Bone mineral density and mammographic density in Mexican women

PubMed Central

Moseson, Heidi; Rice, Megan S.; López-Ridaura, Ruy; Bertrand, Kimberly A.; Torres, Gabriela; Blanco, Margarita; Tamayo-Orozco, Juan Alfredo; Lajous, Martin; Romieu, Isabelle

2016-01-01

Background Bone mineral density (BMD) is a putative marker for lifetime exposure to estrogen. Studies that have explored whether BMD is a determinant of mammographic density (MD) have observed inconsistent results. Therefore, we examined this potential association in a sample of women (N=1,516) from the clinical sub-cohort in the Mexican Teachers’ Cohort (N=115,315). Methods We used multivariable linear regression to assess the association between quartiles of BMD and percent MD, as well as total dense and non-dense area of the breast, stratified by menopausal status. We also examined the associations by body mass index (BMI) (<30kg/m2,, ≥30kg/m2). Results Overall, there was no association between BMD and MD among premenopausal women. However, when we stratified by BMI, there was a modest inverse association between BMD and percent MD (difference between extreme quartiles= −2.8, 95%CI: −5.9, 0.27, p-trend=0.04) among women with BMI <30 kg/m2, but a positive association among obese women (comparable difference=5.1, 95%CI: 0.02, 10.1, p-trend=0.03; p-interaction<0.01). Among postmenopausal women, BMD and percent MD were positively associated after adjustment for BMI (p-trend<0.01). Postmenopausal women in the highest two quartiles of BMD had 4–5 percentage point higher percent MD compared to women in the lowest quartile. The association did not differ by BMI in postmenopausal women (p-interaction=0.76). Conclusion Among obese premenopausal women as well as postmenopausal women, BMD was positively associated with percent MD. Among leaner premenopausal women, BMD and percent MD were modestly inversely associated. These findings support the hypothesis that cumulative exposure to estrogen (as measured by BMD) may influence MD. PMID:26463740

Understanding the link between feelings of mental defeat, self-efficacy and the experience of chronic pain.

PubMed

Hazeldine-Baker, Charlotte E; Salkovskis, Paul M; Osborn, Mike; Gauntlett-Gilbert, Jeremy

2018-05-01

'Mental defeat' (MD) has been identified among people with chronic pain as a type of self-processing related to social role and rank. Research has linked it to anxiety, pain interference and functional disability. The relationship between MD and other cognitive constructs, such as hopelessness and depression, remains poorly understood. This study considers the association between MD, pain symptomatology and self-efficacy in the context of other cognitive factors. In total, 59 participants completed a questionnaire pack assessing anxiety, depression, hopelessness, pain catastrophising and MD in order to examine the relationship with pain symptomatology and self-efficacy. Linear multiple regression analyses showed that anxiety was most strongly associated with pain symptomatology, accounting for 26% of the variance, while catastrophising showed the strongest association with sensory pain and MD the strongest association with affective pain. Finally, MD was found to be strongly associated with pain-related self-efficacy, accounting for 47% of the variance. This research has demonstrated the potential importance of assessing MD in chronic pain patients, suggesting that targeting these cognitions during interventions and therapy could be valuable. Furthermore, the study indicates that MD differs from related cognitive constructs involved in pain, such as depression, hopelessness and catastrophising.

The relationship between better-eye and integrated visual field mean deviation and visual disability.

PubMed

Arora, Karun S; Boland, Michael V; Friedman, David S; Jefferys, Joan L; West, Sheila K; Ramulu, Pradeep Y

2013-12-01

To determine the extent of difference between better-eye visual field (VF) mean deviation (MD) and integrated VF (IVF) MD among Salisbury Eye Evaluation (SEE) subjects and a larger group of glaucoma clinic subjects and to assess how those measures relate to objective and subjective measures of ability/performance in SEE subjects. Retrospective analysis of population- and clinic-based samples of adults. A total of 490 SEE and 7053 glaucoma clinic subjects with VF loss (MD ≤-3 decibels [dB] in at least 1 eye). Visual field testing was performed in each eye, and IVF MD was calculated. Differences between better-eye and IVF MD were calculated for SEE and clinic-based subjects. In SEE subjects with VF loss, models were constructed to compare the relative impact of better-eye and IVF MD on driving habits, mobility, self-reported vision-related function, and reading speed. Difference between better-eye and IVF MD and relationship of better-eye and IVF MD with performance measures. The median difference between better-eye and IVF MD was 0.41 dB (interquartile range [IQR], -0.21 to 1.04 dB) and 0.72 dB (IQR, 0.04-1.45 dB) for SEE subjects and clinic-based patients with glaucoma, respectively, with differences of ≥ 2 dB between the 2 MDs observed in 9% and 18% of the groups, respectively. Among SEE subjects with VF loss, both MDs demonstrated similar associations with multiple ability and performance metrics as judged by the presence/absence of a statistically significant association between the MD and the metric, the magnitude of observed associations (odds ratios, rate ratios, or regression coefficients associated with 5-dB decrements in MD), and the extent of variability in the metric explained by the model (R(2)). Similar associations of similar magnitude also were noted for the subgroup of subjects with glaucoma and subjects in whom better-eye and IVF MD differed by ≥ 2 dB. The IVF MD rarely differs from better-eye MD, and similar associations between VF loss and visual disability are obtained using either MD. Unlike better-eye MD, IVF measurements require extra software/calculation. As such, information from studies using better-eye MD can be more easily integrated into clinical decision-making, making better-eye MD a robust and meaningful method for reporting VF loss severity. Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.

Perceived parenting and risk for major depression in Chinese women

PubMed Central

Gao, J.; Li, Y.; Cai, Y.; Chen, J.; Shen, Y.; Ni, S.; Wei, Y.; Qiu, Y.; Zhu, X.; Liu, Y.; Lu, C.; Chen, C.; Niu, Q.; Tang, C.; Yang, Y.; Wang, Q.; Cui, W.; Xia, J.; Liu, T.; Zhang, J.; Zhao, B.; Guo, Z.; Pan, J.; Chen, H.; Luo, Y.; Sun, L.; Xiao, X.; Chen, Q.; Zhao, X.; He, F.; Lv, L.; Guo, L.; Liu, L.; Li, H.; Shi, S.; Flint, J.; Kendler, K. S.; Tao, M.

2012-01-01

Background In Western countries, a history of major depression (MD) is associated with reports of received parenting that is low in warmth and caring and high in control and authoritarianism. Does a similar pattern exist in women in China? Method Received parenting was assessed by a shortened version of the Parental Bonding Instrument (PBI) in two groups of Han Chinese women: 1970 clinically ascertained cases with recurrent MD and 2597 matched controls. MD was assessed at personal interview. Results Factor analysis of the PBI revealed three factors for both mothers and fathers: warmth, protectiveness, and authoritarianism. Lower warmth and protectiveness and higher authoritarianism from both mother and father were significantly associated with risk for recurrent MD. Parental warmth was positively correlated with parental protectiveness and negatively correlated with parental authoritarianism. When examined together, paternal warmth was more strongly associated with lowered risk for MD than maternal warmth. Furthermore, paternal protectiveness was negatively and maternal protectiveness positively associated with risk for MD. Conclusions Although the structure of received parenting is very similar in China and Western countries, the association with MD is not. High parental protectiveness is generally pathogenic in Western countries but protective in China, especially when received from the father. Our results suggest that cultural factors impact on patterns of parenting and their association with MD. PMID:21943491

Cognitive Risk Factors for Specific Learning Disorder: Processing Speed, Temporal Processing, and Working Memory.

PubMed

Moll, Kristina; Göbel, Silke M; Gooch, Debbie; Landerl, Karin; Snowling, Margaret J

2016-01-01

High comorbidity rates between reading disorder (RD) and mathematics disorder (MD) indicate that, although the cognitive core deficits underlying these disorders are distinct, additional domain-general risk factors might be shared between the disorders. Three domain-general cognitive abilities were investigated in children with RD and MD: processing speed, temporal processing, and working memory. Since attention problems frequently co-occur with learning disorders, the study examined whether these three factors, which are known to be associated with attention problems, account for the comorbidity between these disorders. The sample comprised 99 primary school children in four groups: children with RD, children with MD, children with both disorders (RD+MD), and typically developing children (TD controls). Measures of processing speed, temporal processing, and memory were analyzed in a series of ANCOVAs including attention ratings as covariate. All three risk factors were associated with poor attention. After controlling for attention, associations with RD and MD differed: Although deficits in verbal memory were associated with both RD and MD, reduced processing speed was related to RD, but not MD; and the association with RD was restricted to processing speed for familiar nameable symbols. In contrast, impairments in temporal processing and visuospatial memory were associated with MD, but not RD. © Hammill Institute on Disabilities 2014.

Exploration of amino acid biomarkers in polar ice with the Mars Organic Analyzer

NASA Astrophysics Data System (ADS)

Jayarajah, C.; Botta, O.; Aubrey, A.; Parker, E.; Bada, J.; Mathies, R.

2009-05-01

A portable microfabricated capillary electrophoresis (CE) system named the Mars Organic Analyzer (MOA) has been developed to analyze fluorescently-labeled biomarkers including amino acids, amines, nucleobases, and amino sugars with the goal of life detection on Mars (1,2). This technology has also been shown to be effective in screening the formation of biogenic amines during fermentation (3). The MOA is a part of the Urey instrument package that has been selected for the 2016 European ExoMars mission by ESA. The identification of recent gully erosion sites, observations of ice on and beneath the surface of Mars, and the discovery of large reservoirs of sub-surface ice on Mars point to water-ice as an important target for astrobiological analyses. In addition, the ice samples on the Moon, Mercury, Europa and Enceladus are of interest due to the possibility that they may contain information on biogenic material relevant to the evolution of life. We explore here the use of the MOA instrument for the analysis of amino acids in polar ice samples. The amino acids valine, alanine/serine, glycine, glutamic acid, and aspartic acid were found in the parts-per-billion range from Greenland ice-core samples. Chiral analysis of these samples yielded D/L ratios of 0.51/0.09 for alanine/serine and 0.14/0.06 for aspartic acid. Individual amino acids in the parts-per-trillion range were found in Antarctic ice samples collected from the surface of a meteorite collection area. The distinct amino acid and amine content of these samples indicates that further biomarker characterization of ice samples as a function of sampling location, depth, and structural features will be highly informative. The rapid sensitive analysis capabilities demonstrated here establish the feasibility of using the MOA to analyze the biomarker content of ice samples in planetary exploration. 1. Skelley, A. M.; Scherer, J. R.; Aubrey, A. D.; Grover, W. H.; Ivester, R. H. C., Ehrenfreund, P.; Grunthaner, F. J.; Bada, J. L.; Mathies, R. A. PNAS, 2005, 192, 1041. 2. Skelley, A. M., Cleaves, H. J., Jayarajah, C. N., Bada, J. L. and Mathies, R. A., Astrobiology 2006, 6, 824. 3. Jayarajah, C.N., Skelley, A.M., Fortner, A.D., and Mathies, R.A., Anal. Chem. 2007, 79, 21, 8162.

Tuning Porosity of YBa2Cu3O7-delta Vicinal Films by Insertion of Y2BaCuO5 Nanoparticles (Postprint)

DTIC Science & Technology

2012-02-01

Paranthaman, E. D. Specht , D. M. Kroeger, D. K. Christen, Q. He, B. Saffian, F. A. List, D. F. Lee, P. M. Martin, C. E. Klabunde, E. Hartfield, and V. K...2000. 12B. W. Kang, A. Goyal, D. R. Lee, J. E. Mathis, E. D. Specht , P. M. Martin, D. M. Kroeger, M. Paranthaman, and S. Sathyamurthy, J. Mater. Res

Environmental Impact Research Program: Visual Resources Assessment Procedure for US Army Corps of Engineers

DTIC Science & Technology

1988-03-01

32264. Technical Monitors were Dr. John Bushman and Mr. David P. Buelow, OCE, and Mr. Dave Mathis, Water Resources Support Center, Fort Belvoir, Va. The...Manager for EIRP was Dr. Roger T. Saucier. Dr. John Harrison was Chief, EL. The report was written by Dr. Smardon, Dr. Palmer, Mr. Knopf, Ms. Grinde...Riverfront area will continue. Historic Mill District projects and establishment of the Riverside Parkway System will further unify S the Riverfront

Cigarette smoking and mammographic density in the Danish Diet, Cancer and Health cohort.

PubMed

Jacobsen, Katja Kemp; Lynge, Elsebeth; Vejborg, Ilse; Tjønneland, Anne; von Euler-Chelpin, My; Andersen, Zorana J

2016-02-01

Smoking before first childbirth increases breast cancer risk, but the biological mechanism remains unknown and may involve mammographic density (MD), one of the strongest biomarkers of breast cancer risk. We aimed to examine whether active smoking and passive smoking were associated with MD. For the 5,356 women (4,489 postmenopausal) from the Danish Diet, Cancer and Health cohort (1993-1997) who attended mammographic screening in Copenhagen (1993-2001), we used MD (mixed/dense or fatty) assessed at the first screening after cohort entry. Active smoking (status, duration, and intensity) and passive smoking were assessed at cohort baseline (1993-1997) via questionnaire, together with other breast cancer risk factors. Logistic regression was used to estimate associations (odds ratios, 95 % confidence intervals) between smoking and MD, adjusting for confounders. Two thousand and twenty-six (56.5 %) women had mixed/dense MD, 2,214 (41.4 %) were current, and 1,175 (21.9 %) former smokers. Current smokers had significantly lower odds (0.86, 0.75-0.99) of having mixed/dense MD compared to never smokers, while former smoking was not associated with MD. Inverse association between smoking and MD was strongest in women who initiated smoking before age of 16 years (0.79, 0.64-0.96), smoked ≥15 cigarettes/day (0.83, 0.71-0.98), smoked ≥5 pack-years (0.62, 0.43-0.89), smoked >30 years (0.86, 0.75-0.99), and smoked ≥11 years before first childbirth (0.70, 0.51-0.96). Association between smoking and MD diminished after smoking cessation, with increased odds of having mixed/dense breasts in women who quit smoking >20 years ago as compared to current smokers (1.37, 1.01-1.67). There was no association between passive smoking and MD. We found an inverse association between active smoking and MD.

Detection of trace amino acid biomarkers in ice from extreme environments with the Mars Organic Analyzer

NASA Astrophysics Data System (ADS)

Jayarajah, Christine; Jayarajah, Christine; Botta, Oliver; Aubrey, Andrew; Parker, Eric; Bada, Jeffrey; Mathies, Richard

A portable microfabricated capillary electrophoresis (CE) system named the Mars Organic Analyzer (MOA) has been developed to analyze fluorescently-labeled biomarkers including amino acids, amines, nucleobases, and amino sugars with the goal of life detection on Mars (1,2). This system consists of a multilayer microfabricated glass wafer containing electrophoresis channels as well as microfluidic valves and pumps for sample manipulation, a confocal laser excitation and fluorescence detection system, and integrated CE power supplies. The MOA has been successfully field tested in the Panoche Valley, CA and in the Atacama Desert, Chile, detecting amino acids at the ppb levels (3). In addition, this technology has been shown to be effective in screening the formation of biogenic amines during fermentation (4). The MOA is a part of the Urey instrument package that has been selected for the 2013 European ExoMars mission by ESA. The identification of recent gully erosion sites, observations of ice on and beneath the surface of Mars, and the discovery of large reservoirs of sub-surface ice on Mars point to water-ice as an important target for astrobiological analyses (5). In addition, the ice moons Europa and Enceladus are of astrobiological interest due to the possibility that they may contain liquid water under their ice crusts. Consequently, we explore here the use of the MOA instrument for the analysis of amino acids in polar ice samples. Soil extracts as well as concentrated icecore samples tend to be highly saline and inhomogeneous. Furthermore, brine pockets in ice form potential refugia for extant extra-terrestrial life, rendering near surface ice a key target for the search for a record of past life on the planet (6). Therefore, we have determined the effect of salinity on sample injection parameters in ice-core samples retrieved from Greenland. The amino acids valine, alanine/serine, glycine, glutamic acid, and aspartic acid were found in the parts-per-billion range from these ice-core samples. Chiral analysis of these samples yielded D/L ratios of 0.51/0.09 for alanine/serine and 0.14/0.06 for aspartic acid. Individual amino acids in the parts-per-trillion range were found in Antarctic ice samples collected from the surface of a meteorite collection area. The distinct amino acid and amine content of these samples indicates that further biomarker characterization of ice samples as a function of sampling location, depth, and structural features will be highly informative. The rapid sensitive analysis capabilities demonstrated here establish the feasibility of using the MOA to analyze the biomarker content of ice samples in planetary exploration. 1. Skelley, A. M.; Scherer, J. R.; Aubrey, A. D.; Grover, W. H.; Ivester, R. H. C., Ehrenfreund, P.; Grunthaner, F. J.; Bada, J. L.; Mathies, R. A. Proceedings of the National Academy of Sciences, U.S.A., 2005, 192, 1041-1046. 2. Skelley, A. M., Cleaves, H. J., Jayarajah, C. N., Bada, J. L. and Mathies, R. A., Astrobiology 2006, 6, 824-837. 3. Skelley, A. M., Aubrey, A. D., Willis, P. A., Amashukeli, X., Ehrenfreuend, P. , Bada, J. L., Grunthaner, F. J. and Mathies, R. A. Journal of Geophysical Research 2007, 112, G04S11 4. Jayarajah, C.N., Skelley, A.M., Fortner, A.D., and Mathies, R.A., Analytical Chemistry, 2007, 79, 21, 8162-8169. 5. Sanderson, K., Nature 2006, 414. 800-801. 6. Price, B.P. Proceedings of the National Academy of Sciences, U.S.A., 2000, 97, 1247-1251.

Sensitive Amino Acid Composition and Chirality Analysis in the Martian Regolith with a Microfabricated in situ Analyzer

NASA Astrophysics Data System (ADS)

Skelley, A. M.; Grunthaner, F. J.; Bada, J. L.; Mathies, R. A.

2003-12-01

Recent advances in microfabricated "lab-on-a-chip" technologies have dramatically enhanced the capabilities of chemical and biochemical analyzers. The portability and sensitivity of these devices makes them ideal instruments for in situ chemical analysis on other planets. We have focused our initial studies on amino acid analysis because amino acids are more chemically resistant to decomposition than other biomolecules, and because amino acid chirality is a well-defined biomarker [1]. Previously, we developed a prototype electrophoresis chip, detection system and analysis method where the amino acids were labeled with fluorescein using FITC and then electrophoretically analyzed using g-cyclodextrin as the chiral resolution agent [2]. Extracts of the Murchison meteorite were analyzed, and the D/L ratios determined by microchip CE closely matched those from HPLC and GCMS and exhibited greater precision. Our microchip analyzer has now been further improved by establishing the capability of performing amino acid composition and chirality analyses using fluorescamine rather than FITC [3]. Fluorescamine is advantageous because it reacts more rapidly than FITC, and because excess reagent is hydrolyzed to a non-fluorescent product. Furthermore, the use of fluorescamine facilitates interfacing with the Mars Organic Detector (MOD) [4]. Fluorescamine-amino acids are separated using similar conditions as the FITC-aa, resulting in similar separation times and identical elution orders. Fluorescamine-aa are chirally resolved in the presence of hydroxy-propyl-b-cyclodextrin, and typical limits of detection are ˜ 50 nM. This work establishes the feasibility of combining fluorescamine labeling of amino acids with microfabricated CE devices to develop low-volume, high-sensitivity apparatus for extraterrestrial exploration. The stage is now set for the development of the Mars Organic Analyzer (MOA), a portable analysis system for amino acid extraction and chiral analysis that will combine the capabilities of microchip CE with the previously developed extraction capabilities of MOD [4]. Amino acids are first extracted from soil by sublimation to a cold finger coated with fluorescamine for solid phase labeling. Sample transfer between MOD and the CE device is achieved through a capillary sipper driven by microfabricated valves and pumps [5]. The construction of a portable MOA instrument will facilitate in situ studies of amino acids in Mars analog sites such as the Atacama Desert in Chile. Preliminary chiral analyses of Atacama soil extracts on the microfabricated CE device have shown amino acid detection down to low ppb concentrations. Future field tests in the Atacama Desert will explore the feasibility of the portable CE device for performing in situ amino acid analysis. This work will provide the technology base for the development the Mars Organic Laboratory (MOL), a portable device that will analyze a broad suite of biomolecules, including nucleobases, sugars, and organic acids and bases [6]. [1]J.L. Bada, G.D. McDonald, Icarus 114 (1995) 139. [2]L.D. Hutt, D.P. Glavin, J.L. Bada, R.A. Mathies, Anal. Chem. 71 (1999) 4000. [3]A.M. Skelley, R.A. Mathies, J. Chromatogr. A (2003) in press. [4]G. Kminek, J.L. Bada, O. Botta, D.P. Glavin, F. Grunthaner, Planet. Space Sci. 48 (2000) 1087. [5]W.H. Grover, A.M. Skelley, C.N. Liu, E.T. Lagally, R.A. Mathies, Sens. Actuators B 89 (2003) 325. [6]A.M. Skelley, F.J. Grunthaner, J.F. Bada, R.A. Mathies, in SPIE: Proceedings of the In-Situ Instrument Technologies Meeting, Pasadena, CA, 2002.

The relationship of deiodinase 1 genotype and thyroid function to lifetime history of major depression in three independent populations.

PubMed

Philibert, Robert A; Beach, Steven R H; Gunter, Tracy D; Todorov, Alexandre A; Brody, Gene H; Vijayendran, Meeshanthini; Elliott, Lilly; Hollenbeck, Nancy; Russell, Daniel; Cutrona, Carolyn

2011-07-01

Major depression (MD) is often associated with disturbances of the hypothalamic/pituitary/thyroid (HPT) axis. Unfortunately, whether this association is secondary to common underlying genetic variation or whether the MD-associated disturbances in HPT function are chronic or state-dependent is unknown. To examine these questions, we genotyped 12 single nucleotide polymorphisms identified in previous genome wide association analyses of thyroid function in DNA contributed by 1,555 subjects from three longitudinal ethnically diverse studies that are well-characterized for lifetime MD and thyroid function. We then examined associations between genetic variants and key outcomes of thyroid stimulating hormone, free thyroxine (FT4) and depression. We confirmed prior findings that two variants in deiodinase 1 (DIO1), including a variant in the 3'UTR of DIO1 (rs11206244), were associated with altered FT4 levels in both White and African American subjects. We also found that rs11206244 genotype was associated with lifetime MD in White female subjects, in particular those from high-risk cohorts. However, we found no association of current FT4 levels with lifetime MD in either ethnic group. We conclude that genetic variation influencing thyroid function is a risk factor for MD. Given the evidence from prior studies, further investigations of role of HPT variation in etiology and treatment of MD are indicated. Copyright © 2011 Wiley-Liss, Inc.

Comparison of Mammographic Density Assessed as Volumes and Areas among Women Undergoing Diagnostic Image-Guided Breast Biopsy

PubMed Central

Gierach, Gretchen L.; Geller, Berta M.; Shepherd, John A.; Patel, Deesha A.; Vacek, Pamela M.; Weaver, Donald L.; Chicoine, Rachael E.; Pfeiffer, Ruth M.; Fan, Bo; Mahmoudzadeh, Amir Pasha; Wang, Jeff; Johnson, Jason M.; Herschorn, Sally D.; Brinton, Louise A.; Sherman, Mark E.

2014-01-01

Background Mammographic density (MD), the area of non-fatty appearing tissue divided by total breast area, is a strong breast cancer risk factor. Most MD analyses have employed visual categorizations or computer-assisted quantification, which ignore breast thickness. We explored MD volume and area, using a volumetric approach previously validated as predictive of breast cancer risk, in relation to risk factors among women undergoing breast biopsy. Methods Among 413 primarily white women, ages 40–65, undergoing diagnostic breast biopsies between 2007–2010 at an academic facility in Vermont, MD volume (cm3) was quantified in cranio-caudal views of the breast contralateral to the biopsy target using a density phantom, while MD area (cm2) was measured on the same digital mammograms using thresholding software. Risk factor associations with continuous MD measurements were evaluated using linear regression. Results Percent MD volume and area were correlated (r=0.81) and strongly and inversely associated with age, body mass index (BMI), and menopause. Both measures were inversely associated with smoking and positively associated with breast biopsy history. Absolute MD measures were correlated (r=0.46) and inversely related to age and menopause. Whereas absolute dense area was inversely associated with BMI, absolute dense volume was positively associated. Conclusions Volume and area MD measures exhibit some overlap in risk factor associations, but divergence as well, particularly for BMI. Impact Findings suggest that volume and area density measures differ in subsets of women; notably, among obese women, absolute density was higher with volumetric methods, suggesting that breast cancer risk assessments may vary for these techniques. PMID:25139935

Levels of disability in major depression: findings from the Netherlands Mental Health Survey and Incidence Study (NEMESIS).

PubMed

Kruijshaar, M E; Hoeymans, N; Bijl, R V; Spijker, J; Essink-Bot, M L

2003-10-01

Information on the distribution of disability associated with major depression (MD) across different groups of patients is of interest to health policy and planning. We examined the associations of severity and type (a single or recurrent episode) of MD with disability in a Dutch general population sample. We used data from the first wave (1996) of the Netherlands Mental Health Survey and Incidence Study (NEMESIS). MD 'severity' and 'type' were diagnosed with the help of the Composite International Diagnostic Interview according to DSM-III-R criteria. SF-36 scores, days ill in bed and days absent from work were taken as indicators of disability. The differences in these variables were studied by means of variance and regression analysis. Recurrent MD was found not to be associated with more disability than single episode MD. Higher 'severity' classes were associated with more disability. However, the degree of disability between 'moderate' and 'severe' MD differed only very slightly. The difference in disability between non-depressed and mildly depressed individuals had a larger effect than between each successive pair of 'severity' classes. Three groups of MD can be distinguished based on the associated degree of disability: 'mild', 'moderate to severe' and 'severe with psychotic features'. In the future, these groups can be used to describe the distribution of disability in the depressed population. The marked difference between 'mild' MD and no MD suggests that 'mild' cases should be considered relevant.

The medial dorsal thalamic nucleus and the medial prefrontal cortex of the rat function together to support associative recognition and recency but not item recognition.

PubMed

Cross, Laura; Brown, Malcolm W; Aggleton, John P; Warburton, E Clea

2012-12-21

In humans recognition memory deficits, a typical feature of diencephalic amnesia, have been tentatively linked to mediodorsal thalamic nucleus (MD) damage. Animal studies have occasionally investigated the role of the MD in single-item recognition, but have not systematically analyzed its involvement in other recognition memory processes. In Experiment 1 rats with bilateral excitotoxic lesions in the MD or the medial prefrontal cortex (mPFC) were tested in tasks that assessed single-item recognition (novel object preference), associative recognition memory (object-in-place), and recency discrimination (recency memory task). Experiment 2 examined the functional importance of the interactions between the MD and mPFC using disconnection techniques. Unilateral excitotoxic lesions were placed in both the MD and the mPFC in either the same (MD + mPFC Ipsi) or opposite hemispheres (MD + mPFC Contra group). Bilateral lesions in the MD or mPFC impaired object-in-place and recency memory tasks, but had no effect on novel object preference. In Experiment 2 the MD + mPFC Contra group was significantly impaired in the object-in-place and recency memory tasks compared with the MD + mPFC Ipsi group, but novel object preference was intact. Thus, connections between the MD and mPFC are critical for recognition memory when the discriminations involve associative or recency information. However, the rodent MD is not necessary for single-item recognition memory.

Muscle Dysmorphia Symptomatology and Associated Psychological Features in Bodybuilders and Non-Bodybuilder Resistance Trainers: A Systematic Review and Meta-Analysis.

PubMed

Mitchell, Lachlan; Murray, Stuart B; Cobley, Stephen; Hackett, Daniel; Gifford, Janelle; Capling, Louise; O'Connor, Helen

2017-02-01

Muscle dysmorphia (MD) is associated with a self-perceived lack of size and muscularity, and is characterized by a preoccupation with and pursuit of a hyper-mesomorphic body. MD symptoms may hypothetically be more prevalent in bodybuilders (BBs) than in non-bodybuilder resistance trainers (NBBRTs). Our objective was to compare MD symptomatology in BBs versus NBBRTs and identify psychological and other characteristics associated with MD in these groups. We searched relevant databases from earliest record to February 2015 for studies examining MD symptoms in BBs and/or NBBRTs. Included studies needed to assess MD using a psychometrically validated assessment tool. Study quality was evaluated using an adapted version of the validated Downs and Black tool. We calculated between-group standardized mean difference (effect sizes [ESs]) and 95 % confidence intervals (CIs) for each MD subscale, and performed meta-analysis when five or more studies used the same MD tool. We also extracted data describing psychological or other characteristics associated with MD. Of the 2135 studies initially identified, 31 analyzing data on 5880 participants (BBs: n = 1895, NBBRTs: n = 3523, controls: n = 462) were eligible for inclusion, though study quality was generally poor-moderate (range 7-19/22). Most participants were male (90 %). Eight different MD assessment tools were used. Meta-analysis for five studies all using the Muscle Dysmorphia Inventory (MDI) revealed there was a medium to large pooled ES for greater MD symptomatology in BBs than in NBBRTs on all MDI subscales (ES 0.53-1.12; p ≤ 0.01). Competitive BBs scored higher than non-competitive BBs (ES 1.21, 95 % CI 0.82-1.60; p < 0.001). MD symptoms were associated with anxiety (r 0.32-0.42; p ≤ 0.01), social physique anxiety (r 0.26-0.75; p < 0.01), depression (r 0.23-0.53; p ≤ 0.01), neuroticism (r 0.38; p < 0.001), and perfectionism (r 0.35; p < 0.05) and were inversely associated with self-concept (r -0.32 to -0.36; p < 0.01) and self-esteem (r -0.42 to -0.47; p < 0.01). MD symptomatology was greater in BBs than in NBBRTs. Anxiety and social physique anxiety, depression, neuroticism, and perfectionism were positively associated with MD, while self-concept and self-esteem were negatively associated. It remains unclear whether these characteristics are exacerbated by bodybuilding, or whether individuals with these characteristics are attracted to the bodybuilding context.

Comparison of major depressive disorder and subthreshold depression among older adults in community long-term care.

PubMed

Lee, Mi Jin; Hasche, Leslie K; Choi, Sunha; Proctor, Enola K; Morrow-Howell, Nancy

2013-01-01

This study extends existing knowledge regarding the continuum between major depression (MD) and subthreshold depression (SD) by examining differences in symptomology and associative factors for a subpopulation of older adults with functional disability. Our sample consisted of clients age 60 and above entering public community long term care derived from the baseline survey of a longitudinal study (315 non-depressed, 74 MD, and 221 SD). We used the Diagnostic Interview Schedule to establish diagnoses of MD, the Center for Epidemiological Studies Depression Scale (CES-D) to assess SD, and other self-report measures to explore potential associative factors of demographics, comorbidity, social support, and stressors. No differences in CES-D identified symptoms occurred between the two groups. MD and SD were both associated with lower education, poorer social support, more severe medical conditions, and higher stress when compared to non-depressed older adults. Younger age and being female were associated solely with MD; whereas, worse perceived health and more trouble affording food were associated solely with SD. The only associative factor significantly different between MD and SD was age. Those with MD were more likely to be younger than those with SD. Our findings of symptom profiles and associative factors lend support to the continuum notion of depression. Identification of only older adults within the community long-term care service system who meet criteria for MD would leave many older adults, who also face multiple comorbidities, high levels of stress and social isolation, and substantial depressive symptoms undiagnosed and untreated.

CALS Test Network Handbook

DTIC Science & Technology

1993-03-01

Ltd Gillette Company Dorset, England Boston MA Foreign Broadcast Information Set. Giordano Associates Inc Frederick MD Long Branch NJ Formtek Inc...Associates Orem UT College Park MD InfoDesign Corp Johns Hopkins University Toronto, Ontario Laurel MD Information Spectrum Inc Joint Committee on Printing...Inc Washington DC Bel Air MD Navy Naval Research Laboratory OutSource Inc Washington DC Los Angeles CA 22 i +’ . S.. . -- -,•w• -- w,,Wmwmm mm -- m mmm

Correlates of muscle dysmorphia symptomatology in natural bodybuilders: Distinguishing factors in the pursuit of hyper-muscularity.

PubMed

Mitchell, Lachlan; Murray, Stuart B; Hoon, Matthew; Hackett, Daniel; Prvan, Tania; O'Connor, Helen

2017-09-01

Muscle dysmorphia (MD) is characterized by the pathological pursuit of muscularity and leanness, which includes eating- and exercise-related practices. The aim of this cross-sectional study was to identify correlations of MD symptomatology in natural bodybuilders. An online survey assessing diet, supplementation and training practices, and MD and eating disorder symptoms was completed by male bodybuilders with recent experience competing in a drug-tested competition. Sixty participants (age 29.6±7.1 years) completed the survey. Eating disorder scores (β=.298), rate of pre-competition weight loss (β=.307) and number of competitions (β=-.257) were significant predictors of MD. The association between the EAT-26 and MDDI underscores the salience of disordered eating pathology in presentations of MD. Supporting this, greater rate of pre-competition weight loss, which may reflect disordered eating practices, is also associated with MD symptomatology. The inverse association of competition experience suggests novice bodybuilders may display increased MD symptomatology. Copyright © 2017 Elsevier Ltd. All rights reserved.

Identification of two novel mammographic density loci at 6Q25.1.

PubMed

Brand, Judith S; Li, Jingmei; Humphreys, Keith; Karlsson, Robert; Eriksson, Mikael; Ivansson, Emma; Hall, Per; Czene, Kamila

2015-06-03

Mammographic density (MD) is a strong heritable and intermediate phenotype for breast cancer, but much of its genetic variation remains unexplained. We performed a large-scale genetic association study including 8,419 women of European ancestry to identify MD loci. Participants of three Swedish studies were genotyped on a custom Illumina iSelect genotyping array and percent and absolute mammographic density were ascertained using semiautomated and fully automated methods from film and digital mammograms. Linear regression analysis was used to test for SNP-MD associations, adjusting for age, body mass index, menopausal status and six principal components. Meta-analyses were performed by combining P values taking sample size, study-specific inflation factor and direction of effect into account. Genome-wide significant associations were observed for two previously identified loci: ZNF365 (rs10995194, P = 2.3 × 10(-8) for percent MD and P = 8.7 × 10(-9) for absolute MD) and AREG (rs10034692, P = 6.7 × 10(-9) for absolute MD). In addition, we found evidence of association for two variants at 6q25.1, both of which are known breast cancer susceptibility loci: rs9485370 in the TAB2 gene (P = 4.8 × 10(-9) for percent MD and P = 2.5 × 10(-8) for absolute MD) and rs60705924 in the CCDC170/ESR1 region (P = 2.2 × 10(-8) for absolute MD). Both regions have been implicated in estrogen receptor signaling with TAB2 being a potential regulator of tamoxifen response. We identified two novel MD loci at 6q25.1. These findings underscore the importance of 6q25.1 as a susceptibility region and provide more insight into the mechanisms through which MD influences breast cancer risk.

Cross-sectional-derived determinants of satisfaction with physician-scientist training among Canadian MD/PhD graduates.

PubMed

Twa, David D W; Skinnider, Michael A; Squair, Jordan W; Lukac, Christine D

2017-01-01

Although MD/PhD programs require considerable commitment on behalf of students and learning institutions, they serve as an integral means of training future physician-scientists; individuals who engage in translational medicine. As attrition from these programs has longstanding effects on the community of translational medicine and comes at substantial cost to MD/PhD programs, we aimed to identify determinants that were associated with satisfaction among MD/PhD graduates, a feature that might inform on limiting program attrition. Anonymized data from a national survey of 139 Canadian MD/PhD alumni was analyzed. Factor analysis was conducted to evaluate the reliability of three questions that measured satisfaction and logistic regression was used to assess the association of outcomes with 17 independent determinants. Eighty-one percent of graduates were satisfied with MD/PhD training. Factor analysis confirmed the reliability of the questions measuring satisfaction. Determinants of self-reported satisfaction with physician-scientist training included co-authorship of more than six manuscripts during MD/PhD training. Additionally, protected research time at the place of current appointment was strongly associated with agreement that MD/PhD training had helped career progression. Demographic variables were not associated with any satisfaction indicator. Taken together, the majority of Canadian MD/PhD graduates are satisfied with their physician-scientist training. Project collaboration leading to co-authorships and protected research time were strongly associated with training satisfaction among graduates. If the value of collaboration can be realized among current and future physician-scientist trainees who are dissatisfied with their training, this might ultimately reduce program attrition.

Cognitive arithmetic and problem solving: a comparison of children with specific and general mathematics difficulties.

PubMed

Jordan, N C; Montani, T O

1997-01-01

This study examined problem-solving and number-fact skills in two subgroups of third-grade children with mathematics difficulties (MD): MD-specific (n = 12) and MD-general (n = 12). The MD-specific group had difficulties in mathematics but not in reading, and the MD-general group had difficulties in reading as well as in mathematics. A comparison group of nonimpaired children (n = 24) also was included. The findings showed that on both story and number-fact problems, the MD-specific group performed worse than the nonimpaired group in timed conditions but not in untimed conditions. The MD-general group, on the other hand, performed worse than the nonimpaired group, regardless of whether tasks were timed or not. An analysis of children's strategies in untimed conditions showed that both the MD-specific and the MD-general groups relied more on backup strategies than the nonimpaired group. However, children in the MD-specific group executed backup strategies more skillfully than children in the MD-general group, allowing them to achieve parity with children in the nonimpaired group when tasks were not timed. The findings suggest that children with specific MD have circumscribed deficits associated with fact retrieval, whereas children with general MD have more basic delays associated with problem conceptualization and execution of calculation procedures.

Association of past and recent major depression and menstrual characteristics in midlife: Study of Women's Health Across the Nation.

PubMed

Bromberger, Joyce T; Schott, Laura L; Matthews, Karen A; Kravitz, Howard M; Randolph, John F; Harlow, Sioban; Crawford, Sybil; Green, Robin; Joffe, Hadine

2012-09-01

The aim of this study was to examine the association of a history of major depression (MD) with menstrual problems in a multiethnic sample of midlife women. Participants were 934 women enrolled in the Study of Women's Health Across the Nation, a multisite study of menopause and aging. The outcomes were menstrual bleeding problems and premenstrual symptoms in the year before study entry. The Structured Clinical Interview for the Diagnosis of DSM-IV Axis I Disorders was conducted to determine recent and past psychiatric diagnoses. Covariates included sociodemographic, behavioral, and gynecologic factors. One third of the participants reported heavy bleeding, 20% reported other abnormal bleeding, and 18% reported premenstrual symptoms. One third had past and 11% had recent MD. Past MD was associated with an increased likelihood of heavy bleeding (odds ratio, 1.89; 95% CI, 1.25-2.85), adjusting for recent MD, menopause status, and other covariates. Past MD was not associated with other abnormal bleeding or premenstrual symptoms in the final analysis that adjusted for recent MD. Midlife women with a history of MD are more likely to report heavy bleeding.

Alteration of complex negative emotions induced by music in euthymic patients with bipolar disorder.

PubMed

Choppin, Sabine; Trost, Wiebke; Dondaine, Thibaut; Millet, Bruno; Drapier, Dominique; Vérin, Marc; Robert, Gabriel; Grandjean, Didier

2016-02-01

Research has shown bipolar disorder to be characterized by dysregulation of emotion processing, including biases in facial expression recognition that is most prevalent during depressive and manic states. Very few studies have examined induced emotions when patients are in a euthymic phase, and there has been no research on complex emotions. We therefore set out to test emotional hyperreactivity in response to musical excerpts inducing complex emotions in bipolar disorder during euthymia. We recruited 21 patients with bipolar disorder (BD) in a euthymic phase and 21 matched healthy controls. Participants first rated their emotional reactivity on two validated self-report scales (ERS and MAThyS). They then rated their music-induced emotions on nine continuous scales. The targeted emotions were wonder, power, melancholy and tension. We used a specific generalized linear mixed model to analyze the behavioral data. We found that participants in the euthymic bipolar group experienced more intense complex negative emotions than controls when the musical excerpts induced wonder. Moreover, patients exhibited greater emotional reactivity in daily life (ERS). Finally, a greater experience of tension while listening to positive music seemed to be mediated by greater emotional reactivity and a deficit in executive functions. The heterogeneity of the BD group in terms of clinical characteristics may have influenced the results. Euthymic patients with bipolar disorder exhibit more complex negative emotions than controls in response to positive music. Copyright © 2015 Elsevier B.V. All rights reserved.

