phys. Rev. Lett. 65, 2446-2449 (1990)].

Vanadium-Binding Ability of Nucleoside Diphosphate Kinase from the Vanadium-Rich Fan Worm, Pseudopotamilla occelata.

PubMed

Yamaguchi, Nobuo; Yoshinaga, Masafumi; Kamino, Kei; Ueki, Tatsuya

2016-06-01

Polychaete fan worms and ascidians accumulate high levels of vanadium ions. Several vanadiumbinding proteins, known as vanabins, have been found in ascidians. However, no vanadium-binding factors have been isolated from the fan worm. In the present study, we sought to identify vanadiumbinding proteins in the branchial crown of the fan worm using immobilized metal ion affinity chromatography. A nucleoside diphosphate kinase (NDK) homolog was isolated and determined to be a vanadium-binding protein. Kinase activity of the NDK homologue, PoNDK, was suppressed by the addition of V(IV), but was unaffected by V(V). The effect of V(IV) on PoNDK precedes its activation by Mg(II). This is the first report to describe the relationship between NDK and V(IV). PoNDK is located in the epidermis of the branchial crown, and its distribution is very similar to that of vanadium. These results suggest that PoNDK is associated with vanadium accumulation and metabolism in P. occelata.

Dual hit lipopolysaccharide & oleic acid combination induced rat model of acute lung injury/acute respiratory distress syndrome.

PubMed

Hagawane, T N; Gaikwad, R V; Kshirsagar, N A

2016-05-01

Despite advances in therapy and overall medical care, acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) management remains a problem. Hence the objective of this study was to develop a rat model that mimics human ALI/ARDS. Four groups of Wistar rats, 48 per group were treated with (i) intratracheal (IT) lipopolysaccharide (LPS) (5 mg/kg) dissolved in normal saline (NS), (ii) intravenous (iv) oleic acid (OA) (250 μl/kg) suspension in bovine serum albumin (BSA), (iii) dual hit: IT LPS (2 mg/kg) dissolved in NS and iv OA (100 μl/kg) and (iv) control group: IT NS and iv BSA. From each group at set periods of time various investigations like chest x-rays, respiratory rate (RR), tidal volume (TV), total cell count, differential cell count, total protein count and cytokine levels in bronchoalveolar lavage fluid (BALF), lung wet/dry weight ratio and histopathological examination were done. It was noted that the respiratory rate, and tumour necrosis factor-α (TNF-α) levels were significantly higher at 4 h in the dual hit group as compared to LPS, OA and control groups. Interleukin-6 (IL-6) levels were significantly higher in the dual hit group as compared to LPS at 8 and 24 h, OA at 8 h and control (at all time intervals) group. IL-1β levels were significantly higher in LPS and dual hit groups at all time intervals, but not in OA and control groups. The injury induced in dual hit group was earlier and more sustained as compared to LPS and OA alone. The lung pathology and changes in respiration functions produced by the dual hit model were closer to the diagnostic criteria of ALI/ARDS in terms of clinical manifestations and pulmonary injury and the injury persisted longer as compared to LPS and OA single hit model. Therefore, the ARDS model produced by the dual hit method was closer to the diagnostic criteria of ARDS in terms of clinical manifestations and pulmonary injury.

Somatostatin receptor imaging in non-(131)I-avid metastatic differentiated thyroid carcinoma for determining the feasibility of peptide receptor radionuclide therapy with (177)Lu-DOTATATE: low fraction of patients suitable for peptide receptor radionuclide therapy and evidence of chromogranin A level-positive neuroendocrine differentiation.

PubMed

Jois, Bhargavi; Asopa, Ramesh; Basu, Sandip

2014-06-01

The aim of the study was to evaluate somatostatin receptor expression in non-I-concentrating metastatic differentiated thyroid carcinoma by Ga-DOTATATE PET-CT/Tc-HYNIC-TOC scintigraphy and to determine the feasibility of Lu-DOTATATE (therapeutic analog) therapy in cases with positive Ga-DOTATATE PET-CT/Tc-HYNIC-TOC scintigraphy. In this research study, 19 patients diagnosed with differentiated thyroid carcinoma with non-iodine-concentrating metastasis with elevated serum thyroglobulin levels, attending thyroid outpatient department for follow-up, underwent Ga-DOTATATE PET-CT/Tc-HYNIC-TOC scan for the evaluation of positivity of somatostatin receptor (SSTR). Based on the visual grading, SSTR-positive lesions were graded into 4 categories (grades I-IV) in comparison with the hepatic uptake on the scan. Patients with grades III and IV uptake in lesions (equal to or more than hepatic uptake on scan) were scheduled for Lu-DOTATATE administration. Posttherapy Lu-DOTATATE scan was undertaken during discharge from the isolation ward. Of the 19 patients studied, 12 patients (63%) showed SSTR-positive lesion expression demonstrating uptake ranging from grade I-IV, and 7 patients (37%) did not demonstrate any tracer uptake. On a lesion-specific analysis, of the total 57 metastatic lesions, 4 lesions (7%) demonstrated grade I tracer uptake, 18 lesions (31%) grade II (less than liver), 2 lesions (3.5%) grade III (equal to liver uptake), and 1 lesion showed grade IV uptake (more than liver). Interestingly, an elevated serum chromogranin A level was documented in 3 of the patients with grades III and IV tumor uptake. A comparison of Ga-DOTATATE PET-CT and Tc-HYNIC-TOC in 4 patients who underwent both the scans demonstrated no significant differences in the tracer concentration in the metastatic lesions in any of the patients on visual grading. Based on the criterion of high tracer uptake and the patient consent, finally 2 of 3 patients were treated with Lu-DOTATATE. On follow-up after 3 months, a significant fall in serum thyroglobulin level was noted in one of the patients, and the other patient was lost to follow-up. Avid expression of the SSTR on Ga-DOTATATE PET-CT/Tc-HYNIC-TOC scintigraphy in non-I-concentrating metastatic differentiated thyroid cancer is observed in a relatively low fraction of patients that could favor the feasibility of Lu-DOTATATE therapy. Although seen in a small fraction, taking into account that no treatment exists in this group, somatostatin receptor-targeted imaging can be an alternative diagnostic modality in the therapeutic decision making with peptide receptor radionuclide therapy and monitoring. The documentation of elevated serum chromogranin A level in 3 patients with intense tracer uptake could suggest a possible neuroendocrine differentiation in the affected tissues leading to the expression of chromogranin A along with SSTR-avid expression. This observation needs to be explored in future studies. No definite conclusions can be drawn on the therapeutic efficacy of the Lu-DOTATATE therapy in this group at present, and more prospective research is required in this area.

Exploring Wellness Interventions in Progressive Multiple Sclerosis: an Evidence-Based Review.

PubMed

Venasse, Myriam; Edwards, Thomas; Pilutti, Lara A

2018-04-10

There has been recent interest in the role of lifestyle and wellness-based approaches in the treatment and management of multiple sclerosis (MS). These approaches may be particularly relevant for patients with progressive MS, considering limited therapeutic options currently available. The purpose of this review is to examine the role of wellness-based interventions including exercise training, emotional well-being therapies, and dietary modification in patients with progressive MS. We conducted a literature search on the efficacy of wellness-based interventions in patients with progressive MS published between 1985 and July 2017. The level of evidence for each trial was evaluated using the American Academy of Neurology criteria. Overall, 21 articles reporting on 16 wellness-based interventions were identified: ten trials involved exercise training, three involved emotional wellness therapies, two involved dietary modification, and one was a combined wellness intervention. There is level C evidence (possibly effective; one class II study) for the efficacy of aerobic exercise training on cardiorespiratory fitness in patients with progressive MS. There is level B evidence (probably effective; one class I study) for the efficacy of mindfulness training on psychological distress, depression, anxiety, pain, and quality of life in patients with progressive MS. There is inadequate evidence (level U) for efficacy of dietary modification (one class III study and one class IV study) and combined wellness interventions involving exercise training, meditation, and dietary modification (one class IV study). High-quality research is needed to provide evidence-based recommendations for wellness behaviors and lifestyle change in patients with progressive MS.

Modification of pharmacokinetic and abuse-related effects of cocaine by human-derived cocaine hydrolase in monkeys

PubMed Central

Schindler, Charles W.; Justinova, Zuzana; Lafleur, David; Woods, Doug; Roschke, Viktor; Hallak, Hussein; Sklair-Tavron, Liora; Redhi, Godfrey H.; Yasar, Sevil; Bergman, Jack; Goldberg, Steven R.