A revision of the New World species of Gymnoclasiopa Hendel (Diptera, Ephydridae)

PubMed Central

Mathis, Wayne N.; Zatwarnicki, Tadeusz

2012-01-01

Abstract Species of the shore-fly genus Gymnoclasiopa Hendel from the New World are revised, including Gymnoclasiopa grecorum sp. n. (Alaska. Juneau: Gastineau Channel, Thane Road (S Juneau; 58°16.9'N, 134°22.4'W)) and Gymnoclasiopa matanuska sp. n. (Alaska. Matanuska-Susitna: Palmer (Matanuska River; 61°36.5'N, 149°04.1'W)). We also clarify the status of previously described species, including those now discovered to have Holarctic distributions and/or for which sexual dimorphism was not appreciated and the species was described twice, including Gymnoclasiopa montana (Cresson) as a syn. n. of Gymnoclasiopa bohemanni (Becker). Two species, Gymnoclasiopa bella (Mathis), comb. n., and Gymnoclasiopa chiapas (Mathis), comb. n., are transferred from Ditrichophora to Gymnoclasiopa, and Gymnoclasiopa cana Cresson stat. rev. and Ditrichophora canifrons Cresson, stat. rev. are returned to Ditrichophora, the genus in which Cresson originally described them. A neotype is designated for Gymnoclasiopa tacoma to stabilize the nomenclature of this species. The two excluded species, Ditrichophora cana and Ditrichophora canifrons, are diagnosed and distributional data are also provided. For all known New World species of Gymnoclasiopa, structures of the male terminalia are described for the first time and are fully illustrated. Detailed locality data and distribution maps are also included. To provide context and also to facilitate identification, diagnoses are included for the tribe Discocerinini and genus in addition to a key to the genera and species occurring in the New World. PMID:23275757

Comorbidity between reading disability and math disability: concurrent psychopathology, functional impairment, and neuropsychological functioning.

PubMed

Willcutt, Erik G; Petrill, Stephen A; Wu, Sarah; Boada, Richard; Defries, John C; Olson, Richard K; Pennington, Bruce F

2013-01-01

Reading disability (RD) and math disability (MD) frequently co-occur, but the etiology of this comorbidity is not well understood. Groups with RD only (N = 241), MD only (N = 183), and RD + MD (N = 188) and a control group with neither disorder (N = 411) completed a battery of measures of internalizing and externalizing psychopathology, social and academic functioning, and 10 neuropsychological processes. Groups with RD only, MD only, and RD + MD were significantly impaired versus the control group on nearly all measures, and the group with RD + MD was more impaired than the groups with MD and RD alone on measures of internalizing psychopathology, academic functioning, and 7 of 10 neuropsychological constructs. Multiple regression analyses of the neuropsychological measures indicated that deficits in reading and math were associated with shared weaknesses in working memory, processing speed, and verbal comprehension. In contrast, reading difficulties were uniquely associated with weaknesses in phoneme awareness and naming speed, and math deficits were uniquely associated with weaknesses in set shifting. These results support multiple-deficit neuropsychological models of RD and MD and suggest that RD and MD are distinct but related disorders that co-occur because of shared neuropsychological weaknesses in working memory, processing speed, and verbal comprehension.

Maternal depression and infant development: theory and current evidence.

PubMed

Miklush, Lisa; Connelly, Cynthia D

2013-01-01

Maternal depression (MD) is a condition that has wide-ranging effects on the woman, her family, and the broader global society. It is generally agreed that MD is associated with untoward effects on the developmental trajectory of offspring. The aim of this article is to review the historical and theoretical underpinnings informing current thought linking MD with infant development, and to highlight some of the neuroendocrine and epigenetic processes related to MD and its sequelae. A broad understanding of the association between MD and infant developmental outcomes can inform nursing care of the childbearing family.

Clinical evaluation of Morgellons disease in a cohort of North American patients

PubMed Central

Fesler, Melissa C.; Middelveen, Marianne J.; Stricker, Raphael B.

2018-01-01

Morgellons disease (MD) is a dermatological condition characterized by aberrant production of keratin and collagen fibers in skin. Although infection with Borrelia burgdorferi, the causative agent of Lyme disease (LD), has been associated with MD, relatively few studies have hitherto provided epidemiological evidence regarding this association. A cohort of 1000 seropositive North American LD patients was evaluated for the presence of MD. Patients were diagnosed with MD based on detection of microscopic fibers in skin lesions or under unbroken skin. Demographic and clinical features of MD patients were analyzed, and laboratory testing for tickborne coinfections and other infectious agents, was performed. Subjective and objective features of MD were analyzed using statistical methods. Of 1000 seropositive LD patients, 60 (6%) were diagnosed with MD. Of these 60 patients, 75% were female and 78% presented in the late disseminated stage of MD. All 60 patients (100%) were seropositive for B. burgdorferi infection. Tickborne coinfections in these patients included Babesia spp (62%), Bartonella and Rickettsia (25% each), Ehrlichia (15%) and Anaplasma (10%). Helicobacter pylori was detected in 12% of MD patients. In all, 77% of MD patients had one or more coinfections. This study confirms recent findings that MD occurs in a limited subset of LD patients. The clinical and genetic determinants of MD in LD patients require further study. PMID:29774138

Clinical evaluation of Morgellons disease in a cohort of North American patients.

PubMed

Fesler, Melissa C; Middelveen, Marianne J; Stricker, Raphael B

2018-04-23

Morgellons disease (MD) is a dermatological condition characterized by aberrant production of keratin and collagen fibers in skin. Although infection with Borrelia burgdorferi , the causative agent of Lyme disease (LD), has been associated with MD, relatively few studies have hitherto provided epidemiological evidence regarding this association. A cohort of 1000 seropositive North American LD patients was evaluated for the presence of MD. Patients were diagnosed with MD based on detection of microscopic fibers in skin lesions or under unbroken skin. Demographic and clinical features of MD patients were analyzed, and laboratory testing for tickborne coinfections and other infectious agents, was performed. Subjective and objective features of MD were analyzed using statistical methods. Of 1000 seropositive LD patients, 60 (6%) were diagnosed with MD. Of these 60 patients, 75% were female and 78% presented in the late disseminated stage of MD. All 60 patients (100%) were seropositive for B. burgdorferi infection. Tickborne coinfections in these patients included Babesia spp (62%), Bartonella and Rickettsia (25% each), Ehrlichia (15%) and Anaplasma (10%). Helicobacter pylori was detected in 12% of MD patients. In all, 77% of MD patients had one or more coinfections. This study confirms recent findings that MD occurs in a limited subset of LD patients. The clinical and genetic determinants of MD in LD patients require further study.

Mean diffusivity of globus pallidus associated with verbal creativity measured by divergent thinking and creativity‐related temperaments in young healthy adults

PubMed Central

Taki, Yasuyuki; Sekiguchi, Atsushi; Hashizume, Hiroshi; Nouchi, Rui; Sassa, Yuko; Kotozaki, Yuka; Miyauchi, Carlos Makoto; Yokoyama, Ryoichi; Iizuka, Kunio; Nakagawa, Seishu; Nagase, Tomomi; Kunitoki, Keiko; Kawashima, Ryuta

2015-01-01

Abstract Recent investigations revealed mean diffusivity (MD) in gray matter and white matter areas is correlated with individual cognitive differences in healthy subjects and show unique properties and sensitivity that other neuroimaging tools donot have. In this study, we tested the hypothesis that the MD in the dopaminergic system is associated with individual differences in verbal creativity measured by divergent thinking (VCDT) and novelty seeking based on prior studies suggesting associations between these and dopaminergic functions. We examined this issue in a large sample of right‐handed healthy young adults. We used analyses of MD and a psychological measure of VCDT, as well as personality measures of the Temperament and Character Inventory (TCI). Our results revealed associations between higher VCDT and lower MD in the bilateral globus pallidus. Furthermore, not only higher novelty seeking, but also lower harm avoidance, higher self‐directedness, and higher self‐transcendence were robustly associated with lower MD in the right globus pallidus, whereas higher persistence was associated with lower MD in the left globus pallidus. These personality variables were also associated with VCDT. The globus pallidus receives the dopaminergic input from the substantia nigra and plays a key role in motivation which is critically linked to dopamine. These results suggested the MD in the globus pallidus, underlie the association between VCDT and multiple personalities in TCI including novelty seeking. Hum Brain Mapp 36:1808–1827, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. PMID:25627674

Medical Department, United States Army. Surgery in World War 2. Neurosurgery. Volume 2

DTIC Science & Technology

1959-01-01

that there was no obstruction distal to the opening. They might close spontaneously in either area. If the fistula was small and spontaneous closure did...States Army Editor in Chief Colonel JOHN BOYD COATES, Jr ., MC Editors for Neurosurgery R. GLEN SPURLING, M.D. BARNES WOODHALL, M.D. Associate Editor...M.D. M. ELAOT RANDOLPH, M.D. STERLING BUNNELL, M.D. (dec.) ISIDOR S. RAVDIN, M.D. NORTON CANFIELD, M.D. ALFRED R. SHANDS, Jr ., M.D. B. NOLAND CARTER

Tests of causal links between alcohol abuse or dependence and major depression.

PubMed

Fergusson, David M; Boden, Joseph M; Horwood, L John

2009-03-01

There has been a great deal of research on the comorbidity between alcohol abuse or dependence (AAD) and major depression (MD). However, it is unclear whether AAD increases the risk of MD or vice versa. To examine the associations between AAD and MD using fixed-effects modeling to control for confounding and using structural equation models to ascertain the direction of causality. Data were gathered during the course of the Christchurch Health and Development Study, a 25-year longitudinal study of a birth cohort of children from New Zealand (635 boys, 630 girls). General community sample. The analysis was based on a sample of 1055 participants with available data on AAD and MD at ages 17 to 18, 20 to 21, and 24 to 25 years. Symptom criteria for AAD and MD from the DSM-IV at ages 17 to 18, 20 to 21, and 24 to 25 years as well as measures of life stress, cannabis use, other illicit drug use, affiliation with deviant peers, unemployment, partner substance use, and partner criminality at ages 17 to 18, 20 to 21, and 24 to 25 years. There were significant (P < .001) pooled associations between AAD and MD. Controlling for confounding factors using conditional fixed-effects models and time-dynamic covariate factors reduced the magnitude of these associations, but they remained statistically significant. Structural equation modeling suggested that the best-fitting causal model was one in which AAD led to increased risk of MD. The findings suggest that the associations between AAD and MD were best explained by a causal model in which problems with alcohol led to increased risk of MD as opposed to a self-medication model in which MD led to increased risk of AAD.

The Relationship of Deiodinase 1 Genotype and Thyroid Function to Lifetime History of Major Depression in Three Independent Populations

PubMed Central

Philibert, Robert A.; Beach, Steven R. H.; Gunter, Tracy D.; Todorov, Alexandre A.; Brody, Gene H.; Vijayendran, Meeshanthini; Elliott, Lilly; Hollenbeck, Nancy; Russell, Daniel; Cutrona, Carolyn

2011-01-01

Major depression (MD) is often associated with disturbances of the hypothalamic/pituitary/thyroid (HPT) axis. Unfortunately, whether this association is secondary to common underlying genetic variation or whether the MD-associated disturbances in HPT function are chronic or state-dependent is unknown. To examine these questions, we genotyped 12 single nucleotide polymorphisms identified in previous genome wide association analyses of thyroid function in DNA contributed by 1555 subjects from three longitudinal ethnically diverse studies that are well-characterized for lifetime major depression and thyroid function. We then examined associations between genetic variants and key outcomes of thyroid stimulating hormone (TSH), free thyroxine (FT4) and depression. We confirmed prior findings that two variants in deiodinase 1 (DIO1), including a variant in the 3’ UTR of DIO1 (rs11206244), were associated with altered free thyroxine (FT4) levels in both White and African American subjects. We also found that rs11206244 genotype was associated with lifetime MD in White female subjects, in particular those from high-risk cohorts. However, we found no association of current FT4 levels with lifetime MD in either ethnic group. We conclude that genetic variation influencing thyroid function is a risk factor for MD. Given the evidence from prior studies, further investigations of role of HPT variation in etiology and treatment of MD are indicated. PMID:21563302

Associative learning and regional white matter deficits in mild cognitive impairment.

PubMed

Boespflug, Erin L; Eliassen, James; Welge, Jeffrey; Krikorian, Robert

2014-01-01

While diagnostic criteria for Alzheimer's disease (AD) include neuroimaging biomarkers, there remains no definitive biomarker of mild cognitive impairment (MCI). MCI is a risk factor for AD that may be amenable to early intervention. Early decline in white matter (WM) integrity identified by diffusion tensor imaging (DTI) is a predictor of future progression of neurodegeneration. Identify regionally specific WM differences between individuals with MCI and those with age-associated memory impairment (AAMI) and relationships with specific memory decrements. DTI and neuropsychological data were acquired from 38 participants (23 MCI and 15 AAMI). A region of interest approach was used to evaluate regional differences between groups and correlative relationships with performance on memory tasks. Fornix WM had higher mean (MD), radial (DR), and axial (DA) diffusivity in MCI participants relative to AAMI. Temporal stem (TS) WM had higher MD and DR in MCI than in AAMI. In MCI, TS MD and DR varied, while fornix MD and DR was uniformly high, and in AAMI, TS MD and DR were uniformly low and fornix MD and DR varied. In MCI, TS MD and DA were inversely associated with associative learning but not list learning. In addition to supporting prior evidence implicating the fornix in early AD pathology, these data implicate a profile of neurodegeneration associated with early MCI. Further, they suggest that associative learning tasks are more sensitive to early neurodegeneration and may be useful in identifying individuals at risk for AD.

Dynamic changes in high and low mammographic density human breast tissues maintained in murine tissue engineering chambers during various murine peripartum states and over time.

PubMed

Chew, G L; Huang, D; Huo, C W; Blick, T; Hill, P; Cawson, J; Frazer, H; Southey, M D; Hopper, J L; Henderson, M A; Haviv, I; Thompson, E W

2013-07-01

Mammographic density (MD) is a strong heritable risk factor for breast cancer, and may decrease with increasing parity. However, the biomolecular basis for MD-associated breast cancer remains unclear, and systemic hormonal effects on MD-associated risk is poorly understood. This study assessed the effect of murine peripartum states on high and low MD tissue maintained in a xenograft model of human MD. Method High and low MD human breast tissues were precisely sampled under radiographic guidance from prophylactic mastectomy specimens of women. The high and low MD tissues were maintained in separate vascularised biochambers in nulliparous or pregnant SCID mice for 4 weeks, or mice undergoing postpartum involution or lactation for three additional weeks. High and low MD biochamber material was harvested for histologic and radiographic comparisons during various murine peripartum states. High and low MD biochamber tissues in nulliparous mice were harvested at different timepoints for histologic and radiographic comparisons. Results High MD biochamber tissues had decreased stromal (p = 0.0027), increased adipose (p = 0.0003) and a trend to increased glandular tissue areas (p = 0.076) after murine postpartum involution. Stromal areas decreased (p = 0.042), while glandular (p = 0.001) and adipose areas (p = 0.009) increased in high MD biochamber tissues during lactation. A difference in radiographic density was observed in high (p = 0.0021) or low MD biochamber tissues (p = 0.004) between nulliparous, pregnant and involution groups. No differences in tissue composition were observed in high or low MD biochamber tissues maintained for different durations, although radiographic density increased over time. Conclusion High MD biochamber tissues had measurable histologic changes after postpartum involution or lactation. Alterations in radiographic density occurred in biochamber tissues between different peripartum states and over time. These findings demonstrate the dynamic nature of the human MD xenograft model, providing a platform for studying the biomolecular basis of MD-associated cancer risk.

Prevention of Infections Associated With Combat-Related Eye, Maxillofacial, and Neck Injuries

DTIC Science & Technology

2011-08-01

REVIEW ARTICLE Prevention of Infections Associated With Combat-Related Eye, Maxillofacial, and Neck Injuries Kyle Petersen, DO, FACP, FIDSA...Marcus H Colyer, MD, David K. Hayes, MD, FACS, Robert G. Hale, DDS, R. B1yan Bell, DDS, MD, FACS, and the Prevention of Combat-Related Infections ...article reviews recent data from military and civilian studies to support evidence-based recommendations for the prevention of infections associated

Non-renewable water use on the globe and its implication to sea level change

NASA Astrophysics Data System (ADS)

Oki, T.; Pokhrel, Y. N.; Hanasaki, N.; Koirala, S.; Kanae, S.

2012-12-01

The real hydrological cycles on the Earth are not natural anymore. Global hydrological model simulations of the water cycle and available water resources should have an ability to consider the effects of human interventions on hydrological cycles. Anthropogenic activity modules, such as reservoir operation, crop growth and water demand in croplands, and environmental flows, were incorporated into a land surface model to form a new model, MAT-HI. Total terrestrial water storages (TWS) in large river basins were estimated using the new model by off-line simulation, and compared with the TWS observed by GRACE for 2002-2007. MAT-HI was further coupled with a module representing the ground water level fluctuations, and consists a new land surface scheme HiGW-MAT (Human Intervention and Ground Water coupled MATSIRO). HiGW-MAT is also associated with a scheme tracing the origin and flow path with the consideration on the sources of water withdrawal from stream flow, medium-size reservoirs and nonrenewable groundwater in addition to precipitation to croplands which enabled the assessment of the origin of water producing major crops. Areas highly dependent on nonrenewable groundwater are detected in the Pakistan, Bangladesh, Western part of India, north and western parts of China, some regions in the Arabian Peninsula, and the western part of the United States through Mexico. Cumulative nonrenewable groundwater withdrawals estimated by the model are corresponding fairly well with the country statistics of total groundwater withdrawals. Ground water table depletions in large aquifers in US estimated by HiGW-MAT were compared with in-situ observational data, and the correspondences are very good. Mean global exploitation of ground water for 2000 estimated by HiGW-MAT is 360 km3/y as an excess of ground water withdrawal over natural recharge into aquifer. This unsustainable groundwater use, together with artificial reservoir water impoundment, climate-driven changes in terrestrial water storage and the loss of water from closed basins, could have contributed a sea-level rise of about 0.77mm/y between 1961 and 2003, about 42% of the observed sea-level rise.

Microsatellite markers associated with resistance to Marek's disease in commercial layer chickens.

PubMed

McElroy, J P; Dekkers, J C M; Fulton, J E; O'Sullivan, N P; Soller, M; Lipkin, E; Zhang, W; Koehler, K J; Lamont, S J; Cheng, H H

2005-11-01

The objective of the current study was to identify QTL conferring resistance to Marek's disease (MD) in commercial layer chickens. To generate the resource population, 2 partially inbred lines that differed in MD-caused mortality were intermated to produce 5 backcross families. Vaccinated chicks were challenged with very virulent plus (vv+) MD virus strain 648A at 6 d and monitored for MD symptoms. A recent field isolate of the MD virus was used because the lines were resistant to commonly used older laboratory strains. Selective genotyping was employed using 81 microsatellites selected based on prior results with selective DNA pooling. Linear regression and Cox proportional hazard models were used to detect associations between marker genotypes and survival. Significance thresholds were validated by simulation. Seven and 6 markers were significant based on proportion of false positive and false discovery rate thresholds less than 0.2, respectively. Seventeen markers were associated with MD survival considering a comparison-wise error rate of 0.10, which is about twice the number expected by chance, indicating that at least some of the associations represent true effects. Thus, the present study shows that loci affecting MD resistance can be mapped in commercial layer lines. More comprehensive studies are under way to confirm and extend these results.

SVP-like MADS Box Genes Control Dormancy and Budbreak in Apple

PubMed Central

Wu, Rongmei; Tomes, Sumathi; Karunairetnam, Sakuntala; Tustin, Stuart D.; Hellens, Roger P.; Allan, Andrew C.; Macknight, Richard C.; Varkonyi-Gasic, Erika

2017-01-01

The annual growth cycle of trees is the result of seasonal cues. The onset of winter triggers an endodormant state preventing bud growth and, once a chilling requirement is satisfied, these buds enter an ecodormant state and resume growing. MADS-box genes with similarity to Arabidopsis SHORT VEGETATIVE PHASE (SVP) [the SVP-like and DORMANCY ASSOCIATED MADS-BOX (DAM) genes] have been implicated in regulating flowering and growth-dormancy cycles in perennials. Here, we identified and characterized three DAM-like (MdDAMs) and two SHORT VEGETATIVE PHASE-like (MdSVPs) genes from apple (Malus × domestica ‘Royal Gala’). The expression of MdDAMa and MdDAMc indicated they may play a role in triggering autumn growth cessation. In contrast, the expression of MdDAMb, MdSVPa and MdSVPb suggested a role in maintaining bud dormancy. Consistent with this, ectopic expression of MdDAMb and MdSVPa in ‘Royal Gala’ apple plants resulted in delayed budbreak and architecture change due to constrained lateral shoot outgrowth, but normal flower and fruit development. The association of MdSVPa and MdSVPb expression with floral bud development in the low fruiting ‘Off’ trees of a biennial bearing cultivar ‘Sciros’ suggested the SVP genes might also play a role in floral meristem identity. PMID:28421103

High Mammographic Density in Long-Term Night-Shift Workers: DDM-Spain/Var-DDM.

PubMed

Pedraza-Flechas, Ana María; Lope, Virginia; Sánchez-Contador, Carmen; Santamariña, Carmen; Pedraz-Pingarrón, Carmen; Moreo, Pilar; Ederra, María; Miranda-García, Josefa; Vidal, Carmen; Llobet, Rafael; Aragonés, Nuria; Salas-Trejo, Dolores; Pollán, Marina; Pérez-Gómez, Beatriz

2017-06-01

Background: Night-shift work (NSW) has been suggested as a possible cause of breast cancer, and its association with mammographic density (MD), one of the strongest risk factors for breast cancer, has been scarcely addressed. This study examined NSW and MD in Spanish women. Methods: The study covered 2,752 women aged 45-68 years recruited in 2007-2008 in 7 population-based public breast cancer screening centers, which included 243 women who had performed NSW for at least one year. Occupational data and information on potential confounders were collected by personal interview. Two trained radiologist estimated the percentage of MD assisted by a validated semiautomatic computer tool (DM-scan). Multivariable mixed linear regression models with random screening center-specific intercepts were fitted using log-transformed percentage of MD as the dependent variable and adjusting by known confounding variables. Results: Having ever worked in NSW was not associated with MD [Formula: see text]:0.96; 95% confidence interval (CI), 0.86-1.06]. However, the adjusted geometric mean of the percentage of MD in women with NSW for more than 15 years was 25% higher than that of those without NSW history (MD >15 years :20.7% vs. MD never :16.5%;[Formula: see text]:1.25; 95% CI,1.01-1.54). This association was mainly observed in postmenopausal participants ([Formula: see text]:1.28; 95% CI, 1.00-1.64). Among NSW-exposed women, those with ≤2 night-shifts per week had higher MD than those with 5 to 7 nightshifts per week ([Formula: see text]:1.42; 95% CI, 1.10-1.84). Conclusions: Performing NSW was associated with higher MD only in women with more than 15 years of cumulated exposure. These findings warrant replication in futures studies. Impact: Our findings suggest that MD could play a role in the pathway between long-term NSW and breast cancer. Cancer Epidemiol Biomarkers Prev; 26(6); 905-13. ©2017 AACR . ©2017 American Association for Cancer Research.

Characterization of Ultra High Temperature Ceramics via Transmission Electron Microscopy. Part 2: UHTCs sintered with addition of TaSi2

DTIC Science & Technology

2010-01-21

substituted by Hf in the TaSi2 phase, indicating that this silicide has a great solubility for the group IV metals . At the triple point junctions Ta5Si3...Mathis Müller for his precious help in TEM specimens’ preparations . FA8655-09-M-4002 40 References 1. L. E. Toth: Transition Metal Carbides and...Transition Metal Disilicides,’ Acta Mater., 44, 3035 (1996). 21. H. Pastor and R. Meyer: An Investigation of the Effect of Additions of Metal Silicides

Expression levels of uridine 5'-diphospho-glucuronosyltransferase genes in breast tissue from healthy women are associated with mammographic density.

PubMed

Haakensen, Vilde D; Biong, Margarethe; Lingjærde, Ole Christian; Holmen, Marit Muri; Frantzen, Jan Ole; Chen, Ying; Navjord, Dina; Romundstad, Linda; Lüders, Torben; Bukholm, Ida K; Solvang, Hiroko K; Kristensen, Vessela N; Ursin, Giske; Børresen-Dale, Anne-Lise; Helland, Aslaug

2010-01-01

Mammographic density (MD), as assessed from film screen mammograms, is determined by the relative content of adipose, connective and epithelial tissue in the female breast. In epidemiological studies, a high percentage of MD confers a four to six fold risk elevation of developing breast cancer, even after adjustment for other known breast cancer risk factors. However, the biologic correlates of density are little known. Gene expression analysis using whole genome arrays was performed on breast biopsies from 143 women; 79 women with no malignancy (healthy women) and 64 newly diagnosed breast cancer patients, both included from mammographic centres. Percent MD was determined using a previously validated, computerized method on scanned mammograms. Significance analysis of microarrays (SAM) was performed to identify genes influencing MD and a linear regression model was used to assess the independent contribution from different variables to MD. SAM-analysis identified 24 genes differentially expressed between samples from breasts with high and low MD. These genes included three uridine 5'-diphospho-glucuronosyltransferase (UGT) genes and the oestrogen receptor gene (ESR1). These genes were down-regulated in samples with high MD compared to those with low MD. The UGT gene products, which are known to inactivate oestrogen metabolites, were also down-regulated in tumour samples compared to samples from healthy individuals. Several single nucleotide polymorphisms (SNPs) in the UGT genes associated with the expression of UGT and other genes in their vicinity were identified. Three UGT enzymes were lower expressed both in breast tissue biopsies from healthy women with high MD and in biopsies from newly diagnosed breast cancers. The association was strongest amongst young women and women using hormonal therapy. UGT2B10 predicts MD independently of age, hormone therapy and parity. Our results indicate that down-regulation of UGT genes in women exposed to female sex hormones is associated with high MD and might increase the risk of breast cancer.

Expression levels of uridine 5'-diphospho-glucuronosyltransferase genes in breast tissue from healthy women are associated with mammographic density

PubMed Central

2010-01-01

Introduction Mammographic density (MD), as assessed from film screen mammograms, is determined by the relative content of adipose, connective and epithelial tissue in the female breast. In epidemiological studies, a high percentage of MD confers a four to six fold risk elevation of developing breast cancer, even after adjustment for other known breast cancer risk factors. However, the biologic correlates of density are little known. Methods Gene expression analysis using whole genome arrays was performed on breast biopsies from 143 women; 79 women with no malignancy (healthy women) and 64 newly diagnosed breast cancer patients, both included from mammographic centres. Percent MD was determined using a previously validated, computerized method on scanned mammograms. Significance analysis of microarrays (SAM) was performed to identify genes influencing MD and a linear regression model was used to assess the independent contribution from different variables to MD. Results SAM-analysis identified 24 genes differentially expressed between samples from breasts with high and low MD. These genes included three uridine 5'-diphospho-glucuronosyltransferase (UGT) genes and the oestrogen receptor gene (ESR1). These genes were down-regulated in samples with high MD compared to those with low MD. The UGT gene products, which are known to inactivate oestrogen metabolites, were also down-regulated in tumour samples compared to samples from healthy individuals. Several single nucleotide polymorphisms (SNPs) in the UGT genes associated with the expression of UGT and other genes in their vicinity were identified. Conclusions Three UGT enzymes were lower expressed both in breast tissue biopsies from healthy women with high MD and in biopsies from newly diagnosed breast cancers. The association was strongest amongst young women and women using hormonal therapy. UGT2B10 predicts MD independently of age, hormone therapy and parity. Our results indicate that down-regulation of UGT genes in women exposed to female sex hormones is associated with high MD and might increase the risk of breast cancer. PMID:20799965

Clinical Investigation Program Annual Progress Report

DTIC Science & Technology

1989-10-01

Investigators: Linda K. Kullama, Ph.D., Dr. Kenneth T. Nakamura,MD; Dr. Venkataraman Balaraman, MD, Wayne M. Ichimura, Biomedical Engineer. Department/Section...Investigators: John R. Claybaugh, Ph.D.; Kenneth T. Nakamura, MD; Dr. Venkataraman Balaraman, M.D. Department/Section: Clinical Investigation/Physiology Key...Pigs and Rats Principal ’Investigator: Linda K. Kullama, Ph.D.; John R. Claybaugh, Ph.D. Associate Investigators: Dr. Venkataraman Balaraman, M.D.; Dr

The mediating effect of Mediterranean diet on the relation between smoking and colorectal cancer: a case-control study.

PubMed

Kontou, Niki; Psaltopoulou, Theodora; Soupos, Nick; Polychronopoulos, Evangelos; Xinopoulos, Dimitrios; Linos, Athena; Panagiotakos, Demosthenes B

2013-10-01

The protective role of Mediterranean diet (MD) and the detrimental effect of smoking on colorectal cancer (CRC) have already been shown. The aim of this work was to evaluate the potential mediating effect of MD on the association between the aforementioned factor (smoking) and CRC. It is a case-control study. Two hundred fifty consecutive patients with CRC (63 ± 12 years, 59% males) and 250 age-sex group-matched controls, both from the area of Attica, were studied. Various socio-demographic, clinical, lifestyle (including detailed smoking habits) and dietary characteristics were measured. Adherence to the MD was evaluated using the MedDietScore (theoretical range 0-55). Each unit increase in the MedDietScore was associated with 13% lower likelihood of CRC (P < 0.001). Smoking habits were associated with 2.9-fold the likelihood of CRC among participants who were away from the MD (i.e. MedDietScore < 29) and with 2.1-fold the likelihood of CRC among those who were close to the MD (P < 0.05). Adherence to the MD was associated with a less detrimental association of smoking habits with CRC, suggesting indirect benefits of adherence to this dietary pattern with regards to CRC morbidity and mortality.

Associations of urinary 5-methyl-2'-deoxycytidine and 5-hydroxymethyl-2'-deoxycytidine with phthalate exposure and semen quality in 562 Chinese adult men.

PubMed

Pan, Yitao; Jing, Jun; Yeung, Leo W Y; Sheng, Nan; Zhang, Hongxia; Yao, Bing; Dai, Jiayin

2016-09-01

5-methyl-2'-deoxycytidine (5mdC) and 5-hydroxymethyl-2'-deoxycytidine (5hmdC), products of DNA methylation and hydroxymethylation processes, have been detected previously in human urine, but their associations with environmental chemicals or healthy outcomes are unclear. The present investigation explored the associations between urinary 5mdC and 5hmdC with phthalate exposure and semen quality. We assessed semen parameters including sperm concentration, motility, and morphology, before measuring urinary 5mdC, 5hmdC and 13 phthalate metabolites among 562 subfertile men from Nanjing, China. Urinary 5mdC and 5hmdC were positively associated with the levels of low molecular weight phthalate metabolites (Low-MWP), high molecular weight phthalate metabolites (High-MWP), and the sum of all phthalate metabolites (ΣPAEs), respectively. Urinary 5mdC was associated with below-reference sperm concentration (odds ratios for increasing quartiles=1.0, 2.2, 3.0, 2.0; p for trend =0.02), sperm motility (1.0, 1.1, 1.9, 1.3; p for trend =0.05), and sperm morphology (1.0, 1.4, 2.3, 1.5; p for trend =0.05). Sperm concentration was associated with the highest quartile of urinary 5hmdC [odds ratio=1.9 (95% CI: 1.1, 3.6)]. Our findings showed significant associations between urinary 5mdC and 5hmdC with phthalate metabolites and semen parameters, which suggested urinary 5mdC and 5hmdC may be promising biomarkers in future epidemiological studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Clinical features of and risk factors for major depression with history of postpartum episodes in Han Chinese women: A retrospective study.

PubMed

Yang, Fuzhong; Gardner, Charles O; Bigdeli, Tim; Gao, Jingfang; Zhang, Zhen; Tao, Ming; Liu, Ying; Li, Youhui; Wang, Gang; Shi, Jianguo; Gao, Chengge; Zhang, Kerang; Li, Kan; Wang, Xumei; Liu, Lanfen; Sun, Jing; Du, Bo; Shi, Shenxun; Zhang, Jingbei; Wu, Wenyuan; Wang, Xueyi; Shen, Jianhua; Liu, Tiebang; Gu, Danhua; Liang, Wei; Deng, Hong; Pan, Jiyang; Yang, Lijun; Jian, Hu; Jiang, Guoqin; Meng, Huaqing; Miao, Guodong; Li, Yi; Hu, Chunmei; Huang, Guoping; Zhang, Yutang; Chen, Yunchun; Ha, Baowei; Gao, Shu; Fang, Xiang; Mei, Qiyi; Hong, Xiaohong; Yang, Donglin; Liu, Tieqiao; Fengyu, Yu; Zhong, Hui; Sang, Hong; Chen, Guibing; Cai, Min; Song, Yan; Dong, Jicheng; Shen, Zhenmin; Zhang, Wei; Wang, Xiaoping; Pan, Runde; Liu, Xiaojuan; Li, Yi; Liu, Zhengrong; Zhang, Qiwen; Li, Gongying; Flint, Jonathan; Kendler, Kenneth S

2015-09-01

We sought to investigate the clinical features of and risk factors for recurrent major depression (MD) with history of postpartum episodes (PPD) in Han Chinese women and the differences between first-onset postpartum MD (MD that has its first lifetime depressive episode in the postpartum period) and first-onset non-postpartum MD (MD with history of PPD and has its first lifetime depressive episode in a period other than postpartum). Data were derived from the China, Oxford and Virginia Commonwealth University Experimental Research on Genetic Epidemiology (CONVERGE) study (N=6017 cases) and analyzed in two steps. We first examined the clinical features of and risk factors for MD patients with (N=981) or without (N=4410) a history of PPD. We then compared the differences between first-onset postpartum MD (N=583) and first-onset non-postpartum MD (N=398) in those with a history of PPD. Linear, logistic and multinomial logistic models were employed to measure the associations. A history of PPD was associated with more guilt feelings, greater psychiatric comorbidity, higher neuroticism, earlier onset and more chronicity (OR 0.2-2.8). Severe premenstrual symptoms (PMS) and more childbirths increased the risk of PPD, as did a family history of MD, childhood sexual abuse, stressful life events and lack of social support (OR 1.1-1.3). In the MD with history of PPD subsample, first-onset postpartum MD was associated with fewer recurrent major depressive episodes, less psychiatric comorbidity, lower neuroticism, less severe PMS and fewer disagreements with their husbands (OR 0.5-0.8), but more childbirths (OR 1.2). Data were obtained retrospectively through interview and recall bias may have affected the results. MD with history of PPD in Han Chinese women is typically chronic and severe, with particular risk factors including severe PMS and more childbirths. First-onset postpartum MD and first-onset non-postpartum MD can be partly differentiated by their clinical features and risk factors, but are not clearly distinctive. Copyright © 2015. Published by Elsevier B.V.

Higher adherence to the Mediterranean diet is inversely associated with having hypertension: is low salt intake a mediating factor?

PubMed

La Verde, Melania; Mulè, Serena; Zappalà, Gaetano; Privitera, Gaetano; Maugeri, Giuseppe; Pecora, Francesco; Marranzano, Marina

2018-03-01

Blood pressure (BP) is a major risk factor for population health worldwide and a preventable disease through lifestyle modification. The aim of this study was to assess the association between adherence to the Mediterranean diet (MD) and occurrence of hypertension in a Mediterranean cohort. Demographic and dietary data of 1937 adults were collected in 2014-2015 from the general population of Catania, Sicily (Italy). Food frequency questionnaires and a MD adherence score were used to assess exposure variables. Higher adherence to the MD was inversely associated with hypertension. However, this association was no more significant after adjustment for sodium and potassium intake. These results suggest that salt may exert a mediating effect of high adherence to the MD towards hypertension.

Common genetic variation and novel loci associated with volumetric mammographic density.

PubMed

Brand, Judith S; Humphreys, Keith; Li, Jingmei; Karlsson, Robert; Hall, Per; Czene, Kamila

2018-04-17

Mammographic density (MD) is a strong and heritable intermediate phenotype of breast cancer, but much of its genetic variation remains unexplained. We conducted a genetic association study of volumetric MD in a Swedish mammography screening cohort (n = 9498) to identify novel MD loci. Associations with volumetric MD phenotypes (percent dense volume, absolute dense volume, and absolute nondense volume) were estimated using linear regression adjusting for age, body mass index, menopausal status, and six principal components. We also estimated the proportion of MD variance explained by additive contributions from single-nucleotide polymorphisms (SNP-based heritability [h 2 SNP ]) in 4948 participants of the cohort. In total, three novel MD loci were identified (at P < 5 × 10 - 8 ): one for percent dense volume (HABP2) and two for the absolute dense volume (INHBB, LINC01483). INHBB is an established locus for ER-negative breast cancer, and HABP2 and LINC01483 represent putative new breast cancer susceptibility loci, because both loci were associated with breast cancer in available meta-analysis data including 122,977 breast cancer cases and 105,974 control subjects (P < 0.05). h 2 SNP (SE) estimates for percent dense, absolute dense, and nondense volume were 0.29 (0.07), 0.31 (0.07), and 0.25 (0.07), respectively. Corresponding ratios of h 2 SNP to previously observed narrow-sense h 2 estimates in the same cohort were 0.46, 0.72, and 0.41, respectively. These findings provide new insights into the genetic basis of MD and biological mechanisms linking MD to breast cancer risk. Apart from identifying three novel loci, we demonstrate that at least 25% of the MD variance is explained by common genetic variation with h 2 SNP /h 2 ratios varying between dense and nondense MD components.

Exploration of the Association between Nurses' Moral Distress and Secondary Traumatic Stress Syndrome: Implications for Patient Safety in Mental Health Services

PubMed Central

Christodoulou-Fella, Maria; Papathanassoglou, Elizabeth D. E.

2017-01-01

Work-related moral distress (MD) and secondary traumatic stress syndrome (STSS) may be associated with compromised health status among health professionals, reduced productivity, and inadequate safety of care. We explored the association of MD with the severity of STSS symptoms, along with the mediating role of mental distress symptoms. Associations with emotional exhaustion and professional satisfaction were also assessed. This cross-sectional survey conducted in 206 mental health nurses (MHNs) was employed across public sector community and hospital settings in Cyprus. The analysis revealed that MD (measured by the modified Moral Distress Scale) was positively associated with both STSS (measured by the Secondary Traumatic Stress Scale) and mental distress symptoms (assessed by the General Health Questionnaire-28). The association of MD with STSS symptoms was partially mediated by mental distress symptoms. This association remained largely unchanged after adjusting for gender, age, education, rank, and intention to quit the job. Our findings provide preliminary evidence on the association between MD and STSS symptomatology in MHNs. Situations that may lead health professionals to be in moral distress seem to be mainly related to the work environment; thus interventions related to organizational empowerment of MHNs need to be developed. PMID:29209622

Essential Hypertension—Where Are We Going?

PubMed Central

Ives, Harlan E.

1990-01-01

This discussion was selected from the weekly staff conferences in the Department of Medicine, University of California, San Francisco. Taken from a transcription, it has been edited by Homer A. Boushey, MD, Professor of Medicine, and Nathan M. Bass, MD, PhD, Associate Professor of Medicine, under the direction of Lloyd H. Smith, Jr, MD, Professor of Medicine and Associate Dean in the School of Medicine. Images PMID:2244377

Mammographic density and risk of breast cancer according to tumor characteristics and mode of detection: a Spanish population-based case-control study

PubMed Central

2013-01-01

Introduction It is not clear whether high mammographic density (MD) is equally associated with all subtypes of breast cancer (BC). We investigated the association between MD and subsequent BC, considering invasiveness, means of detection, pathologic subtype, and the time elapsed since mammographic exploration and BC diagnosis. Methods BC cases occurring in the population of women who attended screening from 1997 through 2004 in Navarre, a Spanish region with a fully consolidated screening program, were identified via record linkage with the Navarre Cancer Registry (n = 1,172). Information was extracted from the records of their first attendance at screening in that period. For each case, we randomly selected four controls, matched by screening round, year of birth, and place of residence. Cases were classified according to invasiveness (ductal carcinoma in situ (DCIS) versus invasive tumors), pathologic subtype (considering hormonal receptors and HER2), and type of diagnosis (screen-detected versus interval cases). MD was evaluated by a single, experienced radiologist by using a semiquantitative scale. Data on BC risk factors were obtained by the screening program in the corresponding round. The association between MD and tumor subtype was assessed by using conditional logistic regression. Results MD was clearly associated with subsequent BC. The odds ratio (OR) for the highest MD category (MD >75%) compared with the reference category (MD <10%) was similar for DCIS (OR = 3.47; 95% CI = 1.46 to 8.27) and invasive tumors (OR = 2.95; 95% CI = 2.01 to 4.35). The excess risk was particularly high for interval cases (OR = 7.72; 95% CI = 4.02 to 14.81) in comparison with screened detected tumors (OR = 2.17; 95% CI = 1.40 to 3.36). Sensitivity analyses excluding interval cases diagnosed in the first year after MD assessment or immediately after an early recall to screening yielded similar results. No differences were seen regarding pathologic subtypes. The excess risk associated with MD persisted for at least 7 to 8 years after mammographic exploration. Conclusions Our results confirm that MD is an important risk factor for all types of breast cancer. High breast density strongly increases the risk of developing an interval tumor, and this excess risk is not completely explained by a possible masking effect. PMID:23360535

Arthroscopic management of posterior instability of the shoulder: A systematic review of predictive factors associated with poorer surgical outcomes.

PubMed

Jain, Sachin Ramesh; Sayampanathan, Andrew Arjun; Hwee Chye Tan, Andrew

2017-01-01

We aimed to perform a systematic review to identify factors that may lead to poorer outcomes in arthroscopic surgery for posterior shoulder instability. We searched MEDLINE, Embase and the Cochrane Database of Systematic Reviews for 757 unique articles. We eventually included 22 articles. Data were analysed using Review Manager 5.3. The presence of chondral damage was associated with poorer outcomes as reflected in a higher post-operative Quick Disabilities of theArm, Shoulder and Hand score (mean difference (MD) = 17.1; 95% confidence interval (CI) = 2.82-31.4; p = 0.02), higher WesternOntario Shoulder Instability (WOSI) index (MD = 468.0; 95% CI = 136.5-799.5; p = 0.006), lower Simple Shoulder Test score (MD = -2.40; 95% CI = -4.34 to -0.46; p = 0.02) and a lower Single Assessment Numeric Evaluation score (MD = -15.4; 95% CI = -30.6 to -0.23; p = 0.05). The presence of previous shoulder surgery was associated with poorer outcomes as depicted by a lower American Shoulder and Elbow Society (ASES) score (MD = -93.1; 95% CI = -96.9 to -89.3; p < 0.0001). The availability of workers' compensation was associated with poorer outcomes as revealed by a lower rate of return to work (odds ratio (OR) = 0.02; 95% CI = 0.00-0.20; p = 0.0008). The presence of additional procedures while performing surgery for posterior shoulder instability was associated with poorer outcomes as reflected by lower ASES scores (MD = -6.70; 95% CI = -8.64 to -4.76; p < 0.0001), higher WOSI index (MD = 63.4; 95% CI = 33.0-93.8; p < 0.0001), lower University of California at Los Angeles (UCLA) scores (MD = -2.30; 95% CI = -2.81 to -1.79; p < 0.0001), higher pain scores (MD = 0.72; 95% CI = 0.39-1.05; p < 0.0001) and higher post-operative instability (MD = 0.80; 95% CI = 0.57-1.03; p < 0.0001). The presence of chondral damage, previous shoulder surgery, concomitant surgery and workman's compensation was associated with poorer outcomes for arthroscopic repair of posterior shoulder instability. Further studies should be done to further validate these factors.

Association of spirochetal infection with Morgellons disease.

PubMed

Middelveen, Marianne J; Burugu, Divya; Poruri, Akhila; Burke, Jennie; Mayne, Peter J; Sapi, Eva; Kahn, Douglas G; Stricker, Raphael B

2013-01-01

Morgellons disease (MD) is an emerging multisystem illness characterized by skin lesions with unusual filaments embedded in or projecting from epithelial tissue. Filament formation results from abnormal keratin and collagen expression by epithelial-based keratinocytes and fibroblasts. Recent research comparing MD to bovine digital dermatitis, an animal infectious disease with similar skin features, provided clues that spirochetal infection could play an important role in the human disease as it does in the animal illness. Based on histological staining, immunofluorescent staining, electron microscopic imaging and polymerase chain reaction, we report the detection of Borrelia spirochetes in dermatological tissue of  four randomly-selected MD patients. The association of MD with spirochetal infection provides evidence that this infection may be a significant factor in the illness and refutes claims that MD lesions are self-inflicted and that people suffering from this disorder are delusional. Molecular characterization of the Borrelia spirochetes found in MD patients is warranted.

Association of spirochetal infection with Morgellons disease

PubMed Central

Stricker, Raphael B

2013-01-01

Morgellons disease (MD) is an emerging multisystem illness characterized by skin lesions with unusual filaments embedded in or projecting from epithelial tissue. Filament formation results from abnormal keratin and collagen expression by epithelial-based keratinocytes and fibroblasts. Recent research comparing MD to bovine digital dermatitis, an animal infectious disease with similar skin features, provided clues that spirochetal infection could play an important role in the human disease as it does in the animal illness. Based on histological staining, immunofluorescent staining, electron microscopic imaging and polymerase chain reaction, we report the detection of Borrelia spirochetes in dermatological tissue of  four randomly-selected MD patients. The association of MD with spirochetal infection provides evidence that this infection may be a significant factor in the illness and refutes claims that MD lesions are self-inflicted and that people suffering from this disorder are delusional. Molecular characterization of the Borrelia spirochetes found in MD patients is warranted. PMID:24715950

Mean diffusivity of basal ganglia and thalamus specifically associated with motivational states among mood states.

PubMed

Takeuchi, Hikaru; Taki, Yasuyuki; Sekiguchi, Atsushi; Nouchi, Rui; Kotozaki, Yuka; Nakagawa, Seishu; Miyauchi, Carlos Makoto; Iizuka, Kunio; Yokoyama, Ryoichi; Shinada, Takamitsu; Yamamoto, Yuki; Hanawa, Sugiko; Araki, Tsuyoshi; Kunitoki, Keiko; Sassa, Yuko; Kawashima, Ryuta

2017-03-01

Previously, we proposed that the mean diffusivity (MD), a measure of diffusion tensor imaging (DTI) in areas of the dopaminergic system (MDDS), is associated with motivation. In this study, we tested if and how the motivational state is associated with MD in comparison with other mood states. We also tested the associations of these mood states with multiple cognitive functions. We examined these issues in 766 right-handed healthy young adults. We employed analyses of MD and a psychological measure of the profile of mood states (POMS) as well as multiple cognitive functions. We detected associations between the higher Vigor subscale of POMS and lower MD in the right globus pallidum, right putamen to right posterior insula, right caudate body, and right thalamus, and these associations were highly specific to the Vigor subscale. Similarly, the association of the motivational state with creativity measured by divergent thinking (CMDT) was rather specific and prominent compared with that of the other mood states and cognitive functions. In conclusion, when affective states are finely divided, only the motivational state is associated with MD in the areas related to the dopaminergic system, and psychological mechanisms that had been associated with dopaminergic system (CMDT). These results suggest that these mechanisms specifically contribute to the motivational state and not to the other states, such as depression and anxiety.

Birthweight, early life body size and adult mammographic density: a review of epidemiologic studies.

PubMed

Yochum, Laura; Tamimi, Rulla M; Hankinson, Susan E

2014-10-01

To evaluate the association between birth weight and early life body size with adult mammographic density in the peer-reviewed literature. A comprehensive literature search was conducted through January, 2014. English language articles that assessed adult mammographic density (MD) in relation to early life body size (≤18 years old), or birthweight were included. Nine studies reported results for early life body size and %MD. Both exposure and outcome were assessed at different ages using multiple methods. In premenopausal women, findings were inconsistent; two studies reported significant, inverse associations, one reported a non-significant, inverse association, and two observed no association. Reasons for these inconsistencies were not obvious. In postmenopausal women, four of five studies supported an inverse association. Two of three studies that adjusted for menopausal status found significant, inverse associations. Birthweight and %MD was evaluated in nine studies. No association was seen in premenopausal women and two of three studies reported positive associations in postmenopausal women. Three of four studies that adjusted for menopausal status found no association. Early life body size and birthweight appear unrelated to %MD in premenopausal women while an inverse association in postmenopausal women is more likely. Although based on limited data, birthweight and %MD appear positively associated in postmenopausal women. Given the small number of studies, the multiple methods of data collection and analysis, other methodologic issues, and lack of consistency in results, additional research is needed to clarify this complex association and develop a better understanding of the underlying biologic mechanisms.

Symptomatic Meckel's diverticulum in newborn: two interesting additional cases and review of literature.

PubMed

Bertozzi, Mirko; Melissa, Berardino; Radicioni, Maurizio; Magrini, Elisa; Appignani, Antonino

2013-09-01

This study aimed to review the literature about symptomatic Meckel's diverticulum (MD) in the neonatal period with 2 additional uncommon cases. The authors describe 2 interesting neonatal cases of symptomatic MD and analyze the literature on this topic, with particular reference to the prevalence of sex, age at presentation, most common signs and symptoms, treatment, histology, associated anomalies, and outcome. The first patient was a term newborn with bowel obstruction by a pseudocystic MD. The second patient was a preterm infant with double perforation of the MD and ileum. Literature search for published case reports and case series on this topic reveals only 18 cases of neonatal symptomatic MD. Males are more frequently involved than females, and even preterm infants may be affected. Bowel obstruction (58.3%) and pneumoperitoneum (33.3%) are the most frequent clinical manifestation. Acute inflammation of the MD is the prominent histopathological finding (75%), although it does not seem to be related with the presence of heterotopic tissue within the MD. Surgical treatment is essential. The association of neonatal symptomatic MD with other anomalies is exceptional but is otherwise life threatening despite surgery. Bowel obstruction and pneumoperitoneum are the most frequent clinical manifestations of symptomatic MD in the newborn. Surgery is required for a definitive diagnosis and successful outcome.

The association between Mediterranean Diet Score and glucokinase regulatory protein gene variation on the markers of cardiometabolic risk: an analysis in the European Prospective Investigation into Cancer (EPIC)-Norfolk study.

PubMed

Sotos-Prieto, Mercedes; Luben, Robert; Khaw, Kay-Tee; Wareham, Nicholas J; Forouhi, Nita G

2014-07-14

Consumption of a Mediterranean diet (MD) and genetic variation in the glucokinase regulatory protein (GCKR) gene have been reported to be associated with TAG and glucose metabolism. It is uncertain whether there is any interaction between these factors. Therefore, the aims of the present study were to test the association of adherence to a MD and rs780094 (G>A) SNP in the GCKR gene with the markers of cardiometabolic risk, and to investigate the interaction between genetic variation and MD adherence. We studied 20 986 individuals from the European Prospective Investigation into Cancer (EPIC)-Norfolk study. The relative Mediterranean Diet Score (rMED: range 0-18) was used to assess MD adherence. Linear regression was used to estimate the association between the rMED, genotype and cardiometabolic continuous traits, adjusting for potential confounders. In adjusted analyses, we observed independent associations of MD adherence and genotype with cardiometabolic risk, with the highest risk group (AA genotype; lowest rMED) having higher concentrations of TAG, total cholesterol and apoB (12·5, 2·3 and 3·1%, respectively) v. those at the lowest risk (GG genotype; highest rMED). However, the associations of MD adherence with metabolic markers did not differ by genotype, with no significant gene-diet interactions for lipids or for glycated Hb. In conclusion, we found independent associations of the rMED and of the GCKR genotype with cardiometabolic profile, but found no evidence of interaction between them.

Validity of the Medical College Admission Test for predicting MD-PhD student outcomes.

PubMed

Bills, James L; VanHouten, Jacob; Grundy, Michelle M; Chalkley, Roger; Dermody, Terence S

2016-03-01

The Medical College Admission Test (MCAT) is a quantitative metric used by MD and MD-PhD programs to evaluate applicants for admission. This study assessed the validity of the MCAT in predicting training performance measures and career outcomes for MD-PhD students at a single institution. The study population consisted of 153 graduates of the Vanderbilt Medical Scientist Training Program (combined MD-PhD program) who matriculated between 1963 and 2003 and completed dual-degree training. This population was divided into three cohorts corresponding to the version of the MCAT taken at the time of application. Multivariable regression (logistic for binary outcomes and linear for continuous outcomes) was used to analyze factors associated with outcome measures. The MCAT score and undergraduate GPA (uGPA) were treated as independent variables; medical and graduate school grades, time-to-PhD defense, USMLE scores, publication number, and career outcome were dependent variables. For cohort 1 (1963-1977), MCAT score was not associated with any assessed outcome, although uGPA was associated with medical school preclinical GPA and graduate school GPA (gsGPA). For cohort 2 (1978-1991), MCAT score was associated with USMLE Step II score and inversely correlated with publication number, and uGPA was associated with preclinical GPA (mspGPA) and clinical GPA (mscGPA). For cohort 3 (1992-2003), the MCAT score was associated with mscGPA, and uGPA was associated with gsGPA. Overall, MCAT score and uGPA were inconsistent or weak predictors of training metrics and career outcomes for this population of MD-PhD students.

An Analysis of Success in Systems Program Management.

DTIC Science & Technology

1981-02-27

D’Neill Lt en. Edmund F. O’Connor Lt :en. john B. Hudson I t. Cen. Robert T. Marsh ’t. ’-en. Rotert C . Mathis It. Cen. Z.eorge H. 2yivester...Snaveiy Lt. Gen. Harry E. Goldsworthy Lt. Gen. Robert C . Ruegg Lt. Gen. Thomas P. Gerrity OSD/DDR&E Dr. m.J. Perry Dr. M. Currie Dr. John Foster OSD/PA&E...UNCLASSIFIED NI*2 fflfflfllfllflfflfEEhEhEEE El/llEEEEEl/E- EEEEEE/I/I- mE....-.I/1 Report F33615-8 - C -5184.11 rmi AN ANALYSIS OF SUCCESS IN SYSTEMS

Childhood sexual abuse and the development of recurrent major depression in Chinese women.

PubMed

Chen, Jing; Cai, Yiyun; Cong, Enzhao; Liu, Ying; Gao, Jingfang; Li, Youhui; Tao, Ming; Zhang, Kerang; Wang, Xumei; Gao, Chengge; Yang, Lijun; Li, Kan; Shi, Jianguo; Wang, Gang; Liu, Lanfen; Zhang, Jinbei; Du, Bo; Jiang, Guoqing; Shen, Jianhua; Zhang, Zhen; Liang, Wei; Sun, Jing; Hu, Jian; Liu, Tiebang; Wang, Xueyi; Miao, Guodong; Meng, Huaqing; Li, Yi; Hu, Chunmei; Li, Yi; Huang, Guoping; Li, Gongying; Ha, Baowei; Deng, Hong; Mei, Qiyi; Zhong, Hui; Gao, Shugui; Sang, Hong; Zhang, Yutang; Fang, Xiang; Yu, Fengyu; Yang, Donglin; Liu, Tieqiao; Chen, Yunchun; Hong, Xiaohong; Wu, Wenyuan; Chen, Guibing; Cai, Min; Song, Yan; Pan, Jiyang; Dong, Jicheng; Pan, Runde; Zhang, Wei; Shen, Zhenming; Liu, Zhengrong; Gu, Danhua; Wang, Xiaoping; Liu, Xiaojuan; Zhang, Qiwen; Li, Yihan; Chen, Yiping; Kendler, Kenneth S; Shi, Shenxun; Flint, Jonathan

2014-01-01

Our prior study in Han Chinese women has shown that women with a history of childhood sexual abuse (CSA) are at increased risk for developing major depression (MD). Would this relationship be found in our whole data set? Three levels of CSA (non-genital, genital, and intercourse) were assessed by self-report in two groups of Han Chinese women: 6017 clinically ascertained with recurrent MD and 5983 matched controls. Diagnostic and other risk factor information was assessed at personal interview. Odds ratios (ORs) were calculated by logistic regression. We confirmed earlier results by replicating prior analyses in 3,950 new recurrent MD cases. There were no significant differences between the two data sets. Any form of CSA was significantly associated with recurrent MD (OR 4.06, 95% confidence interval (CI) [3.19-5.24]). This association strengthened with increasing CSA severity: non-genital (OR 2.21, 95% CI 1.58-3.15), genital (OR 5.24, 95% CI 3.52-8.15) and intercourse (OR 10.65, 95% CI 5.56-23.71). Among the depressed women, those with CSA had an earlier age of onset, longer depressive episodes. Recurrent MD patients those with CSA had an increased risk for dysthymia (OR 1.60, 95%CI 1.11-2.27) and phobia (OR 1.41, 95%CI 1.09-1.80). Any form of CSA was significantly associated with suicidal ideation or attempt (OR 1.50, 95% CI 1.20-1.89) and feelings of worthlessness or guilt (OR 1.41, 95% CI 1.02-2.02). Intercourse (OR 3.47, 95%CI 1.66-8.22), use of force and threats (OR 1.95, 95%CI 1.05-3.82) and how strongly the victims were affected at the time (OR 1.39, 95%CI 1.20-1.64) were significantly associated with recurrent MD. In Chinese women CSA is strongly associated with recurrent MD and this association increases with greater severity of CSA. Depressed women with CSA have some specific clinical traits. Some features of CSA were associated with greater likelihood of developing recurrent MD.

AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY 2018 POSITION STATEMENT ON INTEGRATION OF INSULIN PUMPS AND CONTINUOUS GLUCOSE MONITORING IN PATIENTS WITH DIABETES MELLITUS.

PubMed

Grunberger, George; Handelsman, Yehuda; Bloomgarden, Zachary T; Fonseca, Vivian A; Garber, Alan J; Haas, Richard A; Roberts, Victor L; Umpierrez, Guillermo E

2018-03-01

This document represents the official position of the American Association of Clinical Endocrinologists and American College of Endocrinology. Where there are no randomized controlled trials or specific U.S. FDA labeling for issues in clinical practice, the participating clinical experts utilized their judgment and experience. Every effort was made to achieve consensus among the committee members. Position statements are meant to provide guidance, but they are not to be considered prescriptive for any individual patient and cannot replace the judgment of a clinician. AACE/ACE Task Force on Integration of Insulin Pumps and Continuous Glucose Monitoring in the Management of Patients With Diabetes Mellitus Chair George Grunberger, MD, FACP, FACE Task Force Members Yehuda Handelsman, MD, FACP, FNLA, MACE Zachary T. Bloomgarden, MD, MACE Vivian A. Fonseca, MD, FACE Alan J. Garber, MD, PhD, FACE Richard A. Haas, MD, FACE Victor L. Roberts, MD, MBA, FACP, FACE Guillermo E. Umpierrez, MD, CDE, FACP, FACE Abbreviations: AACE = American Association of Clinical Endocrinologists ACE = American College of Endocrinology A1C = glycated hemoglobin BGM = blood glucose monitoring CGM = continuous glucose monitoring CSII = continuous subcutaneous insulin infusion DM = diabetes mellitus FDA = Food & Drug Administration MDI = multiple daily injections T1DM = type 1 diabetes mellitus T2DM = type 2 diabetes mellitus SAP = sensor-augmented pump SMBG = self-monitoring of blood glucose STAR 3 = Sensor-Augmented Pump Therapy for A1C Reduction phase 3 trial.

Birth weight, childhood body mass index, and height in relation to mammographic density and breast cancer: a register-based cohort study.

PubMed

Andersen, Zorana J; Baker, Jennifer L; Bihrmann, Kristine; Vejborg, Ilse; Sørensen, Thorkild I A; Lynge, Elsebeth

2014-01-20

High breast density, a strong predictor of breast cancer may be determined early in life. Childhood anthropometric factors have been related to breast cancer and breast density, but rarely simultaneously. We examined whether mammographic density (MD) mediates an association of birth weight, childhood body mass index (BMI), and height with the risk of breast cancer. 13,572 women (50 to 69 years) in the Copenhagen mammography screening program (1991 through 2001) with childhood anthropometric measurements in the Copenhagen School Health Records Register were followed for breast cancer until 2010. With logistic and Cox regression models, we investigated associations among birth weight, height, and BMI at ages 7 to 13 years with MD (mixed/dense or fatty) and breast cancer, respectively. 8,194 (60.4%) women had mixed/dense breasts, and 716 (5.3%) developed breast cancer. Childhood BMI was significantly inversely related to having mixed/dense breasts at all ages, with odds ratios (95% confidence intervals) ranging from 0.69 (0.66 to 0.72) at age 7 to 0.56 (0.53 to 0.58) at age 13, per one-unit increase in z-score. No statistically significant associations were detected between birth weight and MD, height and MD, or birth weight and breast cancer risk. BMI was inversely associated with breast cancer, with hazard ratios of 0.91 (0.83 to 0.99) at age 7 and 0.92 (0.84 to 1.00) at age 13, whereas height was positively associated with breast cancer risk (age 7, 1.06 (0.98 to 1.14) and age 13, 1.08 (1.00 to 1.16)). After additional adjustment for MD, associations of BMI with breast cancer diminished (age 7, 0.97 (0.88 to 1.06) and age 13, 1.01 (0.93 to 1.11)), but remained with height (age 7, 1.06 (0.99 to 1.15) and age 13, 1.09 (1.01 to 1.17)). Among women 50 years and older, childhood body fatness was inversely associated with the breast cancer risk, possibly via a mechanism mediated by MD, at least partially. Childhood tallness was positively associated with breast cancer risk, seemingly via a pathway independent of MD. Birth weight was not associated with MD or breast cancer in this age group.

The relationship between childhood poverty, military service, and later life depression among men: Evidence from the Health and Retirement Study

PubMed Central

Bareis, Natalie; Mezuk, Briana

2017-01-01

Background Childhood poverty has been associated with depression in adulthood, but whether this relationship extends to later life major depression (MD) or is modified by military service is unclear. Methods Data come from the Health and Retirement Study (HRS) 2010 wave, a longitudinal, nationally representative study of older adults. Men with data on military service and childhood poverty were included (N = 6330). Childhood poverty was assessed by four indicators (i.e., parental unemployment, residential instability) experienced before age 16. Military service was categorized as veteran versus civilian, and during draft versus all-volunteer (after 1973) eras. Past year MD was defined by the Composite International Diagnostic Inventory. Results Four in ten men ever served, with 13.7% in the all-volunteer military. Approximately 12% of civilians, 8% draft era and 24% all-volunteer era veterans had MD. Childhood poverty was associated with higher odds of MD (Odds Ratio (OR): 2.38, 95% Confidence Interval (CI): 1.32–4.32) and higher odds of military service (OR: 2.58, 95% CI: 1.58–4.21). Military service was marginally associated with MD (OR: 1.28, 95% CI: 0.98–1.68) and did not moderate the association between childhood poverty and MD. Limitations Self-report data is subject to recall bias. The HRS did not assess childhood physical and emotional abuse, or military combat exposure. Conclusions Men raised in poverty had greater odds of draft and all-volunteer military service. Early-life experiences, independent of military service, appear associated with greater odds of MD. Assessing childhood poverty in service members may identify risk for depression in later life. PMID:27455351

The relationship between childhood poverty, military service, and later life depression among men: Evidence from the Health and Retirement Study.

PubMed

Bareis, Natalie; Mezuk, Briana

2016-12-01

Childhood poverty has been associated with depression in adulthood, but whether this relationship extends to later life major depression (MD) or is modified by military service is unclear. Data come from the Health and Retirement Study (HRS) 2010 wave, a longitudinal, nationally representative study of older adults. Men with data on military service and childhood poverty were included (N=6330). Childhood poverty was assessed by four indicators (i.e., parental unemployment, residential instability) experienced before age 16. Military service was categorized as veteran versus civilian, and during draft versus all-volunteer (after 1973) eras. Past year MD was defined by the Composite International Diagnostic Inventory. Four in ten men ever served, with 13.7% in the all-volunteer military. Approximately 12% of civilians, 8% draft era and 24% all-volunteer era veterans had MD. Childhood poverty was associated with higher odds of MD (Odds Ratio (OR): 2.38, 95% Confidence Interval (CI): 1.32-4.32) and higher odds of military service (OR: 2.58, 95% CI: 1.58-4.21). Military service was marginally associated with MD (OR: 1.28, 95% CI: 0.98-1.68) and did not moderate the association between childhood poverty and MD. Self-report data is subject to recall bias. The HRS did not assess childhood physical and emotional abuse, or military combat exposure. Men raised in poverty had greater odds of draft and all-volunteer military service. Early-life experiences, independent of military service, appear associated with greater odds of MD. Assessing childhood poverty in service members may identify risk for depression in later life. Copyright © 2016 Elsevier B.V. All rights reserved.

Smoking Cessation Treatment for Patients With Mental Disorders Using CBT and Combined Pharmacotherapy.

PubMed

Loreto, Aline Rodrigues; Carvalho, Carlos Felipe Cavalcanti; Frallonardo, Fernanda Piotto; Ismael, Flavia; Andrade, Arthur Guerra de; Castaldelli-Maia, João Maurício

2017-01-01

The aim of this study was to investigate smoking treatment effectiveness and retention in a population with and without mental disorders (MD). Participants received cognitive behavioral therapy (CBT) plus nicotine patch alone or in combination with other medications (i.e., gum, bupropion, or nortriptyline) for smoking cessation treatment in a Brazilian Psychosocial Care Center unit (CAPS), taking into account sociodemographics and smoking profile covariates. The study involved comparison of treatment success (seven-day point prevalence abstinence at the end of the treatment) and retention (presence of the individual in all of the four medical consultations and six group sessions) in two subsamples of patients with MD (n = 267) and without MD (n = 397) who were included in a six-week treatment provided by a CAPS from 2007 to 2013. The treatment protocol comprised group CBT and pharmacotherapy (nicotine patches, nicotine gums, and bupropion and nortriptyline available, prescribed by psychiatrists). Within patients with MD, CBT plus nicotine patch plus bupropion (aOR = 2.00, 95% CI [1.14, 3.50], p = .015) and CBT plus nicotine patch plus gum (aOR = 2.10, 95% CI [1.04, 4.23], p = .036) were associated with treatment success. Within patients without MD, female gender (aOR = 0.60, 95% CI [0.37, 0.95], p = .031) and lower Heaviness of Smoking Index score (aOR = 0.80, 95% CI [0.65, 0.99], p = .048) were associated with treatment success. No variable was associated with dropout or retention within patients with or without MD. Our findings support the use of CBT plus nicotine patch plus bupropion as well as CBT plus nicotine patch plus gum in samples with high rates of medical, psychiatric, and addiction disorders. These findings support those of previous studies in the general population. Pharmacological treatment associated with group CBT based on cognitive-behavioral concepts and combined with ongoing MD treatment seems to be the best option for smoking cessation treatment among patients with MD. Units that deal with patients with MD, such as CAPS in Brazil, should be encouraged to treat smoking addiction in this population. Future studies should investigate retention rates in other samples of patients with MD.

Rates of glaucomatous visual field change in a large clinical population.

PubMed

Chauhan, Balwantray C; Malik, Rizwan; Shuba, Lesya M; Rafuse, Paul E; Nicolela, Marcelo T; Artes, Paul H

2014-06-10

To determine the rate of glaucomatous visual field change in routine clinical care. Mean deviation (MD) rate was computed in one randomly selected eye of all glaucoma patients and suspects with ≥5 examinations in a tertiary eye-care center. Proportions of "fast" (MD rate, <-1 to -2 dB/y) and "catastrophic" (<-2 dB/y) progressors were determined. The MD rates were computed in tertile groups by the number of examinations, baseline age, and MD. The MD rates were compared to the Canadian Glaucoma Study (CGS), a prospective study with IOP interventions mandated by visual field progression, by pairwise matching of patients by baseline MD. There were 2324 patients with median (interquartile range) baseline age and MD of 65 (56, 74) years and -2.44 (-5.44, -0.86) dB, and follow-up of 7.1 (4.8, 10.2) years with 8 (6, 11) examinations. The median MD rate was -0.05 (0.13, -0.30) dB/y, while the mean follow-up IOP was 17.1 (15.0, 19.7) mm Hg. The MD rate was progressively worse, with a doubling of fast and catastrophic progressors, with each tertile of increasing age. Worse MD rate was associated with lower follow-up IOP. Neither MD rate nor the number of fast and catastrophic progressors was significantly different in clinical care patients matched to CGS patients. Most patients under routine glaucoma care demonstrate slow rates of visual field progression. The MD rate in the current study was similar to an interventional prospective study, but considerably less negative compared to published studies with similar design. Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

Neuronal activity patterns in the mediodorsal thalamus and related cognitive circuits are modulated by metabotropic glutamate receptors

PubMed Central

Copeland, C.S.; Neale, S.A.; Salt, T.E.

2015-01-01

The mediodorsal thalamus (MD) likely plays an important role in cognition as it receives abundant afferent connections from the amygdala and prefrontal cortex (PFC). Indeed, disturbed activity within the MD is thought to precipitate cognitive deficits associated with schizophrenia. As compounds acting at the Group II metabotropic glutamate (mGlu) receptors (subtypes mGlu2/mGlu3) have efficacy in animal models of schizophrenia, we investigated whether a Group II agonist and an mGlu2 positive allosteric modulator (PAM) could modulate MD activity. Extracellular single-unit recordings were made in vivo from MD neurones in anaesthetised rats. Responses were elicited by electrical stimulation of the PFC and/or amygdala, with Group II compounds locally applied as required. The Group II agonist reduced inhibition evoked in the MD: an effect manifested as an increase in short-latency responses, and a decrease in long-latency burst-firing. This disinhibitory action of the Group II receptors in the MD represents a mechanism of potential therapeutic importance as increased inhibition in the MD has been associated with cognitive deficit-onset. Furthermore, as co-application of the mGlu2 PAM did not potentiate the Group II agonist effects in the MD, we suggest that the Group II disinhibitory effect is majority-mediated via mGlu3. This heterogeneity in Group II receptor thalamic physiology bears consequence, as compounds active exclusively at the mGlu2 subtype are unlikely to perturb maladapted MD firing patterns associated with cognitive deficits, with activity at mGlu3 receptors possibly more appropriate. Indeed, polymorphisms in the mGlu3, but not the mGlu2, gene have been detected in patients with schizophrenia. PMID:25576798

Adherence to Mediterranean diet in relation to bone mineral density and risk of fracture: a systematic review and meta-analysis of observational studies.

PubMed

Malmir, Hanieh; Saneei, Parvane; Larijani, Bagher; Esmaillzadeh, Ahmad

2017-06-21

We aimed to systematically review available data on the association between adherence to MD and BMD as well as risk of fractures and to summarize this information through a meta-analysis. Previous studies in the field of adherence to MD in relation to BMD and risk of fracture were selected through searching PubMed, Scopus, ISI Web of Science and Google Scholar databases prior to June, 2016 using Mesh and non-Mesh relevant keywords. In the meta-analysis of four effect sizes, obtained from three studies, we found that adherence to MD was associated with a 21% reduced risk of hip fracture (overall RR 0.79; 95% CIs 0.72-0.87). Adherence to MD was positively associated with lumber spine ' s (mean difference of BMD comparing highest and lowest categories of MD score 0.12; 95% CI 0.06-0.19 g/cm 2 ), femoral neck (0.10; 0.06-0.15 g/cm 2 ) and total hip (0.11; 0.09-0.14 g/cm 2 ) BMD. Meta-regression of included observational studies revealed a significant inverse linear association between Mediterranean diet score and risk of hip fracture, such that one unit increase in the score of Mediterranean diet was associated with a reduction in the risk of hip fracture (RR 0.95, 95% CI 0.92-0.98 p = 0.01). Adherence to MD was associated with a reduced risk of fracture as well as with a higher mean BMD.

Trypsin-sensitive modulation of intestinal epithelial MD-2 as mechanism of lipopolysaccharide tolerance.

PubMed

Cario, Elke; Golenbock, Douglas T; Visintin, Alberto; Rünzi, Michael; Gerken, Guido; Podolsky, Daniel K

2006-04-01

Intestinal epithelial cells (IEC) are constantly exposed to both high concentrations of the bacterial ligand LPS and the serine protease trypsin. MD-2, which contains multiple trypsin cleavage sites, is an essential accessory glycoprotein required for LPS recognition and signaling through TLR4. The aim of this study was to characterize the expression and subcellular distribution of intestinal epithelial MD-2 and to delineate potential functional interactions with trypsin and then alteration in inflammatory bowel disease (IBD). Although MD-2 protein expression was minimal in primary IEC of normal colonic or ileal mucosa, expression was significantly increased in IEC from patients with active IBD colitis, but not in ileal areas from patients with severe Crohn's disease. Endogenous MD-2 was predominantly retained in the calnexin-calreticulin cycle of the endoplasmic reticulum; only a small fraction was exported to the Golgi. MD-2 expression correlated inversely with trypsin activity. Biochemical evidence and in vitro experiments demonstrated that trypsin exposure resulted in extensive proteolysis of endogenous and soluble MD-2 protein, but not of TLR4 in IEC, and was associated with desensitization of IEC to LPS. In conclusion, the present study suggests that endoplasmic reticulum-associated MD-2 expression in IBD may be altered by ileal protease in inflammation, leading to impaired LPS recognition and hyporesponsiveness through MD-2 proteolysis in IEC, thus implying a physiologic mechanism that helps maintain LPS tolerance in the intestine.

Morgellons disease: a filamentous borrelial dermatitis.

PubMed

Middelveen, Marianne J; Stricker, Raphael B

2016-01-01

Morgellons disease (MD) is a dermopathy characterized by multicolored filaments that lie under, are embedded in, or project from skin. Although MD was initially considered to be a delusional disorder, recent studies have demonstrated that the dermopathy is associated with tickborne infection, that the filaments are composed of keratin and collagen, and that they result from proliferation of keratinocytes and fibroblasts in epithelial tissue. Culture, histopathological and molecular evidence of spirochetal infection associated with MD has been presented in several published studies using a variety of techniques. Spirochetes genetically identified as Borrelia burgdorferi sensu stricto predominate as the infective agent in most of the Morgellons skin specimens studied so far. Other species of Borrelia including Borrelia garinii , Borrelia miyamotoi , and Borrelia hermsii have also been detected in skin specimens taken from MD patients. The optimal treatment for MD remains to be determined.

Morgellons disease: a filamentous borrelial dermatitis

PubMed Central

Middelveen, Marianne J; Stricker, Raphael B

2016-01-01

Morgellons disease (MD) is a dermopathy characterized by multicolored filaments that lie under, are embedded in, or project from skin. Although MD was initially considered to be a delusional disorder, recent studies have demonstrated that the dermopathy is associated with tickborne infection, that the filaments are composed of keratin and collagen, and that they result from proliferation of keratinocytes and fibroblasts in epithelial tissue. Culture, histopathological and molecular evidence of spirochetal infection associated with MD has been presented in several published studies using a variety of techniques. Spirochetes genetically identified as Borrelia burgdorferi sensu stricto predominate as the infective agent in most of the Morgellons skin specimens studied so far. Other species of Borrelia including Borrelia garinii, Borrelia miyamotoi, and Borrelia hermsii have also been detected in skin specimens taken from MD patients. The optimal treatment for MD remains to be determined. PMID:27789971

Influence of family history of major depression, bipolar disorder, and suicide on clinical features in patients with major depression and bipolar disorder.

PubMed

Serretti, Alessandro; Chiesa, Alberto; Calati, Raffaella; Linotte, Sylvie; Sentissi, Othman; Papageorgiou, Konstantinos; Kasper, Siegfried; Zohar, Joseph; De Ronchi, Diana; Mendlewicz, Julien; Amital, Daniela; Montgomery, Stuart; Souery, Daniel

2013-03-01

The extent to which a family history of mood disorders and suicide could impact on clinical features of patients suffering from major depression (MD) and bipolar disorder (BD) has received relatively little attention so far. The aim of the present work is, therefore, to assess the clinical implications of the presence of at least one first- and/or second-degree relative with a history of MD, BD and suicide in a large sample of patients with MD or BD. One thousand one hundred and fifty-seven subjects with MD and 686 subjects with BD were recruited within the context of two large projects. The impact of a family history of MD, BD, and suicide-considered both separately and together-on clinical and socio-demographic variables was investigated. A family history of MD, BD, and suicide was more common in BD patients than in MD patients. A positive family history of mood disorders and/or suicide as well as a positive family history of MD and BD separately considered, but not a positive history of suicide alone, were significantly associated with a comorbidity with several anxiety disorders and inversely associated with age of onset. The clinical implications as well as the limitations of our findings are discussed.

Association of neonatal necrotizing enterocolitis with myeloid differentiation-2 and GM2 activator protein genetic polymorphisms.

PubMed

Zhou, Wei; Yuan, Weiming; Huang, Longguang; Wang, Ping; Rong, Xiao; Tang, Juan

2015-07-01

The aim of the present study was to investigate the association of neonatal necrotizing enterocolitis (NEC) with myeloid differentiation-(MD-2) and GM2 activator protein (GM2A) genetic polymorphisms. Gene resequencing of the MD-2 and GM2A gene exons was performed on 42 neonates, diagnosed with NEC (NEC group), as well as in the rs11465996 locus, located in the MD-2 gene promoter region. The aim was to detect the genetic polymorphisms present in the neonates with NEC and compare the functional polymorphic loci with 83 neonates without NEC (control group), who had been born during the same period. A polymorphic locus with abnormal frequency was detected in the exon region of the MD-2 gene. In the NEC group, the frequency of genotypes carrying the low frequency allele (G) in the rs11465996 locus (MD-2 promoter region) was significantly higher compared with the control group (χ(2)=4.388, P=0.036). Furthermore, the frequencies of genotypes carrying the low frequency A and C alleles in the rs1048719 (GM2A gene exon 1) and rs2075783 loci (GM2A intron), respectively, were significantly higher in the NEC group compared with the control group (χ(2)=4.316, P=0.038; and χ(2)=13.717, P=0.000, respectively). In addition, the rs11465996 polymorphism in the MD-2 gene promoter region was found to be associated with the severity of NEC. Furthermore, the rs2075783 polymorphism in the GM2A gene exon 1 and the rs1048719 polymorphism in the intron region of this gene, were associated with the occurrence of NEC. The present study demonstrated that gene polymorphisms of MD-2 and GM2A were associated with the occurrence or severity of NEC; however, further in-depth exploration is required to clarify the associations between genetic predispositions to polymorphisms, and NEC.

Metabolic syndrome and mammographic density: The Study of Women’s Health Across the Nation (SWAN)

PubMed Central

Conroy, Shannon M.; Butler, Lesley M.; Harvey, Danielle; Gold, Ellen B.; Sternfeld, Barbara; Greendale, Gail A.; Habel, Laurel A.

2013-01-01

The metabolic syndrome (MetS) is associated with an increase in breast cancer risk. In this study, we evaluated whether the MetS was associated with an increase in percent mammographic density (MD), a breast cancer risk factor. We used linear regression and mixed models to examine the cross-sectional and longitudinal associations of the MetS and components of the MetS to percent MD in 790 pre- and early perimenopausal women enrolled in the Study of Women’s Health Across the Nation (SWAN). In cross-sectional analyses adjusted for body mass index (BMI), modest inverse associations were observed between percent MD and the MetS (β = −2.5, SE = 1.9, p = 0.19), abdominal adiposity (β = −4.8, SE = 1.9, p = 0.01) and raised glucose (β = −3.7, SE = 2.4, p = 0.12). In longitudinal models adjusted for covariates including age and BMI, abdominal adiposity (β = 0.34, SE = 0.17, p = 0.05) was significantly positively associated with slower annual decline in percent MD with time. In conclusion, our results do not support the hypothesis that the MetS increases breast cancer risk via a mechanism reflected by an increase in percent MD. PMID:21105041

Trapped in a Daydream: Daily Elevations in Maladaptive Daydreaming Are Associated With Daily Psychopathological Symptoms.