2011-01-01

Although substantial research effort has focused on developing pharmacological treatments for cocaine abuse, no effective medications have been developed. Recent studies show that enzymes that metabolize cocaine in the periphery, forestalling its entry into the brain, can prevent cocaine toxicity and its behavioral effects in rodents. Here we report on effects of one such enzyme (Albu-CocH) on the pharmacokinetic and behavioral effects of cocaine in squirrel monkeys. Albu-CocH was developed from successive mutations of human butyrylcholinesterase (BChE) and has 1000-fold greater catalytic activity against cocaine than naturally occurring BChE. Pharmacokinetic studies showed that Albu-CocH (5 mg/kg) had a half-life of 56.6 hours in squirrel monkeys. In these studies, plasma levels of cocaine following i.v. 1 mg/kg cocaine were reduced two hours after administration of Albu-CocH, whereas plasma levels of the cocaine metabolite ecgonine methyl ester were increased. These effects were still evident 72 hrs following Albu-CocH administration. In behavioral experiments in monkeys, pretreatment with 5 mg/kg Albu-CocH dramatically decreased self-administration of a reinforcing dose of i.v. cocaine (30 μg/kg/injection) for over 24 hours. Pretreatment with 5 mg/kg Albu-CocH also attenuated the reinstatement of extinguished cocaine self-administration by an i.v. priming injection of cocaine (0.1 or 0.3 mg/kg) and, in separate studies, attenuated the discriminative stimulus effects of cocaine. The ability of Albu-CocH to attenuate the abuse-related effects of cocaine in squirrel monkeys indicates that further investigation of BChE mutants as potential treatment for cocaine abuse and toxicity is warranted. PMID:22264200

A field study on chemistry, S(IV) oxidation rates and vertical transport during fog conditions

NASA Astrophysics Data System (ADS)

Joos, F.; Baltensperger, U.

An extensive fog study was carried out in the central plateu of Switzerland. Ninety-seven fog samples were collected along with aerosol filter and cascade impactor samples, and measurements of O 3, SO 2, NO, NO x, PAN, temperature, and wind speed and direction. Maximum levels in fogwater were 4.3, 4.4., 0.033, 1.7, 0.5, 0.024 and 9.2 mmol ℓ -1 for Cl -, NO 3-, NO 2-, SO 42-, S(IV), oxalate and NH 4+, respectively. pH varied between 2.9 and 7.1. Sixteen additional elements were determined in the fog samples by ICP. The sum of the concentrations of SO 42- and S(IV) agreed very with the total sulfur concentration as determined by ICP. A substantial excess of S(IV) (up to 0.2 mmol ℓ -1) compared to Henry and acid-base equilibrium calculations was found, which can probably be attributed to complex formations with aldehydes. S(IV) oxidation rates of up to 650 nmol ℓ -1 s -1 with ozone and of up to 100 nmol ℓ -1 s -1 with NO 2 were calculated. S(IV) oxidation due to PAN, NO 2- and Fe(III) was of minor importance. A substantial fraction of the major ions was present in the intersitial aerosol (aerosol particles < 4 μm) even during fog conditions. High correlations were found for NH 4+, NO 32-. From their ratios in the fog water and the aerosol (< 4 μm) it could be concluded that at least 40% of NO 3- and 20% of NH 4+ in fog water was due to gas phase scavenging. Increasing concentrations in fog water were found during fog dissipation. Concentrations decreased with increasing height. A vertical transport model including turbulent diffusion and droplet sedimentation is introduced, which matches the experimental data of this vertical profile.

Determining the hospital trauma financial impact in a statewide trauma system.

PubMed

Mabry, Charles D; Kalkwarf, Kyle J; Betzold, Richard D; Spencer, Horace J; Robertson, Ronald D; Sutherland, Michael J; Maxson, Robert T

2015-04-01

There have been no comprehensive studies across an organized statewide trauma system using a standardized method to determine cost. Trauma financial impact includes the following costs: verification, response, and patient care cost (PCC). We conducted a survey of participating trauma centers (TCs) for federal fiscal year 2012, including separate accounting for verification and response costs. Patient care cost was merged with their trauma registry data. Seventy-five percent of the 2012 state trauma registry had data submitted. Each TC's reasonable cost from the Medicare Cost Report was adjusted to remove embedded costs for response and verification. Cost-to-charge ratios were used to give uniform PCC across the state. Median (mean ± SD) costs per patient for TC response and verification for Level I and II centers were $1,689 ($1,492 ± $647) and $450 ($636 ± $431) for Level III and IV centers. Patient care cost-median (mean ± SD) costs for patients with a length of stay >2 days rose with increasing Injury Severity Score (ISS): ISS <9: $6,787 ($8,827 ± $8,165), ISS 9 to 15: $10,390 ($14,340 ± $18,395); ISS 16 to 25: $15,698 ($23,615 ± $21,883); and ISS 25+: $29,792 ($41,407 ± $41,621), and with higher level of TC: Level I: $13,712 ($23,241 ± $29,164); Level II: $8,555 ($13,515 ± $15,296); and Levels III and IV: $8,115 ($10,719 ± $11,827). Patient care cost rose with increasing ISS, length of stay, ICU days, and ventilator days for patients with length of stay >2 days and ISS 9+. Level I centers had the highest mean ISS, length of stay, ICU days, and ventilator days, along with the highest PCC. Lesser trauma accounted for lower charges, payments, and PCC for Level II, III, and IV TCs, and the margin was variable. Verification and response costs per patient were highest for Level I and II TCs. Copyright © 2015 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Increasing Communication Skills: A Case Study of a Man with Autism Spectrum Disorder and Vision Loss

ERIC Educational Resources Information Center

Kee, S. Brian; Casey, Laura Baylot; Cea, Clayton R.; Bicard, David F.; Bicard, Sara E.

2012-01-01

According to the "Diagnostic and Statistical Manual of Mental Disorders" (DSM-IV-TR; American Psychiatric Association, APA, 2000), autism is a neurodevelopmental disorder that is characterized by impairments in social and communicative behaviors with great variations in ability, depending on developmental level, intelligence, and chronological…

Blood plasma apolipoproteins A-I and B in different types of hyperlipoproteinaemia: comparative analysis of population groups in Moscow and Prague.

PubMed

Metel'skaya, V A; Ceska, R; Perova, N V; Sobra, J

1988-01-01

The level of blood plasma apolipoproteins A-I and B was studied in Moscow and Prague residents with different types of hyperlipoproteinaemia (HLP). The analysis proceeded in two directions. On the one hand, lipoprotein (LP) spectra in residents of both cities with the same type of LP disturbance (HLP type IIa, IIb or IV) were compared; in Prague lipid and apolipoprotein content was compared in inhabitants with a normal lipid level and those with HLP types I, III and V. The analysis showed that inhabitants of Prague with types II and IV HLP have a higher concentrations of high density LP cholesterol. At the same time, it was found that the apolipoprotein profile of blood plasma LP in HLP patients was similar to that in patients living elsewhere. The authors regard comparative study of LP system disturbances in residents of different cities and countries differing in their geographical, ethnic and ecological conditions as a promising approach to understanding the mechanisms responsible for the development of HLP.

HIV infection among intravenous drug users: epidemiology and risk reduction.

PubMed

Des Jarlais, D C; Friedman, S R

1987-07-01

Research on the epidemiology of HIV infection among IV drug users is still at a relatively early stage. Multilocation studies that would permit better geographic comparisons are greatly needed. Multi-method studies within single geographic areas are also needed to assess possible biases with respect to sample recruitment and data collection procedures. The continuation of the epidemic provides a changing historical context that complicates any comparisons. Despite these problems, there are some consistencies that can be seen across studies. Studies of HIV seroprevalence among IV drug users show wide variation among cities in the United States and Europe. The time that the virus was introduced into the IV drug using group within the city is one factor in explaining these differences; other cross-city factors have yet to be identified. Once HIV has been introduced into the IV drug use group within a particular geographic area, there is the possibility of rapid spread up to seroprevalence levels of 50% or greater. Thus, a currently low seroprevalence rate should not be seen as a stable situation. Frequency of injection and sharing of equipment with multiple other drug users (particularly at shooting galleries) have been frequently associated with HIV exposure. Being female, ethnicity (in the USA) and engaging in prostitution also may be associated with increased risk for HIV exposure, suggesting that prevention programs should include special consideration of sex and ethnic differences. Studies of AIDS risk reduction show that substantial proportions of IV drug users are changing their behavior to avoid exposure to HIV. This risk reduction is probably more advanced in New York, with its high seroprevalence and incidence of cases, but is also occurring in cities with lower seroprevalence and limited numbers of cases. The primary forms of risk reduction are increasing the use of sterile equipment, reducing the number of needle sharing partners, and reducing the frequency of injection. These behavior changes are very similar to the frequently identified behavioral risk factors associated with HIV exposure, suggesting that they should be effective in at least slowing the spread of HIV among IV drug users. No linkage of risk reduction to decreases in seroconversion has yet been shown, however, and greater risk reduction is clearly required. A variety of prevention strategies will probably be needed to reduce the spread of HIV among IV drug users. Prevention of initiation into drug injection is an undeniable long-term goal for the control of HIV infection, but there is very little research being conducted in this area.

Child and youth practice area publications in the American Journal of Occupational Therapy in 2008 and 2009: a content analysis, methodology overview, and summary.

PubMed

Brown, Ted

2010-01-01

In this review, 39 articles published in the American journal of occupational therapy in 2008 and 2009 that were categorized in the practice area of children and youth were examined using content analysis. The most frequent type of research published was basic research, which accounted for 38.5% (n=15) of the 39 studies published on the topic. Instrument development and testing and effectiveness studies were the next two most frequently noted research approaches, accounting for 25.6% (n=10) and 20.5% (n=8) of the studies, respectively. Among the 8 effectiveness studies, the level of evidence distribution was as follows: Level I, 3; Level III, 2; Level IV, 1; and Level V, 2. Quantitative studies were the predominant research paradigm used with 76.9% (n=30) of the studies.

Current Evidence Regarding the Diagnostic Methods for Pediatric Lumbar Spondylolisthesis: A Report From the Scoliosis Research Society Evidence Based Medicine Committee.

PubMed

Kim, Han Jo; Crawford, Charles H; Ledonio, Charles; Bess, Shay; Larson, A Noelle; Gates, Marilyn; Oetgen, Matthew; Sanders, James O; Burton, Douglas

Structured literature review. The Scoliosis Research Society (SRS) requested an assessment of the current state of peer-reviewed evidence regarding pediatric lumbar spondylolisthesis with the goal of identifying what is known and what gaps remain in further understanding the diagnostic methods for pediatric spondylolisthesis. Spondylolisthesis in the lumbar spine is common among children and adolescents and no formal synthesis of the published literature regarding diagnostic methods has been previously performed. A comprehensive literature search was performed. Abstracts were reviewed and data from included studies were analyzed by the committee. From 6600 initial citations with abstract, 663 articles underwent full-text review. The best available evidence for the clinical questions regarding diagnostic methods was provided by 26 included studies. Six of the studies were graded as Level III (retrospective comparative), and represent the current best available evidence whereas 20 of the studies were graded as Level IV (retrospective case series) evidence. No Level V (expert opinion) studies were included in the final list. None of the studies were graded as Level I or Level II. Plain radiography is the workhorse imaging modality for diagnosing spondylolisthesis. No association between radiologic grade of spondylolisthesis and clinical presentation were noted; however, grade III and IV slips more often required surgery, and increasing slip angles were associated with worse baseline outcome scores. There is Level III evidence that the Meyerding grade appears to be more accurate for measuring slip percentage whereas the Lonstein Slip angle and Dubousset Lumbosacral Kyphosis angles are the best for measuring lumbosacral kyphosis in spondylolisthesis. In addition, higher sacral table index, pelvic incidence, sacral slope, and lower sacral table angle were associated with spondylolisthesis. True incidence could not be determined by the current literature available. However, studies in adolescent athletes demonstrated an incidence of 6% to 7% across studies. The current "best available" evidence to guide the diagnosis and characterization of pediatric spondylolisthesis is presented. Future studies are needed to provide more high-quality evidence to answer these clinically relevant questions. Level III, review of Level III studies. Copyright © 2017 Scoliosis Research Society. Published by Elsevier Inc. All rights reserved.

Intraepithelial lymphocytes in relation to NIH category IV prostatitis in autopsy prostate.

PubMed

Dikov, Dorian; Bachurska, Svitlana; Staikov, Dimitri; Sarafian, Victoria

2015-07-01

Quantitative analysis of the number, normal and pathologic ratios between lymphocytes and epithelial cells (ECs), and the significance of intraepithelial lymphocytes (IELs) in normal prostatic epithelium, benign prostatic hyperplasia (BPH), and high grade prostatic intraepithelial neoplasia (PIN) in relation to NIH category IV prostatitis (histologic prostatitis: HP) was studied in autopsy prostate. IELs were analysed in 59 autopsy prostates, which was routinely embedded in paraffin and immunohistochemically stained for CD3. An average of 300-500 ECs were counted per case. The number of IELs was calculated as the mean/100 ECs. Category IV prostatitis was evaluated using NIH consensus grading system in terms of anatomical localization and grade. In healthy individuals the mean number of IELs/100 ECs was 0.61 ± 0.34% or ≤1 lymphocyte/100 ECs, which is considered as the normal basal level of prostate IELs. In category IV prostatitis, the mean number of IELs/100 ECs was 8.53 ± 3.25% or 5-11 lymphocytes/100 ECs. The number of IELs in both around and inside inflammation areas correlated to the grade and location of HP (P < 0.0001 and P < 0.0003), the presence of acute glandular inflammation (P < 0.0001), the scattered stromal lymphocytes (P = 0.029), and BPH and PIN associated prostatic inflammation (P < 0.0001). The study presents the first attempt to examine and score the basic quantitative values of prostatic IELs in normal prostate and in relation to category IV prostatitis. The detected normal upper limit of CD3+ IELs is 1 lymphocyte/100 ECs in the normal prostate epithelium. This is considered as an organ specific characteristic of the prostate-associated lymphoid tissue (PALT). Values >5 IELs/100 ECs indicate the presence of category IV prostatitis. The severity of inflammation correlates to the number of IELs. There is an intimate link between the quantity of the IELs, the degree of the severity and the localization of category IV prostatitis. HP is a chronic and dynamic inflammatory process affecting the whole prostate gland. The increased number of IELs suggests the immune or autoimmune character of category IV prostatitis, BPH and inflammatory preneoplastic (PIN) lesions in the prostatic tumor environment. © 2015 Wiley Periodicals, Inc.

Rapid tachyphylaxis to hemodynamic effects of PACAP-27 after inhibition of nitric oxide synthesis

NASA Technical Reports Server (NTRS)

Whalen, E. J.; Travis, M. D.; Johnson, A. K.; Lewis, S. J.

1999-01-01

The vasodilator effects of pituitary adenylate cyclase-activating polypeptide (PACAP)-27 are subject to tachyphylaxis in rats treated with the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). We examined whether this tachyphylaxis could be prevented by administration of the putative endothelium-derived nitrosyl factor S-nitroso-L-cysteine (L-SNC) and whether L-SNC may exert its effects via increases in cGMP levels in vascular smooth muscle. Five doses of PACAP-27 (2 nmol/kg iv) produced pronounced vasodilator responses in saline-treated rats. These responses were not subject to tachyphylaxis. The first injection of PACAP-27 (2 nmol/kg iv) in L-NAME-treated (50 micromol/kg iv) rats produced vasodilator responses similar to those in saline-treated rats, whereas subsequent injections produced progressively smaller responses. The injection of L-SNC (1,200 nmol/kg iv) before each injection of PACAP-27 prevented tachyphylaxis to the Gs protein-coupled receptor agonist in L-NAME-treated rats, whereas equihypotensive doses of the NO donor sodium nitroprusside (100 micrograms/kg iv) did not. The injection of the membrane-permeant cGMP analog 8-(4-chlorophenylthio)guanosine 3',5'-cyclic monophosphate (8-CPT-cGMP; 30 micromol/kg iv) to L-NAME-treated rats restored resting hemodynamic values to pre-L-NAME levels but did not prevent the development of tachyphylaxis to PACAP-27. These results suggest that nitrosyl factors prevent the development of tachyphylaxis to the hemodynamic actions of PACAP-27. These nitrosyl factors may act independently of their ability to generate cGMP in vascular smooth muscle.

Accentuated hyperparathyroidism in type II Bartter syndrome.

PubMed

Landau, Daniel; Gurevich, Evgenia; Sinai-Treiman, Levana; Shalev, Hannah

2016-07-01

Bartter syndrome (BS) may be associated with different degrees of hypercalciuria, but marked parathyroid hormone (PTH) abnormalities have not been described. We compared clinical and laboratory data of patients with either ROMK-deficient type II BS (n = 14) or Barttin-deficient type IV BS (n = 20). Only BS-IV patients remained mildly hypokalemic in spite of a higher need for potassium supplementation. Estimated glomerular filtration rate (eGFR) was mildly decreased in only four BS-IV patients. Average PTH values were significantly higher in BS-II (160.6 ± 85.8 vs. 92.5 ± 48 pg/ml in BS-IV, p = 0.006). In both groups, there was a positive correlation between age and log(PTH). Levels of 25(OH) vitamin D were not different. Total serum calcium was lower (within normal limits) and age-related serum phosphate (Pi)-SDS was increased in BS-II (1.19 ± 0.71 vs. 0.01 ± 1.04 in BS-IV, p < 0.001). The GFR threshold for Pi reabsorption was higher in BS-II (5.63 ± 1.25 vs. 4.36 ± 0.98, p = 0.002). Spot urine calcium/creatinine ratio and nephrocalcinosis rate (100 vs. 16 %) were higher in the BS-II group. PTH, serum Pi levels, and urinary threshold for Pi reabsorption are significantly elevated in type II vs. type IV BS, suggesting a PTH resistance state. This may be a response to more severe long-standing hypercalciuria, leading to a higher rate of nephrocalcinosis in BS-II.

Differential Effects of Oral and Intravenous Lipid Administration on Key Molecules Related to Energy Homeostasis

PubMed Central

Vamvini, Maria T.; Hamnvik, Ole-Petter; Sahin-Efe, Ayse; Gavrieli, Anna; Dincer, Fadime; Farr, Olivia M.