PubMed

Soffer-Dudek, Nirit; Somer, Eli

2018-01-01

Background: Maladaptive Daydreaming (MD) characterizes individuals who engage in vivid, fanciful daydreaming for hours on end, neglecting real-life relationships and responsibilities, resulting in clinical distress and functional impairment. Sufferers have embraced the term MD in cyber-communities devoted to this problem because it seemed to uniquely fit their experience and since existing diagnostic labels and their therapies seemed inadequate. However, scientific research in the field has been scarce, relying on cross-sectional or case study designs. Existing knowledge on MD suggests the involvement of dissociative and obsessive-compulsive symptoms, as well as positive reinforcement comparable to processes in addiction disorders. The present study aimed to rigorously explore factors that accompany MD employing a longitudinal daily-diary design, hypothesizing that temporal increases in MD will associate concurrently with, and will temporally precede, other symptoms and emotional changes. In addition, we aimed to explore which symptoms may act as precursors to increases in MD, in order to identify possible mechanisms bringing about daydreaming in these individuals. Methods: In a sample of 77 self-diagnosed individuals with MD we assessed relevant daily symptoms for 14 days, including MD, depression, general anxiety, social anxiety, obsessive-compulsive symptoms, and dissociation, as well as positive and negative emotion. Results: Increases in MD were strongly related to concurrent increases in all other symptoms and negative emotion, and to decreased positive emotion. Obsessive-compulsive symptoms, dissociation, and negative emotion also temporally followed MD. Obsessive-compulsive symptoms were the only consistent temporal antecedent of MD. Conclusions: MD and obsessive-compulsive symptoms coincided in what seems to be a vicious cycle; understanding possible shared mechanisms between these symptoms may inform our understanding of the etiology of MD. For example, Serotonin levels may possibly be involved in the development or maintenance of this condition. The findings may also provide clues as to potentially beneficial interventions for treating MD. For example, perhaps utilizing response prevention techniques may be useful for curbing or intercepting unwanted daydreaming. Future studies on MD should address its compulsory nature.

Mitochondrial dysfunction in autism spectrum disorders: a systematic review and meta-analysis

PubMed Central

Rossignol, D A; Frye, R E

2012-01-01

A comprehensive literature search was performed to collate evidence of mitochondrial dysfunction in autism spectrum disorders (ASDs) with two primary objectives. First, features of mitochondrial dysfunction in the general population of children with ASD were identified. Second, characteristics of mitochondrial dysfunction in children with ASD and concomitant mitochondrial disease (MD) were compared with published literature of two general populations: ASD children without MD, and non-ASD children with MD. The prevalence of MD in the general population of ASD was 5.0% (95% confidence interval 3.2, 6.9%), much higher than found in the general population (∼0.01%). The prevalence of abnormal biomarker values of mitochondrial dysfunction was high in ASD, much higher than the prevalence of MD. Variances and mean values of many mitochondrial biomarkers (lactate, pyruvate, carnitine and ubiquinone) were significantly different between ASD and controls. Some markers correlated with ASD severity. Neuroimaging, in vitro and post-mortem brain studies were consistent with an elevated prevalence of mitochondrial dysfunction in ASD. Taken together, these findings suggest children with ASD have a spectrum of mitochondrial dysfunction of differing severity. Eighteen publications representing a total of 112 children with ASD and MD (ASD/MD) were identified. The prevalence of developmental regression (52%), seizures (41%), motor delay (51%), gastrointestinal abnormalities (74%), female gender (39%), and elevated lactate (78%) and pyruvate (45%) was significantly higher in ASD/MD compared with the general ASD population. The prevalence of many of these abnormalities was similar to the general population of children with MD, suggesting that ASD/MD represents a distinct subgroup of children with MD. Most ASD/MD cases (79%) were not associated with genetic abnormalities, raising the possibility of secondary mitochondrial dysfunction. Treatment studies for ASD/MD were limited, although improvements were noted in some studies with carnitine, co-enzyme Q10 and B-vitamins. Many studies suffered from limitations, including small sample sizes, referral or publication biases, and variability in protocols for selecting children for MD workup, collecting mitochondrial biomarkers and defining MD. Overall, this evidence supports the notion that mitochondrial dysfunction is associated with ASD. Additional studies are needed to further define the role of mitochondrial dysfunction in ASD. PMID:21263444

Relationship between consecutive deterioration of mean deviation value and progression of visual field defect in open-angle glaucoma.

PubMed

Naito, Tomoko; Yoshikawa, Keiji; Mizoue, Shiro; Nanno, Mami; Kimura, Tairo; Suzumura, Hirotaka; Takeda, Ryuji; Shiraga, Fumio

2015-01-01

To analyze the relationship between consecutive deterioration of mean deviation (MD) value and glaucomatous visual field (VF) progression in open-angle glaucoma (OAG), including primary OAG and normal tension glaucoma. The subjects of the study were patients undergoing treatment for OAG who had performed VF tests at least 10 times with a Humphrey field analyzer (SITA standard, C30-2 program). The VF progression was defined by a significantly negative MD slope (MD slope worsening) at the final VF test during the follow-up period. The relationship between the MD slope worsening and the consecutive deterioration of MD value were retrospectively analyzed. A total of 165 eyes of 165 patients were included in the analysis. Significant progression of VF defects was observed in 72 eyes of 72 patients (43.6%), while no significant progression was evident in 93 eyes of 93 patients (56.4%). There was significant relationship between the frequency of consecutive deterioration of MD value and MD slope worsening (P<0.0001, Cochran-Armitage trend test). A significant association was observed for MD slope worsening in the eyes with three (odds ratio: 2.1, P=0.0224) and four (odds ratio: 3.6, P=0.0008) consecutive deterioration of MD value in multiple logistic regression analysis, but no significant association in the eyes with two consecutive deterioration (odds ratio: 1.1, P=0.8282). The eyes with VF progression had significantly lower intraocular pressure reduction rate (P<0.01). This retrospective study has shown that three or more consecutive deterioration of MD value might be a predictor to future significant MD slope worsening in OAG.

Past major depression and smoking cessation outcome: a systematic review and meta-analysis update

PubMed Central

Hitsman, Brian; Papandonatos, George D.; McChargue, Dennis E.; DeMott, Andrew; Herrera, María José; Spring, Bonnie; Borrelli, Belinda; Niaura, Raymond

2012-01-01

Aims To update our prior meta-analysis that showed past major depression (MD+) to be unrelated to smoking cessation outcome [Hitsman et al. J Consult Clin Psychol 2003; 71:657–63]. Methods Eligible trials included 14 from our original review and 28 identified through an updated systematic review (2000–2009). We coded for assessment of past MD, exclusion for recent MD episode (MDE; ≤6 months versus no exclusion), duration/modality of cognitive behavioral treatment (CBT; face-to-face versus self-help), and other factors. To minimize influence of experimental treatments that may selectively benefit MD+ smokers, we analyzed placebo/lowest intensity control arms only. Study-specific odds ratios (ORs) for the effect of past MD on short-term (≤3 months) and long-term (≥6 months) abstinence were estimated and combined using random effects. Two-way interaction models of past MD with study methodology and treatment factors were used to evaluate hypothesized moderators of the past MD-abstinence association. Results MD+ smokers had 17% lower odds of short-term abstinence (n=35, OR=0.83, 95% CI=0.72–0.95, p=0.009) and 19% lower odds of long-term abstinence (n=38, OR=0.81, 95% CI=0.67–0.97, p=0.023) than MD− smokers after excluding the sole study of varenicline because of its antidepressant properties. The association between past MD and abstinence was affected by methodological (recent MDE exclusion, type of MD assessment) and treatment (CBT modality) factors. Conclusions Past major depression has a modest adverse effect on abstinence during and after smoking cessation treatment. An increased focus on the identification of effective treatments or treatment adaptations that eliminate this disparity in smoking cessation for MD+ smokers is needed. PMID:23072580

Shorter sleep duration and better sleep quality are associated with greater tissue density in the brain.

PubMed

Takeuchi, Hikaru; Taki, Yasuyuki; Nouchi, Rui; Yokoyama, Ryoichi; Kotozaki, Yuka; Nakagawa, Seishu; Sekiguchi, Atsushi; Iizuka, Kunio; Yamamoto, Yuki; Hanawa, Sugiko; Araki, Tsuyoshi; Miyauchi, Carlos Makoto; Shinada, Takamitsu; Sakaki, Kohei; Nozawa, Takayuki; Ikeda, Shigeyuki; Yokota, Susumu; Daniele, Magistro; Sassa, Yuko; Kawashima, Ryuta

2018-04-11

Poor sleep quality is associated with unfavorable psychological measurements, whereas sleep duration has complex relationships with such measurements. The aim of this study was to identify the associations between microstructural properties of the brain and sleep duration/sleep quality in a young adult. The associations between mean diffusivity (MD), a measure of diffusion tensor imaging (DTI), and sleep duration/sleep quality were investigated in a study cohort of 1201 normal young adults. Positive correlations between sleep duration and MD of widespread areas of the brain, including the prefrontal cortex (PFC) and the dopaminergic systems, were identified. Negative correlations between sleep quality and MD of the widespread areas of the brain, including the PFC and the right hippocampus, were also detected. Lower MD has been previously associated with more neural tissues in the brain. Further, shorter sleep duration was associated with greater persistence and executive functioning (lower Stroop interference), whereas good sleep quality was associated with states and traits relevant to positive affects. These results suggest that bad sleep quality and longer sleep duration were associated with aberrant neurocognitive measurements in the brain in healthy young adults.

Auditory selective attention in adolescents with major depression: An event-related potential study.

PubMed

Greimel, E; Trinkl, M; Bartling, J; Bakos, S; Grossheinrich, N; Schulte-Körne, G

2015-02-01

Major depression (MD) is associated with deficits in selective attention. Previous studies in adults with MD using event-related potentials (ERPs) reported abnormalities in the neurophysiological correlates of auditory selective attention. However, it is yet unclear whether these findings can be generalized to MD in adolescence. Thus, the aim of the present ERP study was to explore the neural mechanisms of auditory selective attention in adolescents with MD. 24 male and female unmedicated adolescents with MD and 21 control subjects were included in the study. ERPs were collected during an auditory oddball paradigm. Depressive adolescents tended to show a longer N100 latency to target and non-target tones. Moreover, MD subjects showed a prolonged latency of the P200 component to targets. Across groups, longer P200 latency was associated with a decreased tendency of disinhibited behavior as assessed by a behavioral questionnaire. To be able to draw more precise conclusions about differences between the neural bases of selective attention in adolescents vs. adults with MD, future studies should include both age groups and apply the same experimental setting across all subjects. The study provides strong support for abnormalities in the neurophysiolgical bases of selective attention in adolecents with MD at early stages of auditory information processing. Absent group differences in later ERP components reflecting voluntary attentional processes stand in contrast to results reported in adults with MD and may suggest that adolescents with MD possess mechanisms to compensate for abnormalities in the early stages of selective attention. Copyright © 2014 Elsevier B.V. All rights reserved.

Childhood Sexual Abuse and the Development of Recurrent Major Depression in Chinese Women

PubMed Central

Chen, Jing; Cai, Yiyun; Cong, Enzhao; Liu, Ying; Gao, Jingfang; Li, Youhui; Tao, Ming; Zhang, Kerang; Wang, Xumei; Gao, Chengge; Yang, Lijun; Li, Kan; Shi, Jianguo; Wang, Gang; Liu, Lanfen; Zhang, Jinbei; Du, Bo; Jiang, Guoqing; Shen, Jianhua; Zhang, Zhen; Liang, Wei; Sun, Jing; Hu, Jian; Liu, Tiebang; Wang, Xueyi; Miao, Guodong; Meng, Huaqing; Li, Yi; Hu, Chunmei; Li, Yi; Huang, Guoping; Li, Gongying; Ha, Baowei; Deng, Hong; Mei, Qiyi; Zhong, Hui; Gao, Shugui; Sang, Hong; Zhang, Yutang; Fang, Xiang; Yu, Fengyu; Yang, Donglin; Liu, Tieqiao; Chen, Yunchun; Hong, Xiaohong; Wu, Wenyuan; Chen, Guibing; Cai, Min; Song, Yan; Pan, Jiyang; Dong, Jicheng; Pan, Runde; Zhang, Wei; Shen, Zhenming; Liu, Zhengrong; Gu, Danhua; Wang, Xiaoping; Liu, Xiaojuan; Zhang, Qiwen; Li, Yihan; Chen, Yiping; Kendler, Kenneth S.; Shi, Shenxun; Flint, Jonathan

2014-01-01

Background Our prior study in Han Chinese women has shown that women with a history of childhood sexual abuse (CSA) are at increased risk for developing major depression (MD). Would this relationship be found in our whole data set? Method Three levels of CSA (non-genital, genital, and intercourse) were assessed by self-report in two groups of Han Chinese women: 6017 clinically ascertained with recurrent MD and 5983 matched controls. Diagnostic and other risk factor information was assessed at personal interview. Odds ratios (ORs) were calculated by logistic regression. Results We confirmed earlier results by replicating prior analyses in 3,950 new recurrent MD cases. There were no significant differences between the two data sets. Any form of CSA was significantly associated with recurrent MD (OR 4.06, 95% confidence interval (CI) [3.19–5.24]). This association strengthened with increasing CSA severity: non-genital (OR 2.21, 95% CI 1.58–3.15), genital (OR 5.24, 95% CI 3.52–8.15) and intercourse (OR 10.65, 95% CI 5.56–23.71). Among the depressed women, those with CSA had an earlier age of onset, longer depressive episodes. Recurrent MD patients those with CSA had an increased risk for dysthymia (OR 1.60, 95%CI 1.11–2.27) and phobia (OR 1.41, 95%CI 1.09–1.80). Any form of CSA was significantly associated with suicidal ideation or attempt (OR 1.50, 95% CI 1.20–1.89) and feelings of worthlessness or guilt (OR 1.41, 95% CI 1.02–2.02). Intercourse (OR 3.47, 95%CI 1.66–8.22), use of force and threats (OR 1.95, 95%CI 1.05–3.82) and how strongly the victims were affected at the time (OR 1.39, 95%CI 1.20–1.64) were significantly associated with recurrent MD. Conclusions In Chinese women CSA is strongly associated with recurrent MD and this association increases with greater severity of CSA. Depressed women with CSA have some specific clinical traits. Some features of CSA were associated with greater likelihood of developing recurrent MD. PMID:24489940

Abelson Helper Integration Site-1 Gene Variants on Major Depressive Disorder and Bipolar Disorder

PubMed Central

Porcelli, Stefano; Han, Changsu; Lee, Soo-Jung; Patkar, Ashwin A.; Masand, Prakash S.; Balzarro, Beatrice; Alberti, Siegfried; De Ronchi, Diana; Serretti, Alessandro

2014-01-01

Objective The present study aimed to explore whether 4 single nucleotide polymorphisms (SNPs) within the AHI1 gene could be associated with major depressive disorder (MD) and bipolar disorder (BD), and whether they could predict clinical outcomes in mood disorders. Methods One hundred and eighty-four (184) patients with MD, 170 patients with BD and 170 healthy controls were genotyped for 4 AHI1 SNPs (rs11154801, rs7750586, rs9647635 and rs9321501). Baseline and final clinical measures for MD patients were assessed through the Hamilton Rating Scale for Depression (HAM-D). Allelic and genotypic frequencies in MD and BD subjects were compared with those of each disorder and healthy group using the χ2 statistics. Repeated measures ANOVA was used to test possible influences of SNPs on treatment efficacy. Results The rs9647635 A/A was more represented in subjects with BD as compared with MD and healthy subjects together. The rs9647635 A/A was also more presented in patients with MD than in healthy subjects. With regard to the allelic analysis, rs9647635 A allele was more represented in subjects with BD compared with healthy subjects, while it was not observed between patients with MD and healthy subjects. Conclusion Our findings provide potential evidence of an association between some variants of AHI1 and mood disorders susceptibility but not with clinical outcomes. However, we will need to do more adequately-powered and advanced association studies to draw any conclusion due to clear limitations. PMID:25395981

Assessment of Chemical Solution Synthesis and Properties of Gd2Zr2O7 Thin Films as Buffer Layers for Second-Generation High-Temperature Superconductor Wires (Postprint)

DTIC Science & Technology

2012-02-01

AC05-00OR22725. REFERENCES 1. D.P. Norton, A. Goyal, J.D. Budai, D.K. Christen, D.M. Kroeger, E.D. Specht , Q. He, B. Saffian, M. Paranthaman, C.E...critical current density. Science 274, 755 (1996). 2. A. Goyal, D.P. Norton, J.D. Budai, M. Paranthaman, E.D. Specht , D.M. Kroeger, D.K. Christen, Q...D.K. Christen, M. Paranthaman, E.D. Specht , J.D. Budai, Q. He, B. Saffian, F.A. List, D.F. Lee, E. Hatfield, P.M. Martin, C.E. Klabunde, J. Mathis

The effects of the mediterranean diet on biomarkers of vascular wall inflammation and plaque vulnerability in subjects with high risk for cardiovascular disease. A randomized trial.

PubMed

Casas, Rosa; Sacanella, Emilio; Urpí-Sardà, Mireia; Chiva-Blanch, Gemma; Ros, Emilio; Martínez-González, Miguel-Angel; Covas, Maria-Isabel; Salas-Salvadó, Jordi; Fiol, Miquel; Arós, Fernando; Estruch, Ramon

2014-01-01

Adherence to the Mediterranean diet (MD) is associated with reduced morbidity and mortality due to cardiovascular disease. However, how the MD exerts its effects is not fully known. To assess the 12-month effects of two enhanced MDs compared to a low-fat diet on inflammatory biomarkers related to atherosclerosis and plaque vulnerability in a subcohort of the PREDIMED (Prevención con Dieta Mediterránea) study. A total of 164 participants at high risk for cardiovascular disease were randomized into three diet groups: MD supplemented with 50mL/d of extra virgin olive oil (MD+EVOO) or 30 g/d of nuts (MD+Nuts) and a low-fat diet. Changes in classical cardiovascular risk factors, inflammatory biomarkers of atherosclerosis and plaque vulnerability were measured after 12 months of intervention. Compared to participants in the low-fat diet group, those receiving MD+EVOO and MD+Nuts showed a higher decrease in systolic (6mmHg) and diastolic (3mmHg) blood pressure (P = 0.02; both), as well as a reduction of 10% and 8% in LDL-cholesterol (P = 0.04), respectively. Patients in the MD+Nuts group showed a significant reduction of 34% in CD40 expression on monocyte surface compared to low-fat diet patients (P = 0.03). In addition, inflammatory biomarkers related to plaque instability such as C-reactive protein and interleukin-6 were reduced by 45% and 35% and 95% and 90% in the MD+EVOO and MD+Nuts groups, respectively (P<0.05; all) compared to the low-fat diet group. Likewise, sICAM and P-selectin were also reduced by 50% and 27%, respectively in the MD+EVOO group (P = 0.04) and P-selectin by 19% in MD+Nuts group (P = 0.04) compared to the low-fat diet group. Adherence to the MD is associated with an increase in serum markers of atheroma plaque stability which may explain, at least in part, the protective role of MD against ischemic heart disease. www.controlled-trials.com ISRCTN35739639.

Enhancing the Breadth and Efficacy of Therapeutic Vaccines for Breast Cancer

DTIC Science & Technology

2017-01-01

research professor, 1 post-doctoral fellow, and 3 research associates. We have worked closely with our surgery, medical oncology , and pathology...MD – project PI (40% effort) Personnel 2. John Yim, MD – CoH Surgical Oncology (5% effort) 3. Joanne Mortimer, MD – CoH Medical Oncology (no

Which Instructional Practices Most Help First Grade Students with and without Mathematics Difficulties?

PubMed

Morgan, Paul L; Farkas, George; Maczuga, Steve

2015-06-01

We used population-based, longitudinal data to investigate the relation between mathematics instructional practices used by 1 st grade teachers in the U.S. and the mathematics achievement of their students. Factor analysis identified four types of instructional activities (i.e., teacher-directed, student-centered, manipulatives/calculators, movement/music) and eight types of specific skills taught (e.g., adding two-digit numbers). First-grade students were then classified into five groups on the basis of their fall and/or spring of kindergarten mathematics achievement-three groups with mathematics difficulties (MD) and two without MD. Regression analysis indicated that a higher percentage of MD students in 1 st grade classrooms was associated with greater use by teachers of manipulatives/calculators and movement/music to teach mathematics. Yet follow-up analysis for each of the MD and non-MD groups indicated that only teacher-directed instruction was significantly associated with the achievement of students with MD (covariate-adjusted ES s = .05-.07). The largest predicted effect for a specific instructional practice was for routine practice and drill. In contrast, for both groups of non-MD students, teacher-directed and student-centered instruction had approximately equal, statistically significant positive predicted effects (covariate-adjusted ES s = .03-.04). First-grade teachers in the U.S. may need to increase their use of teacher-directed instruction if they are to raise the mathematics achievement of students with MD.

Long-Term Sickness Absence Due to Mental Disorders Is Associated with Individual Features and Psychosocial Work Conditions

PubMed Central

da Silva-Junior, João Silvestre; Fischer, Frida Marina

2014-01-01

Aims Sickness absence is a socioeconomic global burden. In Brazil, mental disorders are the third leading cause of social security benefits payments. The aim of the present study was to compare factors associated with long-term sickness absence between workers who claimed social benefits due to mental disorders or by other causes. We investigated individual features and occupational characteristics. In addition, we evaluated psychosocial factors at work assessed by the Demand-Control-Support (DCS) and Effort-Reward Imbalance (ERI) models, and whether they were associated with long-term sickness absence due to mental disorders (LTSA-MD). Methods The present case-control study was conducted in São Paulo, Brazil. The sample (n = 385) included workers on sick leave for more than 15 days. Cases were the participants with disabling psychiatric illnesses, and controls were the ones with other disabling diseases. Interviews were conducted to assess individual features (sociodemographic data, health habits/lifestyle, health conditions) and occupational characteristics. The participants' perception of exposure to dimensions of the DCS and ERI models was also recorded. Multiple logistic regressions were performed to evaluate the association between independent variables and LTSA-MD. Results All the regression analyses showed that LTSA-MD was associated with female sex, self-reported white skin color, higher education level, high tobacco consumption, high alcohol intake, two or more comorbidities, exposure to violence at work, high job strain and low social support at work, effort-reward imbalance and high overcommitment to work. LTSA-MD was associated with separate and combined DCS and ERI stress models. Conclusions Individual features and work conditions were associated with LTSA-MD. Combined analysis of stress models showed that psychosocial factors at work were significantly associated with LTSA-MD. Resourceful use of this information may contribute to the implementation of preventive actions and strategies to facilitate return to work targeting the populations most susceptible to mental disorders. PMID:25531900

Long-term sickness absence due to mental disorders is associated with individual features and psychosocial work conditions.

PubMed

Silva-Junior, João Silvestre da; Fischer, Frida Marina

2014-01-01

Sickness absence is a socioeconomic global burden. In Brazil, mental disorders are the third leading cause of social security benefits payments. The aim of the present study was to compare factors associated with long-term sickness absence between workers who claimed social benefits due to mental disorders or by other causes. We investigated individual features and occupational characteristics. In addition, we evaluated psychosocial factors at work assessed by the Demand-Control-Support (DCS) and Effort-Reward Imbalance (ERI) models, and whether they were associated with long-term sickness absence due to mental disorders (LTSA-MD). The present case-control study was conducted in São Paulo, Brazil. The sample (n = 385) included workers on sick leave for more than 15 days. Cases were the participants with disabling psychiatric illnesses, and controls were the ones with other disabling diseases. Interviews were conducted to assess individual features (sociodemographic data, health habits/lifestyle, health conditions) and occupational characteristics. The participants' perception of exposure to dimensions of the DCS and ERI models was also recorded. Multiple logistic regressions were performed to evaluate the association between independent variables and LTSA-MD. All the regression analyses showed that LTSA-MD was associated with female sex, self-reported white skin color, higher education level, high tobacco consumption, high alcohol intake, two or more comorbidities, exposure to violence at work, high job strain and low social support at work, effort-reward imbalance and high overcommitment to work. LTSA-MD was associated with separate and combined DCS and ERI stress models. Individual features and work conditions were associated with LTSA-MD. Combined analysis of stress models showed that psychosocial factors at work were significantly associated with LTSA-MD. Resourceful use of this information may contribute to the implementation of preventive actions and strategies to facilitate return to work targeting the populations most susceptible to mental disorders.

Dietary Intervention Restored Menses in Female Athletes with Exercise-Associated Menstrual Dysfunction with Limited Impact on Bone and Muscle Health

PubMed Central

Cialdella-Kam, Lynn; Guebels, Charlotte P.; Maddalozzo, Gianni F.; Manore, Melinda M.

2014-01-01

Exercise-related menstrual dysfunction (ExMD) is associated with low energy availability (EA), decreased bone mineral density (BMD), and increased risk of musculoskeletal injury. We investigated whether a 6-month carbohydrate-protein (CHO-PRO) supplement (360 kcal/day, 54 g CHO/day, 20 g PRO/day) intervention would improve energy status and musculoskeletal health and restore menses in female athletes (n = 8) with ExMD. At pre/post-intervention, reproductive and thyroid hormones, bone health (BMD, bone mineral content, bone markers), muscle strength/power and protein metabolism markers, profile of mood state (POMS), and energy intake (EI)/energy expenditure (7 day food/activity records) were measured. Eumenorrheic athlete controls with normal menses (Eumen); n = 10) were measured at baseline. Multiple linear regressions were used to evaluate differences between groups and pre/post-intervention blocking on participants. Improvements in EI (+382 kcal/day; p = 0.12), EA (+417 kcal/day; p = 0.17) and energy balance (EB; +466 kcal/day; p = 0.14) were observed with the intervention but were not statistically significant. ExMD resumed menses (2.6 ± 2.2-months to first menses; 3.5 ± 1.9 cycles); one remaining anovulatory with menses. Female athletes with ExMD for >8 months took longer to resume menses/ovulation and had lower BMD (low spine (ExMD = 3; Eumen = 1); low hip (ExMD = 2)) than those with ExMD for <8 months; for 2 ExMD the intervention improved spinal BMD. POMS fatigue scores were 15% lower in ExMD vs. Eumen (p = 0.17); POMS depression scores improved by 8% in ExMD (p = 0.12). EI, EA, and EB were similar between groups, but the intervention (+360 kcal/day) improved energy status enough to reverse ExMD despite no statistically significant changes in EI. Similar baseline EA and EB between groups suggests that some ExMD athletes are more sensitive to EA and EB fluctuations. PMID:25090245

Dietary intervention restored menses in female athletes with exercise-associated menstrual dysfunction with limited impact on bone and muscle health.

PubMed

Cialdella-Kam, Lynn; Guebels, Charlotte P; Maddalozzo, Gianni F; Manore, Melinda M

2014-07-31

Exercise-related menstrual dysfunction (ExMD) is associated with low energy availability (EA), decreased bone mineral density (BMD), and increased risk of musculoskeletal injury. We investigated whether a 6-month carbohydrate-protein (CHO-PRO) supplement (360 kcal/day, 54 g CHO/day, 20 g PRO/day) intervention would improve energy status and musculoskeletal health and restore menses in female athletes (n = 8) with ExMD. At pre/post-intervention, reproductive and thyroid hormones, bone health (BMD, bone mineral content, bone markers), muscle strength/power and protein metabolism markers, profile of mood state (POMS), and energy intake (EI)/energy expenditure (7 day food/activity records) were measured. Eumenorrheic athlete controls with normal menses (Eumen); n = 10) were measured at baseline. Multiple linear regressions were used to evaluate differences between groups and pre/post-intervention blocking on participants. Improvements in EI (+382 kcal/day; p = 0.12), EA (+417 kcal/day; p = 0.17) and energy balance (EB; +466 kcal/day; p = 0.14) were observed with the intervention but were not statistically significant. ExMD resumed menses (2.6 ± 2.2-months to first menses; 3.5 ± 1.9 cycles); one remaining anovulatory with menses. Female athletes with ExMD for >8 months took longer to resume menses/ovulation and had lower BMD (low spine (ExMD = 3; Eumen = 1); low hip (ExMD = 2)) than those with ExMD for <8 months; for 2 ExMD the intervention improved spinal BMD. POMS fatigue scores were 15% lower in ExMD vs. Eumen (p = 0.17); POMS depression scores improved by 8% in ExMD (p = 0.12). EI, EA, and EB were similar between groups, but the intervention (+360 kcal/day) improved energy status enough to reverse ExMD despite no statistically significant changes in EI. Similar baseline EA and EB between groups suggests that some ExMD athletes are more sensitive to EA and EB fluctuations.

Association of 24 h maternal deprivation with a saline injection in the neonatal period alters adult stress response and brain monoamines in a sex-dependent fashion.

PubMed

Cabbia, Rafael; Consoli, Amanda; Suchecki, Deborah

2018-04-01

Maternal deprivation (MD) disinhibits the adrenal glands, rendering them responsive to various stressors, including saline injection, and this increased corticosterone (CORT) response can last for as long as 2 h. In the present study, we tested the hypothesis that association of MD on day 11 with a saline injection would alter emotional behavior, CORT response, and brain monoamine levels, in male and female adult rats. Rats were submitted to the novelty suppressed feeding (NSF), the sucrose negative contrast test (SNCT), social investigation test (SIT), and the elevated plus maze (EPM). One quarter of each group was not tested (providing basal values of CORT and brain monoamines) and the remainder was decapitated 15, 45, or 75 min after the EPM, to assess CORT reactivity. Monoamine levels were determined in the hypothalamus (HPT), frontal cortex (FC), amygdala (AMY), ventral, and dorsal hippocampus (vHPC, dHPC, respectively). MD reduced food intake, in the home-cage, and latency to eat in the NSF in both sexes; females explored less the target animal in the SIT and explored more the open arms of the EPM than males; the CORT response to the EPM was greater in maternally-deprived males and females than in their control counterparts, and this response was further elevated in maternally-deprived females injected with saline. Regarding monoamine levels, females were less affected, showing isolated effects of the stressors, while in males, MD increased 5-HT levels in the HPT and decreased this monoamine in the FC, MD associated with saline reduced dopamine levels in all brain regions, except the HPT. MD at 11 days did not alter emotional behaviors in adult rats, but had an impact in neurobiological parameters associated with this class of behaviors. The impact of MD associated with saline on dopamine levels suggests that males may be vulnerable to motivation-related disorders.

Changes of visual-field global indices after cataract surgery in primary open-angle glaucoma patients.

PubMed

Seol, Bo Ram; Jeoung, Jin Wook; Park, Ki Ho

2016-11-01

To determine changes of visual-field (VF) global indices after cataract surgery and the factors associated with the effect of cataracts on those indices in primary open-angle glaucoma (POAG) patients. A retrospective chart review of 60 POAG patients who had undergone phacoemulsification and intraocular lens insertion was conducted. All of the patients were evaluated with standard automated perimetry (SAP; 30-2 Swedish interactive threshold algorithm; Carl Zeiss Meditec Inc.) before and after surgery. VF global indices before surgery were compared with those after surgery. The best-corrected visual acuity, intraocular pressure (IOP), number of glaucoma medications before surgery, mean total deviation (TD) values, mean pattern deviation (PD) value, and mean TD-PD value were also compared with the corresponding postoperative values. Additionally, postoperative peak IOP and mean IOP were evaluated. Univariate and multivariate logistic regression analyses were performed to identify the factors associated with the effect of cataract on global indices. Mean deviation (MD) after cataract surgery was significantly improved compared with the preoperative MD. Pattern standard deviation (PSD) and visual-field index (VFI) after surgery were similar to those before surgery. Also, mean TD and mean TD-PD were significantly improved after surgery. The posterior subcapsular cataract (PSC) type showed greater MD changes than did the non-PSC type in both the univariate and multivariate logistic regression analyses. In the univariate logistic regression analysis, the preoperative TD-PD value and type of cataract were associated with MD change. However, in the multivariate logistic regression analysis, type of cataract was the only associated factor. None of the other factors was associated with MD change. MD was significantly affected by cataracts, whereas PSD and VFI were not. Most notably, the PSC type showed better MD improvement compared with the non-PSC type after cataract surgery. Clinicians therefore should carefully analyze VF examination results for POAG patients with the PSC type.

Depression, anxiety, and prevalent diabetes in the Chinese population: Findings from the China Kadoorie Biobank of 0.5 million people

PubMed Central

Mezuk, Briana; Chen, Yiping; Yu, Canqing; Guo, Yu; Bian, Zheng; Collins, Rory; Chen, Junshi; Pang, Zengchang; Wang, Huijun; Peto, Richard; Que, Xiangsan; Zhang, Hui; Tan, Zhongwen; Kendler, Kenneth S.; Li, Liming; Chen, Zhengming

2013-01-01

Objective Despite previous investigation, uncertainty remains about the nature of the associations of major depression (MD) with type 2 diabetes mellitus (T2DM), particularly in adult Chinese, and the relevance of generalized anxiety disorder (GAD) for T2DM. Methods Cross-sectional data from the China Kadoorie Biobank Study, a sample of approximately 500,000 adults from 10 geographically defined regions of China, were analyzed. Past year MD and GAD were assessed using the Composite International Diagnostic Inventory. T2DM was defined as either having self-reported physician diagnosis of diabetes at age 30 or later (“clinically-identified” cases) or having a non-fasting blood glucose ≥11.1 mmol/L or fasting blood glucose ≥7.0 mmol/L but no prior diagnosis of diabetes (“screen-detected” cases). Logistic regression was used to assess the relationship between MD and GAD with clinically-identified and screen-detected T2DM, adjusting for demographic characteristics and health behaviors. Results The prevalence of T2DM was 5.3% (3.2% clinically-identified and 2.1% screen-detected). MD was significantly associated with clinically-identified T2DM (Odds ratio [OR]: 1.75, 95% Confidence Interval (CI): 1.47 – 2.08), but not with screen-detected T2DM (OR: 1.18, 95% CI: 0.92 – 1.51). GAD was associated with both clinically-identified (OR: 2.14, 95% CI: 1.60 – 2.88) and screen-detected (OR: 1.44, 95% CI: 0.99 – 2.08) T2DM. The relationship between MD and GAD with T2DM was moderated by obesity. Conclusion MD is associated with clinically-identified, but not screen-detected T2DM. GAD is associated with both clinically-identified and screen-detected T2DM. The relationship between MD and T2DM is strongest among those who are not obese. PMID:24290039

MdHIR proteins repress anthocyanin accumulation by interacting with the MdJAZ2 protein to inhibit its degradation in apples

PubMed Central

Chen, Ke-Qin; Zhao, Xian-Yan; An, Xiu-Hong; Tian, Yi; Liu, Dan-Dan; You, Chun-Xiang; Hao, Yu-Jin

2017-01-01

In higher plants, jasmonate ZIM-domain (JAZ) proteins negatively regulate the biosynthesis of anthocyanins by interacting with bHLH transcription factors. However, it is largely unknown if and how other regulators are involved in this process. In this study, the apple MdJAZ2 protein was characterized in regards to its function in the negative regulation of anthocyanin accumulation and peel coloration. MdJAZ2 was used as a bait to screen a cDNA library using the yeast two-hybrid method. The hypersensitive induced reaction (HIR) proteins, MdHIR2 and MdHIR4, were obtained from this yeast two-hybrid. The ZIM domain of MdJAZ2 and the PHB domain of the MdHIR proteins are necessary for their interactions. The interactions were further verified using an in vitro pull-down assay. Subsequently, immunoblotting assays demonstrated that MdHIR4 enhanced the stability of the MdJAZ2-GUS protein. Finally, a viral vector-based transformation method showed that MdHIR4 inhibited anthocyanin accumulation and fruit coloration in apple by modulating the expression of genes associated with anthocyanin biosynthesis. PMID:28317851

Physician Payment Reform—An Idea Whose Time Has Come

PubMed Central

Lee, Philip R.

1990-01-01

These discussions are selected from the weekly staff conferences in the Department of Medicine, University of California, San Francisco. Taken from transcriptions, they are prepared by Homer A. Boushey, MD, Professor of Medicine, and Nathan M. Bass, MD, PhD, Associate Professor of Medicine, under the direction of Lloyd H. Smith, Jr, MD, Professor of Medicine and Associate Dean in the School of Medicine. Requests for reprints should be sent to the Department of Medicine, University of California, San Francisco, School of Medicine, San Francisco, CA 94143. PMID:2185598

The Multiple-Demand System in the Novelty of Musical Improvisation: Evidence from an MRI Study on Composers.

PubMed

Lu, Jing; Yang, Hua; He, Hui; Jeon, Seun; Hou, Changyue; Evans, Alan C; Yao, Dezhong

2017-01-01

The multiple-demand (MD) system has proven to be associated with creating structured mental programs in comprehensive behaviors, but the functional mechanisms of this system have not been clarified in the musical domain. In this study, we explored the hypothesis that the MD system is involved in a comprehensive music-related behavior known as musical improvisation. Under a functional magnetic resonance imaging (fMRI) paradigm, 29 composers were recruited to improvise melodies through visual imagery tasks according to familiar and unfamiliar cues. We found that the main regions of the MD system were significantly activated during both musical improvisation conditions. However, only a greater involvement of the intraparietal sulcus (IPS) within the MD system was shown when improvising with unfamiliar cues. Our results revealed that the MD system strongly participated in musical improvisation through processing the novelty of melodies, working memory, and attention. In particular, improvising with unfamiliar cues required more musical transposition manipulations. Moreover, both functional and structural analyses indicated evidence of neuroplasticity in MD regions that could be associated with musical improvisation training. These findings can help unveil the functional mechanisms of the MD system in musical cognition, as well as improve our understanding of musical improvisation.

The Multiple-Demand System in the Novelty of Musical Improvisation: Evidence from an MRI Study on Composers

PubMed Central

Lu, Jing; Yang, Hua; He, Hui; Jeon, Seun; Hou, Changyue; Evans, Alan C.; Yao, Dezhong

2017-01-01

The multiple-demand (MD) system has proven to be associated with creating structured mental programs in comprehensive behaviors, but the functional mechanisms of this system have not been clarified in the musical domain. In this study, we explored the hypothesis that the MD system is involved in a comprehensive music-related behavior known as musical improvisation. Under a functional magnetic resonance imaging (fMRI) paradigm, 29 composers were recruited to improvise melodies through visual imagery tasks according to familiar and unfamiliar cues. We found that the main regions of the MD system were significantly activated during both musical improvisation conditions. However, only a greater involvement of the intraparietal sulcus (IPS) within the MD system was shown when improvising with unfamiliar cues. Our results revealed that the MD system strongly participated in musical improvisation through processing the novelty of melodies, working memory, and attention. In particular, improvising with unfamiliar cues required more musical transposition manipulations. Moreover, both functional and structural analyses indicated evidence of neuroplasticity in MD regions that could be associated with musical improvisation training. These findings can help unveil the functional mechanisms of the MD system in musical cognition, as well as improve our understanding of musical improvisation. PMID:29311776

76 FR 9407 - Fraternity Federal Savings & Loan Association, Baltimore, MD; Approval of Conversion Application

Federal Register 2010, 2011, 2012, 2013, 2014

2011-02-17

... DEPARTMENT OF THE TREASURY Office of Thrift Supervision [AC-58 OTS No. 01292 and H 4762] Fraternity Federal Savings & Loan Association, Baltimore, MD; Approval of Conversion Application Notice is hereby given that on February 10, 2011, the Office of Thrift Supervision approved the application of...

Apple FLOWERING LOCUS T proteins interact with transcription factors implicated in cell growth and organ development.

PubMed

Mimida, Naozumi; Kidou, Shin-Ichiro; Iwanami, Hiroshi; Moriya, Shigeki; Abe, Kazuyuki; Voogd, Charlotte; Varkonyi-Gasic, Erika; Kotoda, Nobuhiro

2011-05-01

Understanding the flowering process in apple (Malus × domestica Borkh.) is essential for developing methods to shorten the breeding period and regulate fruit yield. It is known that FLOWERING LOCUS T (FT) acts as a transmissible floral inducer in the Arabidopsis flowering network system. To clarify the molecular network of two apple FT orthologues, MdFT1 and MdFT2, we performed a yeast two-hybrid screen to identify proteins that interact with MdFT1. We identified several transcription factors, including two members of the TCP (TEOSINTE BRANCHED1, CYCLOIDEA and PROLIFERATING CELL FACTORs) family, designated MdTCP2 and MdTCP4, and an Arabidopsis thaliana VOZ1 (Vascular plant One Zinc finger protein1)-like protein, designated MdVOZ1. MdTCP2 and MdVOZ1 also interacted with MdFT2 in yeast. The expression domain of MdTCP2 and MdVOZ1 partially overlapped with that of MdFT1 and MdFT2, most strikingly in apple fruit tissue, further suggesting a potential interaction in vivo. Constitutive expression of MdTCP2, MdTCP4 and MdVOZ1 in Arabidopsis affected plant size, leaf morphology and the formation of leaf primordia on the adaxial side of cotyledons. On the other hand, chimeric MdTCP2, MdTCP4 and MdVOZ1 repressors that included the ethylene-responsive transcription factors (ERF)-associated amphiphilic repression (EAR) domain motif influenced reproduction and inflorescence architecture in transgenic Arabidopsis. These results suggest that MdFT1 and/or MdFT2 might be involved in the regulation of cellular proliferation and the formation of new tissues and that they might affect leaf and fruit development by interacting with TCP- and VOZ-family proteins. DDBJ accession nos. AB531019 (MdTCP2a mRNA), AB531020 (MdTCP2b mRNA), AB531021 (MdTCP4a mRNA), AB531022 (MdTCP4b mRNA) and AB531023 (MdVOZ1a mRNA). © The Author 2011. Published by Oxford University Press. All rights reserved.