2016-01-01

Context: The spectrum of lipid-induced changes in the secretion of hormones important in energy homeostasis has not yet been fully elucidated. Objective: To identify potential incretin-like effects in response to lipid administration, we examined the short-term effect of iv vs oral lipids on key molecules regulating energy homeostasis. Design, Intervention, and Participants: After a 10-hour overnight fast, 26 subjects were randomized to receive an oral lipid load, a 10% iv lipid emulsion, a 20% iv lipid emulsion, or an iv saline infusion. We obtained blood samples at 30-minute intervals for the first 2 hours and hourly thereafter for a total of 6 hours. Main Outcome Measures: Circulating levels of insulin, glucose, c-peptide, free fatty acids, incretins (glucagon-like peptide-1, gastric inhibitory polypeptide), glucagon, peptide YY, ghrelin, fibroblast growth factor 21, fetuin A, irisin, omentin, and adiponectin were measured. Results: Oral lipid ingestion resulted in higher glucagon-like peptide-1, gastric inhibitory polypeptide, glucagon, and peptide YY levels, compared with the other three groups (incremental area under the curve P = .003, P < .001, P < .001, P < .001, respectively). The 20% lipid emulsion, leading to higher free fatty acid levels, resulted in greater insulin, c-peptide, and fibroblast growth factor 21 responses compared with placebo and the other two groups (incremental area under the curve P = .002, P = .005, P < .001, P < .001, respectively). Omentin, adiponectin, fetuin A, and irisin levels were not affected by either mode of lipid administration. Conclusions: Metabolic responses to lipids depend on the route of administration. Only iv lipids trigger a dose-dependent fibroblast growth factor 21 secretion, which is nonglucagon mediated. Intravenous lipids also induce hyperinsulinemia without concurrent decreases in glucose, a phenomenon observed in insulin-resistant states. Orally administered lipids mostly affect gastrointestinal tract-secreted molecules important in glucose and energy homeostasis such as glucagon, incretins, and peptide YY. PMID:26964729

Assessing Internalizing, Externalizing, and Attention Problems in Young Children: Validation of the MacArthur HBQ

ERIC Educational Resources Information Center

Lemery-Chalfant, Kathryn; Schreiber, Jane E.; Schmidt, Nicole L.; Van Hulle, Carol A.; Essex, Marilyn J.; Goldsmith, H. H.

2007-01-01

Objective: To test the validity of the MacArthur Health and Behavior Questionnaire (HBQ) using receiver operating characteristic (ROC) analysis to determine optimal thresholds for the HBQ in predicting Diagnostic Interview Schedule for Children Version-IV (DISC-IV)diagnoses. The roles of child sex, level of impairment, and physical health in…

Module Measurements | Photovoltaic Research | NREL

Science.gov Websites

prototype concentrator evaluation test bed, and the Daystar DS-10/125 portable I-V curve tracer. Standard Evaluation Test Bed. We developed this test bed to be able to evaluate I-V characteristics throughout the day a function of time, temperature, and light level. This test bed data set is also used to evaluate

National Comorbidity Survey Replication Adolescent Supplement (NCS-A): III. Concordance of DSM-IV/CIDI Diagnoses with Clinical Reassessments

ERIC Educational Resources Information Center

Kessler, Ronald C.; Avenevoli, Shelli; Green, Jennifer; Gruber, Michael J.; Guyer, Margaret; He, Yulei; Jin, Robert; Kaufman, Joan; Sampson, Nancy A.; Zaslavsky, Alan M.; Merikangas, Kathleen R.

2009-01-01

The Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) diagnoses that was based on the World Health Organization's Composite International Diagnostic Interview (CIDI) and implemented in the National comorbidity survey replication adolescent supplement is found to have good individual-level concordance with diagnosis based on blinded…

The FIND-CKD study--a randomized controlled trial of intravenous iron versus oral iron in non-dialysis chronic kidney disease patients: background and rationale.

PubMed

Macdougall, Iain C; Bock, Andreas; Carrera, Fernando; Eckardt, Kai-Uwe; Gaillard, Carlo; Van Wyck, David; Roubert, Bernard; Cushway, Timothy; Roger, Simon D

2014-04-01

Rigorous data are sparse concerning the optimal route of administration and dosing strategy for iron therapy with or without concomitant erythropoiesis-stimulating agent (ESA) therapy for the management of iron deficiency anaemia in patients with non-dialysis dependent chronic kidney disease (ND-CKD). FIND-CKD was a 56-week, open-label, multicentre, prospective, randomized three-arm study (NCT00994318) of 626 patients with ND-CKD and iron deficiency anaemia randomized to (i) intravenous (IV) ferric carboxymaltose (FCM) at an initial dose of 1000 mg iron with subsequent dosing as necessary to target a serum ferritin level of 400-600 µg/L (ii) IV FCM at an initial dose of 200 mg with subsequent dosing as necessary to target serum ferritin 100-200 µg/L or (iii) oral ferrous sulphate 200 mg iron/day. The primary end point was time to initiation of other anaemia management (ESA therapy, iron therapy other than study drug or blood transfusion) or a haemoglobin (Hb) trigger (two consecutive Hb values <10 g/dL without an increase of ≥ 0.5 g/dL). The background, rationale and study design of the trial are presented here. The study has been completed and results are expected in late 2013. FIND-CKD was the longest randomized trial of IV iron therapy to date. Its findings will address several unanswered questions regarding iron therapy to treat iron deficiency anaemia in patients with ND-CKD. It was also the first randomized trial to utilize both a high and low serum ferritin target range to adjust IV iron dosing, and the first not to employ Hb response as its primary end point.

DSM-IV post-traumatic stress disorder among World Trade Center responders 11-13 years after the disaster of 11 September 2001 (9/11).

PubMed

Bromet, E J; Hobbs, M J; Clouston, S A P; Gonzalez, A; Kotov, R; Luft, B J

2016-03-01

Post-traumatic symptomatology is one of the signature effects of the pernicious exposures endured by responders to the World Trade Center (WTC) disaster of 11 September 2001 (9/11), but the long-term extent of diagnosed Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV) post-traumatic stress disorder (PTSD) and its impact on quality of life are unknown. This study examines the extent of DSM-IV PTSD 11-13 years after the disaster in WTC responders, its symptom profiles and trajectories, and associations of active, remitted and partial PTSD with exposures, physical health and psychosocial well-being. Master's-level psychologists administered sections of the Structured Clinical Interview for DSM-IV and the Range of Impaired Functioning Tool to 3231 responders monitored at the Stony Brook University World Trade Center Health Program. The PTSD Checklist (PCL) and current medical symptoms were obtained at each visit. In all, 9.7% had current, 7.9% remitted, and 5.9% partial WTC-PTSD. Among those with active PTSD, avoidance and hyperarousal symptoms were most commonly, and flashbacks least commonly, reported. Trajectories of symptom severity across monitoring visits showed a modestly increasing slope for active and decelerating slope for remitted PTSD. WTC exposures, especially death and human remains, were strongly associated with PTSD. After adjusting for exposure and critical risk factors, including hazardous drinking and co-morbid depression, PTSD was strongly associated with health and well-being, especially dissatisfaction with life. This is the first study to demonstrate the extent and correlates of long-term DSM-IV PTSD among responders. Although most proved resilient, there remains a sizable subgroup in need of continued treatment in the second decade after 9/11.

The response of claudin-like transmembrane septate junction proteins to altered environmental ion levels in the larval mosquito Aedes aegypti.

PubMed

Jonusaite, Sima; Kelly, Scott P; Donini, Andrew

2016-07-01

Septate junctions (SJs) occlude the paracellular pathway and function as paracellular diffusion barriers within invertebrate epithelia. However, integral components of SJs and their contribution to barrier properties have received considerably less attention than those of vertebrate occluding junctions. In arthropods, SJ proteins have only been identified in Drosophila and among these are three integral claudin-like proteins, Megatrachea (Mega), Sinuous (Sinu) and Kune-kune (Kune), as well as a receptor-like transmembrane SJ protein known as Neurexin IV (Nrx IV). In this study, mega, sinu, kune and nrx IV are identified and characterized in aquatic larvae of the mosquito Aedes aegypti and a role for these proteins in ionoregulatory homeostasis is considered. Transcripts encoding Mega, Sinu, Kune and Nrx IV were found in iono/osmoregulatory tissues such as the midgut, Malpighian tubules, hindgut and anal papillae, but abundance was greater in the hindgut and anal papillae. Using immunohistochemical and western blot analysis it was found that Kune localized to the regions of intercellular contact between epithelial cells of the rectum and posterior midgut and in the apical membrane domain of the syncytial epithelium of anal papillae. To investigate a potential role for integral SJ proteins in larval A. aegypti iono/osmoregulation, abundance was examined in animals reared in freshwater or brackish water (30 % seawater). In iono/osmoregulatory epithelia, larvae exhibited tissue-specific alterations in mega mRNA and Kune protein abundance, but not sinu or nrx IV mRNA. These studies provide a first look at the potential contribution of integral SJ components to iono/osmoregulatory homeostasis in an aquatic invertebrate.

Severe interpersonal violence against children in sport: Associated mental health problems and quality of life in adulthood.