High adherence to the Mediterranean diet is associated with cardiovascular protection in higher but not in lower socioeconomic groups: prospective findings from the Moli-sani study.

PubMed

Bonaccio, Marialaura; Di Castelnuovo, Augusto; Pounis, George; Costanzo, Simona; Persichillo, Mariarosaria; Cerletti, Chiara; Donati, Maria Benedetta; de Gaetano, Giovanni; Iacoviello, Licia

2017-10-01

It is uncertain whether the cardiovascular benefits associated with Mediterranean diet (MD) may differ across socioeconomic groups. Prospective analysis on 18991 men and women aged ≥35 years from the general population of the Moli-sani cohort (Italy). Adherence to MD was appraised by the Mediterranean diet score (MDS). Household income (euros/year) and educational level were used as indicators of socioeconomic status. Hazard ratios (HR) were calculated by multivariable Cox proportional hazard models. Over 4.3 years of follow-up, 252 cardiovascular disease (CVD) events occurred. Overall, a two-point increase in MDS was associated with 15% reduced CVD risk (95% confidence interval: 1% to 27%). Such association was evident in highly (HR = 0.43; 0.25-0.72) but not in less (HR = 0.94; 0.78-1.14) educated subjects (P for interaction = 0.042). Similarly, CVD advantages associated with the MD were confined to the high household income group (HR = 0.39; 0.23-0.66, and HR = 1.01; 0.79-1.29 for high- and low-income groups, respectively; P for interaction = 0.0098). In a subgroup of individuals of different socioeconomic status but sharing similar MDS, diet-related disparities were found as different intakes of antioxidants and polyphenols, fatty acids, micronutrients, dietary antioxidant capacity, dietary diversity, organic vegetables and whole grain bread consumption. MD is associated with lower CVD risk but this relationship is confined to higher socioeconomic groups. In groups sharing similar scores of adherence to MD, diet-related disparities across socioeconomic groups persisted. These nutritional gaps may reasonably explain at least in part the socioeconomic pattern of CVD protection from the MD. © The Author 2017; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association

Intratympanic steroids injection is effective for the treatment of drop attacks with Ménière's disease and delayed endolymphatic hydrops

PubMed Central

Liu, Bo; Leng, Yangming; Zhou, Renhong; Liu, Jingjing; Liu, Dongdong; Zhang, Su-Lin; Kong, Wei-Jia

2016-01-01

Abstract Drop attack (DA) associated with Ménière's disease (MD) and delayed endolymphatic hydrops (DEH) is not common and may cause life-threatening clinical problems. The intratympanic dexamethasone (ITD) is one of primary treatments for MD or DEH. Our study investigated the effect of ITD on the DA associated with endolymphatic hydrops (EH). We retrospectively reviewed 10 patients with MD- and DEH-associated DA between January 2009 and December 2013 in Outpatient Department of Otolaryngology, Union Hospital, Wuhan, China. Among them, 7 patients (5 cases with MD, 2 cases of DEH) received ITD (4 times, on weekly basis). Further repeated ITD courses or intratympanic gentamicin (ITG) were given if the vertigo was not satisfactorily controlled. The number of DA and status of vertigo control after intratympanic injection were evaluated. After a follow-up study lasting from 19 to 35 months, DA in 5 cases (71.4%) disappeared after initial ITD course. In 2 cases, DA was altogether controlled after an additional intratympanic injection (repeated ITD or/and ITG). This study showed that ITD promises to be a first-line conservative treatment for MD- or DEH-related DA since the steroid possesses no inner-ear toxicity. Furthermore, for MD- or DEH-related DA refractory to ITD, ITG can be an effective alternative. PMID:28033296

MdPIN1b encodes a putative auxin efflux carrier and has different expression patterns in BC and M9 apple rootstocks.

PubMed

Gan, Zengyu; Wang, Yi; Wu, Ting; Xu, Xuefeng; Zhang, Xinzhong; Han, Zhenhai

2018-03-01

Lower promoter activity is closely associated with lower MdPIN1b expression in the M9 interstem, which might contribute to the dwarfing effect in apple trees. Apple trees grafted onto dwarfing rootstock Malling 9 (M9) produce dwarfing tree architecture with high yield and widely applying in production. Previously, we have reported that in Malus 'Red Fuji' (RF) trees growing on M9 interstem and Baleng Crab (BC) rootstock, IAA content was relatively higher in bark tissue of M9 interstem than that in scion or rootstock. As IAA polar transportation largely depends on the PIN-FORMED (PIN) auxin efflux carrier. Herein, we identify two putative auxin efflux carrier genes in Malus genus, MdPIN1a and MdPIN1b, which were closely related to the AtPIN1. We found that MdPIN1b was expressed preferentially in BC and M9, and the expression of MdPIN1b was significantly lower in the phloem of M9 interstem than that in the scion and rootstock. The distinct expression of MdPIN1b and IAA content were concentrated in the cambium and adjacent xylem or phloem, and MdPIN1b protein was localized on cell plasma membrane in onion epidermal cells transiently expressing 35S:MdPIN1b-GFP fusion protein. Interestingly, an MdPIN1b mutant allele in the promoter region upstream of M9 exhibited decreased MdPIN1b expression compared to BC. MdPIN1b over-expressing interstem in tobacco exhibited increased polar auxin transport. It is proposed that natural allelic differences decreased promoter activity is closely associated with lower MdPIN1b expression in the M9 interstem, which might limit the basipetal transport of auxin, and in turn might contribute to the dwarfing effect. Taken together, these results reveal allelic variation underlying an important apple rootstock trait, and specifically a novel molecular genetic mechanism underlying dwarfing mechanism.

[Medical Association of the Croatian Coast and Gorski kotar].

PubMed

Bakasun, Vjekoslav; Frković, Aleksandra

2009-01-01

In the Province Hospital Susak the Medical Association of the Croatian Coast and Gorski kotar was founded on October 2nd, 1936. At that time on the territory of the former District of Susak there were 59 physicians. The inauguration meeting was attended by 41 physicians and 26 of them voted for the autonomous Association rather than for one within the Croatian Medical Association of Zagreb. Vladimir Blaz, M.D. was the first elected president. During the Italian occupation in the 2nd World War Association's activities were interrupted. After five years of inactivity, the Association was restored at its constituting session held on June 8th, 1946, when Zdravko Kucić, M.D. was elected president. The Medical Association Rijeka-Susak was founded on September 24th, 1947 and the first elected president was Fran Bakarcić, M.D. It still kept functioning as an autonomous association. The following year the Association became the subsidiary of the Croatian Medical Association.

Generalized Anxiety and Major Depressive syndrome ...

EPA Pesticide Factsheets

Objective: Environmental exposure to manganese (Mn) may cause generalized anxiety (GA) and major depression (MD) in residents living in Mn-exposed areas. Marietta and East Liverpool are two Ohio towns identified as having elevated levels of Mn. The objective was to determine if levels of Mn exposure were associated with levels of GA and MD.Participants and methods: 186 participants (Mean age: 55.0 ± 10.80) were examined. Levels of air-Mn were assessed over a period of ten years using U.S. EPA’s AERMOD dispersion model. Average air-Mn exposure was 0.53 μg/m3 in the two towns. The GA syndrome was comprised of anxiety, obsessive-compulsive, and phobic scales from the Symptom Checklist (SCL-90-R). The MD syndrome was comprised of depression, anxiety, and psychoticism scales also from the SCL-90-R. Linear regression models were used to determine the relationship between Mn and GA, MD and the specific components of each.Results: Elevated air-Mn was associated with GA (β= 0.240, p=0.002), and MD (β= 0.202, p=0.011). Air-Mn was associated with specific components of GA anxiety (β= 0.255, p=0.001), phobic anxiety (β= 0.159, p=0.046), and obsessive-compulsive (β= 0.197, p=0.013). Similarly, components of MD syndrome suggested an association as well: depression (β= 0.180, p=0.023), anxiety (β= 0.255, p=0.001), and psychoticism (β= 0.188, p=0.018). Conclusions: The results suggest that residents with elevated exposure to environmental Mn have elevated levels of

Non-Linear Association between Cerebral Amyloid Deposition and White Matter Microstructure in Cognitively Healthy Older Adults.

PubMed

Wolf, Dominik; Fischer, Florian U; Scheurich, Armin; Fellgiebel, Andreas

2015-01-01

Cerebral amyloid-β accumulation and changes in white matter (WM) microstructure are imaging characteristics in clinical Alzheimer's disease and have also been reported in cognitively healthy older adults. However, the relationship between amyloid deposition and WM microstructure is not well understood. Here, we investigated the impact of quantitative cerebral amyloid load on WM microstructure in a group of cognitively healthy older adults. AV45-positron emission tomography and diffusion tensor imaging (DTI) scans of forty-four participants (age-range: 60 to 89 years) from the Alzheimer's Disease Neuroimaging Initiative were analyzed. Fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (DR), and axial diffusivity (DA) were calculated to characterize WM microstructure. Regression analyses demonstrated non-linear (quadratic) relationships between amyloid deposition and FA, MD, as well as RD in widespread WM regions. At low amyloid burden, higher deposition was associated with increased FA as well as decreased MD and DR. At higher amyloid burden, higher deposition was associated with decreased FA as well as increased MD and DR. Additional regression analyses demonstrated an interaction effect between amyloid load and global WM FA, MD, DR, and DA on cognition, suggesting that cognition is only affected when amyloid is increasing and WM integrity is decreasing. Thus, increases in FA and decreases in MD and RD with increasing amyloid load at low levels of amyloid burden may indicate compensatory processes that preserve cognitive functioning. Potential mechanisms underlying the observed non-linear association between amyloid deposition and DTI metrics of WM microstructure are discussed.

Developmental Precursors of Moral Disengagement and the Role of Moral Disengagement in the Development of Antisocial Behavior

PubMed Central

Shaw, Daniel S.; Moilanen, Kristin L.

2010-01-01

The purpose of the study was to advance our understanding of the developmental precursors of Moral Disengagement (MD) and the role of MD in the development of antisocial behavior from early risk among an ethnically diverse sample of 187 low-income boys followed prospectively from ages 1.5 to 17. Results indicated associations between early rejecting parenting, neighborhood impoverishment, and child empathy and later MD. The link between some of these early constructs and later antisocial behavior was mediated by MD. Finally, in an exploratory path model both MD and biases in social information processing were found to mediate separate paths from early risk factors to later antisocial behavior. Results were partially consistent with the notion that adolescent MD was predicted by a combination of early family, neighborhood, and child risk factors, and that MD may be a mechanism underlying some boys' risk of antisocial behavior. PMID:19777337

A dsRNA-binding protein MdDRB1 associated with miRNA biogenesis modifies adventitious rooting and tree architecture in apple.

PubMed

You, Chun-Xiang; Zhao, Qiang; Wang, Xiao-Fei; Xie, Xing-Bin; Feng, Xiao-Ming; Zhao, Ling-Ling; Shu, Huai-Rui; Hao, Yu-Jin

2014-02-01

Although numerous miRNAs have been already isolated from fruit trees, knowledge about miRNA biogenesis is largely unknown in fruit trees. Double-strand RNA-binding (DRB) protein plays an important role in miRNA processing and maturation; however, its role in the regulation of economically important traits is not clear yet in fruit trees. EST blast and RACE amplification were performed to isolate apple MdDRB1 gene. Following expression analysis, RNA binding and protein interaction assays, MdDRB1 was transformed into apple callus and in vitro tissue cultures to characterize the functions of MdDRB1 in miRNA biogenesis, adventitious rooting, leaf development and tree growth habit. MdDRB1 contained two highly conserved DRB domains. Its transcripts existed in all tissues tested and are induced by hormones. It bound to double-strand RNAs and interacted with AtDCL1 (Dicer-Like 1) and MdDCL1. Chip assay indicated its role in miRNA biogenesis. Transgenic analysis showed that MdDRB1 controls adventitious rooting, leaf curvature and tree architecture by modulating the accumulation of miRNAs and the transcript levels of miRNA target genes. Our results demonstrated that MdDRB1 functions in the miRNA biogenesis in a conserved way and that it is a master regulator in the formation of economically important traits in fruit trees. © 2013 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

Which Instructional Practices Most Help First Grade Students with and without Mathematics Difficulties?

PubMed Central

Morgan, Paul L.; Farkas, George; Maczuga, Steve

2015-01-01

We used population-based, longitudinal data to investigate the relation between mathematics instructional practices used by 1st grade teachers in the U.S. and the mathematics achievement of their students. Factor analysis identified four types of instructional activities (i.e., teacher-directed, student-centered, manipulatives/calculators, movement/music) and eight types of specific skills taught (e.g., adding two-digit numbers). First-grade students were then classified into five groups on the basis of their fall and/or spring of kindergarten mathematics achievement—three groups with mathematics difficulties (MD) and two without MD. Regression analysis indicated that a higher percentage of MD students in 1st grade classrooms was associated with greater use by teachers of manipulatives/calculators and movement/music to teach mathematics. Yet follow-up analysis for each of the MD and non-MD groups indicated that only teacher-directed instruction was significantly associated with the achievement of students with MD (covariate-adjusted ESs = .05–.07). The largest predicted effect for a specific instructional practice was for routine practice and drill. In contrast, for both groups of non-MD students, teacher-directed and student-centered instruction had approximately equal, statistically significant positive predicted effects (covariate-adjusted ESs = .03–.04). First-grade teachers in the U.S. may need to increase their use of teacher-directed instruction if they are to raise the mathematics achievement of students with MD. PMID:26180268

Sex, stressful life events, and adult onset depression and alcohol dependence: are men and women equally vulnerable?

PubMed

Slopen, Natalie; Williams, David R; Fitzmaurice, Garrett M; Gilman, Stephen E

2011-08-01

Higher rates of major depression (MD) among females, and of alcohol dependence (AD) among males, are among the most routinely reported findings in psychiatric epidemiology. One of the most often pursued explanations for sex differences in both disorders suggests that males and females have a differential vulnerability to stressors, which is manifested in sex-specific ways (MD for females, AD for males). However, existing evidence in support of this explanation is mixed. In the present study, we investigated sex differences in the association between stressful life events and MD and AD in a large national sample of adults in the United States (n = 32,744) using a prospective design. Logistic regression was used to estimate associations between stressful life events and both MD and AD; sex-specific effects of stress on MD and AD were evaluated by testing interaction terms between sex and stressors in the prediction of both outcomes. The number of stressful life events was predictive of first onset MD and AD. This was true for both males and females, and sex-by-stress interaction terms did not support the hypothesis that sex-specific responses to stressful life events lead to sex differences in first onset of MD and AD among adults. These results indicate the resistance of sex differences in MD and AD to simple explanations, and suggest the need for more nuanced models that incorporate both physiological and social aspects of vulnerability. Copyright © 2011 Elsevier Ltd. All rights reserved.

Coarse-Grained MD Simulations and Protein-Protein Interactions: The Cohesin-Dockerin System.

PubMed

Hall, Benjamin A; Sansom, Mark S P

2009-09-08

Coarse-grained molecular dynamics (CG-MD) may be applied as part of a multiscale modeling approach to protein-protein interactions. The cohesin-dockerin interaction provides a valuable test system for evaluation of the use of CG-MD, as structural (X-ray) data indicate a dual binding mode for the cohesin-dockerin pair. CG-MD simulations (of 5 μs duration) of the association of cohesin and dockerin identify two distinct binding modes, which resemble those observed in X-ray structures. For each binding mode, ca. 80% of interfacial residues are predicted correctly. Furthermore, each of the binding modes identified by CG-MD is conformationally stable when converted to an atomistic model and used as the basis of a conventional atomistic MD simulation of duration 20 ns.

Hypnosis in the Treatment of Major Depression: An Analysis of Heart Rate Variability.

PubMed

Chen, Xiuwen; Yang, Rongqian; Ge, Lulu; Luo, Jie; Lv, Ruixue

2017-01-01

Hypnosis is an adjuvant treatment of major depression (MD). Heart rate variability (HRV) can assess the autonomic nervous system, which is associated with MD, and HRV is decreased in MD patients. There is a lack of research on HRV changes before, during, and after the use of hypnosis in MD patients. A total of 21 MD patients participated in this study, and 5-minute electrocardiograms were recorded before, during, and after hypnosis. Compared with the prehypnotic condition, HRV parameters significantly (p < .01) increased in the hypnotic and posthypnotic conditions. The results suggest that hypnosis treatment should bring some functional improvement to the autonomic nervous system. HRV is potentially a useful tool that quantifies the physiological impact of hypnosis treatment in MD patients.

Improved Statistical Sampling and Accuracy with Accelerated Molecular Dynamics on Rotatable Torsions.

PubMed

Doshi, Urmi; Hamelberg, Donald

2012-11-13

In enhanced sampling techniques, the precision of the reweighted ensemble properties is often decreased due to large variation in statistical weights and reduction in the effective sampling size. To abate this reweighting problem, here, we propose a general accelerated molecular dynamics (aMD) approach in which only the rotatable dihedrals are subjected to aMD (RaMD), unlike the typical implementation wherein all dihedrals are boosted (all-aMD). Nonrotatable and improper dihedrals are marginally important to conformational changes or the different rotameric states. Not accelerating them avoids the sharp increases in the potential energies due to small deviations from their minimum energy conformations and leads to improvement in the precision of RaMD. We present benchmark studies on two model dipeptides, Ace-Ala-Nme and Ace-Trp-Nme, simulated with normal MD, all-aMD, and RaMD. We carry out a systematic comparison between the performances of both forms of aMD using a theory that allows quantitative estimation of the effective number of sampled points and the associated uncertainty. Our results indicate that, for the same level of acceleration and simulation length, as used in all-aMD, RaMD results in significantly less loss in the effective sample size and, hence, increased accuracy in the sampling of φ-ψ space. RaMD yields an accuracy comparable to that of all-aMD, from simulation lengths 5 to 1000 times shorter, depending on the peptide and the acceleration level. Such improvement in speed and accuracy over all-aMD is highly remarkable, suggesting RaMD as a promising method for sampling larger biomolecules.

1492--the medical consequences.

PubMed

Camargo, C A

1994-06-01

This discussion was selected from the weekly staff conferences in the Department of Medicine, University of California, San Francisco. Taken from a transcription, it has been edited by Nathan M. Bass, MD, PhD, Associate Professor of Medicine, under the direction of Lloyd H. Smith Jr, MD, Professor of Medicine and Associate Dean in the School of Medicine.

Association between macular degeneration and mild to moderate chronic kidney disease: A nationwide population-based study.

PubMed

Chen, Chun-Yu; Dai, Ciou-Sia; Lee, Chin-Chan; Shyu, Yu-Chiau; Huang, Ting-Shuo; Yeung, Ling; Sun, Chi-Chin; Yang, Huang-Yu; Wu, I-Wen

2017-03-01

Chronic kidney disease (CKD) and macular degeneration (MD) are 2 grave diseases leading to significant disability secondary to renal failure and blindness. The 2 diseases share not only common risk factors but also similar pathogenic mechanisms to renal and retinal injuries. Previous epidemiological studies indicated association between these 2 diseases. However, this concept is challenged by recent investigations. Patients with mild to moderate CKD (n = 30,696) between January 1, 1995 and December 31, 2005 were selected from the Taiwan National Health Insurance Database. Controls (n = 122,784) were matched by age, gender, diabetes mellitus type 2, and hypertension status (1:4 ratios). The risk of MD was compared between the 2 groups. The mean age of patients was 54.9 ± 15.7 years. The proportion of MD was 2.7% in mild to moderate CKD patients and 1.9% in normal controls (P < 0.001); and, 0.39% and 0.26% (P < 0.001) in advanced MD. Mild to moderate CKD patients had higher risk for MD [adjusted odds ratio (OR), 1.301; 95% confidence interval (CI), 1.200-1.411; P < 0.001] than normal renal function subjects. The association was more pronounced for advanced MD. From all age strata (10 years increase), the presence of CKD in those patients aged less than 40 years had highest OR for all MD (OR = 2.125, 95% CI: 1.417-3.186, P < 0.001). The results were consistent in interaction terms, highlighting the importance of CKD in young age patient for risk of MD. The high risk for MD in mild to moderate CKD patients remains significant after adjustment for personal habits (alcohol drinking and smoking, model 1; OR: 1.371; 95% CI: 1.265-1.486; P < 0.001), comorbidities (dyslipidemia, cerebrovascular disease, and peripheral vascular disease, model 2; OR: 1.369; 95% CI: 1.264-1.484; P < 0.001) and all these factors (model 3; OR: 1.320, 95% CI: 1.218-1.431, P < 0.001). This association was consistent in the subanalysis, excluding those patients with diabetic retinopathy. Proper diagnosis and timely intervention should be warranted to retard visual loss of these patients.

Natural resistance to Meningococcal Disease related to CFH loci: Meta-analysis of genome-wide association studies.

PubMed

Martinón-Torres, Federico; Png, Eileen; Khor, Chiea Chuen; Davila, Sonia; Wright, Victoria J; Sim, Kar Seng; Vega, Ana; Fachal, Laura; Inwald, David; Nadel, Simon; Carrol, Enitan D; Martinón-Torres, Nazareth; Alonso, Sonia Marcos; Carracedo, Angel; Morteruel, Elvira; López-Bayón, Julio; Torre, Andrés Concha; Monge, Cristina Calvo; de Aguilar, Pilar Azcón González; Torné, Elisabeth Esteban; Martínez-Padilla, María Del Carmen; Martinón-Sánchez, José María; Levin, Michael; Hibberd, Martin L; Salas, Antonio

2016-11-02

Meningococcal disease (MD) remains an important infectious cause of life threatening infection in both industrialized and resource poor countries. Genetic factors influence both occurrence and severity of presentation, but the genes responsible are largely unknown. We performed a genome-wide association study (GWAS) examining 5,440,063 SNPs in 422 Spanish MD patients and 910 controls. We then performed a meta-analysis of the Spanish GWAS with GWAS data from the United Kingdom (combined cohorts: 897 cases and 5,613 controls; 4,898,259 SNPs). The meta-analysis identified strong evidence of association (P-value ≤ 5 × 10 -8 ) in 20 variants located at the CFH gene. SNP rs193053835 showed the most significant protective effect (Odds Ratio (OR) = 0.62, 95% confidence interval (C.I.) = 0.52-0.73; P-value = 9.62 × 10 -9 ). Five other variants had been previously reported to be associated with susceptibility to MD, including the missense SNP rs1065489 (OR = 0.64, 95% C.I.) = 0.55-0.76, P-value = 3.25 × 10 -8 ). Theoretical predictions point to a functional effect of rs1065489, which may be directly responsible for protection against MD. Our study confirms the association of CFH with susceptibility to MD and strengthens the importance of this link in understanding pathogenesis of the disease.

A dual positional specific lipoxygenase functions in the generation of flavor compounds during climacteric ripening of apple

PubMed Central

Schiller, Doreen; Contreras, Carolina; Vogt, Jörg; Dunemann, Frank; Defilippi, Bruno G; Beaudry, Randolph; Schwab, Wilfried

2015-01-01

Lipoxygenase (LOX) is an important contributor to the formation of aroma-active C6 aldehydes in apple (Malus × domestica) fruit upon tissue disruption but little is known about its role in autonomously produced aroma volatiles from intact tissue. We explored the expression of 22 putative LOX genes in apple throughout ripening, but only six LOXs were expressed in a ripening-dependent manner. Recombinant LOX1:Md:1a, LOX1:Md:1c, LOX2:Md:2a and LOX2:Md:2b proteins showed 13/9-LOX, 9-LOX, 13/9-LOX and 13-LOX activity with linoleic acid, respectively. While products of LOX1:Md:1c and LOX2:Md:2b were S-configured, LOX1:Md:1a and LOX2:Md:2a formed 13(R)-hydroperoxides as major products. Site-directed mutagenesis of Gly567 to an alanine converted the dual positional specific LOX1:Md:1a to an enzyme with a high specificity for 9(S)-hydroperoxide formation. The high expression level of the corresponding MdLOX1a gene in stored apple fruit, the genetic association with a quantitative trait locus for fruit ester and the remarkable agreement in regio- and stereoselectivity of the LOX1:Md:1a reaction with the overall LOX activity found in mature apple fruits, suggest a major physiological function of LOX1:Md:1a during climacteric ripening of apples. While LOX1:Md:1c, LOX2:Md:2a and LOX2:Md:2b may contribute to aldehyde production in immature fruit upon cell disruption our results furnish additional evidence that LOX1:Md:1a probably regulates the availability of precursors for ester production in intact fruit tissue. PMID:26504564

Report of the NIH Panel to Define Principles of Therapy of HIV Infection and Guidelines for the Use of Antiretroviral Agents in HIV-Infected Adults and Adolescents. Vol. 47/No. RR-5.

DTIC Science & Technology

1998-04-25

MA David Cooper, M.D. National Center for HIV Epidemiology and Clinical Research Sydney, NSW, Australia Stephen Follansbee, M.D. Davies...National Association of People with AIDS Washington, DC David Barr, J.D. Forum for Collaborative HIV Research Washington, DC Samuel Bozzette, M.D...Mellors, M.D. University of Pittsburgh Pittsburgh, PA David Nash, M.D. Thomas Jefferson University Philadelphia, PA Sallie Perryman New York

A comparison of the clinical characteristics of women with recurrent major depression with and without suicidal symptomatology.

PubMed

Bi, B; Xiao, X; Zhang, H; Gao, J; Tao, M; Niu, H; Wang, Y; Wang, Q; Chen, C; Sun, N; Li, K; Fu, J; Gan, Z; Sang, W; Zhang, G; Yang, L; Tian, T; Li, Q; Yang, Q; Sun, L; Li, Ying; Rong, H; Guan, C; Zhao, X; Ye, D; Zhang, Y; Ma, Z; Li, H; He, K; Chen, J; Cai, Y; Zhou, C; Luo, Y; Wang, S; Gao, S; Liu, J; Guo, L; Guan, J; Kang, Z; Di, D; Li, Yajuan; Shi, S; Li, Yihan; Chen, Y; Flint, J; Kendler, K; Liu, Y

2012-12-01

The relationship between recurrent major depression (MD) in women and suicidality is complex. We investigated the extent to which patients who suffered with various forms of suicidal symptomatology can be distinguished from those subjects without such symptoms. We examined the clinical features of the worst episode in 1970 Han Chinese women with recurrent DSM-IV MD between the ages of 30 and 60 years from across China. Student's t tests, and logistic and multiple logistic regression models were used to determine the association between suicidality and other clinical features of MD. Suicidal symptomatology is significantly associated with a more severe form of MD, as indexed by both the number of episodes and number of MD symptoms. Patients reporting suicidal thoughts, plans or attempts experienced a significantly greater number of stressful life events. The depressive symptom most strongly associated with lifetime suicide attempt was feelings of worthlessness (odds ratio 4.25, 95% confidence interval 2.9-6.3). Excessive guilt, diminished concentration and impaired decision-making were also significantly associated with a suicide attempt. This study contributes to the existing literature on risk factors for suicidal symptomatology in depressed women. Identifying specific depressive symptoms and co-morbid psychiatric disorders may help improve the clinical assessment of suicide risk in depressed patients. These findings could be helpful in identifying those who need more intense treatment strategies in order to prevent suicide.

Cross-sectional associations between high-deprivation home and neighbourhood environments, and health-related variables among Liverpool children

PubMed Central

Noonan, Robert J; Boddy, Lynne M; Knowles, Zoe R; Fairclough, Stuart J

2016-01-01

Objectives (1) To investigate differences in health-related, home and neighbourhood environmental variables between Liverpool children living in areas of high deprivation (HD) and medium-to-high deprivation (MD) and (2) to assess associations between these perceived home and neighbourhood environments and health-related variables stratified by deprivation group. Design Cross-sectional study. Setting 10 Liverpool primary schools in 2014. Participants 194 children aged 9–10 years. Main outcome measures Health-related variables (self-reported physical activity (PA) (Physical Activity Questionnaire for Older Children, PAQ-C), cardiorespiratory fitness, body mass index (BMI) z-scores, waist circumference), home environment variables: (garden/backyard access, independent mobility, screen-based media restrictions, bedroom media) and neighbourhood walkability (Neighbourhood Environment Walkability Scale for Youth, NEWS-Y). Explanatory measures Area deprivation. Results There were significant differences between HD and MD children's BMI z-scores (p<0.01), waist circumference (p<0.001) and cardiorespiratory fitness (p<0.01). HD children had significantly higher bedroom media availability (p<0.05) and independent mobility scores than MD children (p<0.05). MD children had significantly higher residential density and neighbourhood aesthetics scores, and lower crime safety, pedestrian and road traffic safety scores than HD children, all of which indicated higher walkability (p<0.01). HD children's BMI z-scores (β=−0.29, p<0.01) and waist circumferences (β=−0.27, p<0.01) were inversely associated with neighbourhood aesthetics. HD children's PA was negatively associated with bedroom media (β=−0.24, p<0.01), and MD children's PA was positively associated with independent mobility (β=0.25, p<0.01). MD children's independent mobility was inversely associated with crime safety (β=−0.28, p<0.01) and neighbourhood aesthetics (β=−0.24, p<0.05). Conclusions Children living in HD areas had the least favourable health-related variables and were exposed to home and neighbourhood environments that are unconducive to health-promoting behaviours. Less access to bedroom media equipment and greater independent mobility were strongly associated with higher PA in HD and MD children, respectively. Facilitating independent mobility and encouraging outdoor play may act as effective strategies to enhance PA levels and reduce sedentary time in primary school-aged children. PMID:26769779

Features of mood associated with high body weight in females with fibromyalgia.

PubMed

Alciati, Alessandra; Atzeni, Fabiola; Grassi, Massimiliano; Caldirola, Daniela; Sarzi-Puttini, Piercarlo; Angst, Jules; Perna, Giampaolo

2018-01-01

Fibromyalgia (FM) is a common syndrome whose main characteristic is chronic widespread musculoskeletal pain, the severity of which is frequently worsened by concomitant obesity. Major depression (MD), particularly as part of a bipolar spectrum disorder (BSD), is associated with both obesity and FM. To evaluate the relationship between lifetime MD, hypomanic symptoms and the body mass index (BMI) in patients with FM. Of the 115 patients originally screened, 87 women with FM finally entered the study. Forty-nine patients (57%) had a lifetime diagnosis of MD, assessed by a structured clinical interview based on DSM-IV criteria, and four of them (4.6%) had a current MD episode. Lifetime hypomanic symptoms were measured by means of the self-rated Hypomania Checklist. According to the international criteria for BMI, FM patients were classified as under/normal-weight (61%), overweight (30%) and obese (9%). 62 patients (71.2%) with FM had a bipolar spectrum disorder (BSD). Thirty (48.3%) of them met criteria for bipolar II disorder, 32 (51,6%) for bipolar disorder NOS (18 FM patients with MD associated to sub-syndromal hypomanic syndrome and 14 with hypomanic syndrome without MD). No patient had a bipolar I disorder. Only one patient met the criteria for a major depressive disorder (MDD). There was no significant difference in mean BMI between the patients with and without a lifetime diagnosis of MD, but there was a positive association between the level of hypomanic symptoms and BMI values (p<0.009). When hypomania was considered categorically as hypomanic syndrome there was no significant effect on BMI. Our finding adds to previous evidence indicating that hypomanic symptoms are a central feature of FM. In the case of the early identification of high-level hypomanic symptoms, body weight should be closely monitored in order to prevent obesity and its detrimental impact on females with FM. Copyright © 2017 Elsevier Inc. All rights reserved.

Association between Mediterranean diet and hand grip strength in older adult women.

PubMed

Barrea, Luigi; Muscogiuri, Giovanna; Di Somma, Carolina; Tramontano, Giovanni; De Luca, Vincenzo; Illario, Maddalena; Colao, Annamaria; Savastano, Silvia

2018-04-03

Mediterranean Diet (MD) is an eating pattern associated with multiple healthy benefits, including the conservation of skeletal muscle. Frailty is a major geriatric syndrome characterized by low muscle strength. The Hand Grip Strength (HGS) is the most frequently used indicator of muscle functional capacity for clinical purposes. The association between the adherence to the MD and HGS in elderly has not yet fully investigated. The goal of this study was to examine the association between the adherence to the MD and HGS in a not hospitalized elderly who participated in the project PERsonalised ict Supported Services for Independent Living and Active Ageing (PERSSILAA). Eighty-four elderly women were consecutively enrolled (aged 60-85 years) in this cross-sectional observational study. Anthropometric measures were evaluated. A validated 14-item questionnaire PREDIMED (PREvención con DIeta MEDiterránea) was used for the assessment of adherence to the MD. Dietary data were collected by a 7-day food records. Muscle strength was measured by HGS using a grip strength dynamometer (KERN & SOHN GmbH). The majority of participants were overweight (46.4%). An average adherence to the MD was found in 52.4% of participants, while the minority of them showed a low adherence (21.4%). HGS > cut-point of 20 kg were found in 43 subjects (51.2%). According to the adherence to MD, 39% participants with HGS values higher than cut-point presented a high adherence score compared with 14% of those with lower values of HGS (p = 0.018). The participants with HGS > cut-point presented significantly higher PREDIMED score than those with HGS < cut-point (p < 0.001). Based on ROC curves, the most sensitive and specific cut-point for the PREDIMED score to predict HGS categories was ≥8. No evident correlations were observed between HGS and age, while HGS was negatively correlated with hip circumference (r = -0.233, p = 0.033) and BMI (r = -0.219, p = 0.045), and positively correlated with PREDIMED score (r = 0.598, p < 0.001). At binomial logistic regression analysis almost all 14-items of PREDIMED questionnaire were significantly associated with HGS adjusted for BMI. At multinomial logistic regression analysis to assess the association of the three classes of adherence to the MD with the HGS, after adjusting for BMI the lowest adherence to MD was associated with the lowest Odds Ratio of HGS (p < 0.001). This study evidenced a positive association between the adherence to the MD and muscle strength in a sample of active elderly women, stratified according to the HGS > cut-point of 20 kg. Our study highlights the usefulness of the developing health services to detect and prevent age-associated decline in physical performance in elderly subjects by addressing nutritional and physical intervention. Copyright © 2018 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Genetic Study of White Matter Integrity in UK Biobank (N=8448) and the Overlap With Stroke, Depression, and Dementia.

PubMed

Rutten-Jacobs, Loes C A; Tozer, Daniel J; Duering, Marco; Malik, Rainer; Dichgans, Martin; Markus, Hugh S; Traylor, Matthew

2018-06-01

Structural integrity of the white matter is a marker of cerebral small vessel disease, which is the major cause of vascular dementia and a quarter of all strokes. Genetic studies provide a way to obtain novel insights in the disease mechanism underlying cerebral small vessel disease. The aim was to identify common variants associated with microstructural integrity of the white matter and to elucidate the relationships of white matter structural integrity with stroke, major depressive disorder, and Alzheimer disease. This genome-wide association analysis included 8448 individuals from UK Biobank-a population-based cohort study that recruited individuals from across the United Kingdom between 2006 and 2010, aged 40 to 69 years. Microstructural integrity was measured as fractional anisotropy- (FA) and mean diffusivity (MD)-derived parameters on diffusion tensor images. White matter hyperintensity volumes (WMHV) were assessed on T2-weighted fluid-attenuated inversion recovery images. We identified 1 novel locus at genome-wide significance ( VCAN [versican]: rs13164785; P =3.7×10 -18 for MD and rs67827860; P =1.3×10 -14 for FA). LD score regression showed a significant genome-wide correlation between FA, MD, and WMHV (FA-WMHV rG 0.39 [SE, 0.15]; MD-WMHV rG 0.56 [SE, 0.19]). In polygenic risk score analysis, FA, MD, and WMHV were significantly associated with lacunar stroke, MD with major depressive disorder, and WMHV with Alzheimer disease. Genetic variants within the VCAN gene may play a role in the mechanisms underlying microstructural integrity of the white matter in the brain measured as FA and MD. Mechanisms underlying white matter alterations are shared with cerebrovascular disease, and inherited differences in white matter microstructure impact on Alzheimer disease and major depressive disorder. © 2018 The Authors.

Obstacles delaying the prompt deployment of piston-type mechanical cardiopulmonary resuscitation devices during emergency department resuscitation: a video-recording and time-motion study.

PubMed

Huang, Edward Pei-Chuan; Wang, Hui-Chih; Ko, Patrick Chow-In; Chang, Anna Marie; Fu, Chia-Ming; Chen, Jiun-Wei; Liao, Yen-Chen; Liu, Hung-Chieh; Fang, Yao-De; Yang, Chih-Wei; Chiang, Wen-Chu; Ma, Matthew Huei-Ming; Chen, Shyr-Chyr

2013-09-01

The quality of cardiopulmonary resuscitation (CPR) is important to survival after cardiac arrest. Mechanical devices (MD) provide constant CPR, but their effectiveness may be affected by deployment timeliness. To identify the timeliness of the overall and of each essential step in the deployment of a piston-type MD during emergency department (ED) resuscitation, and to identify factors associated with delayed MD deployment by video recordings. Between December 2005 and December 2008, video clips from resuscitations with CPR sessions using a MD in the ED were reviewed using time-motion analyses. The overall deployment timeliness and the time spent on each essential step of deployment were measured. There were 37 CPR recordings that used a MD. Deployment of MD took an average 122.6 ± 57.8s. The 3 most time-consuming steps were: (1) setting the device (57.8 ± 38.3s), (2) positioning the patient (33.4 ± 38.0 s), and (3) positioning the device (14.7 ± 9.5s). Total no flow time was 89.1 ± 41.2s (72.7% of total time) and associated with the 3 most time-consuming steps. There was no difference in the total timeliness, no-flow time, and no-flow ratio between different rescuer numbers, time of day of the resuscitation, or body size of patients. Rescuers spent a significant amount of time on MD deployment, leading to long no-flow times. Lack of familiarity with the device and positioning strategy were associated with poor performance. Additional training in device deployment strategies are required to improve the benefits of mechanical CPR. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Effect of self-reported quality of sleep on mobility in older adults.

PubMed

Malinowska, Katarzyna B; Okura, Mika; Ogita, Mihoko; Yamamoto, Miki; Nakai, Toshimi; Numata, Tomoko; Tsuboyama, Tadao; Arai, Hidenori

2016-02-01

Quality of sleep (QOS) has been shown to have an affect on mental and physical well-being, and quality of life. However, few studies have investigated how sleep affects mobility in older adults. The aim of the present study was to examine the relationship between QOS and mobility disorder (MD) in community-dwelling older adults. Data collected through self-administered questionnaires was analyzed for 4564 Japanese older adults. Sleep outcomes included two self-reported questions regarding QOS. Logistic regression analysis was used to analyze the association between sleep and MD both by the QOS questions independently and grouped together by the two QOS questions into three groups: often sleeps well and good awakening (GG), does not often sleep well and bad awakening (BB) and a group with one of each (GB/BG). After adjustment for age, sex and depression, both those who did not often sleep well and those with poor awakening were more likely to show MD (OR 1.45, 95% CI 1.29-1.75), (OR 1.77, 95% CI 1.50-2.08), respectively. When grouped by both questions, those in the BB group had the least favorable outcome with increased odds ratio for possessing a MD (OR 1.95, 95% CI 1.61-2.37), compared with GB group (OR 1.40, 95% CI 1.18-1.67). Often sleeping well and good morning awakening were both associated with MD, suggesting that self reported QOS is associated with MD. Further research is required to investigate whether improving sleep quality could be a possible means of preventing and reversing MD in older adults. © 2015 Japan Geriatrics Society.

Hemangioma

MedlinePlus

... 38. Review Date 10/24/2016 Updated by: David L. Swanson, MD, Vice Chair of Medical Dermatology, Associate Professor of Dermatology, Mayo Medical School, Scottsdale, AZ. Also reviewed by David Zieve, MD, MHA, Isla Ogilvie, PhD, and the ...

Pityriasis alba

MedlinePlus

... 10. Review Date 5/2/2017 Updated by: David L. Swanson, MD, Vice Chair of Medical Dermatology, Associate Professor of Dermatology, Mayo Medical School, Scottsdale, AZ. Also reviewed by David Zieve, MD, MHA, Medical Director, Brenda Conaway, Editorial ...

Spider angioma

MedlinePlus

... 650. Review Date 10/24/2016 Updated by: David L. Swanson, MD, Vice Chair of Medical Dermatology, Associate Professor of Dermatology, Mayo Medical School, Scottsdale, AZ. Also reviewed by David Zieve, MD, MHA, Isla Ogilvie, PhD, and the ...