PubMed

Vertommen, Tine; Kampen, Jarl; Schipper-van Veldhoven, Nicolette; Uzieblo, Kasia; Van Den Eede, Filip

2018-02-01

In a recent large-scale prevalence study of interpersonal violence (IV) against child athletes in the Netherlands and Belgium we found that 9% of adult respondents who participated in organized sports before the age of 18 had experienced severe psychological violence, 8% severe physical violence, and 6% severe sexual violence in various sport settings. While the general literature has repeatedly shown that exposure to IV during childhood is associated with mental health problems in adulthood and to a lesser extent with reduced quality of life (QOL), these relationships have not been demonstrated in (former) athletes. Thus, the current study aims to assess the association of severe childhood IV in sport and adult wellbeing. Depression, anxiety, and somatization were assessed in the same general population sample (N = 4043) using the Brief Symptom Inventory (BSI-18) and QOL with the World Health Organization Quality of Life questionnaire (WHOQOL-Brèf). The association between severe IV in sport and adult wellbeing was investigated using multiple linear regression while controlling for demographics, recent life events, and relatives' psychological problems. We found severe sexual, physical, and psychological childhood IV in sport to be associated with more adult psychological distress and reduced QOL. Polyvictimization shows the strongest correlation with poorer wellbeing and QOL. Recent life events, relatives' psychological problems, marital status, and level of education were significant covariates in the psychological symptoms and QOL assessed. We hope that these new insights prompt sport administrators to implement broad spectrum child protection measures and raise the awareness of mental health professionals about the necessity to also screen for adverse childhood experiences in the sport context. Copyright © 2017 Elsevier Ltd. All rights reserved.

Inducible nitric oxide synthase evoked nitric oxide counteracts capsaicin-induced airway smooth muscle contraction, but exacerbates plasma extravasation.

PubMed

Li, Ping-Chia; Shaw, Chen-Fu; Kuo, Tin-Fan; Chien, Chiang-Ting

2005-04-18

The contribution of nitric oxide (NO) to capsaicin-evoked airway responses was investigated in rats. The measurement of plasma NO level, airway dynamics, airway smooth muscle electromyogram, and plasma extravasation by India ink and Evans blue leakage technique was adapted. Capsaicin-evoked hypotension, bronchoconstriction, trachea plasma extravasation as well as increases in plasma NO level in a dose-dependent manner. L-732138 (NK1 receptor antagonist) or SR-48968 (NK2 receptor antagonist) pretreatment reduced capsaicin-enhanced hypotension, bronchoconstriction, plasma extravasation, and plasma NO level. N(G)-nitro-L-Arginine methyl ester (L-NAME, 10 mg/kg, i.v.), a non-selective NO synthase (NOS) inhibitor, or aminoguanidine (10 mg/kg, i.v.), a selective inducible NOS (iNOS) inhibitor, reduced capsaicin-induced increases in plasma NO level and protected against capsaicin-induced plasma extravasation, whereas L-arginine (150 mg/kg, i.v.), a NO precursor, enhanced capsaicin-evoked plasma NO level and plasma extravasation. L-Arginine pretreatment ameliorated capsaicin-induced bronchoconstriction, whereas L-NAME and aminoguanidine exaggerated capsaicin-induced bronchoconstriction. In summary, NK1 and NK2 receptors and iNOS play a role in NO formation and on capsaicin-induced bronchoconstriction and plasma extravasation. NO generated by iNOS counteracts tachykinin-mediated bronchoconstriction, but exacerbates tachykinin-mediated plasma extravasation.

Theoretical transition probabilities, oscillator strengths, and radiative lifetimes of levels in Pb IV

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

Alonso-Medina, A.; Colon, C., E-mail: cristobal.colon@upm.e; Porcher, P.

2011-01-15

Transition probabilities and oscillator strengths of 176 spectral lines with astrophysical interest arising from 5d{sup 10}ns (n = 7,8), 5d{sup 10}np (n = 6,7), 5d{sup 10}nd (n = 6,7), 5d{sup 10}5f, 5d{sup 10}5g, 5d{sup 10}nh (n = 6,7,8), 5d{sup 9}6s{sup 2}, and 5d{sup 9}6s6p configurations, and radiative lifetimes for 43 levels of Pb IV, have been calculated. These values were obtained in intermediate coupling (IC) and using relativistic Hartree-Fock calculations including core-polarization effects. For the IC calculations, we use the standard method of least-square fitting from experimental energy levels by means of the Cowan computer code. The inclusion in thesemore » calculations of the 5d{sup 10}7p and 5d{sup 10}5f configurations has facilitated a complete assignment of the energy levels in the Pb IV. Transition probabilities, oscillator strengths, and radiative lifetimes obtained are generally in good agreement with the experimental data.« less

Assessing DSM-IV symptoms of panic attack in the general population: an item response analysis.

PubMed

Sunderland, Matthew; Hobbs, Megan J; Andrews, Gavin; Craske, Michelle G

2012-12-20

Unexpected panic attacks may represent a non-specific risk factor for future depression and anxiety disorders. The examination of panic symptoms and associated latent severity levels may lead to improvements in the identification, prevention, and treatment of panic attacks and subsequent psychopathology for 'at risk' individuals in the general population. The current study utilised item response theory to assess the DSM-IV symptoms of panic in relation to the latent severity level of the panic attack construct in a sample of 5913 respondents from the National Epidemiologic Survey on Alcohol and Related conditions. Additionally, differential item functioning (DIF) was assessed to determine if each symptom of panic targets the same level of latent severity between different sociodemographic groups (male/female, young/old). Symptoms indexing 'choking', 'fear of dying', and 'tingling/numbness' are some of the more severe symptoms of panic whilst 'heart racing', 'short of breath', 'tremble/shake', 'dizzy/faint', and 'perspire' are some of the least severe symptoms. Significant levels of DIF were detected in the 'perspire' symptom between males and females and the 'fear of dying' symptom between young and old respondents. The current study was limited to examining cross-sectional data from respondents who had experienced at least one panic attack across their lifetime. The findings of the current study provide additional information regarding panic symptoms in the general population that may enable researchers and clinicians to further refine the detection of 'at-risk' individuals who experience threshold and sub-threshold levels of panic. Copyright © 2012 Elsevier B.V. All rights reserved.

Influence of hyperthyroidism on growth hormone secretion.

PubMed

Valcavi, R; Dieguez, C; Zini, M; Muruais, C; Casanueva, F; Portioli, I

1993-05-01

Hyperthyroidism is associated with altered GH secretion. Whether this is due to changes of somatotroph responsiveness or reflects an alteration in negative feedback signals at the hypothalamic level is unknown. We therefore performed a series of studies to shed some light onto this issue. Study 1: GHRH (1 microgram/kg b.w.) was injected i.v. in 38 hyperthyroid patients and in 30 normal subjects; in 11 of the patients the GHRH test was repeated following methimazole-induced remission of hyperthyroidism. Study 2: hGH (2 U i.v.) or saline were administered 3 hours prior to GHRH; six hyperthyroid patients and six normal subjects were studied. Study 3: ten normal subjects and ten hyperthyroid patients were given 75 g oral glucose or water 30 minutes before GHRH. Study 4: 11 normal subjects and eight hyperthyroid patients were studied. TRH or vehicle were dissolved in 250 ml of saline solution and infused at a rate of 400 micrograms/h for 150 minutes. Thirty minutes after the beginning of the infusions, L-arginine (30 g infused over 45 min i.v.) was administered. Hyperthyroid patients were compared to normal subjects. Growth hormone was measured by RIA at 15-minute intervals. GH responses to GHRH were subnormal in hyperthyroid patients. Following antithyroid drug treatment with methimazole, GH responses to GHRH increased in these patients in comparison to pretreatment values. Serum IGF-I levels, which were elevated before treatment, decreased after methimazole administration. Exogenous GH administration induced a clear decrease of GH responses to GHRH in both control and hyperthyroid subjects. On the other hand, oral glucose load decreased the GH responses to GHRH in normal but not in hyperthyroid subjects. TRH administration did not modify the GH responses to arginine in either normal subjects or hyperthyroid patients. Hyperthyroidism is associated with increased serum IGF-I levels and marked alterations in the neuroregulation of GH secretion. These changes involve decreased GH responsiveness to GHRH at the pituitary level and, at the hypothalamic level, a lack of suppressive effect of an oral glucose load. The normal inhibitory effect of exogenous GH administration but not of an oral glucose load in hyperthyroid patients suggests that these two feedback signals act through different mechanisms. The lack of effect of a TRH infusion on GH responses to L-arginine in normal and hyperthyroid patients makes an inhibitory role for TRH in GH secretion unlikely, at least in Caucasian subjects.

The effect of MgSO4 addition and the increasing doses of calcium and phosphorus during ending drying period on the occurrence of hypocalcaemia and hypophosphataemia in dairy cows.