Rhinophyma

MedlinePlus

... 7. Review Date 10/24/2016 Updated by: David L. Swanson, MD, Vice Chair of Medical Dermatology, Associate Professor of Dermatology, Mayo Medical School, Scottsdale, AZ. Also reviewed by David Zieve, MD, MHA, Isla Ogilvie, PhD, and the ...

Presence of muscle dysmorphia symptomology among male weightlifters.

PubMed

Hildebrandt, Tom; Schlundt, David; Langenbucher, James; Chung, Tammy

2006-01-01

Limited research exists on muscle dysmorphia (MD) in men and in nonclinical populations. The current study evaluated types of body image disturbance among 237 male weightlifters. Latent class analysis of 8 measures of body image disturbance revealed 5 independent types of respondents: Dysmorphic, Muscle Concerned, Fat Concerned, Normal Behavioral, and Normal. One-way analysis of variance of independent measures of body image disturbance and associated psychopathology confirmed significant differences between groups. The Dysmorphic group reported a pattern of body image disturbance consistent with MD by displaying a high overall level of body image disturbance, symptoms of associated psychopathology, steroid use, and appearance-controlling behavior. Findings generally supported classifying MD as a subtype of body dysmorphic disorder and an obsessive-compulsive spectrum disorder. Implications for studying body image disturbance in male weightlifters, and further evaluation of the MD diagnostic criteria are discussed.

Muscle dysmorphia in Hungarian non-competitive male bodybuilders.

PubMed

Babusa, B; Túry, F

2012-03-01

Muscle dysmorphia (MD) has been described as a male body image disorder, characterized by a pathological preoccupation with muscle size. The aim of the study was to examine the MD features, eating disorder characteristics and body attitudes in non-competitive male bodybuilders in a Hungarian sample. Sixty male bodybuilders and 60 undergraduate university students completed the self-report questionnaires of the Muscle Appearance Satisfaction Scale, the Body Attitude Test and the Eating Disorders Inventory. MD was associated with current bodybuilding activity, higher ideal body weight and eating disorder characteristics. Moreover, current selfreported steroid users displayed higher tendency for MD symptoms than self-reported steroid non-users. Results emphasize the relationship between MD symptoms, eating disorder characteristics and steroid use. MD and body image related concerns among men could be a wide-spread phenomena also in the Central-Eastern European region.

1492—The Medical Consequences

PubMed Central

Camargo, Carlos A.

1994-01-01

This discussion was selected from the weekly staff conferences in the Department of Medicine, University of California, San Francisco. Taken from a transcription, it has been edited by Nathan M. Bass, MD, PhD, Associate Professor of Medicine, under the direction of Lloyd H. Smith Jr, MD, Professor of Medicine and Associate Dean in the School of Medicine. Images PMID:7519808

Adherence to the Mediterranean diet and risk of lung cancer in the Netherlands Cohort Study.

PubMed

Schulpen, Maya; van den Brandt, Piet A

2018-03-01

The evidence on a cancer-protective effect of the Mediterranean diet (MD) is still limited. Therefore, we investigated the association between MD adherence and lung cancer risk. Data were used from 120 852 participants of the Netherlands Cohort Study (NLCS), aged 55-69 years. Dietary habits were assessed at baseline (1986) using a validated FFQ and alternate and modified Mediterranean diet scores (aMED and mMED, respectively), including and excluding alcohol, were calculated. After 20·3 years of follow-up, 2861 lung cancer cases and 3720 subcohort members (case-cohort design) could be included in multivariable Cox regression analyses. High (6-8) v. low (0-3) aMED excluding alcohol was associated with non-significantly reduced lung cancer risks in men and women with hazard ratios of 0·91 (95 % CI 0·72, 1·15) and 0·73 (95 % CI 0·49, 1·09), respectively. aMED-containing models generally fitted better than mMED-containing models. In never smokers, a borderline significant decreasing trend in lung cancer risk was observed with increasing aMED excluding alcohol. Analyses stratified by the histological lung cancer subtypes did not identify subtypes with a particularly strong inverse relation with MD adherence. Generally, the performance of aMED and World Cancer Research Fund/American Institute for Cancer Research dietary score variants without alcohol was comparable. In conclusion, MD adherence was non-significantly inversely associated with lung cancer risk in the NLCS. Future studies should focus on differences in associations across the sexes and histological subtypes. Furthermore, exclusion of alcohol from MD scores should be investigated more extensively, primarily with respect to a potential role of the MD in cancer prevention.

High-level adherence to a Mediterranean diet beneficially impacts the gut microbiota and associated metabolome.

PubMed

De Filippis, Francesca; Pellegrini, Nicoletta; Vannini, Lucia; Jeffery, Ian B; La Storia, Antonietta; Laghi, Luca; Serrazanetti, Diana I; Di Cagno, Raffaella; Ferrocino, Ilario; Lazzi, Camilla; Turroni, Silvia; Cocolin, Luca; Brigidi, Patrizia; Neviani, Erasmo; Gobbetti, Marco; O'Toole, Paul W; Ercolini, Danilo

2016-11-01

Habitual diet plays a major role in shaping the composition of the gut microbiota, and also determines the repertoire of microbial metabolites that can influence the host. The typical Western diet corresponds to that of an omnivore; however, the Mediterranean diet (MD), common in the Western Mediterranean culture, is to date a nutritionally recommended dietary pattern that includes high-level consumption of cereals, fruit, vegetables and legumes. To investigate the potential benefits of the MD in this cross-sectional survey, we assessed the gut microbiota and metabolome in a cohort of Italian individuals in relation to their habitual diets. We retrieved daily dietary information and assessed gut microbiota and metabolome in 153 individuals habitually following omnivore, vegetarian or vegan diets. The majority of vegan and vegetarian subjects and 30% of omnivore subjects had a high adherence to the MD. We were able to stratify individuals according to both diet type and adherence to the MD on the basis of their dietary patterns and associated microbiota. We detected significant associations between consumption of vegetable-based diets and increased levels of faecal short-chain fatty acids, Prevotella and some fibre-degrading Firmicutes, whose role in human gut warrants further research. Conversely, we detected higher urinary trimethylamine oxide levels in individuals with lower adherence to the MD. High-level consumption of plant foodstuffs consistent with an MD is associated with beneficial microbiome-related metabolomic profiles in subjects ostensibly consuming a Western diet. This study was registered at clinical trials.gov as NCT02118857. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Association between global DNA hypomethylation in leukocytes and risk of breast cancer.

PubMed

Choi, Ji-Yeob; James, Smitha R; Link, Petra A; McCann, Susan E; Hong, Chi-Chen; Davis, Warren; Nesline, Mary K; Ambrosone, Christine B; Karpf, Adam R

2009-11-01

Global DNA hypomethylation may result in chromosomal instability and oncogene activation, and as a surrogate of systemic methylation activity, may be associated with breast cancer risk. Samples and data were obtained from women with incident early-stage breast cancer (I-IIIa) and women who were cancer free, frequency matched on age and race. In preliminary analyses, genomic methylation of leukocyte DNA was determined by measuring 5-methyldeoxycytosine (5-mdC), as well as methylation analysis of the LINE-1-repetitive DNA element. Further analyses used only 5-mdC levels. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for risk of breast cancer in relation to amounts of methylation. In a subset of samples tested (n = 37), 5-mdC level was not correlated with LINE-1 methylation. 5-mdC level in leukocyte DNA was significantly lower in breast cancer cases than healthy controls (P = 0.001), but no significant case-control differences were observed with LINE-1 methylation (P = 0.176). In the entire data set, we noted significant differences in 5-mdC levels in leukocytes between cases (n = 176) and controls (n = 173); P value < 0.001. Compared with women in the highest 5-mdC tertile (T3), women in the second (T2; OR = 1.49, 95% CI = 0.84-2.65) and lowest tertile (T1; OR = 2.86, 95% CI = 1.65-4.94) had higher risk of breast cancer (P for trend < or = 0.001). Among controls only and cases and controls combined, only alcohol intake was found to be inversely associated with methylation levels. These findings suggest that leukocyte DNA hypomethylation is independently associated with development of breast cancer.

Exploring the association between Morgellons disease and Lyme disease: identification of Borrelia burgdorferi in Morgellons disease patients.

PubMed

Middelveen, Marianne J; Bandoski, Cheryl; Burke, Jennie; Sapi, Eva; Filush, Katherine R; Wang, Yean; Franco, Agustin; Mayne, Peter J; Stricker, Raphael B

2015-02-12

Morgellons disease (MD) is a complex skin disorder characterized by ulcerating lesions that have protruding or embedded filaments. Many clinicians refer to this condition as delusional parasitosis or delusional infestation and consider the filaments to be introduced textile fibers. In contrast, recent studies indicate that MD is a true somatic illness associated with tickborne infection, that the filaments are keratin and collagen in composition and that they result from proliferation and activation of keratinocytes and fibroblasts in the skin. Previously, spirochetes have been detected in the dermatological specimens from four MD patients, thus providing evidence of an infectious process. Based on culture, histology, immunohistochemistry, electron microscopy and molecular testing, we present corroborating evidence of spirochetal infection in a larger group of 25 MD patients. Irrespective of Lyme serological reactivity, all patients in our study group demonstrated histological evidence of epithelial spirochetal infection. Strength of evidence based on other testing varied among patients. Spirochetes identified as Borrelia strains by polymerase chain reaction (PCR) and/or in-situ DNA hybridization were detected in 24/25 of our study patients. Skin cultures containing Borrelia spirochetes were obtained from four patients, thus demonstrating that the organisms present in dermatological specimens were viable. Spirochetes identified by PCR as Borrelia burgdorferi were cultured from blood in seven patients and from vaginal secretions in three patients, demonstrating systemic infection. Based on these observations, a clinical classification system for MD is proposed. Our study using multiple detection methods confirms that MD is a true somatic illness associated with Borrelia spirochetes that cause Lyme disease. Further studies are needed to determine the optimal treatment for this spirochete-associated dermopathy.

A fingerprint marker from early gestation associated with diabetes in middle age: The Dutch Hunger Winter Families Study

PubMed Central

Kahn, Henry S; Graff, Mariaelisa; Stein, Aryeh D; Lumey, L H

2009-01-01

Background Fetal programming of diabetes might originate in early pregnancy when fingerprints are permanently established. The mean dermatoglyphic ridge count difference between fingertips 1 and 5 (‘Md15’) varies with the early prenatal environment. We hypothesized that Md15 would be associated with adult-onset diabetes. Methods We obtained Md15 from 577 Dutch adults (aged 58.9 years, SD 1.1) whose births in 1943–47 were documented in maternity records and from 260 of their same-sex siblings for whom birth weights were not available. Of these 837 participants, complete anthropometry and diabetes status (from history or glucose tolerance test) were obtained for 819. Results After adjustment for age, sex, parental diabetes and adult anthropometry, fingerprint Md15 was associated with prevalent diabetes [odds ratio (OR) = 1.37 per 1 SD (95% confidence interval 1.02–1.84)]. This relationship held [OR = 1.40 (1.03–1.92)] for diabetic cases restricted to those recently diagnosed (within 7 years). In the birth series restricted to recently diagnosed cases, the mutually adjusted ORs were 1.34 (1.00–1.79) per SD of Md15 and 0.83 (0.62–1.10) per SD of birth weight. Further adjustments for maternal smoking, conception season or prenatal famine exposure in 1944–45 did not alter these estimates. Among 42 sibling pairs discordant for diabetes, the diabetic sibling had higher Md15 by 3.5 (0.6–6.3) after multivariable adjustment. Conclusions Diabetes diagnosed at age 50+ years was associated with a fingerprint marker established in early gestation, irrespective of birth weight. Fingerprints may provide a useful tool to investigate prenatal developmental plasticity. PMID:18684786

Decline of the Mediterranean diet at a time of economic crisis. Results from the Moli-sani study.

PubMed

Bonaccio, M; Di Castelnuovo, A; Bonanni, A; Costanzo, S; De Lucia, F; Persichillo, M; Zito, F; Donati, M B; de Gaetano, G; Iacoviello, L

2014-08-01

Adherence to Mediterranean diet (MD) is reportedly declining in the last decades. We aimed to investigate the adherence to MD over the period 2005-2010 and exploring the possible role of the global economic crisis in accounting for the changing in the dietary habits in Italy. Cross-sectional analysis in a population-based cohort study which randomly recruited 21,001 southern Italian citizens enrolled within the Moli-sani study. Food intake was determined by the Italian EPIC food frequency questionnaire. Adherence to MD was appraised by the Italian Mediterranean Index (IMI). A wealth score was derived to evaluate the economic position and used together with other socioeconomic indicators. Highest prevalence of adherence to MD was observed during the years 2005-2006 (31.3%) while the prevalence dramatically fell down in the years 2007-2010 (18.3%; P<0.0001). The decrease was stronger in the elderly, less affluent groups, and among those living in urban areas. Accordingly, we observed that in 2007-2010 socioeconomic indicators were strongly associated with higher adherence to MD, whereas no association was detected in the years before the economic crisis began; both wealth score and education were major determinants of high adherence to MD with 31% (95%CI: 18-46%) higher adherence to this pattern within the wealthier group compared to the less affluent category. Adherence to MD has considerably decreased over the last few years. In 2007-2010 socioeconomic indicators have become major determinants of adherence to MD, a fact likely linked to the economic downturn. Copyright © 2014 Elsevier B.V. All rights reserved.

The Structural Basis for Lipid and Endotoxin Binding in RP105-MD-1, and Consequences for Regulation of Host Lipopolysaccharide Sensitivity.

PubMed

Ortiz-Suarez, Maite L; Bond, Peter J

2016-01-05

MD-1 is a member of the MD-2-related lipid-recognition (ML) family, and associates with RP105, a cell-surface protein that resembles Toll-like receptor 4 (TLR4). The RP105⋅MD-1 complex has been proposed to play a role in fine-tuning the innate immune response to endotoxin such as bacterial lipopolysaccharide (LPS) via TLR4⋅MD-2, but controversy surrounds its mechanism. We have used atomically detailed simulations to reveal the structural basis for ligand binding and consequent functional dynamics of MD-1 and the RP105 complex. We rationalize reports of endogenous phospholipid binding, by showing that they prevent collapse of the malleable MD-1 fold, before refining crystallographic models and uncovering likely binding modes for LPS analogs. Subsequent binding affinity calculations reveal that endotoxin specificity arises from the entropic cost of expanding the MD-1 cavity to accommodate bulky lipid tails, and support the role of MD-1 as a "sink" that sequesters endotoxin from TLR4 and stabilizes RP105/TLR4 interactions. Copyright © 2016 Elsevier Ltd. All rights reserved.

The bZIP transcription factor MdHY5 regulates anthocyanin accumulation and nitrate assimilation in apple.

PubMed

An, Jian-Ping; Qu, Feng-Jia; Yao, Ji-Fang; Wang, Xiao-Na; You, Chun-Xiang; Wang, Xiao-Fei; Hao, Yu-Jin

2017-01-01

The basic leucine zipper (bZIP) transcription factor HY5 plays a multifaceted role in plant growth and development. Here the apple MdHY5 gene was cloned based on its homology with Arabidopsis HY5 . Expression analysis demonstrated that MdHY5 transcription was induced by light and abscisic acid treatments. Electrophoretic mobility shift assays and transient expression assays subsequently showed that MdHY5 positively regulated both its own transcription and that of MdMYB10 by binding to E-box and G-box motifs, respectively. Furthermore, we obtained transgenic apple calli that overexpressed the MdHY5 gene, and apple calli coloration assays showed that MdHY5 promoted anthocyanin accumulation by regulating expression of the MdMYB10 gene and downstream anthocyanin biosynthesis genes. In addition, the transcript levels of a series of nitrate reductase genes and nitrate uptake genes in both wild-type and transgenic apple calli were detected. In association with increased nitrate reductase activities and nitrate contents, the results indicated that MdHY5 might be an important regulator in nutrient assimilation. Taken together, these results indicate that MdHY5 plays a vital role in anthocyanin accumulation and nitrate assimilation in apple.

Correlates Associated with Unipolar Depressive Disorders in a Latino Population

PubMed Central

Correa-Fernandez, Virmarie; Carrión-Baralt, José R.; Alegría, Margarita; Albizu-García, Carmen E.

2014-01-01

Background This study reports the comparison and associations of demographic, clinical, and psychosocial correlates with three unipolar depressive disorders: dysthymia (DYS), major depression (MD), and double depression (DD), and examines to which extent these variables predict the disorders. Sampling and Method Previously collected data from 563 adults from a community in Puerto Rico were analyzed. One hundred and thirty individuals with DYS, 260 with MD, and 173 with DD were compared by demographic variables, psychiatric and physical comorbidity, familial psychopathology, psychosocial stressors, functional impairment, self-reliance, problem recognition and formal use of mental health services. Multinomial regression was used to assess the association of the predictor variables with each of the three disorders. Results Similarities outweighed the discrepancies between disorders. The main differences observed were between MD and DD, while DYS shared common characteristics with both MD and DD. After other variables were controlled, anxiety, functional impairment, and problem recognition most strongly predicted a DD diagnosis while age predicted a DYS diagnosis. Conclusion MD, DYS, and DD are not completely different disorders but they do differ in key aspects that might be relevant for nosology, research, and practice. A dimensional system that incorporates specific categories of disorders would better reflect the different manifestations of unipolar depressive disorders. PMID:23006435

Fungal nail infection

MedlinePlus

... 268. Review Date 10/24/2016 Updated by: David L. Swanson, MD, Vice Chair of Medical Dermatology, Associate Professor of Dermatology, Mayo Medical School, Scottsdale, AZ. Also reviewed by David Zieve, MD, MHA, Isla Ogilvie, PhD, and the ...

Apple fruit acidity is genetically diversified by natural variations in three hierarchical epistatic genes MdSAUR37, MdPP2CH and MdALMTII.

PubMed

Jia, Dongjie; Shen, Fei; Wang, Yi; Wu, Ting; Xu, Xuefeng; Zhang, Xinzhong; Han, Zhenhai

2018-05-11

Many efforts have been made to map quantitative trait loci (QTLs) to facilitate practical marker-assisted selection (MAS) in plants. In the present study, we identified four genome-wide major QTLs responsible for apple fruit acidity by MapQTL and BSA-seq analyses using two independent pedigree-based populations. Candidate genes were screened in major QTL regions, and three functional gene markers, including a non-synonymous A/G single nucleotide polymorphism (SNP) in the coding region of MdPP2CH, a 36-bp insertion in the promoter of MdSAUR37, and a previously reported SNP in MdALMTII, were validated to influence the malate content of apple fruits. In addition, MdPP2CH inactivated three vacuolar H + -ATPases (MdVHA-A3, MdVHA-B2 and MdVHA-D2) and one aluminium-activated malate transporter (MdALMTII) via dephosphorylation and negatively influenced fruit malate accumulation. The dephosphotase activity of MdPP2CH was suppressed by MdSAUR37, which implied a higher hierarchy of genetic interaction. Therefore, the MdSAUR37/MdPP2CH/MdALMTII chain cascaded hierarchical epistatic genetic effects to precisely determine apple fruit malate content. An A/G SNP (-1010) on MdMYB44 promoter region from a major QTL (qtl08.1) was closely associated with fruit malate content. The predicted phenotype values (PPVs) were estimated using the tentative genotype values of the gene markers, and the PPVs were significantly correlated with the observed phenotype values. Our findings provide an insight into plant genome-based selection in apples and will aid in conducting research to understand the physiological fundamentals of quantitative genetics. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Cost Computations for Cyber Fighter Associate

DTIC Science & Technology

2015-05-01

associate. Aberdeen Proving Ground (MD): Army Research Laboratory (US); in press. 2 Harman D, Brown S, Henz B, Marvel LM. A communication protocol... Harman , et al.2 A specific class called ListenThread was created for multithreaded listeners. When ListenThread is instantiated, it is passed a given...2. Harman D, Brown S, Henz B, Marvel LM. A communication protocol for CyAMS and the cyber associate interface. Aberdeen Proving Ground (MD): US Army

Cartilage Degeneration, Subchondral Mineral and Meniscal Mineral Densities in Hartley and Strain 13 Guinea Pigs

PubMed Central

Sun, Yubo; Scannell, Brian P; Honeycutt, Patrick R; Mauerhan, David R; H, James Norton; Hanley Jr, Edward N

2015-01-01

Osteoarthritis is a joint disease involved in articular cartilage, subchondral bone, meniscus and synovial membrane. This study sought to examine cartilage degeneration, subchondral bone mineral density (BMD) and meniscal mineral density (MD) in male Hartley, female Hartley and female strain 13 guinea pigs to determine the association of cartilage degeneration with subchondral BMD and meniscal MD. Cartilage degeneration, subchondral BMD and meniscal MD in 12 months old guinea pigs were examined with histochemistry, X-ray densitometry and calcium analysis. We found that male Hartley guinea pigs had more severe cartilage degeneration, subchondral BMD and meniscal MD than female Hartley guinea pigs, but not female strain 13 guinea pigs. Female strain 13 guinea pigs had more severe cartilage degeneration and higher subchondral BMD, but not meniscal MD, than female Hartley guinea pigs. These findings indicate that higher subchondral BMD, not meniscal MD, is associated with more severe cartilage degeneration in the guinea pigs and suggest that abnormal subchondral BMD may be a therapeutic target for OA treatment. These findings also indicate that the pathogenesis of OA in the male guinea pigs and female guinea pigs are different. Female strain 13 guinea pig may be used to study female gender-specific pathogenesis of OA. PMID:26401159

Mediterranean diet and risk of pancreatic cancer in the European Prospective Investigation into Cancer and Nutrition cohort.

PubMed

Molina-Montes, Esther; Sánchez, María-José; Buckland, Genevieve; Bueno-de-Mesquita, H B As; Weiderpass, Elisabete; Amiano, Pilar; Wark, Petra A; Kühn, Tilman; Katzke, Verena; Huerta, José María; Ardanaz, Eva; Quirós, José Ramón; Affret, Aurélie; His, Mathilde; Boutron-Ruault, Marie-Christine; Peeters, Petra H; Ye, Weimin; Sund, Malin; Boeing, Heiner; Iqbal, Khalid; Ohlsson, Bodil; Sonestedt, Emily; Tjønneland, Anne; Petersen, Kristina En; Travis, Ruth C; Skeie, Guri; Agnoli, Claudia; Panico, Salvatore; Palli, Domenico; Tumino, Rosario; Sacerdote, Carlotta; Freisling, Heinz; Huybrechts, Inge; Overvad, Kim; Trichopoulou, Antonia; Bamia, Christina; Vasilopoulou, Effie; Wareham, Nick; Khaw, Kay-Tee; Cross, Amanda J; Ward, Heather A; Riboli, Elio; Duell, Eric J

2017-03-14

The Mediterranean diet (MD) has been proposed as a means for cancer prevention, but little evidence has been accrued regarding its potential to prevent pancreatic cancer. We investigated the association between the adherence to the MD and pancreatic cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Over half a million participants from 10 European countries were followed up for over 11 years, after which 865 newly diagnosed exocrine pancreatic cancer cases were identified. Adherence to the MD was estimated through an adapted score without the alcohol component (arMED) to discount alcohol-related harmful effects. Cox proportional hazards regression models, stratified by age, sex and centre, and adjusted for energy intake, body mass index, smoking status, alcohol intake and diabetes status at recruitment, were used to estimate hazard ratios (HRs) associated with pancreatic cancer and their corresponding 95% confidence intervals (CIs). Adherence to the arMED score was not associated with risk of pancreatic cancer (HR high vs low adherence=0.99; 95% CI: 0.77-1.26, and HR per increments of two units in adherence to arMED=1.00; 95% CI: 0.94-1.06). There was no convincing evidence for heterogeneity by smoking status, body mass index, diabetes or European region. There was also no evidence of significant associations in analyses involving microscopically confirmed cases, plausible reporters of energy intake or other definitions of the MD pattern. A high adherence to the MD is not associated with pancreatic cancer risk in the EPIC study.

Cognitive Functions and Neurodevelopmental Disorders Involving the Prefrontal Cortex and Mediodorsal Thalamus

PubMed Central

Ouhaz, Zakaria; Fleming, Hugo; Mitchell, Anna S.

2018-01-01

The mediodorsal nucleus of the thalamus (MD) has been implicated in executive functions (such as planning, cognitive control, working memory, and decision-making) because of its significant interconnectivity with the prefrontal cortex (PFC). Yet, whilst the roles of the PFC have been extensively studied, how the MD contributes to these cognitive functions remains relatively unclear. Recently, causal evidence in monkeys has demonstrated that in everyday tasks involving rapid updating (e.g., while learning something new, making decisions, or planning the next move), the MD and frontal cortex are working in close partnership. Furthermore, researchers studying the MD in rodents have been able to probe the underlying mechanisms of this relationship to give greater insights into how the frontal cortex and MD might interact during the performance of these essential tasks. This review summarizes the circuitry and known neuromodulators of the MD, and considers the most recent behavioral, cognitive, and neurophysiological studies conducted in monkeys and rodents; in total, this evidence demonstrates that MD makes a critical contribution to cognitive functions. We propose that communication occurs between the MD and the frontal cortex in an ongoing, fluid manner during rapid cognitive operations, via the means of efference copies of messages passed through transthalamic routes; the conductance of these messages may be modulated by other brain structures interconnected to the MD. This is similar to the way in which other thalamic structures have been suggested to carry out forward modeling associated with rapid motor responding and visual processing. Given this, and the marked thalamic pathophysiology now identified in many neuropsychiatric disorders, we suggest that changes in the different subdivisions of the MD and their interconnections with the cortex could plausibly give rise to a number of the otherwise disparate symptoms (including changes to olfaction and cognitive functioning) that are associated with many different neuropsychiatric disorders. In particular, we will focus here on the cognitive symptoms of schizophrenia and suggest testable hypotheses about how changes to MD-frontal cortex interactions may affect cognitive processes in this disorder. PMID:29467603

Lipid Accumulation Product (LAP) and Visceral Adiposity Index (VAI) as Markers of Insulin Resistance and Metabolic Associated Disturbances in Young Argentine Women with Polycystic Ovary Syndrome.

PubMed

Abruzzese, Giselle A; Cerrrone, Gloria E; Gamez, Juan M; Graffigna, Mabel N; Belli, Susana; Lioy, Gustavo; Mormandi, Eduardo; Otero, Patricia; Levalle, Oscar A; Motta, Alicia B

2017-01-01

Polycystic ovary syndrome (PCOS) is an endocrine disorder. PCOS women are at high risk of developing insulin resistance (IR) and cardiovascular disorders since young age. We aimed to study the reliability of lipid accumulation product (LAP) and visceral adiposity index (VAI) as markers of metabolic disturbances (MD) associated with IR in young reproductive aged PCOS patients. We also evaluated the association between LAP and VAI and the presence of hyperandrogenism. In a cross-sectional study, 110 PCOS patients and 88 control women (18-35 years old) were recruited. PCOS patients were divided into 2 groups, as hyperandrogenic and non-hyperandrogenic considering the signs of hyperandrogenism (clinical or biochemical). Anthropometric measurements were taken and blood samples collected. Metabolic and anthropometric characteristics and their association with IR and associated MD were evaluated and LAP and VAI were calculated. LAP and VAI were compared with TC/HDL-c and TG/HDL-c to define the best markers of MD in this population. Independently of the phenotype, young PCOS patients showed high IR and dyslipidemia. Both LAP and VAI showed to be more effective markers to assess MD and IR in these young women than TG/HDL-c or TC/HDL-c [cut-off values: LAP: 18.24 (sensitivity: 81.43% specificity: 73.49%), positive predictive value (PPV): 75.0%, negative predictive value (NPV): 77.27%, VAI: 2.19 (sensitivity: 81.16% specificity: 72.15% PPV: 74.65% NPV: 72.22%)]. LAP and VAI are representative markers to assess MD associated with IR in young PCOS patients. All PCOS patients, independently of their androgenic condition, showed high metabolic risk. © Georg Thieme Verlag KG Stuttgart · New York.

Association of Bruch's membrane opening and optic disc morphology to axial length and visual field defects in eyes with primary open-angle glaucoma.

PubMed

Nakanishi, Hideo; Suda, Kenji; Yoshikawa, Munemitsu; Akagi, Tadamichi; Kameda, Takanori; Ikeda, Hanako Ohashi; Yokota, Satoshi; Kurimoto, Yasuo; Tsujikawa, Akitaka

2018-03-01

To examine the morphology of Bruch's membrane opening (BMO), optic disc, and peripapillary atrophy (PPA) by scanning laser ophthalmoscopy (SLO) and spectral-domain optical coherence tomography (SD-OCT), and to determine their association with the axial length and visual field defects. This was a cross-sectional study of 94 eyes of 56 subjects; 77 eyes were diagnosed with primary open-angle glaucoma and 17 eyes as normal. The margins of the optic disc were determined in the SLO images, and that of the BMO in the SD-OCT images. The ovality and area of the BMO and the optic disc were measured. The beta and gamma-PPA areas were also measured. The association of each parameter with the axial length and the mean deviation (MD) of the visual field tests was determined by generalized estimating equations (GEEs). The optic disc ovality was associated with the axial length and the MD (β = -0.47, P = 7.6 × 10 -4 and β = 0.12, P = 0.040). The BMO ovality was not significantly associated with the axial length and the MD. The BMO area was associated with the axial length (β = 0.30, P = 0.029). A larger BMO area was associated with a thinner BMO-based neuroretinal rim width (BMO-MRW) after adjustments for the MD (β = -0.30, P = 2.1 × 10 -4 ). The beta- and gamma-PPA areas were associated with the axial length (β = 0.50, P = 7.4 × 10 -5 and β = 0.62, P = 4.2 × 10 -6 ). The optic disc ovality was associated with both the axial length and MD, whereas BMO ovality was not. Attention should be paid to the influence of the axial length-related enlargement of the BMO.

Colorectal Cancer—A New Look at an Old Problem

PubMed Central

Toribara, Neil W.

1994-01-01

This discussion was selected from the weekly staff conferences in the Department of Medicine, University of California, San Francisco. Taken from a transcription, it has been edited by Nathan M. Bass, MD, PhD, Associate Professor of Medicine, under the direction of Lloyd H. Smith Jr. MD, Professor of Medicine and Associate Dean in the School of Medicine. Images PMID:7810127

Association of circulating adipokines with metabolic dyslipidemia in obese versus non-obese individuals.

PubMed

Rahimlou, Mehran; Mirzaei, Khadijeh; Keshavarz, Seyed Ali; Hossein-Nezhad, Arash

2016-01-01

Previous studies have shown that circulating adipokines may play an important role in the pathogenesis of some obesity related chronic disease such as dyslipidemia and type2 diabetes mellitus. The aim of the present study was to investigate the association between vaspin, omentin-1 and retinol binding protein-4 levels with metabolic dyslipidemia (MD) criteria in obese and non-obese individuals. The study was conducted on 170 obese and 81 non-obese individuals. After collecting the blood samples, serum levels metabolic parameters as well as three circulating adipokines and body composition were measured. No significant difference was noted regarding the mean serum levels of omentin-1 and vaspin between the obese and non-obese groups, while, serum level of RBP4 was significantly higher in the non-obese group. We found the 0.22 increased risk of MD in obese individuals with higher RBP4 concentration. After the adjustment for confounding factors, this association was still significant. No significant association was noted between MD and its components relative risks with omentin-1 and vaspin levels. Our study demonstrated that circulating RBP4 was significantly higher in the obese individuals which may increase the risk of MD in them. Further researches are needed to address this association. Copyright © 2015 Diabetes India. Published by Elsevier Ltd. All rights reserved.

Chronic methadone use, poor bowel visualization and failed colonoscopy: A preliminary study

PubMed Central

Verma, Siddharth; Fogel, Joshua; Beyda, David J; Bernstein, Brett; Notar-Francesco, Vincent; Mohanty, Smruti R

2012-01-01

AIM: To examine effects of chronic methadone usage on bowel visualization, preparation, and repeat colonoscopy. METHODS: In-patient colonoscopy reports from October, 2004 to May, 2009 for methadone dependent (MD) patients were retrospectively evaluated and compared to matched opioid naive controls (C). Strict criteria were applied to exclude patients with risk factors known to cause constipation or gastric dysmotility. Colonoscopy reports of all eligible patients were analyzed for degree of bowel visualization, assessment of bowel preparation (good, fair, or poor), and whether a repeat colonoscopy was required. Bowel visualization was scored on a 4 point scale based on multiple prior studies: excellent = 1, good = 2, fair = 3, or poor = 4. Analysis of variance (ANOVA) and Pearson χ2 test were used for data analyses. Subgroup analysis included correlation between methadone dose and colonoscopy outcomes. All variables significantly differing between MD and C groups were included in both univariate and multivariate logistic regression analyses. P values were two sided, and < 0.05 were considered statistically significant. RESULTS: After applying exclusionary criteria, a total of 178 MD patients and 115 C patients underwent a colonoscopy during the designated study period. A total of 67 colonoscopy reports for MD patients and 72 for C were included for data analysis. Age and gender matched controls were randomly selected from this population to serve as controls in a numerically comparable group. The average age for MD patients was 52.2 ± 9.2 years (range: 32-72 years) years compared to 54.6 ± 15.5 years (range: 20-81 years) for C (P = 0.27). Sixty nine percent of patients in MD and 65% in C group were males (P = 0.67). When evaluating colonoscopy reports for bowel visualization, MD patients had significantly greater percentage of solid stool (i.e., poor visualization) compared to C (40.3% vs 6.9%, P < 0.001). Poor bowel preparation (35.8% vs 9.7%, P < 0.001) and need for repeat colonoscopy (32.8% vs 12.5%, P = 0.004) were significantly higher in MD group compared to C, respectively. Under univariate analysis, factors significantly associated with MD group were presence of fecal particulate [odds ratio (OR), 3.89, 95% CI: 1.33-11.36, P = 0.01] and solid stool (OR, 13.5, 95% CI: 4.21-43.31, P < 0.001). Fair (OR, 3.82, 95% CI: 1.63-8.96, P = 0.002) and poor (OR, 8.10, 95% CI: 3.05-21.56, P < 0.001) assessment of bowel preparation were more likely to be associated with MD patients. Requirement for repeat colonoscopy was also significant higher in MD group (OR, 3.42, 95% CI: 1.44-8.13, P = 0.01). In the multivariate analyses, the only variable independently associated with MD group was presence of solid stool (OR, 7.77, 95% CI: 1.66-36.47, P = 0.01). Subgroup analysis demonstrated a general trend towards poorer bowel visualization with higher methadone dosage. ANOVA analysis demonstrated that mean methadone dose associated with presence of solid stool (poor visualization) was significantly higher compared to mean dosage for clean colon (excellent visualization, P = 0.02) or for those with liquid stool only (good visualization, P = 0.01). CONCLUSION: Methadone dependence is a risk factor for poor bowel visualization and leads to more repeat colonoscopies. More aggressive bowel preparation may be needed in MD patients. PMID:22969198

Morphological, structural, and functional alterations of the prefrontal cortex and the basolateral amygdala after early lesion of the rat mediodorsal thalamus.

PubMed

Ouhaz, Zakaria; Ba-M'hamed, Saadia; Bennis, Mohamed

2017-08-01

Early postnatal damage to the mediodorsal thalamus (MD) produces deficits in cognition and behavior believed to be associated with early prefrontal cortical maldevelopment. We assessed the role of MD afferents during development on the morphological and functional maturation of the prefrontal cortex (PFC) and the basolateral amygdala (BLA). Sprague-Dawley rat pups (n = 56) received a bilateral electrolytic lesion of the MD or a MD Sham lesion on postnatal day 4. 7 weeks later, all rats were tested in anxiety-related and cognitive paradigms using the elevated plus maze and novel object recognition tests. Following behavioral testing (P70), rats were killed and the baseline expression of C-Fos protein and the number of GABAergic neurons were evaluated in the PFC and the BLA. The dendritic morphology and spine density in the PFC using Golgi-Cox staining was also evaluated. Adult rats with early postnatal bilateral MD damage exhibited disrupted recognition memory and increased anxiety-like behaviors. The lesion also caused a significant diminution of C-Fos immunolabeling and an increase of the number of GABAergic neurons in the PFC. In the BLA, the number of GABAergic neurons was significantly reduced, associated with an increase in C-Fos immunolabeling. Furthermore, in the PFC the lesion induced a significant reduction in dendritic branching and spine density. Our data are consistent with the hypothesis that the MD plays a role in the development of the PFC and, therefore, may be a good animal model to investigate cognitive symptoms associated with schizophrenia.

A Pilot Study: Dietary Energy Density is Similar between Active Women with and without Exercise-Associated Menstrual Dysfunction

PubMed Central

Hand, Taryn M.; Howe, Stephanie; Cialdella-Kam, Lynn; Hoffman, Charlotte P. Guebels; Manore, Melinda

2016-01-01

Low energy availability (EA) (e.g., insufficient energy intake (EI) to match energy needs, including exercise energy expenditure) has been identified as a primary contributor to exercise-associated menstrual dysfunction (ExMD) in active women. For health reasons, active women may self-select diets lower in energy density (ED, kcal/g), which can inadvertently contribute to inadequate EI. Using data from two studies, we compared the ED of active women with ExMD (n = 9; 24 ± 6 years) to eumenorrheic (EU) active controls (EU: n = 18, 27 ± 6 years). ED was calculated from 6 to 7 days weighted food records using two methods: with/without beverages. ANOVA and Wilcoxon Rank-Sum were used to test group differences. ED was not different between groups, but there was a trend toward a lower median ED (10%) (p = 0.049 unadjusted; p = 0.098 adjusted) in the ExMD-group (Method 1—all beverages: ExMD = 1.01 kcal/g (range = 0.52–1.41), EU = 1.22 kcal/g (range = 0.72–1.72); Method 2—without beverages: ExMD = 1.51 kcal/g (range = 1.26–2.06), EU = 1.69 kcal/g (range = 1.42–2.54)). This lower ED represents a 9% decrease (~219 kcal/day) in EI (ExMD = 2237 ± 378 kcal/day; EU = 2456 ± 470 kcal/day; p > 0.05). EI and macro/micronutrient intakes were similar for groups. In the ExMD-group, low ED could contribute to lower EI and EA. Future research should examine the interaction of ED and exercise on appetite, EI, and EA in active women, especially those with ExMD. PMID:27104560

NCI intramural research highlighted at 2014 AACR meeting

Cancer.gov

This year’s American Association for Cancer Research meeting featured plenary talks by two NCI scientists, Steven Rosenberg, M.D., and Louis Staudt, M.D., Ph.D., that highlighted the challenges in developing varied and potentially synergistic treatments f

Malaria, Moderate to Severe Anaemia, and Malarial Anaemia in Children at Presentation to Hospital in the Mount Cameroon Area: A Cross-Sectional Study

PubMed Central

Taiwe, Germain Sotoing

2016-01-01

Background. Malaria remains a major killer of children in Sub-Saharan Africa, while anaemia is a public health problem with significant morbidity and mortality. Examining the factors associated with moderate to severe anaemia (MdSA) and malarial anaemia as well as the haematological characteristics is essential. Methodology. Children (1–14 years) at presentation at the Regional Hospital Annex-Buea were examined clinically and blood samples were collected for malaria parasite detection and full blood count evaluation. Results. Plasmodium falciparum, anaemia, and malarial anaemia occurred in 33.8%, 62.0%, and 23.6% of the 216 children, respectively. Anaemia prevalence was significantly higher in malaria parasite positive children and those with fever than their respective counterparts. MdSA and moderate to severe malarial anaemia (MdSMA) were detected in 38.0% and 15.3% of the participants, respectively. The prevalence of MdSA was significantly higher in children whose household head had no formal education, resided in the lowland, or was febrile, while MdSMA was significantly higher in febrile children only. Children with MdSMA had significantly lower mean white blood cell, lymphocyte, and platelet counts while the mean granulocyte count was significantly higher. Conclusion. Being febrile was the only predictor of both MdSA and MdSMA. More haematological insult occurred in children with MdSMA compared to MdSA. PMID:27895939

Comparison of mean deviation with AGIS and CIGTS scores in association with structural parameters in glaucomatous eyes.