PubMed

Bodarski, R; Kinal, S; Preś, J; Slupczyńska, M; Twardoń, J

2013-01-01

The aim of the presented study was the estimation of optimal Ca and P levels applied before calving together with anionic salt addition, as an element of hypocalcaemia and hypophosphataemia prevention. The experiment was carried out during the dry period on 48 cows with similar milk yield in the previous lactation. Cows were divided into four groups. In group I (control) the amount of minerals was in accordance to NRC standards. In experimental groups (groups II-IV), two weeks before calving, cows received 140 g/day/head of hydrated magnesium sulphate to achieve dietary cation-anion difference at the level of about 50 mEq/kg DM. In groups II and III cows received calcium carbonate (100 g/day) 10 days a.p. (antepartum) (group II), or 5 days a.p. (group III), while cows in IV group received dicalcium phosphate (100 g/day) for 5 days a.p. Application of MgSO4 x 7H20 significantly affected the urine pH of cows from group III and IV 4-5 d. before calving - 6.45 and 6.81, respectively. The acidification of urine was observed after calving in group IV (7.13). In cows from group II (100 CaCO3 10 days a.p.) urine pH decline was not found (7.97-7.75). In that group the incidences of hypophosphatemia were noted (blood serum inorganic P level 1.41-1.46 mmol/1). Addition of magnesium sulphate prevented hypocalcaemia occurrence -- 4-5 d. before calving the concentration of ionized Ca in blood serum was 1.11, 1.13 and 1.16 mmol/1 (respectively for group II, III and IV). Reproductive functions were significantly improved after the application of CaCO3 and CaHPO4 for 5 days a.p. in comparison with control and group II -- progesterone concentration in the blood serum on the 45th day of lactation was 1.396 - 1.409 versus 0.799 - 0.401. The correlation between progesterone and inorganic P level in serum was almost significant. Based on the obtained results a treatment optimal in prevention of hypocalcaemia and hypophosphataemia is the application of 50 g CaCO3 and 50 g of CaHPO4 for the last 5 days of the dry period together with MgSO4 x 7H20 given for 14 days a.p.

Abnormally high levels of anti-collagen type IV IgG antibodies in the serum of patients with a clinically isolated syndrome correlate with an increased risk of conversion to MS.

PubMed

Sadarzanska-Terzieva, Behidhe; Tzvetanov, Plamen; Hegde, Vishwajit; Al-Hashel, Jasem Y; Rousseff, Rossen Т; Haralanov, Lubomir; Stamenov, Boyko; Atanassova, Milena; Marinova, Iveta; Marinova, Anna; Rousseva, Adelaida

2015-06-01

To investigate anti-collagen-type-IV serum antibodies (ACIVAbs) levels in patients with clinically isolated syndrome (CIS), and to determine their predictive value for conversion into multiple sclerosis (MS). Serum levels of IgM and IgG ACIVAbs in 40 untreated patients with CIS (13 male, mean age 34.85±11.4 years, range 16-58 years) were compared to those of 27 gender- and age-matched healthy controls. ACIVAbs were quantified using ELISA. Patients were followed for 5 years by clinical examination and MRI studies. Thirty two patients (80%) converted to MS (converted CIS, C-CIS group) while the rest 8 (20%) did not (non-converted CIS, NC-CIS). The C-CIS patients had significantly higher levels of IgG ACIVAb compared to NC-CIS while the IgM levels did not differ between C-CIS and NC-CIS. Conversion to MS occurred in 66% of patients with IgG ACIVAbs levels exceeding the 95th percentile found in controls. IgG ACIVAbs levels correlated positively with the serum levels of matrix metalloproteinases type 9 (r = 0.37; p = 0.003) and inversely with those of tissue inhibitor of metalloproteinases type 1 (r = -0.43; p = 0.0008). High serum levels of IgG ACIVAbs in patients with CIS correlate strongly with increased risk of conversion to MS. Copyright © 2015 Elsevier B.V. All rights reserved.

Miami-Dade Community College 1984 Institutional Self-Study. Volume IV: Student Information and Performance Standards (Advisement and Graduation Information System, Academic Alert, Standards of Academic Progress).

ERIC Educational Resources Information Center

Miami-Dade Community Coll., FL.

Part of a systematic, in-depth assessment of Miami-Dade Community College's (MDCC's) educational programs, student support systems, and selected campus-level activities, this volume of the college's institutional self-study report examines the impact and effectiveness of student information systems and performance standards. This report presents…

Family Study of Borderline Personality Disorder and Its Sectors of Psychopathology

PubMed Central

Gunderson, John G.; Zanarini, Mary C.; Choi-Kain, Lois W.; Mitchell, Karen S.; Jang, Kerry L.; Hudson, James I.

2011-01-01

Context The familiality of borderline personality disorder (BPD) and its sectors of psychopathology are incompletely understood. Objectives To assess the familial aggregation of BPD and its 4 major sectors (affective, interpersonal, behavioral, and cognitive) and test whether the relationship of the familial and nonfamilial associations among these sectors can be accounted for by a latent BPD construct. Design Family study, with direct interviews of probands and relatives. Setting A psychiatric hospital (McLean Hospital) and the Boston-area community. Participants A total of 368 probands (132 with BPD, 134 without BPD, and 102 with major depressive disorder) and 885 siblings and parents of probands. Main Assessments The Diagnostic Interview for DSM-IV Personality Disorders and the Revised Diagnostic Interview for Borderlines (DIB-R) were used to assess borderline psychopathology, and the Structured Clinical Interview for DSM-IV was used to assess major depressive disorder. Results Borderline personality disorder meeting both DSM-IV and DIB-R criteria showed substantial familial aggregation for BPD in individuals with a family member with BPD vs those without a family member with BPD, using proband-relative pairs (risk ratio, 2.9; 95% confidence interval, 1.5–5.5) as well as using all pairs of family members (3.9; 1.7–9.0). All 4 sectors of BPD psychopathology aggregated significantly in families, using both DSM-IV and DIB-R definitions (correlation of traits among all pairs of family members ranged from 0.07 to 0.27), with the affective and interpersonal sectors showing the highest levels; however, the level of familial aggregation of BPD was higher than that of the individual sectors. The relationship among the sectors was best explained by a common pathway model in which the sectors represent manifestations of a latent BPD construct. Conclusions Familial factors contribute to BPD and its sectors of psychopathology. Borderline personality disorder may arise from a unitary liability that finds expression in its sectors of psychopathology. PMID:21727257

Risk prediction with procalcitonin and clinical rules in community-acquired pneumonia

PubMed Central

Huang, David T.; Weissfeld, Lisa A.; Kellum, John A.; Yealy, Donald M.; Kong, Lan; Martino, Michael; Angus, Derek C.

2009-01-01

Objective The Pneumonia Severity Index (PSI) and CURB-65 predict outcomes in community acquired pneumonia (CAP), but have limitations. Procalcitonin, a biomarker of bacterial infection, may provide prognostic information in CAP. Our objective was to describe the pattern of procalcitonin in CAP, and determine if procalcitonin provides prognostic information beyond PSI and CURB-65. Methods We conducted a multi-center prospective cohort study in 28 community and teaching emergency departments. Patients presenting with a clinical and radiographic diagnosis of CAP were enrolled. We stratified procalcitonin levels a priori into four tiers – I: < 0.1; II: ≥ 0.1 to <0.25; III: ≥ 0.25 to < 0.5; and IV: ≥ 0.5 ng/ml. Primary outcome was 30d mortality. Results 1651 patients formed the study cohort. Procalcitonin levels were broadly spread across tiers: 32.8% (I), 21.6% (II), 10.2% (III), 35.4% (IV). Used alone, procalcitonin had modest test characteristics: specificity (35%), sensitivity (92%), positive likelihood ratio (LR) (1.41), and negative LR (0.22). Adding procalcitonin to PSI in all subjects minimally improved performance. Adding procalcitonin to low risk PSI subjects (Class I–III) provided no additional information. However, subjects in procalcitonin tier I had low 30d mortality regardless of clinical risk, including those in higher risk classes (1.5% vs. 1.6% for those in PSI Class I–III vs. Class IV/V). Among high risk PSI subjects (Class IV/V), one quarter (126/546) were in procalcitonin tier I, and the negative LR of procalcitonin tier I was 0.09. Procalcitonin tier I was also associated with lower burden of other adverse outcomes. Similar results were seen with CURB-65 stratification. Conclusions Selective use of procalcitonin as an adjunct to existing rules may offer additional prognostic information in high risk patients. PMID:18342993

Family study of borderline personality disorder and its sectors of psychopathology.

PubMed

Gunderson, John G; Zanarini, Mary C; Choi-Kain, Lois W; Mitchell, Karen S; Jang, Kerry L; Hudson, James I

2011-07-01

The familiality of borderline personality disorder (BPD) and its sectors of psychopathology are incompletely understood. To assess the familial aggregation of BPD and its 4 major sectors (affective, interpersonal, behavioral, and cognitive) and test whether the relationship of the familial and nonfamilial associations among these sectors can be accounted for by a latent BPD construct. Family study, with direct interviews of probands and relatives. A psychiatric hospital (McLean Hospital) and the Boston-area community. A total of 368 probands (132 with BPD, 134 without BPD, and 102 with major depressive disorder) and 885 siblings and parents of probands. MAIN ASSESSMENTS: The Diagnostic Interview for DSM-IV Personality Disorders and the Revised Diagnostic Interview for Borderlines (DIB-R) were used to assess borderline psychopathology, and the Structured Clinical Interview for DSM-IV was used to assess major depressive disorder. Borderline personality disorder meeting both DSM-IV and DIB-R criteria showed substantial familial aggregation for BPD in individuals with a family member with BPD vs those without a family member with BPD, using proband-relative pairs (risk ratio, 2.9; 95% confidence interval, 1.5-5.5) as well as using all pairs of family members (3.9; 1.7-9.0). All 4 sectors of BPD psychopathology aggregated significantly in families, using both DSM-IV and DIB-R definitions (correlation of traits among all pairs of family members ranged from 0.07 to 0.27), with the affective and interpersonal sectors showing the highest levels; however, the level of familial aggregation of BPD was higher than that of the individual sectors. The relationship among the sectors was best explained by a common pathway model in which the sectors represent manifestations of a latent BPD construct. Familial factors contribute to BPD and its sectors of psychopathology. Borderline personality disorder may arise from a unitary liability that finds expression in its sectors of psychopathology.