PubMed

Naka, Maiko; Kanamori, Akiyasu; Tatsumi, Yasuko; Fujioka, Miyuki; Nagai-Kusuhara, Azusa; Nakamura, Makoto; Negi, Akira

2009-01-01

To evaluate which of the 3 clinically used visual field indices including mean deviation (MD), Advanced Glaucoma Intervention Study (AGIS) score, and Collaborative Initial Glaucoma Treatment Study (CIGTS) score are best in evaluating functional damage of glaucomatous optic neuropathy. In 213 glaucomatous eyes, peripapillary retinal nerve fiber layer thickness (RNFLT) and optic disc configuration were measured with Stratus optical coherence tomography and Heidelberg Retina Tomograph-2, respectively. Visual field was measured with standard automated perimetry 30-2. Correlations of the structural parameters compared with the 3 VF indices using second polynomial regression were calculated. In addition, these correlations were analyzed among eyes of 3 different stages of glaucoma, as defined by MD score (early, MD> or =-6 dB; moderate, -12 dB< or =MD<-6 dB; advanced, MD<-12 dB). Among structure-function relationships in all subjects, the highest correlation determination (R) was MD with RNFLT (=0.298). CIGTS score showed better R than MD or AGIS score with rim area, but these values were not higher than any R with RNFLT. In analyses of 3 groups depending on MD, statistically significant structure-function correlations were observed only in patients with an advanced stage. No clear difference was found among MD and AGIS/CIGTS scores in expressing functional damage of glaucomatous eyes. MD is suggested to be no worse than others in monitoring glaucoma in clinical setting.

Symptoms of muscle dysmorphia, body dysmorphic disorder, and eating disorders in a nonclinical population of adult male weightlifters in Australia.

PubMed

Nieuwoudt, Johanna E; Zhou, Shi; Coutts, Rosanne A; Booker, Ray

2015-05-01

The current study aimed to (a) determine the rates of symptoms of muscle dysmorphia (MD), body dysmorphic disorder (BDD), and eating disorder; (b) determine the relationships among symptoms of MD, BDD, and eating disorders; and (c) provide a comprehensive comparison of symptoms of MD, BDD, and eating disorders in a nonclinical population of adult male weightlifters in Australia. The participants (N = 648, mean age = 29.5 years, SD = 10.1) participated in an online survey, consisting of Muscle Appearance Satisfaction Scale, the Body Dysmorphic Disorder Questionnaire, and the Eating Attitude Test-26. Results indicated that 110 participants (17%) were at risk of having MD, 69 participants (10.6%) were at risk of having BDD, and 219 participants (33.8%) were at risk of having an eating disorder. Furthermore, 36 participants (5.6%) were found at risk of having both MD and BDD, and 60 participants (9.3%) were at risk of having both MD and an eating disorder. Significant correlations and associations were found between symptoms of MD and BDD, and symptoms of MD and eating disorders. Support was provided for the comorbidity of, and symptomatic similarities between, symptoms of MD and BDD, and symptoms of MD and eating disorders. This may reflect a shared pathogenesis between symptoms of MD, BDD, and eating disorders. Strength and conditioning professionals, exercise scientists, athletic trainers, and personal trainers should be aware that adult males who are working out with weights (i.e., free weights or machines) may be at increased risk of having MD, BDD, and eating disorders.

A novel triazine ring compound (MD568) exerts in vivo and in vitro effects on lipid metabolism.

PubMed

Jia, Dan; Li, Ziwen; Gao, Ying; Feng, Yifan; Li, Weimin

2018-07-01

In this study, we investigated the toxicity and biological activity of a novel triazine ring compound named magnolol derivative 568 (MD568). The LD 50 of MD568 was determined in Sprague-Dawley (SD) rats by intraperitoneal injection. Treatment of high fat diet-induced obese rats with MD568 demonstrated that MD568 displayed significant anti-obesity effects. MD568 markedly reduced body weight, blood lipid contents, white adipose tissue (WAT) and liver mass in obese rats. In addition, MD568 modulated lesions in WAT through regulating PPAR-Ɣ, C/EBP-a, SREBP-1c and FABP-4 proteins in the liver through regulating PPAR-α, SREBP-1c and FABP-4. We also evaluated the effects of MD568 on the proliferation and differentiation of 3T3-L1 pre-adipocytes and investigated the underlying mechanism by microarray analysis. Results showed that MD568 has good inhibitory activity on lipogenesis and lipid accumulation in 3T3-L1 pre-adipocytes. The protein expression levels of the adipogenic transcription factors PPAR-Ɣ, C/EBP-a, SREBP-1c and FABP-4 were reduced by MD568. In addition, the gene expression of FAS and LDL was also significantly down-regulated by MD568. Microarray data enrichment analysis demonstrated that the underlying mechanism of action of MD568 may be related to its regulatory effects on genes associated with the biological processes or pathways in lipid metabolism. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Characterization of three chalcone synthase-like genes from apple (Malus x domestica Borkh.).

PubMed

Yahyaa, Mosaab; Ali, Samah; Davidovich-Rikanati, Rachel; Ibdah, Muhammad; Shachtier, Alona; Eyal, Yoram; Lewinsohn, Efraim; Ibdah, Mwafaq

2017-08-01

Apple (Malus x domestica Brokh.) is a widely cultivated deciduous tree species of significant economic importance. Apple leaves accumulate high levels of flavonoids and dihydrochalcones, and their formation is dependent on enzymes of the chalcone synthase family. Three CHS genes were cloned from apple leaves and expressed in Escherichia coli. The encoded recombinant enzymes were purified and functionally characterized. In-vitro activity assays indicated that MdCHS1, MdCHS2 and MdCHS3 code for proteins exhibiting polyketide synthase activity that accepted either p-dihydrocoumaroyl-CoA, p-coumaroyl-CoA, or cinnamoyl-CoA as starter CoA substrates in the presence of malonyl-CoA, leading to production of phloretin, naringenin chalcone, and pinocembrin chalcone. MdCHS3 coded a chalcone-dihydrochalcone synthase enzyme with narrower substrate specificity than the previous ones. The apparent Km values of MdCHS3 for p-dihydrocoumaryl-CoA and p-coumaryl-CoA were both 5.0 μM. Expression analyses of MdCHS genes varied according to tissue type. MdCHS1, MdCHS2 and MdCHS3 expression levels were associated with the levels of phloretin accumulate in the respective tissues. Copyright © 2017 Elsevier Ltd. All rights reserved.

Incidental finding of carcinoid tumor on Meckel’s diverticulum: case report and literature review, should prophylactic resection be recommended?

PubMed Central

2014-01-01

Meckel’s diverticulum (MD) is the most common congenital anomaly of the gastrointestinal tract and is caused by incomplete obliteration of the vitelline duct during intrauterine life. MD affects less than 2% of the population. In most cases, MD is asymptomatic and the estimated average complication risk of MD carriers, which is inversely proportional to age, ranges between 2% and 4%. The most common MD-related complications are gastrointestinal bleeding, intestinal obstruction and acute phlogosis. Excision is mandatory in the case of symptomatic diverticula regardless of age, while surgical treatment for asymptomatic diverticula remains controversial. According to the majority of studies, the incidental finding of MD in children is an indication for surgical resection, while the management of adults is not yet unanimous. In this case report, we describe the prophylactic resection of an incidentally detected MD, which led to the removal of an occult mucosal carcinoid tumor. In literature, the association of MD and carcinoid tumor is reported as a rare finding. Even though the strategy for adult patients of an incidental finding of MD during surgery performed for other reasons divides the experts, we recommend prophylactic excision in order to avoid any further risk. PMID:24884768

Use of FGF-21 as a Biomarker of Mitochondrial Disease in Clinical Practice.

PubMed

Morovat, Alireza; Weerasinghe, Gayani; Nesbitt, Victoria; Hofer, Monika; Agnew, Thomas; Quaghebeur, Geralrine; Sergeant, Kate; Fratter, Carl; Guha, Nishan; Mirzazadeh, Mehdi; Poulton, Joanna

2017-08-21

Recent work has suggested that fibroblast growth factor-21 (FGF-21) is a useful biomarker of mitochondrial disease (MD). We routinely measured FGF-21 levels on patients who were investigated at our centre for MD and evaluated its diagnostic performance based on detailed genetic and other laboratory findings. Patients' FGF-21 results were assessed by the use of age-adjusted z -scores based on normalised FGF-21 values from a healthy population. One hundred and fifty five patients were investigated. One hundred and four of these patients had molecular evidence for MD, 27 were deemed to have disorders other than MD (non-MD), and 24 had possible MD. Patients with defects in mitochondrial DNA (mtDNA) maintenance ( n = 32) and mtDNA rearrangements ( n = 17) had the highest median FGF-21 among the MD group. Other MD patients harbouring mtDNA point mutations ( n = 40) or mutations in other autosomal genes ( n = 7) and those with partially characterised MD had lower FGF-21 levels. The area under the receiver operating characteristic curve for distinguishing MD from non-MD patients was 0.69. No correlation between FGF-21 and creatinine, creatine kinase, or cardio-skeletal myopathy score was found. FGF-21 was significantly associated with plasma lactate and ocular myopathy. Although FGF-21 was found to have a low sensitivity for detecting MD, at a z -score of 2.8, its specificity was above 90%. We suggest that a high serum concentration of FGF-21 would be clinically useful in MD, especially in adult patients with chronic progressive external ophthalmoplegia, and may enable bypassing muscle biopsy and directly opting for genetic analysis. Availability of its assay has thus modified our diagnostic pathway.

Use of FGF-21 as a Biomarker of Mitochondrial Disease in Clinical Practice

PubMed Central

Weerasinghe, Gayani; Nesbitt, Victoria; Hofer, Monika; Agnew, Thomas; Quaghebeur, Geralrine; Sergeant, Kate; Guha, Nishan; Mirzazadeh, Mehdi; Poulton, Joanna

2017-01-01

Recent work has suggested that fibroblast growth factor-21 (FGF-21) is a useful biomarker of mitochondrial disease (MD). We routinely measured FGF-21 levels on patients who were investigated at our centre for MD and evaluated its diagnostic performance based on detailed genetic and other laboratory findings. Patients’ FGF-21 results were assessed by the use of age-adjusted z-scores based on normalised FGF-21 values from a healthy population. One hundred and fifty five patients were investigated. One hundred and four of these patients had molecular evidence for MD, 27 were deemed to have disorders other than MD (non-MD), and 24 had possible MD. Patients with defects in mitochondrial DNA (mtDNA) maintenance (n = 32) and mtDNA rearrangements (n = 17) had the highest median FGF-21 among the MD group. Other MD patients harbouring mtDNA point mutations (n = 40) or mutations in other autosomal genes (n = 7) and those with partially characterised MD had lower FGF-21 levels. The area under the receiver operating characteristic curve for distinguishing MD from non-MD patients was 0.69. No correlation between FGF-21 and creatinine, creatine kinase, or cardio-skeletal myopathy score was found. FGF-21 was significantly associated with plasma lactate and ocular myopathy. Although FGF-21 was found to have a low sensitivity for detecting MD, at a z-score of 2.8, its specificity was above 90%. We suggest that a high serum concentration of FGF-21 would be clinically useful in MD, especially in adult patients with chronic progressive external ophthalmoplegia, and may enable bypassing muscle biopsy and directly opting for genetic analysis. Availability of its assay has thus modified our diagnostic pathway. PMID:28825656

Effects of Tamoxifen and oestrogen on histology and radiographic density in high and low mammographic density human breast tissues maintained in murine tissue engineering chambers.

PubMed

Chew, G L; Huo, C W; Huang, D; Blick, T; Hill, P; Cawson, J; Frazer, H; Southey, M C; Hopper, J L; Britt, K; Henderson, M A; Haviv, I; Thompson, E W

2014-11-01

Mammographic density (MD) is a strong risk factor for breast cancer. It is altered by exogenous endocrine treatments, including hormone replacement therapy and Tamoxifen. Such agents also modify breast cancer (BC) risk. However, the biomolecular basis of how systemic endocrine therapy modifies MD and MD-associated BC risk is poorly understood. This study aims to determine whether our xenograft biochamber model can be used to study the effectiveness of therapies aimed at modulating MD, by examine the effects of Tamoxifen and oestrogen on histologic and radiographic changes in high and low MD tissues maintained within the biochamber model. High and low MD human tissues were precisely sampled under radiographic guidance from prophylactic mastectomy fresh specimens of high-risk women, then inserted into separate vascularized murine biochambers. The murine hosts were concurrently implanted with Tamoxifen, oestrogen or placebo pellets, and the high and low MD biochamber tissues maintained in the murine host environment for 3 months, before the high and low MD biochamber tissues were harvested for histologic and radiographic analyses. The radiographic density of high MD tissue maintained in murine biochambers was decreased in Tamoxifen-treated mice compared to oestrogen-treated mice (p = 0.02). Tamoxifen treatment of high MD tissue in SCID mice led to a decrease in stromal (p = 0.009), and an increase in adipose (p = 0.023) percent areas, compared to placebo-treated mice. No histologic or radiographic differences were observed in low MD biochamber tissue with any treatment. High MD biochamber tissues maintained in mice implanted with Tamoxifen, oestrogen or placebo pellets had dynamic and measurable histologic compositional and radiographic changes. This further validates the dynamic nature of the MD xenograft model, and suggests the biochamber model may be useful for assessing the underlying molecular pathways of Tamoxifen-reduced MD, and in testing of other pharmacologic interventions in a preclinical model of high MD.

Stigma and demographic correlates of help-seeking intentions in returning service members.

PubMed

Blais, Rebecca K; Renshaw, Keith D

2013-02-01

Many U.S. Iraq/Afghanistan-era veterans return from deployment with posttraumatic stress (PTS) symptoms, but few veterans seek psychological help. Research on barriers to care is growing, but the link between stigma and help-seeking is understudied. The present study examined anticipated enacted stigma from military and nonmilitary sources, self-stigma, PTS, perceived likelihood of deploying again, marital status, and history of mental health care engagement as correlates of help-seeking intentions from a mental health professional or medical doctor/advance practice registered nurse (MD/APRN) in a sample of 165 combat veterans. Using structural equation modeling, results demonstrated that self-stigma was negatively associated with help-seeking intentions from a mental health professional and MD/APRN with small-to-medium effect sizes. Being married was positively associated with help-seeking intentions from a mental health professional and MD/APRN with small effect sizes. History of previous mental health care engagement was positively associated with help-seeking intentions from a mental health professional with a medium effect size, but unrelated to help-seeking intentions from a MD/APRN. Anticipated enacted stigma from any source, PTS, and greater perceived likelihood of deploying again were unrelated to help-seeking intentions from a mental health professional and MD/APRN. Implications for interventions aimed at decreasing self-stigma and increasing intention to seek help are discussed. Copyright © 2013 International Society for Traumatic Stress Studies.

[Association between Minamata disease status and activities of daily living among inhabitants in previously methylmercury-polluted areas].

PubMed

Ushijima, Kayo; Sung, Woncheol; Kawakita, Minoru; Mukai, Yoshito; Tamura, Kenji; Tanaka, Shiro; Tanaka, Mika; Maruyama, Sadami

2008-07-01

Minamata disease (MD), first discovered in 1956, is a neurological disorder caused by mercury poisoning due to daily intake of fish and shellfish that have been contaminated by methylmercury discharged from chemical factories. However, reports of ill health increased sharply following the 2004 Supreme Court ruling instructing the Japanese government to pay damages to MD patients. We examined the distribution of disability in activities of daily living (ADL), and the association between MD status in terms of compensation system and ADL disability among the general population of previously methylmercury-polluted areas. Data were collected by two-stage stratified sampling of residents 40-79 years old in 172 postal-code areas on the Shiranui Sea coast, the endemic area of MD. Questionnaires were distributed to eligible subjects (n = 2100) and collected at a later visit or by mail. Information on demographic factors, basic ADL (BADL), and instrumental ADL (IADL) was obtained using questionnaires. We performed logistic regression analysis to assess the relationship between MD status in terms of compensation system and ADL disability. We classified the 1422 residents who completed the questionnaire in accordance with their MD status in terms of compensation system: Early (those who received MD compensation before the Supreme Court decision), Recent (those who applied for compensation after the Supreme Court decision), Not Yet (those who have not yet applied for compensation, but have health-related anxieties about MD effects), and Normal (those who have not applied for compensation, and do not have health-related anxieties about MD effects). Adjusting for confounding factors, MD status was significantly associated with the disability grades of BADL and IADL with an increasing trend in the order of Normal, Not Yet, Recent, and Early. The odds ratios (95% CI) based on Normal were 2.08 (1.08-4.01), 3.87 (2.14-7.01), and 4.50 (2.66-7.61) for BADL and 2.41 (1.62-3.61), 3.20 (2.12-4.85) and 3.68 (2.52-5.38) in Not Yet, Recent, and Early for IADL, respectively. Early, Recent, and Not Yet had lower ADL grades than Normal. Moreover, the population with a low ADL grade and health-related anxieties had increased throughout the previously methylmercury-polluted areas. The issue of ill health among populations living in previously methylmercury-polluted areas should be addressed in the wider context of public and community health.

Predictive value of health-related fitness tests for self-reported mobility difficulties among high-functioning elderly men and women.

PubMed

Hämäläinen, H Pauliina; Suni, Jaana H; Pasanen, Matti E; Malmberg, Jarmo J; Miilunpalo, Seppo I

2006-06-01

The functional independence of elderly populations deteriorates with age. Several tests of physical performance have been developed for screening elderly persons who are at risk of losing their functional independence. The purpose of the present study was to investigate whether several components of health-related fitness (HRF) are valid in predicting the occurrence of self-reported mobility difficulties (MD) among high-functioning older adults. Subjects were community-dwelling men and women, born 1917-1941, who participated in the assessment of HRF [6.1-m (20-ft) walk, one-leg stand, backwards walk, trunk side-bending, dynamic back extension, one-leg squat, 1-km walk] and who were free of MD in 1996 (no difficulties in walking 2- km, n=788; no difficulties in climbing stairs, n=647). Postal questionnaires were used to assess the prevalence of MD in 1996 and the occurrence of new MD in 2002. Logistic regression analysis was used as the statistical method. Both inability to perform the backwards walk and a poorer result in it were associated with risk of walking difficulties in the logistic model, with all the statistically significant single test items included. Results of 1-km walk time and one-leg squat strength test were also associated with risk, although the squat was statistically significant only in two older birth cohorts. Regarding stair-climbing difficulties, poorer results in the 1-km walk, dynamic back extension and one-leg squat tests were associated with increased risk of MD. The backwards walk, one-leg squat, dynamic back extension and 1-km walk tests were the best predictors of MD. These tests are recommended for use in screening high-functioning older people at risk of MD, as well as to target physical activity counseling to those components of HRF that are important for functional independence.

Cost analysis of mandibular distraction versus tracheostomy in neonates with Pierre Robin sequence.

PubMed

Runyan, Christopher M; Uribe-Rivera, Armando; Karlea, Audrey; Meinzen-Derr, Jareen; Rothchild, Dawn; Saal, Howard; Hopkin, Robert J; Gordon, Christopher B

2014-11-01

To evaluate costs associated with surgical treatment for neonates with Pierre Robin sequence (PRS). Retrospective cohort study. Cincinnati Children's Hospital Medical Center. With Institutional Review Board approval, we retrospectively studied neonates with PRS treated from 2001 to 2009 with either tracheostomy (Trach), mandibular distraction (MD), or Trach with subsequent MD (Trach+MD). Actual charges over a 3-year period associated with operative costs, hospital stay, imaging and sleep studies, clinic visits, and related emergency room visits were collected. Home tracheostomy care charges were estimated individually for each patient. Charges were compared using regression and appropriate statistical analyses. Forty-seven neonates were included in the study (MD, n = 26; Trach, n = 12; Trach+MD, n = 9). Trach group patients had 2.6-fold higher charges than the MD group despite no difference in length of hospital stay. This difference increased to 7.3-fold when including home trach care-related costs. Trach+MD group patients had longer hospital lengths of stay and higher operation room (OR) fees, but no increased total charges compared with the Trach only group. For patients with severe PRS, mandibular distraction provides significant cost savings over tracheostomy ($300,000 per patient over 3 years). Increased costs with tracheostomy come from greater hospital-related charges, more frequent airway procedures, a higher incidence of gastrostomy tube feeds, and home trach care costs. A careful examination of long-term outcomes will be critical as mandibular distraction continues to gain acceptance for treatment of PRS. © American Academy of Otolaryngology-Head and Neck Surgery Foundation 2014.

Co-existence of Benign Paroxysmal Positional Vertigo and Meniere's Syndrome.

PubMed

Yetişer, Sertaç

2017-04-01

Recent studies indicate interrelation of benign paroxysmal positional vertigo (BPPV) and Meniere's disease (MD). These two entities may have different clinical characteristics. Five hundred thirty patients with BPPV evaluated between 2009-2015 were enrolled in the study. 351 patients who had no clear problem associated with BPPV (idiopathic) and 17 patients with MD were analyzed in detail. The age, sex, site of involvement, type of BPPV, symptom duration, and treatment outcome were compared. Meniere's disease + BPPV was more common in the female population (2/15; 7.5 v 127/224; 1.8, p<0.05). Comparative analysis of average age was not statistically significant (42.82±9.94 v. 40.29±1.65, p=0.601). There was no difference in right and left ear involvement between groups. Lateral canal involvement was more common in the BPPV + MD group (9/17; 53% v. 100/351; 28%, p<0.05). BPPV was ipsilateral to the ear with MD in 75% of patients and it was present before the diagnosis of BPPV in 82.3% of patients. Comparative analysis of cure rate between idiopathic BPPV and BPPV + MD after one session was significant (64.7% v 78%, p<0.05). Benign paroxysmal positional vertigo associated with MD presented a divergent picture. It was more frequent in females. Lateral canal involvement was higher. Patients had MD before the development of BPPV and they had prolonged symptoms, which raised a question of diagnostic delay since these two problems were in the same ear in majority of patients. Finally, relief of symptoms required more attempts of repositioning maneuvers.

First record of Trypanosoma chattoni in Brazil and occurrence of other Trypanosoma species in Brazilian frogs (Anura, Leptodactylidae).

PubMed

Lemos, M; Morais, D H; Carvalho, V T; D'Agosto, M

2008-02-01

The present study provides the first record of Trypanosoma chattoni Mathis and Leger, 1911, in a new host, Leptodactylus fuscus Schneider, 1799 (Anura, Leptodactylidae), and the occurrence of Trypanosoma rotatorium-like species in Leptodactylus chaquensis Cei, 1950. The anurans were captured in the State of Mato Grosso, Brazil. Blood samples were obtained by cardiac puncture, and blood smears were examined for the presence of hemoparasites. The Trypanosoma rotatorium-like species in this study refers to a short-bodied trypomastigote that has a conspicuous undulating membrane but lacks a free flagellum; T. chattoni refers to a monomorphic parasite that has a rounded body, a kinetoplast adjacent to the nucleus, and a short flagellum.

78 FR 3496 - Maryland Disaster Number MD-00025

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-16

... SMALL BUSINESS ADMINISTRATION [Disaster Declaration 13394 and 13395] Maryland Disaster Number MD-00025 AGENCY: U.S. Small Business Administration. ACTION: Amendment 3. SUMMARY: This is an amendment of.... (Catalog of Federal Domestic Assistance Numbers 59002 and 59008) James E. Rivera, Associate Administrator...

The knock-down of the expression of MdMLO19 reduces susceptibility to powdery mildew (Podosphaera leucotricha) in apple (Malus domestica).

PubMed

Pessina, Stefano; Angeli, Dario; Martens, Stefan; Visser, Richard G F; Bai, Yuling; Salamini, Francesco; Velasco, Riccardo; Schouten, Henk J; Malnoy, Mickael

2016-10-01

Varieties resistant to powdery mildew (PM; caused by Podosphaera leucotricha) are a major component of sustainable apple production. Resistance can be achieved by knocking-out susceptibility S-genes to be singled out among members of the MLO (Mildew Locus O) gene family. Candidates are MLO S-genes of phylogenetic clade V up-regulated upon PM inoculation, such as MdMLO11 and 19 (clade V) and MdMLO18 (clade VII). We report the knock-down through RNA interference of MdMLO11 and 19, as well as the complementation of resistance with MdMLO18 in the Arabidopsis thaliana triple mlo mutant Atmlo2/6/12. The knock-down of MdMLO19 reduced PM disease severity by 75%, whereas the knock-down of MdMLO11, alone or in combination with MdMLO19, did not result in any reduction or additional reduction of susceptibility compared with MdMLO19 alone. The test in A. thaliana excluded a role for MdMLO18 in PM susceptibility. Cell wall appositions (papillae) were present in both PM-resistant and PM-susceptible plants, but were larger in resistant lines. No obvious negative phenotype was observed in plants with mlo genes knocked down. Apparently, MdMLO19 plays the pivotal role in apple PM susceptibility and its knock-down induces a very significant level of resistance. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

Studies of the TLR4-associated protein MD-2 using yeast-display and mutational analyses

PubMed Central

Mattis, Daiva M.; Chervin, Adam; Ranoa, Diana; Kelley, Stacy; Tapping, Richard; Kranz, David M.

2015-01-01

Bacterial lipopolysaccharide (LPS) activates the innate immune system by forming a complex with myeloid differentiation factor 2 (MD-2) and Toll-like receptor 4 (TLR4), which is present on antigen presenting cells. MD-2 plays an essential role in this activation of the innate immune system as a member of the ternary complex, TLR4:MD-2:LPS. With the goal of further understanding the molecular details of the interaction of MD-2 with LPS and TLR4, and possibly toward engineering dominant negative regulators of the MD-2 protein, here we subjected MD-2 to a mutational analysis using yeast display. The approach included generation of site-directed alanine mutants, and ligand-driven selections of MD-2 mutant libraries. Our findings showed that: 1) proline mutations in the F119-K132 loop that binds LPS were strongly selected for enhanced yeast surface stability, 2) there was a preference for positive-charged side chains (R/K) at residue 120 for LPS binding, and negative-charged side chains (D/E) for TLR4 binding, 3) aromatic residues were strongly preferred at F119 and F121 for LPS binding, and 4) an MD-2 mutant (T84N/D101A/S118A/S120D/K122P) exhibited increased binding to TLR4 but decreased binding to LPS. These studies revealed the impact of specific residues and regions of MD-2 on the binding of LPS and TLR4, and they provide a framework for further directed evolution of the MD-2 protein. PMID:26320630

Morphostructural MRI abnormalities related to neuropsychiatric disorders associated to multiple sclerosis.

PubMed

Bonavita, Simona; Tedeschi, Gioacchino; Gallo, Antonio

2013-01-01

Multiple Sclerosis associated neuropsychiatric disorders include major depression (MD), obsessive-compulsive disorder (OCD), bipolar affective disorder, euphoria, pseudobulbar affect, psychosis, and personality change. Magnetic Resonance Imaging (MRI) studies focused mainly on identifying morphostructural correlates of MD; only a few anecdotal cases on OCD associated to MS (OCD-MS), euphoria, pseudobulbar affect, psychosis, personality change, and one research article on MRI abnormalities in OCD-MS have been published. Therefore, in the present review we will report mainly on neuroimaging abnormalities found in MS patients with MD and OCD. All together, the studies on MD associated to MS suggest that, in this disease, depression is linked to a damage involving mainly frontotemporal regions either with discrete lesions (with those visible in T1 weighted images playing a more significant role) or subtle normal appearing white matter abnormalities. Hippocampal atrophy, as well, seems to be involved in MS related depression. It is conceivable that grey matter pathology (i.e., global and regional atrophy, cortical lesions), which occurs early in the course of disease, may involve several areas including the dorsolateral prefrontal cortex, the orbitofrontal cortex, and the anterior cingulate cortex whose disruption is currently thought to explain late-life depression. Further MRI studies are necessary to better elucidate OCD pathogenesis in MS.

Morphostructural MRI Abnormalities Related to Neuropsychiatric Disorders Associated to Multiple Sclerosis

PubMed Central

Bonavita, Simona; Tedeschi, Gioacchino; Gallo, Antonio

2013-01-01

Multiple Sclerosis associated neuropsychiatric disorders include major depression (MD), obsessive-compulsive disorder (OCD), bipolar affective disorder, euphoria, pseudobulbar affect, psychosis, and personality change. Magnetic Resonance Imaging (MRI) studies focused mainly on identifying morphostructural correlates of MD; only a few anecdotal cases on OCD associated to MS (OCD-MS), euphoria, pseudobulbar affect, psychosis, personality change, and one research article on MRI abnormalities in OCD-MS have been published. Therefore, in the present review we will report mainly on neuroimaging abnormalities found in MS patients with MD and OCD. All together, the studies on MD associated to MS suggest that, in this disease, depression is linked to a damage involving mainly frontotemporal regions either with discrete lesions (with those visible in T1 weighted images playing a more significant role) or subtle normal appearing white matter abnormalities. Hippocampal atrophy, as well, seems to be involved in MS related depression. It is conceivable that grey matter pathology (i.e., global and regional atrophy, cortical lesions), which occurs early in the course of disease, may involve several areas including the dorsolateral prefrontal cortex, the orbitofrontal cortex, and the anterior cingulate cortex whose disruption is currently thought to explain late-life depression. Further MRI studies are necessary to better elucidate OCD pathogenesis in MS. PMID:23691320

Prefrontal cortex and mediodorsal thalamus reduced connectivity is associated with spatial working memory impairment in rats with inflammatory pain.

PubMed

Cardoso-Cruz, Helder; Sousa, Mafalda; Vieira, Joana B; Lima, Deolinda; Galhardo, Vasco

2013-11-01

The medial prefrontal cortex (mPFC) and the mediodorsal thalamus (MD) form interconnected neural circuits that are important for spatial cognition and memory, but it is not known whether the functional connectivity between these areas is affected by the onset of an animal model of inflammatory pain. To address this issue, we implanted 2 multichannel arrays of electrodes in the mPFC and MD of adult rats and recorded local field potential activity during a food-reinforced spatial working memory task. Recordings were performed for 3weeks, before and after the establishment of the pain model. Our results show that inflammatory pain caused an impairment of spatial working memory performance that is associated with changes in the activity of the mPFC-MD circuit; an analysis of partial directed coherence between the areas revealed a global decrease in the connectivity of the circuit. This decrease was observed over a wide frequency range in both the frontothalamic and thalamofrontal directions of the circuit, but was more evident from MD to mPFC. In addition, spectral analysis revealed significant oscillations of power across frequency bands, namely with a strong theta component that oscillated after the onset of the painful condition. Finally, our data revealed that chronic pain induces an increase in theta/gamma phase coherence and a higher level of mPFC-MD coherence, which is partially conserved across frequency bands. The present results demonstrate that functional disturbances in mPFC-MD connectivity are a relevant cause of deficits in pain-related working memory. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Association between global DNA hypomethylation in leukocytes and risk of breast cancer

PubMed Central

Choi, Ji-Yeob; James, Smitha R.; Link, Petra A.; McCann, Susan E.; Hong, Chi-Chen; Davis, Warren; Nesline, Mary K.; Ambrosone, Christine B.; Karpf, Adam R.

2009-01-01

Background: Global DNA hypomethylation may result in chromosomal instability and oncogene activation, and as a surrogate of systemic methylation activity, may be associated with breast cancer risk. Methods: Samples and data were obtained from women with incident early-stage breast cancer (I–IIIa) and women who were cancer free, frequency matched on age and race. In preliminary analyses, genomic methylation of leukocyte DNA was determined by measuring 5-methyldeoxycytosine (5-mdC), as well as methylation analysis of the LINE-1-repetitive DNA element. Further analyses used only 5-mdC levels. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for risk of breast cancer in relation to amounts of methylation. Results: In a subset of samples tested (n = 37), 5-mdC level was not correlated with LINE-1 methylation. 5-mdC level in leukocyte DNA was significantly lower in breast cancer cases than healthy controls (P = 0.001), but no significant case–control differences were observed with LINE-1 methylation (P = 0.176). In the entire data set, we noted significant differences in 5-mdC levels in leukocytes between cases (n = 176) and controls (n = 173); P value < 0.001. Compared with women in the highest 5-mdC tertile (T3), women in the second (T2; OR = 1.49, 95% CI = 0.84–2.65) and lowest tertile (T1; OR = 2.86, 95% CI = 1.65–4.94) had higher risk of breast cancer (P for trend ≤0.001). Among controls only and cases and controls combined, only alcohol intake was found to be inversely associated with methylation levels. Conclusion: These findings suggest that leukocyte DNA hypomethylation is independently associated with development of breast cancer. PMID:19584139

Center of excellence for mobile sensor data-to-knowledge (MD2K).

PubMed

Kumar, Santosh; Abowd, Gregory D; Abraham, William T; al'Absi, Mustafa; Beck, J Gayle; Chau, Duen Horng; Condie, Tyson; Conroy, David E; Ertin, Emre; Estrin, Deborah; Ganesan, Deepak; Lam, Cho; Marlin, Benjamin; Marsh, Clay B; Murphy, Susan A; Nahum-Shani, Inbal; Patrick, Kevin; Rehg, James M; Sharmin, Moushumi; Shetty, Vivek; Sim, Ida; Spring, Bonnie; Srivastava, Mani; Wetter, David W

2015-11-01

Mobile sensor data-to-knowledge (MD2K) was chosen as one of 11 Big Data Centers of Excellence by the National Institutes of Health, as part of its Big Data-to-Knowledge initiative. MD2K is developing innovative tools to streamline the collection, integration, management, visualization, analysis, and interpretation of health data generated by mobile and wearable sensors. The goal of the big data solutions being developed by MD2K is to reliably quantify physical, biological, behavioral, social, and environmental factors that contribute to health and disease risk. The research conducted by MD2K is targeted at improving health through early detection of adverse health events and by facilitating prevention. MD2K will make its tools, software, and training materials widely available and will also organize workshops and seminars to encourage their use by researchers and clinicians. © The Author 2015. Published by Oxford University Press on behalf of the American Medical Informatics Association. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Sleep patterns, sleep disorders and mammographic density in spanish women: The DDM-Spain/Var-DDM study.

PubMed

Pedraza-Flechas, Ana María; Lope, Virginia; Moreo, Pilar; Ascunce, Nieves; Miranda-García, Josefa; Vidal, Carmen; Sánchez-Contador, Carmen; Santamariña, Carmen; Pedraz-Pingarrón, Carmen; Llobet, Rafael; Aragonés, Nuria; Salas-Trejo, Dolores; Pollán, Marina; Pérez-Gómez, Beatriz

2017-05-01

We explored the relationship between sleep patterns and sleep disorders and mammographic density (MD), a marker of breast cancer risk. Participants in the DDM-Spain/var-DDM study, which included 2878 middle-aged Spanish women, were interviewed via telephone and asked questions on sleep characteristics. Two radiologists assessed MD in their left craneo-caudal mammogram, assisted by a validated semiautomatic-computer tool (DM-scan). We used log-transformed percentage MD as the dependent variable and fitted mixed linear regression models, including known confounding variables. Our results showed that neither sleeping patterns nor sleep disorders were associated with MD. However, women with frequent changes in their bedtime due to anxiety or depression had higher MD (e β :1.53;95%CI:1.04-2.26). Copyright © 2017 Elsevier B.V. All rights reserved.

An improved method to characterise the modulation of small-scale turbulent by large-scale structures

NASA Astrophysics Data System (ADS)

Agostini, Lionel; Leschziner, Michael; Gaitonde, Datta

2015-11-01

A key aspect of turbulent boundary layer dynamics is ``modulation,'' which refers to degree to which the intensity of coherent large-scale structures (LS) cause an amplification or attenuation of the intensity of the small-scale structures (SS) through large-scale-linkage. In order to identify the variation of the amplitude of the SS motion, the envelope of the fluctuations needs to be determined. Mathis et al. (2009) proposed to define this latter by low-pass filtering the modulus of the analytic signal built from the Hilbert transform of SS. The validity of this definition, as a basis for quantifying the modulated SS signal, is re-examined on the basis of DNS data for a channel flow. The analysis shows that the modulus of the analytic signal is very sensitive to the skewness of its PDF, which is dependent, in turn, on the sign of the LS fluctuation and thus of whether these fluctuations are associated with sweeps or ejections. The conclusion is that generating an envelope by use of a low-pass filtering step leads to an important loss of information associated with the effects of the local skewness of the PDF of the SS on the modulation process. An improved Hilbert-transform-based method is proposed to characterize the modulation of SS turbulence by LS structures

Functional identification and regulatory analysis of Δ6-fatty acid desaturase from the oleaginous fungus Mucor sp. EIM-10.

PubMed

Jiang, Xianzhang; Liu, Hongjiao; Niu, Yongchao; Qi, Feng; Zhang, Mingliang; Huang, Jianzhong

2017-03-01

To enlarge the diversity of the desaturases associated with PUFA biosynthesis and to better understand the transcriptional regulation of desaturases, a Δ 6 -desaturase gene (Md6) from Mucor sp. and its 5'-upstream sequence was functionally identified in Saccharomyces cerevisiae. Expression of the Δ 6 -fatty acid desaturase (Md6) in S. cerevisiae showed that Md6 could convert linolenic acid to γ-linolenic acid. Computational analysis of the promoter of Md6 suggested it contains several eukaryotic fundamental transcription regulatory elements. In vivo functional analysis of the promoter showed the 5'-upstream sequence of Md6 could initiate expression of GFP and Md6 itself in S. cerevisiae. A series deletion analysis of the promoter suggested that sequence between -919 to -784 bp (relative to start site) named as eMd6 is the key factor for high activity of Δ 6 -desaturase. The activity of Δ 6 -desaturase was increased by 2.8-fold and 2.5-fold when the eMd6 sequence was placed upstream of -434 with forward or reverse orientations respectively. To our best knowledge, the native promoter of Md6 from Mucor is the strongest promoter for Δ 6 -desaturase reported so far and the sequence between -919 to -784 bp is an enhancer for Δ 6 -desaturase activity.

Visual experience and subsequent sleep induce sequential plastic changes in putative inhibitory and excitatory cortical neurons

PubMed Central

Aton, Sara J.; Broussard, Christopher; Dumoulin, Michelle; Seibt, Julie; Watson, Adam; Coleman, Tammi; Frank, Marcos G.

2013-01-01

Ocular dominance plasticity in the developing primary visual cortex is initiated by monocular deprivation (MD) and consolidated during subsequent sleep. To clarify how visual experience and sleep affect neuronal activity and plasticity, we continuously recorded extragranular visual cortex fast-spiking (FS) interneurons and putative principal (i.e., excitatory) neurons in freely behaving cats across periods of waking MD and post-MD sleep. Consistent with previous reports in mice, MD induces two related changes in FS interneurons: a response shift in favor of the closed eye and depression of firing. Spike-timing–dependent depression of open-eye–biased principal neuron inputs to FS interneurons may mediate these effects. During post-MD nonrapid eye movement sleep, principal neuron firing increases and becomes more phase-locked to slow wave and spindle oscillations. Ocular dominance (OD) shifts in favor of open-eye stimulation—evident only after post-MD sleep—are proportional to MD-induced changes in FS interneuron activity and to subsequent sleep-associated changes in principal neuron activity. OD shifts are greatest in principal neurons that fire 40–300 ms after neighboring FS interneurons during post-MD slow waves. Based on these data, we propose that MD-induced changes in FS interneurons play an instructive role in ocular dominance plasticity, causing disinhibition among open-eye–biased principal neurons, which drive plasticity throughout the visual cortex during subsequent sleep. PMID:23300282

The AINTEGUMENTA genes, MdANT1 and MdANT2, are associated with the regulation of cell production during fruit growth in apple (Malus × domestica Borkh.)

PubMed Central

2012-01-01

Background Fruit growth in apple (Malus × domestica Borkh.) is mediated by cell production and expansion. Genes involved in regulating these processes and thereby fruit growth, are not well characterized. We hypothesized that the apple homolog(s) of AINTEGUMENTA (ANT), an APETALA2–repeat containing transcription factor, regulates cell production during fruit growth in apple. Results Two ANT genes, MdANT1 and MdANT2, were isolated from apple and their expression was studied during multiple stages of fruit development. MdANT1 and MdANT2 expression was high during early fruit growth coincident with the period of cell production, rapidly declined during exit from cell production, and remained low during the rest of fruit development. The effects of increase in carbohydrate availability during fruit growth were characterized. Increase in carbohydrate availability enhanced fruit growth largely through an increase in cell production. Expression of MdANT1 and MdANT2 increased sharply by up to around 5-fold in response to an increase in carbohydrate availability. Expression of the ANT genes was compared across two apple genotypes, ‘Gala’ and ‘Golden Delicious Smoothee’ (GS), which differ in the extent of fruit growth, largely due to differences in cell production. In comparison to ‘Gala’, the larger fruit-size genotype, GS, displayed higher levels and a longer duration of MdANT1 and MdANT2 expression. Expression of the ANTs and cell cycle genes in the fruit core and cortex tissues isolated using laser capture microdissection was studied. During early fruit growth, expression of the MdANTs was higher within the cortex, the tissue that constitutes the majority of the fruit. Additionally, MdANT1 and MdANT2 expression was positively correlated with that of A- and B-type CYCLINS, B-type CYCLIN-DEPENDENT-KINASES (CDKBs) and MdDEL1. Conclusions Multiple lines of evidence from this study suggest that MdANT1 and MdANT2 regulate cell production during fruit growth in apple. ANTs may coordinate the expression of cell proliferation genes and thereby affect the competence of cells for cell production during fruit growth. Together, data from this study implicate MdANT1 and MdANT2 in the regulation of fruit growth in apple. PMID:22731507

The AINTEGUMENTA genes, MdANT1 and MdANT2, are associated with the regulation of cell production during fruit growth in apple (Malus × domestica Borkh.).