Body composition, diet, and physical activity: a longitudinal cohort study in preschoolers with cerebral palsy.

PubMed

Oftedal, Stina; Davies, Peter Sw; Boyd, Roslyn N; Stevenson, Richard D; Ware, Robert S; Keawutan, Piyapa; Benfer, Katherine A; Bell, Kristie L

2017-02-01

Altered body composition in children with cerebral palsy (CP) could be due to differences in energy intake, habitual physical activity (HPA), and sedentary time. We investigated the longitudinal relation between the weight-for-age z score (WZ), fat-free mass (FFM), percentage of body fat (%BF), and modifiable lifestyle factors for all Gross Motor Function Classification System (GMFCS) levels (I-V). The study was a longitudinal population-based cohort study of children with CP who were aged 18-60 mo (364 assessments in 161 children; boys: 61%; mean ± SD recruitment age: 2.8 ± 0.9 y; GMFCS: I, 48%; II, 11%; III, 15%; IV, 11%; and V, 15%). A deuterium dilution technique or bioelectrical impedance analysis was used to estimate FFM, and the %BF was calculated. Energy intake, HPA, and sedentary time were measured with the use of a 3-d weighed food diary and accelerometer wear. Data were analyzed with the use of a mixed-model analysis. Children in GMFCS group I did not differ from age- and sex-specific reference children with typical development for weight. Children in GMFCS group IV were lighter-for-age, and children in GMFCS group V had a lower FFM-for-height than those in GMFCS group I. Children in GMFCS groups II-V had a higher %BF than that of children in GMFCS group I, with the exception of orally fed children in GMFCS group V. The mean %BF of children with CP classified them as overfat or obese. There was a positive association between energy intake and FFM and also between HPA level and FFM for children in GMFCS group I. Altered body composition was evident in preschool-age children with CP across functional capacities. Gross motor function, feeding method, energy intake, and HPA level in GMFCS I individuals are the strongest predictors of body composition in children with CP between the ages of 18 and 60 mo. © 2017 American Society for Nutrition.

The behavior of dissolved inorganic selenium in the Changjiang Estuary

NASA Astrophysics Data System (ADS)

Chang, Yan; Zhang, Jing; Qu, Jianguo; Zhang, Guosen; Zhang, Anyu; Zhang, Ruifeng

2016-02-01

To investigate the behavior of inorganic selenium species in the Changjiang Estuary, samples were taken during summer (July 2011) and winter (March 2012). Dissolved inorganic selenium (DISe) concentrations averaged 1.79 nmol/L in summer and 1.24 nmol/L in winter; the average selenite [Se(IV)] to selenate [Se(VI)] ratio [Se(IV)/Se(VI)] was 0.42 in summer and 0.61 in winter. The data show that Se(IV) and Se(VI) concentrations in the estuary behaved strictly conservatively during winter but non-conservatively during summer due to adsorption by suspended particulate matter (SPM) and assimilation by phytoplankton. In addition, the Se concentration distributions in the Changjiang Estuary were controlled by three water masses, each with a specific Se(IV)/Se(VI) ratio "signature": the Changjiang Water input, the Taiwan Warm Current, and the Yellow Sea Coastal Current. The Se(IV) concentrations were related to the nitrate, silicate, and phosphate concentrations in the estuary. The DISe and Se(IV) concentrations were comparable to those found in other coastal regions and estuaries, which were considered to be natural levels.

Genetic ablation or pharmacological blockade of dipeptidyl peptidase IV does not impact T cell-dependent immune responses

PubMed Central

Vora, Kalpit A; Porter, Gene; Peng, Roche; Cui, Yan; Pryor, Kellyann; Eiermann, George; Zaller, Dennis M

2009-01-01

Background Current literature suggests that dipeptidyl peptidase IV (DPP-IV; CD26) plays an essential role in T-dependent immune responses, a role that could have important clinical consequences. To rigorously define the role of DPP-IV in the immune system, we evaluated genetic and pharmacological inhibition of the enzyme on T-dependent immune responses in vivo. Results The DPP-IV null animals mounted robust primary and secondary antibody responses to the T dependent antigens, 4-hydroxy-3-nitrophenylacetyl-ovalbumin (NP-Ova) and 4-hydroxy-3-nitrophenylacetyl-chicken gamma globulin (NP-CGG), which were comparable to wild type mice. Serum levels of antigen specific IgM, IgG1, IgG2a, IgG2b and IgG3 were similar between the two groups of animals. DPP-IV null animals mounted an efficient germinal center reaction by day 10 after antigen stimulation that was comparable to wild type mice. Moreover, the antibodies produced by DPP-IV null animals after repeated antigenic challenge were affinity matured. Similar observations were made using wild type animals treated with a highly selective DPP-IV inhibitor during the entire course of the experiments. T cell recall responses to ovalbumin and MOG peptide, evaluated by measuring proliferation and IL-2 release from cells isolated from draining lymph nodes, were equivalent in DPP-IV null and wild type animals. Furthermore, mice treated with DPP-IV inhibitor had intact T-cell recall responses to MOG peptide. In addition, female DPP-IV null and wild type mice treated with DPP-IV inhibitor exhibited normal and robust in vivo cytotoxic T cell responses after challenge with cells expressing the male H-Y minor histocompatibility antigen. Conclusion These data indicate Selective inhibition of DPP-IV does not impair T dependent immune responses to antigenic challenge. PMID:19358731

The combined effect of administration of intravenous and topical tranexamic acid on blood loss and transfusion rate in total knee arthroplasty: Combined tranexamic acid for TKA.

PubMed

Yuan, Z F; Yin, H; Ma, W P; Xing, D L

2016-08-01

Tranexamic acid (TXA) is an antifibrinolytic agent used as a blood-sparing technique in total knee arthroplasty (TKA), and is routinely administered by intravenous (IV) or intra-articular (IA) injection. Recently, a novel method of TXA administration, the combined IV and IA application of TXA, has been applied in TKA. However, the scientific evidence of combined administration of TXA in TKA is still meagre. This meta-analysis aimed to investigate the efficacy and safety of combined IV and IA TXA in patients undergoing TKA. A systematic search was carried out in PubMed, the Cochrane Clinical Trial Register (Issue12 2015), Embase, Web of Science and the Chinese Biomedical Database. Only randomised controlled trials (RCT) evaluating the efficacy and safety of combined use TXA in TKA were identified. Two authors independently identified the eligible studies, extracted data and assessed the methodological quality of included studies. Meta-analysis was conducted using Review Manager 5.3 software. A total of ten RCTs (1143 patients) were included in this study. All the included studies were randomised and the quality of included studies still needed improvement. The results indicated that, compared with either placebo or the single-dose TXA (IV or IA) group, the combination of IV and IA TXA group had significantly less total blood loss, hidden blood loss, total drain output, a lower transfusion rate and a lower drop in haemoglobin level. There were no statistically significant differences in complications such as wound infection and deep vein thrombosis between the combination group and the placebo or single-dose TXA group. Compared with placebo or the single-dose TXA, the combined use of IV and IA TXA provided significantly better results with respect to all outcomes related to post-operative blood loss without increasing the risk of thromboembolic complications in TKA.Cite this article: Z. F. Yuan, H. Yin, W. P. Ma, D. L. Xing. The combined effect of administration of intravenous and topical tranexamic acid on blood loss and transfusion rate in total knee arthroplasty: combined tranexamic acid for TKA. Bone Joint Res 2016;5:353-361. DOI: 10.1302/2046-3758.58.BJR-2016-0001.R2. © 2016 Ma et al.

Concordances and discrepancies between ICD-10 and DSM-IV criteria for anxiety disorders in childhood and adolescence

PubMed Central

2012-01-01

Background Mental disorders are classified by two major nosological systems, the ICD-10 and the DSM-IV-TR, consisting of different diagnostic criteria. The present study investigated the diagnostic concordance between the two systems for anxiety disorders in childhood and adolescence, in particular for separation anxiety disorder (SAD), specific phobia, social phobia, and generalized anxiety disorder (GAD). Methods A structured clinical interview, the Kinder-DIPS, was administered to 210 children and 258 parents. The percentage of agreement, kappa, and Yule’s Y coefficients were calculated for all diagnoses. Specific criteria causing discrepancies between the two classification systems were identified. Results DSM-IV-TR consistently classified more children than ICD-10 with an anxiety disorder, with a higher concordance between DSM-IV-TR and the ICD-10 child section (F9) than with the adult section (F4) of the ICD-10. This result was found for all four investigated anxiety disorders. The results revealed low to high levels of concordance and poor to good agreement between the classification systems, depending on the anxiety disorder. Conclusions The two classification systems identify different children with an anxiety disorder. However, it remains an open question, whether the research results can be generalized to clinical practice since DSM-IV-TR is mainly used in research while ICD-10 is widely established in clinical practice in Europe. Therefore, the population investigated by the DSM (research population) is not identical with the population examined using the ICD (clinical population). PMID:23267678

A survey of the intravenous sedation status in one provincial dental clinic center for the disabled in Korea

PubMed Central

Seok, Ujeong; Ji, Sangeun; Yoo, Seunghoon; Kim, Jongsoo; Kim, Seungoh

2016-01-01

Background The objective of the present study was to examine the status of patients who had received dental treatment under intravenous (IV) sedation at Chungnam Dental Clinic for the Disabled in Korea from its inception to the present time, and to review the analysis results. Methods Retrospective analysis was performed on 305 cases of patients who had received dental treatments under IV sedation between January 2011 and May 2016. The analysis examined the patient's sex, age, primary reason for IV sedation, duration of anesthesia and dental treatment, type of dental treatment performed, number of clinical departments involved in the dental treatment and level of multidisciplinary cooperation, and annual trends. Results Most dental treatments using intravenous sedation were performed on medically disabled patients or dentally disabled patients with an extreme gag reflex or dental phobia. The mean duration of IV sedation was 72.5 min, while the mean duration of treatment was 58.0 min. The types of dental treatments included surgical treatment (n = 209), periodontal treatment (n = 28), prosthodontic treatment (n = 28), restorative treatment (n = 23), implant surgery (n = 22), endodontic treatment (n = 9), reduction of temporomandibular joint dislocation (n = 1), and treatment of traumatic injuries (n = 1), with treatments mostly performed on adult patients. Conclusions With increasing demand for minimally painful treatment, cases using IV sedation are on an upward trend and are expected to continue to increase. PMID:28879305

Indications and Outcomes for Microfracture as an Adjunct to Hip Arthroscopy for Treatment of Chondral Defects in Patients With Femoroacetabular Impingement: A Systematic Review.

PubMed

MacDonald, Austin E; Bedi, Asheesh; Horner, Nolan S; de Sa, Darren; Simunovic, Nicole; Philippon, Marc J; Ayeni, Olufemi R

2016-01-01

To evaluate the indications, preoperative workup outcomes, and postoperative rehabilitation of patients with femoroacetabular impingement (FAI) receiving microfracture as an adjunct to hip arthroscopy for chondral defects. The electronic databases MEDLINE, EMBASE, and PubMed were searched and screened in duplicate for studies involving patients with FAI treated arthroscopically with microfracture of the hip for chondral defects either solely or as an adjunct to hip arthroscopy. Data regarding indications, investigations, outcomes, and postoperative rehabilitation were abstracted from eligible studies. The references of included studies were additionally searched, and descriptive statistics are provided. There were 12 studies included in this review, involving 267 patients. With the exception of a single, one-patient case report, 11 of the 12 studies reported positive outcomes after hip arthroscopy with microfracture. Only 0.7% of the total patients experienced a complication, and 1.1% required further surgery on the basis of outcomes evaluated at a mean follow-up of 29.5 (range, 4 to 60) months across the studies. Eight of 12 studies discussed the preoperative workup of these patients, with X-rays and magnetic resonance imaging being the most common preoperative imaging used. There was little reported on weight-bearing status during postoperative rehabilitation. The outcomes reported in the literature after hip arthroscopy with microfracture for chondral defects are, in general, positive, with a very low percentage of patients requiring further surgery or experiencing complications. The most common indication used in the literature for microfracture is a full-thickness, focal chondral defect (Outerbridge grade IV). The vast majority of literature recommends limited weight bearing after microfracture; however, there was significant variation among the specific rehabilitation protocols used. More research is needed to explore what indications and postoperative rehabilitation result in the best outcomes for patients. Level IV, systematic review of Level II, III, and IV studies. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Effect of berberine on PPARα-NO signalling pathway in vascular smooth muscle cell proliferation induced by angiotensin IV.

PubMed

Qiu, Hongmei; Wu, Yang; Wang, Quanhua; Liu, Changqing; Xue, Lai; Wang, Hong; Wu, Qin; Jiang, Qingsong

2017-12-01

The available treatments for the abnormal proliferation of vascular smooth muscle cells (VSMCs) are still dismal. Berberine has been demonstrated to possess extensive medicine activity, yet relatively little is known about its effect on VSMCs proliferation. Many studies showed that PPARα and NO participated in the process of VSMCs proliferation. To evaluate the effect of berberine and its possible influence on PPARα-NO pathway in angiotensin IV-stimulated VSMCs. The primary VSMCs were cultured with the tissue explants method, and the proliferation was characterized by MTT and protein content. Protein and mRNA expression were measured by Western blot and real-time RT-PCR, respectively. NO synthase (NOS) activity was measured using a spectrophotometric assay, and NO concentration was measured using the Griess assay. Angiotensin IV (0.1 nmol/L)-induced VSMCs proliferation was evidenced by increasing the optical density at A 490 and total protein content (p < 0.01), which was inhibited by berberine (10, 30 and 100 μmol/L) in a concentration-dependent manner (p < 0.05). Angiotensin IV decreased the expression of PPARα at mRNA and protein level (p < 0.05), which occurred in parallel with declining eNOS mRNA expression, NOS activity and NO concentration (p < 0.01). Berberine at 30 μmol/L reversed the effects of angiotensin IV in VSMCs (p < 0.05), which were abolished by MK 886 (0.3 μmol/L) (p < 0.05). The results support the therapeutic effects of berberine on angiotensin IV-induced proliferation in cultured VSMCs at least partially through targeting the PPARα-NO signalling pathway.

Methodological variations and their effects on reported medication administration error rates.

PubMed

McLeod, Monsey Chan; Barber, Nick; Franklin, Bryony Dean

2013-04-01

Medication administration errors (MAEs) are a problem, yet methodological variation between studies presents a potential barrier to understanding how best to increase safety. Using the UK as a case-study, we systematically summarised methodological variations in MAE studies, and their effects on reported MAE rates. Nine healthcare databases were searched for quantitative observational MAE studies in UK hospitals. Methodological variations were analysed and meta-analysis of MAE rates performed using studies that used the same definitions. Odds ratios (OR) were calculated to compare MAE rates between intravenous (IV) and non-IV doses, and between paediatric and adult doses. We identified 16 unique studies reporting three MAE definitions, 44 MAE subcategories and four different denominators. Overall adult MAE rates were 5.6% of a total of 21 533 non-IV opportunities for error (OE) (95% CI 4.6% to 6.7%) and 35% of a total of 154 IV OEs (95% CI 2% to 68%). MAEs were five times more likely in IV than non-IV doses (pooled OR 5.1; 95% CI 3.5 to 7.5). Including timing errors of ±30 min increased the MAE rate from 27% to 69% of 320 IV doses in one study. Five studies were unclear as to whether the denominator included dose omissions; omissions accounted for 0%-13% of IV doses and 1.8%-5.1% of non-IV doses. Wide methodological variations exist even within one country, some with significant effects on reported MAE rates. We have made recommendations for future MAE studies; these may be applied both within and outside the UK.

Iron deficiency intravenous substitution in a Swiss academic primary care division: analysis of practices

PubMed Central

Varcher, Monica; Zisimopoulou, Sofia; Braillard, Olivia; Favrat, Bernard; Junod Perron, Noëlle

2016-01-01

Background Iron deficiency is a common problem in primary care and is usually treated with oral iron substitution. With the recent simplification of intravenous (IV) iron administration (ferric carboxymaltose) and its approval in many countries for iron deficiency, physicians may be inclined to overutilize it as a first-line substitution. Objective The aim of this study was to evaluate iron deficiency management and substitution practices in an academic primary care division 5 years after ferric carboxymaltose was approved for treatment of iron deficiency in Switzerland. Methods All patients treated for iron deficiency during March and April 2012 at the Geneva University Division of Primary Care were identified. Their medical files were analyzed for information, including initial ferritin value, reasons for the investigation of iron levels, suspected etiology, type of treatment initiated, and clinical and biological follow-up. Findings were assessed using an algorithm for iron deficiency management based on a literature review. Results Out of 1,671 patients, 93 were treated for iron deficiency. Median patients’ age was 40 years and 92.5% (n=86) were female. The average ferritin value was 17.2 μg/L (standard deviation 13.3 μg/L). The reasons for the investigation of iron levels were documented in 82% and the suspected etiology for iron deficiency was reported in 67%. Seventy percent of the patients received oral treatment, 14% IV treatment, and 16% both. The reasons for IV treatment as first- and second-line treatment were reported in 57% and 95%, respectively. Clinical and biological follow-up was planned in less than two-thirds of the cases. Conclusion There was no clear overutilization of IV iron substitution. However, several steps of the iron deficiency management were not optimally documented, suggesting shortcuts in clinical reasoning. PMID:27445502