PubMed

Dash, Madhumita; Malladi, Anish

2012-06-25

Fruit growth in apple (Malus × domestica Borkh.) is mediated by cell production and expansion. Genes involved in regulating these processes and thereby fruit growth, are not well characterized. We hypothesized that the apple homolog(s) of AINTEGUMENTA (ANT), an APETALA2-repeat containing transcription factor, regulates cell production during fruit growth in apple. Two ANT genes, MdANT1 and MdANT2, were isolated from apple and their expression was studied during multiple stages of fruit development. MdANT1 and MdANT2 expression was high during early fruit growth coincident with the period of cell production, rapidly declined during exit from cell production, and remained low during the rest of fruit development. The effects of increase in carbohydrate availability during fruit growth were characterized. Increase in carbohydrate availability enhanced fruit growth largely through an increase in cell production. Expression of MdANT1 and MdANT2 increased sharply by up to around 5-fold in response to an increase in carbohydrate availability. Expression of the ANT genes was compared across two apple genotypes, 'Gala' and 'Golden Delicious Smoothee' (GS), which differ in the extent of fruit growth, largely due to differences in cell production. In comparison to 'Gala', the larger fruit-size genotype, GS, displayed higher levels and a longer duration of MdANT1 and MdANT2 expression. Expression of the ANTs and cell cycle genes in the fruit core and cortex tissues isolated using laser capture microdissection was studied. During early fruit growth, expression of the MdANTs was higher within the cortex, the tissue that constitutes the majority of the fruit. Additionally, MdANT1 and MdANT2 expression was positively correlated with that of A- and B-type CYCLINS, B-type CYCLIN-DEPENDENT-KINASES (CDKBs) and MdDEL1. Multiple lines of evidence from this study suggest that MdANT1 and MdANT2 regulate cell production during fruit growth in apple. ANTs may coordinate the expression of cell proliferation genes and thereby affect the competence of cells for cell production during fruit growth. Together, data from this study implicate MdANT1 and MdANT2 in the regulation of fruit growth in apple.

Growth, the Mediterranean diet and the buying power of adolescents in Greece.

PubMed

Grammatikopoulou, Maria G; Gkiouras, Konstantinos; Daskalou, Efstratia; Apostolidou, Eirini; Theodoridis, Xenophon; Stylianou, Charilaos; Galli-Tsinopoulou, Assimina; Tsigga, Maria; Dardavessis, Theodore; Chourdakis, Michael

2018-06-01

The aim of the present cross-sectional study was to evaluate associations between pocket money, Mediterranean diet (MD) adherence and growth among Greek adolescents. A total of 319 (157 boys and 162 girls) Greek adolescents, aged 10-18 years participated in the study. Pocket money was recorded, MD adherence was assessed with the KIDMED score and growth was evaluated using the World Health Organization (WHO) growth charts. Participants receiving pocket money exceeding 6.0€ daily demonstrated increased fast-food consumption and breakfast skipping. Overall, a negative relationship was revealed between pocket money and obesity. However, lower allowance receivers were less likely to be obese, consume fruit per day and more likely to consume breakfast and sweets, compared to average pocket money receivers. Increased MD adherence was associated with a lower risk of overweight and as expected, unhealthy eating habits were observed among obese adolescents. Interrelationships tend to exist between MD adherence, pocket money and growth among adolescents.

Impact of videogame play on the brain's microstructural properties: cross-sectional and longitudinal analyses.

PubMed

Takeuchi, H; Taki, Y; Hashizume, H; Asano, K; Asano, M; Sassa, Y; Yokota, S; Kotozaki, Y; Nouchi, R; Kawashima, R

2016-12-01

Videogame play (VGP) has been associated with numerous preferred and non-preferred effects. However, the effects of VGP on the development of microstructural properties in children, particularly those associated with negative psychological consequences of VGP, have not been identified to date. The purpose of this study was to investigate this issue through cross-sectional and longitudinal prospective analyses. In the present study of humans, we used the diffusion tensor imaging mean diffusivity (MD) measurement to measure microstructural properties and examined cross-sectional correlations with the amount of VGP in 114 boys and 126 girls. We also assessed correlations between the amount of VGP and longitudinal changes in MD that developed after 3.0±0.3 (s.d.) years in 95 boys and 94 girls. After correcting for confounding factors, we found that the amount of VGP was associated with increased MD in the left middle, inferior and orbital frontal cortex; left pallidum; left putamen; left hippocampus; left caudate; right putamen; right insula; and thalamus in both cross-sectional and longitudinal analyses. Regardless of intelligence quotient type, higher MD in the areas of the left thalamus, left hippocampus, left putamen, left insula and left Heschl gyrus was associated with lower intelligence. We also confirmed an association between the amount of VGP and decreased verbal intelligence in both cross-sectional and longitudinal analyses. In conclusion, increased VGP is directly or indirectly associated with delayed development of the microstructure in extensive brain regions and verbal intelligence.

Impact of videogame play on the brain's microstructural properties: cross-sectional and longitudinal analyses

PubMed Central

Takeuchi, H; Taki, Y; Hashizume, H; Asano, K; Asano, M; Sassa, Y; Yokota, S; Kotozaki, Y; Nouchi, R; Kawashima, R

2016-01-01

Videogame play (VGP) has been associated with numerous preferred and non-preferred effects. However, the effects of VGP on the development of microstructural properties in children, particularly those associated with negative psychological consequences of VGP, have not been identified to date. The purpose of this study was to investigate this issue through cross-sectional and longitudinal prospective analyses. In the present study of humans, we used the diffusion tensor imaging mean diffusivity (MD) measurement to measure microstructural properties and examined cross-sectional correlations with the amount of VGP in 114 boys and 126 girls. We also assessed correlations between the amount of VGP and longitudinal changes in MD that developed after 3.0±0.3 (s.d.) years in 95 boys and 94 girls. After correcting for confounding factors, we found that the amount of VGP was associated with increased MD in the left middle, inferior and orbital frontal cortex; left pallidum; left putamen; left hippocampus; left caudate; right putamen; right insula; and thalamus in both cross-sectional and longitudinal analyses. Regardless of intelligence quotient type, higher MD in the areas of the left thalamus, left hippocampus, left putamen, left insula and left Heschl gyrus was associated with lower intelligence. We also confirmed an association between the amount of VGP and decreased verbal intelligence in both cross-sectional and longitudinal analyses. In conclusion, increased VGP is directly or indirectly associated with delayed development of the microstructure in extensive brain regions and verbal intelligence. PMID:26728566

Mediterranean dietary pattern in pregnant women and offspring risk of overweight and abdominal obesity in early childhood: the INMA birth cohort study.

PubMed

Fernández-Barrés, S; Romaguera, D; Valvi, D; Martínez, D; Vioque, J; Navarrete-Muñoz, E M; Amiano, P; Gonzalez-Palacios, S; Guxens, M; Pereda, E; Riaño, I; Tardón, A; Iñiguez, C; Arija, V; Sunyer, J; Vrijheid, M

2016-12-01

Animal models have suggested that maternal diet quality may reduce offspring obesity risk regardless of maternal body weight; however, evidence from human studies is scarce. The aim of this study was to evaluate associations between adherence to the Mediterranean diet (MD) during pregnancy and childhood overweight and abdominal obesity risk at 4 years of age. We analysed 1827 mother-child pairs from the Spanish 'Infancia y Medio Ambiente' cohort study, recruited between 2003 and 2008. Diet was assessed during pregnancy using a food frequency questionnaire and MD adherence by the relative Mediterranean diet score (rMED). Overweight (including obesity) was defined as an age-specific and sex-specific body mass index ≥85th percentile (World Health Organization referent), and abdominal obesity as a waist circumference (WC) >90th percentile. Multivariate adjusted linear and logistic regression models were used to evaluate associations between pregnancy rMED and offspring overweight and abdominal obesity. There was no association between rMED and body mass index z-score, whereas there was a significant association between higher adherence to MD and lower WC (β of high vs. low rMED: -0.62 cm; 95% confidence interval: -1.10, -0.14 cm, P for trend = 0.009). Pregnancy adherence to the MD was not associated with childhood overweight risk, but it was associated with lower WC, a marker of abdominal obesity. © 2016 World Obesity Federation.

Mathematical learning disorder in school-age children with attention-deficit hyperactivity disorder.

PubMed

Capano, Lucia; Minden, Debbie; Chen, Shirley X; Schacher, Russell J; Ickowicz, Abel

2008-06-01

To explore the prevalence of mathematics disorder (MD) relative to reading disorders (RD) in school-age children with attention-deficit hyperactivity disorder (ADHD) and examine the effects of age, sex, cooccurring conduct disorder (CD), and ADHD subtype on this comorbidity. Participants were school-age children (n = 476) with confirmed DSM-IV diagnosis of ADHD. The assessment included semistructured parent and teacher interviews and standardized measures of intelligence, academic attainment, and language abilities. Based on the presence or absence of concurrent learning disorders, we compared the emerging 4 groups: ADHD-only, ADHD + MD, ADHD + RD, and ADHD + MD + RD. Overall prevalence of comorbid ADHD + MD was 18.1%. Age, sex, ADHD subtypes, or comorbid CD did not affect the frequency of MD. Children with concurrent ADHD and either MD or RD attained lower IQ, language, and academic scores than those with ADHD alone. Children with ADHD + MD + RD were more seriously impaired and demonstrated distinct deficits in receptive and expressive language. MDs are relatively common in school-age children with ADHD and are frequently associated with RDs. Children with ADHD + MD + RD are more severely impaired. These deficits simply cannot be explained as consequences of ADHD and might have unique biological underpinnings, with implications for diagnostic classification and therapeutic interventions.

Apolipoprotein M T-778C polymorphism is associated with serum lipid levels and the risk of coronary artery disease in the Chinese population: a meta-analysis.

PubMed

Zhang, Zhi; Chu, Guang; Yin, Rui-Xing

2013-09-16

The apolipoprotein M (APOM) T-778C gene polymorphism has been associated with serum lipid levels and the risk of coronary artery disease (CAD), but the results are inconclusive. The purpose of this meta-analysis was to detect the association between the APOM T-778C polymorphism and serum lipid levels and the risk of CAD in the Chinese population. Databases of MEDLINE, EMBASE, the Cochrane Library and CNKI were systematically searched. Data were extracted using standardized methods. The association was assessed by mean difference (MD) with 95% confidence intervals (CI) or odds ratio (OR) with 95% CI. Ten studies with 4,413 patients were included in this meta-analysis. Pooled effects indicated that CT+CC group had higher levels of total cholesterol (TC) (MD:-0.36, 95% CI: -0.53 - -0.19, P < 0.0001) and low-density lipoprotein cholesterol (LDL-C) (MD: -0.08, 95% CI: -0.16 - -0.01, P = 0.03) than TT group. There was no difference in the levels of triglyceride (MD: 0.06, 95% CI: -0.04 - 0.15, P = 0.22) and high-density lipoprotein cholesterol (MD: 0.00, 95% CI: -0.03-0.03, P = 0.93) between TT and CT+CC groups. Pooled effects showed that CAD group had higher CT+CC genotype frequency than control group (OR: 1.97, 95% CI: 1.62-2.39, P < 0.00001; heterogeneity test x(2) = 2.96, P = 0.71, I(2) = 0%). The results of the current meta-analysis show that the CT+CC group has higher levels of TC and LDL-C than the TT group. Moreover, there is also a prominent association between APOM T-778C polymorphism and the risk of CAD in the Chinese population, the CT+CC genotype is associated with increased risk of CAD.

Adherence to Mediterranean diet and risk of gastric cancer: results of a case-control study in Italy.

PubMed

Stojanovic, Jovana; Giraldi, Luca; Arzani, Dario; Pastorino, Roberta; Biondi, Alberto; Persiani, Roberto; Boccia, Stefania; Leoncini, Emanuele

2017-11-01

The aim of this study is to evaluate the association between adherence to Mediterranean diet (MD) and gastric cancer (GC). A case-control study was carried out at the Fondazione Policlinico 'A. Gemelli' (Rome, Italy) from 2003 to 2015. A total of 223 incident cases and 223 controls were interviewed. Dietary intake was assessed through a validated food frequency questionnaire that collected information on more than 25 food items. The association between adherence to MD and risk of GC was quantified by calculating Odds Ratios (OR) and 95% confidence intervals (CI). The analysis reports that a higher adherence to MD is associated with a reduced risk of GC (OR: 0.70; 95% CI: 0.61-0.81). A high consumption of vegetables (OR: 0.34; 95% CI: 0.14-0.85), legumes (OR: 0.13; 95% CI: 0.06-0.29), and fish (OR: 0.33; 95% CI: 0.15-0.68), as well as low consumption of meat (OR: 0.29; 95% CI: 0.10-0.85) and alcohol (OR: 0.46; 95% CI: 0.24-0.90) are consistently related to a lower risk of GC. Our study indicates a protective role of the MD eating pattern and MD individual components against GC. Our results showed a beneficial role of high vegetable, legume, and fish consumption, along with low intake of alcohol and meat in the development of GC.

Association Between Blood Pressure and Adherence to French Dietary Guidelines.

PubMed

Lelong, Helene; Blacher, Jacques; Menai, Mehdi; Galan, Pilar; Fezeu, Leopold; Hercberg, Serge; Kesse-Guyot, Emmanuelle

2016-08-01

Adopting a healthy diet like the Dietary Approach to Stop Hypertension (DASH) or Mediterranean diet (MD) represents a major lifestyle for blood pressure (BP) control in general population. Nutritional policies, such as the French Nutrition and Health Program (Programme National Nutrition Santé or PNNS), have been implemented in several countries with the aims of preventing chronic diseases. The objective of our study was to investigate association between BP and adherence to PNNS guidelines compared with adherence to DASH or MD. We conducted a cross-sectional study in 11,302 untreated participants from the NutriNet-Santé study, a French web-based cohort study. Three validated scores reflecting adherence to PNNS guidelines, DASH diet, and MD were calculated from repeated 24-hour records. Three BP measurements using a standardized protocol were collected. Multivariate linear models were used to assess the associations between the dietary scores and BP. In women, independent of age, socioeconomic status, body mass index, tobacco use, alcohol consumption, and physical activity, adherence to PNNS guidelines was inversely significantly associated with systolic BP (β = -0.63, P < 0.0001). This association was of similar amplitude that between BP and adherence to DASH-style diet (β = -0.66, P < 0.0001) or MD (β = -0.63, P = 0.0002). No significant association was found in men. Adherence to French nutritional recommendations was found negatively associated with BP at the same magnitude as adherence to well-known dietary pattern in the prevention and treatment of hypertension. © American Journal of Hypertension, Ltd 2016. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Assessing the allelotypic effect of two aminocyclopropane carboxylic acid synthase-encoding genes MdACS1 and MdACS3a on fruit ethylene production and softening in Malus

PubMed Central

Dougherty, Laura; Zhu, Yuandi; Xu, Kenong

2016-01-01

Phytohormone ethylene largely determines apple fruit shelf life and storability. Previous studies demonstrated that MdACS1 and MdACS3a, which encode 1-aminocyclopropane-1-carboxylic acid synthases (ACS), are crucial in apple fruit ethylene production. MdACS1 is well-known to be intimately involved in the climacteric ethylene burst in fruit ripening, while MdACS3a has been regarded a main regulator for ethylene production transition from system 1 (during fruit development) to system 2 (during fruit ripening). However, MdACS3a was also shown to have limited roles in initiating the ripening process lately. To better assess their roles, fruit ethylene production and softening were evaluated at five time points during a 20-day post-harvest period in 97 Malus accessions and in 34 progeny from 2 controlled crosses. Allelotyping was accomplished using an existing marker (ACS1) for MdACS1 and two markers (CAPS866 and CAPS870) developed here to specifically detect the two null alleles (ACS3a-G289V and Mdacs3a) of MdACS3a. In total, 952 Malus accessions were allelotyped with the three markers. The major findings included: The effect of MdACS1 was significant on fruit ethylene production and softening while that of MdACS3a was less detectable; allele MdACS1–2 was significantly associated with low ethylene and slow softening; under the same background of the MdACS1 allelotypes, null allele Mdacs3a (not ACS3a-G289V) could confer a significant delay of ethylene peak; alleles MdACS1–2 and Mdacs3a (excluding ACS3a-G289V) were highly enriched in M. domestica and M. hybrid when compared with those in M. sieversii. These findings are of practical implications in developing apples of low and delayed ethylene profiles by utilizing the beneficial alleles MdACS1-2 and Mdacs3a. PMID:27231553

The prevalence, clinical correlates and structure of phobic fears in Han Chinese women with recurrent major depression.

PubMed

Yang, Fuzhong; Qiu, Jianyin; Zhao, Hongsu; Wang, Zhoubing; Tao, Danhong; Xiao, Xue; Niu, Qihui; Wang, Qian; Li, Yajuan; Guo, Liyang; Li, Jianying; Li, Kan; Xia, Jing; Wang, Lina; Shang, Xiaofang; Sang, Wenhua; Gan, Zhaoyu; He, Kangmei; Zhao, Xiaochuan; Tian, Tian; Xu, Dan; Gu, Danhua; Weng, Xiaoqin; Li, Haimin; Tian, Jing; Yang, Lijun; Li, Qiang; Yang, Qingzhen; Wang, Hui; Dang, Yamei; Dai, Lei; Cui, Yanping; Ye, Dong; Cao, Juling; Guo, Li; Kang, Zhen; Liu, Jimeng; Chen, Bin; Liu, Jinhua; Zhang, Jinling; Yang, Donglin; Jiao, Bin; Yu, Fengyu; Geng, Feng; Li, Ling; Yang, Haiying; Dai, Hong; Wang, Hongli; Liu, Caixing; Liu, Haijun; Peng, Longyan; Wang, Xiaoping; Wei, Shaojun; Liu, Xiaojuan; Li, Chang; Liu, Zhengrong; Zhang, Qiwen; Di, Dongchuan; Shi, Shenxun; Flint, Jonathan; Kendler, Kenneth S

2014-03-01

Phobic fears are common in the general population and among individuals with major depression (MD). We know little about the prevalence, clinical correlates, and structure of phobic fears in Chinese women with MD. We assessed 22 phobic fears in 6017 Han Chinese women with MD. We used exploratory factor analysis to examine the structure of these phobic fears. We examined the relationship between individual phobic fears and the severity of MD, neuroticism, comorbid panic disorder, generalized anxiety disorder and dysthymia using logistic regression models. The frequency of phobic fears ranged from 3.0% (eating in public) to 36.0% (snakes). Phobic fears were significantly associated with more severe MD, high neuroticism, and co-morbid panic disorder, generalized anxiety disorder and dysthymia. Our factor analysis suggested four underlying subgroups of phobic fears which differed in their clinical correlates, severity and patterns of comorbidity. Data were collected retrospectively through interview and recall bias may have affected the results. Phobic fears are correlated with comorbid MD and more severe MD. These phobic fears clearly subdivide into four subgroups that differ meaningfully from each other. Copyright © 2014 Elsevier B.V. All rights reserved.

Effect of exogenous GA3 and its inhibitor paclobutrazol on floral formation, endogenous hormones, and flowering-associated genes in 'Fuji' apple (Malus domestica Borkh.).

PubMed

Zhang, Songwen; Zhang, Dong; Fan, Sheng; Du, Lisha; Shen, Yawen; Xing, Libo; Li, Youmei; Ma, Juanjuan; Han, Mingyu

2016-10-01

Gibberellins (GAs) reduce apple (Malus domestica) flowering rates; however, the mechanism of their action is not fully understood. To gain a better insight into gibberellin-regulated flowering, here, 5 year-old 'Fuji' apple trees were used to explore the responses of hormones [GA1+3, GA4+7, indole-3-acetic acid (IAA), zeatin-riboside (ZR), and abscisic acid (ABA)], and gibberellin- and flowering-associated genes, to applications of gibberellin acid (GA3) and paclobutrazol (PAC). Results showed that GA3 relatively stimulated vegetative growth and delayed floral induction. Moreover, GA3 spraying significantly affected contents of all endogenous hormones and all the genes tested in at least one time points: the content of endogenous GAs was increased instantly and that of ZR was reduced at 44 days after fullbloom (DAF), which might constitute an unfavorable factor for flower formation; MdKO (ent-kaurene oxidase gene) and MdGA20ox (GA20 oxidase gene) were significantly repressed by a high level of GAs through the negative feedback regulation of GA; additionally, the MdSPLs (SQUAMOSA-PROMOTER BINDING PROTEIN-LIKE) in this study were all significantly repressed by GA3 but promoted by PAC; the expression of MdFT1/2 (FLOWERING LOCUS T), MdSOC1 (SUPPRESSOR OF OVEREXPRESSION OF CONSTANS1) and MdAP1 (APETALA1) in GA3-treated buds changed in the same way, and they were repressed at 44 DAF. We suppose that GA3 spraying disrupts the balance between ZR and GAs, and inhibits floral induction, probably by suppressing MdSPLs and the floral integrators in flower induction, which ultimately contributed to inhibiting flower formation. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

The Weather and Ménière's Disease: A Longitudinal Analysis in the UK.

PubMed

Schmidt, Wiebke; Sarran, Christophe; Ronan, Natalie; Barrett, George; Whinney, David J; Fleming, Lora E; Osborne, Nicholas J; Tyrrell, Jessica

2017-02-01

Changes in the weather influence symptom severity in Ménière's disease (MD). MD is an unpredictable condition that significantly impacts on quality of life. It is suggested that fluctuations in the weather, especially atmospheric pressure may influence the symptoms of MD. However, to date, limited research has investigated the impact of the weather on MD. In a longitudinal study, a mobile phone application collected data from 397 individuals (277 females and 120 males with an average age of 50 yr) from the UK reporting consultant-diagnosed MD. Daily symptoms (vertigo, aural fullness, tinnitus, hearing loss, and attack prevalence) and GPS locations were collected; these data were linked with Met Office weather data (including atmospheric pressure, humidity, temperature, visibility, and wind speed). Symptom severity and attack prevalence were reduced on days when atmospheric pressure was higher. When atmospheric pressure was below 1,013 hectopascals, the risk of an attack was 1.30 (95% confidence interval: 1.10, 1.54); when the humidity was above 90%, the risk of an attack was 1.26 (95% confidence interval 1.06, 1.49). This study provides the strongest evidence to date that changes in atmospheric pressure and humidity are associated with symptom exacerbation in MD. Improving our understanding of the role of weather and other environmental triggers in Ménière's may reduce the uncertainty associated with living with this condition, significantly contributing to improved quality of life.

The Weather and Ménière’s Disease: A Longitudinal Analysis in the UK

PubMed Central

Schmidt, Wiebke; Sarran, Christophe; Ronan, Natalie; Barrett, George; Whinney, David J.; Fleming, Lora E.; Osborne, Nicholas J.; Tyrrell, Jessica

2016-01-01

Hypothesis Changes in the weather influence symptom severity in Ménière’s disease (MD). Background MD is an unpredictable condition that significantly impacts on quality of life. It is suggested that fluctuations in the weather, especially atmospheric pressure may influence the symptoms of MD. However, to date, limited research has investigated the impact of the weather on MD. Methods In a longitudinal study, a mobile phone application collected data from 397 individuals (277 females and 120 males with an average age of 50 yr) from the UK reporting consultant-diagnosed MD. Daily symptoms (vertigo, aural fullness, tinnitus, hearing loss, and attack prevalence) and GPS locations were collected; these data were linked with Met Office weather data (including atmospheric pressure, humidity, temperature, visibility, and wind speed). Results Symptom severity and attack prevalence were reduced on days when atmospheric pressure was higher. When atmospheric pressure was below 1,013 hectopascals, the risk of an attack was 1.30 (95% confidence interval: 1.10, 1.54); when the humidity was above 90%, the risk of an attack was 1.26 (95% confidence interval 1.06, 1.49). Conclusion This study provides the strongest evidence to date that changes in atmospheric pressure and humidity are associated with symptom exacerbation in MD. Improving our understanding of the role of weather and other environmental triggers in Ménière’s may reduce the uncertainty associated with living with this condition, significantly contributing to improved quality of life. PMID:27861300

Expression of xyloglucan endotransglucosylase/hydrolase (XTH) genes and XET activity in ethylene treated apple and tomato fruits.

PubMed

Muñoz-Bertomeu, J; Miedes, E; Lorences, E P

2013-09-01

Xyloglucan endotransglucosylase/hydrolase (XTHs: EC 2.4.1.207 and/or EC 3.2.1.151), a xyloglucan modifying enzyme, has been proposed to have a role during tomato and apple fruit ripening by loosening the cell wall. Since the ripening of climacteric fruits is controlled by endogenous ethylene biosynthesis, we wanted to study whether XET activity was ethylene-regulated, and if so, which specific genes encoding ripening-regulated XTH genes were indeed ethylene-regulated. XET specific activity in tomato and apple fruits was significantly increased by the ethylene treatment, as compared with the control fruits, suggesting an increase in the XTH gene expression induced by ethylene. The 25 SlXTH protein sequences of tomato and the 11 sequences MdXTH of apple were phylogenetically analyzed and grouped into three major clades. The SlXTHs genes with highest expression during ripening were SlXTH5 and SlXTH8 from Group III-B, and in apple MdXTH2, from Group II, and MdXTH10, and MdXTH11 from Group III-B. Ethylene was involved in the regulation of the expression of different SlXTH and MdXTH genes during ripening. In tomato fruit fifteen different SlXTH genes showed an increase in expression after ethylene treatment, and the SlXTHs that were ripening associated were also ethylene dependent, and belong to Group III-B (SlXTH5 and SlXTH8). In apple fruit, three MdXTH showed an increase in expression after the ethylene treatment and the only MdXTH that was ripening associated and ethylene dependent was MdXTH10 from Group III-B. The results indicate that XTH may play an important role in fruit ripening and a possible relationship between XTHs from Group III-B and fruit ripening, and ethylene regulation is suggested. Copyright © 2013 Elsevier GmbH. All rights reserved.

Behavior of visual field index in advanced glaucoma.

PubMed

Rao, Harsha L; Senthil, Sirisha; Choudhari, Nikhil S; Mandal, Anil K; Garudadri, Chandra S

2013-01-14

To evaluate the magnitude of Visual Field Index (VFI) change attributable to change in the estimation algorithm from the pattern deviation probability plot (PDPP) to the total deviation probability plot (TDPP) when the mean deviation (MD) crosses -20 decibels (dB). In a retrospective study, 37 stable glaucoma eyes in which MD of the VFs crossed -20 dB were identified. For each eye, a pair of VFs was selected so that one VF of the pair had a MD better than but close to -20 dB and the other had a MD worse than but again close to -20 dB. The change in VFI in the VF pairs and its associations with the number of points in probability plots with normal threshold sensitivities were evaluated. Similar pairs of VFs from 28 stable glaucoma eyes where the MD crossed -10 dB were chosen as controls. The change in VFI in VF pairs when the MD crossed 20 dB ranged from 3% to 33% (median: 15%), while the change when MD crossed -10 dB ranged from 1% to 8% (median: 4%). Difference in the number of points with normal threshold sensitivities in PDPP when MD was better than -20 dB compared to those in TDPP when MD crossed -20 dB significantly influenced the VFI change (R(2) = 0.65). Considering the eccentricity of these points further explained the VFI change (R(2) = 0.81). The decrease in VFI when MD crosses -20 dB can be highly variable. This has to be considered with the use of VFI in clinical and research settings.

Comparative levels of excessive daytime sleepiness in common medical disorders.

PubMed

Stroe, Alice F; Roth, Thomas; Jefferson, Catherine; Hudgel, David W; Roehrs, Timothy; Moss, Kenneth; Drake, Christopher L

2010-10-01

Sleep restriction and sleep disorders are common causes of excessive daytime sleepiness (EDS). Medical disorders (MD) can also cause EDS, but previous studies have used non-standardized measures, selected samples, or have examined EDS in singular disorders. This study describes the relative degree of EDS associated with medical disorders to provide comparative data across a range of common medical conditions in a large unselected community-based sample. Responses of 2612 individuals (aged 18-65) were assessed after excluding those with suspected sleep disordered breathing, narcolepsy, and shift workers. Participants across a range of medical disorders were evaluated using the Epworth Sleepiness Scale (ESS) and patient reports of nocturnal sleep. Sixty-seven percent of the sample reported a MD. The prevalence of EDS (ESS>or=10) was 31.4% in individuals with MD and increased as a function of a number of MD (0 MD=29.4%, 1 MD=28.4%, 2 MD=31.0%, 3 MD=35.3%, 4 MD=38.4%). Disorders which were independent predictors of EDS were ulcers OR=2.21 (95% CI=1.35-3.61), migraines OR=1.36 (95% CI=1.08-1.72), and depression OR=1.46 (95% CI=1.16-1.83) after controlling for other conditions, age, gender, time in bed, caffeine, smoking and alcohol use. Participants with ulcers had the highest prevalence of sleepiness, 50.0%, as well as the highest level of problems falling asleep (40.8%) and awakenings during the night (62.5%). Individuals with ulcers, migraines, and depression have independent and clinically significant levels of EDS relative to other common MD.

Marek’s disease virus-induced transient cecal tonsil atrophy

USDA-ARS?s Scientific Manuscript database

Marek’s disease (MD) is a lymphoproliferative disease of domestic chickens that is caused by a highly cell-associated oncogenic '-herpesvirus, Marek’s disease virus (MDV). MDV replicates in chicken lymphocytes and establishes a latent infection within CD4+ T cells. MD is characterized by bursal/th...

Immune responses in cecal tonsils of MDV-infected chickens

USDA-ARS?s Scientific Manuscript database

Marek’s disease (MD) is a lymphoproliferative disease of domestic chickens that is caused by a highly cell-associated oncogenic '-herpesvirus, Marek’s disease virus (MDV). MDV replicates in chicken lymphocytes and establishes a latent infection within CD4+ T cells. Clinical signs of MD include dep...

Establishment of an Aerosal-Based Marek's Disease Virus Infection Model

USDA-ARS?s Scientific Manuscript database

Marek’s disease virus (MDV), which is the causative agent of Marek’s disease (MD), is shed by infected chickens and transmitted to other chickens through the respiratory route. Experimental reproduction of MD has been commonly done either by intra-abdominal inoculation of cell-associated MDV or by e...

Transcriptome and proteome profiling of host responses to Marek's disease virus in chickens

USDA-ARS?s Scientific Manuscript database

Marek’s disease (MD) is an immunosuppressive and proliferative disease of domestic chickens caused by a highly oncogenic cell-associated alpha-herpesvirus, named Marek’s disease virus (MDV). Despite the availability of highly efficacious vaccines for control of MD and existence of lines of chickens ...

Cancer Prevention: Distinguishing Strength of Evidence from Strength of Opinion

Cancer.gov

Barnett S. Kramer, MD, MPH, Associate Director for Disease Prevention and Director of the Office of Medical Applications of Research in the Office of Disease Prevention, Office of the Director, National Institutes of Health, Bethesda, MD, presented "Cancer Prevention: Distinguishing Strength of Evidence from Strength of Opinion".

White matter abnormalities in Gulf War veterans with posttraumatic stress disorder: A pilot study.

PubMed

Bierer, Linda M; Ivanov, Iliyan; Carpenter, David M; Wong, Edmund W; Golier, Julia A; Tang, Cheuk Y; Yehuda, Rachel

2015-01-01

Gulf War veterans were exposed to environmental toxins not present in other combat theaters resulting in a unique biological signature that only partially resembles that seen in other combat veterans with PTSD. Thus it is important to determine if brain abnormalities seen in non-Gulf War veterans with PTSD are also present in Gulf War veterans. In this pilot study, diffusion tensor imaging (DTI) tractography was used to assess the ultra-structural integrity of fronto-limbic white matter connections in Gulf War veterans with and without PTSD. The effects of chronic multisymptom illness on DTI measures was also evaluated. Subjects were 20 previously studied Gulf War veterans on whom MRIs had been obtained. Mean diffusivity (MD) and fractional anisotropy (FA) were determined for left and right cingulum bundle by DTI tractography and compared in separate analyses for 12 veterans with, and 8 without PTSD. The effect of chronic multisymptom illness and it's interaction with PTSD, were similarly investigated using multivariate ACOVA. Partial correlations were used to test the associations of both DTI indices with PTSD severity and plasma cortisol, controlling for whole brain volume. Significantly lower MD was demonstrated in the right cingulum bundle among Gulf War veterans with PTSD. There were no significant differences in MD or FA in the left cingulum bundle. The presence of chronic multisymptom illness significantly attenuated the PTSD associated decrement in right cingulum MD. Clinician and self-rated PTSD symptom severity scores were significantly associated with reduced MD and increased FA in the right cingulum. Similar associations were observed for 8am plasma cortisol in a subset of participants. The preliminary findings indicate increased structural integrity - supporting enhanced connectivity - between right amygdala and anterior cingulate cortex in PTSD. This effect was strongest among Gulf War veterans without chronic multisymptom illness. The association of both MD and FA in the right cingulum with PTSD severity, and with heightened glucocorticoid responsivity, suggests that these DTI findings are a reflection of current PTSD illness expression. Although based on a small sample, these microstructural observations are consistent with a functional model suggesting increased amygdala responsivity in association with anterior cingulate modulation in PTSD. Copyright © 2014. Published by Elsevier Ltd.

Investigating the Role of Mitochondrial Haplogroups in Genetic Predisposition to Meningococcal Disease

PubMed Central

Salas, Antonio; Fachal, Laura; Marcos-Alonso, Sonia; Vega, Ana; Martinón-Torres, Federico

2009-01-01

Background and Aims Meningococcal disease remains one of the most important infectious causes of death in industrialized countries. The highly diverse clinical presentation and prognosis of Neisseria meningitidis infections are the result of complex host genetics and environmental interactions. We investigated whether mitochondrial genetic background contributes to meningococcal disease (MD) susceptibility. Methodology/Principal Findings Prospective controlled study was performed through a national research network on MD that includes 41 Spanish hospitals. Cases were 307 paediatric patients with confirmed MD, representing the largest series of MD patients analysed to date. Two independent sets of ethnicity-matched control samples (CG1 [N = 917]), and CG2 [N = 616]) were used for comparison. Cases and controls underwent mtDNA haplotyping of a selected set of 25 mtDNA SNPs (mtSNPs), some of them defining major European branches of the mtDNA phylogeny. In addition, 34 ancestry informative markers (AIMs) were genotyped in cases and CG2 in order to monitor potential hidden population stratification. Samples of known African, Native American and European ancestry (N = 711) were used as classification sets for the determination of ancestral membership of our MD patients. A total of 39 individuals were eliminated from the main statistical analyses (including fourteen gypsies) on the basis of either non-Spanish self-reported ancestry or the results of AIMs indicating a European membership lower than 95%. Association analysis of the remaining 268 cases against CG1 suggested an overrepresentation of the synonym mtSNP G11719A variant (Pearson's chi-square test; adjusted P-value = 0.0188; OR [95% CI] = 1.63 [1.22–2.18]). When cases were compared with CG2, the positive association could not be replicated. No positive association has been observed between haplogroup (hg) status of cases and CG1/CG2 and hg status of cases and several clinical variants. Conclusions We did not find evidence of association between mtSNPs and mtDNA hgs with MD after carefully monitoring the confounding effect of population sub-structure. MtDNA variability is particularly stratified in human populations owing to its low effective population size in comparison with autosomal markers and therefore, special care should be taken in the interpretation of seeming signals of positive associations in mtDNA case-control association studies. PMID:20019817

Polarized Ends of Human Macula Densa Cells: Ultrastructural Investigation and Morphofunctional Correlations.

PubMed

Cangiotti, Angela Maria; Lorenzi, Teresa; Zingaretti, Maria Cristina; Fabri, Mara; Morroni, Manrico

2018-05-01

The morphology of the kidney macula densa (MD) has extensively been investigated in animals, whereas human studies are scanty. We studied the fine structure of human MD cells focusing on their apical and basal ends and correlating structure and function. The MD region was examined by transmission electron microscopy in six renal biopsies from patients with kidney disease. Ultrastructural analysis of MD cells was performed on serial sections. MD cells show two polarized ends. The apical portion is characterized by a single, immotile cilium associated with microvilli; apically, cells are joined by adhering junctions. In the basal portion, the cytoplasm contains small, dense granules and numerous, irregular cytoplasmic projections extending to the adjacent extraglomerular mesangium. The projections often contain small, dense granules. A reticulated basement membrane around MD cells separates them from the extraglomerular mesangium. Although the fact that tissue specimens came from patients with kidney disease mandates extreme caution, ultrastructural examination confirmed that MD cells have sensory features due to the presence of the primary cilium, that they are connected by apical adhering junctions forming a barrier that separates the tubular flow from the interstitium, and that they present numerous basal interdigitations surrounded by a reticulated basement membrane. Conceivably, the latter two features are related to the functional activity of the MD. The small, dense granules in the basal cytoplasm and in cytoplasmic projections are likely related to the paracrine function of MD cells. Anat Rec, 301:922-931, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Prenatal exposure to maternal and paternal depressive symptoms and white matter microstructure in children.

PubMed

El Marroun, Hanan; Zou, Runyu; Muetzel, Ryan L; Jaddoe, Vincent W; Verhulst, Frank C; White, Tonya; Tiemeier, Henning

2018-04-01

Prenatal maternal depression has been associated with multiple problems in offspring involving affect, cognition, and neuroendocrine functioning. This suggests that prenatal depression influences neurodevelopment. However, the underlying neurodevelopmental mechanism remains unclear. We prospectively assessed whether maternal depressive symptoms during pregnancy and at the child's age 3 years are related to white matter microstructure in 690 children. The association of paternal depressive symptoms with childhood white matter microstructure was assessed to evaluate genetic or familial confounding. Parental depressive symptoms were measured using the Brief Symptom Inventory. In children aged 6-9 years, we used diffusion tensor imaging to assess white matter microstructure characteristics including fractional anisotropy (FA) and mean diffusivity (MD). Exposure to maternal depressive symptoms during pregnancy was associated with higher MD in the uncinate fasciculus and to lower FA and higher MD in the cingulum bundle. No associations of maternal depressive symptoms at the child's age of 3 years with white matter characteristics were observed. Paternal depressive symptoms also showed a trend toward significance for a lower FA in the cingulum bundle. Prenatal maternal depressive symptoms were associated with higher MD in the uncinate fasciculus and the cingulum bundle. These structures are part of the limbic system, which is involved in motivation, emotion, learning, and memory. As paternal depressive symptoms were also related to lower FA in the cingulum, the observed effect may partly reflect a genetic predisposition and shared environmental family factors and to a lesser extent a specific intrauterine effect. © 2018 Wiley Periodicals, Inc.

American Burn Association Practice Guidelines: Burn Shock Resuscitation

DTIC Science & Technology

2008-02-01

Ann Surg 1979;189: 546–52. 39. Jelenko C III, Williams JB, Wheeler ML, et al. Studies in shock and resuscitation, I: use of a hypertonic, albumin...SUMMARY ARTICLE American Burn Association Practice Guidelines Burn Shock Resuscitation Tam N. Pham, MD,* Leopoldo C . Cancio, MD,† Nicole S. Gibran...practice guidelines burn shock resuscitation 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Pham T. N., Cancio L. C

Genome-wide association study unravels the genetic control of the apple volatilome and its interplay with fruit texture.

PubMed

Farneti, Brian; Di Guardo, Mario; Khomenko, Iuliia; Cappellin, Luca; Biasioli, Franco; Velasco, Riccardo; Costa, Fabrizio

2017-03-01

Fruit quality represents a fundamental factor guiding consumers' preferences. Among apple quality traits, volatile organic compounds and texture features play a major role. Proton Transfer Reaction-Time of Flight-Mass Spectrometry (PTR-ToF-MS), coupled with an artificial chewing device, was used to profile the entire apple volatilome of 162 apple accessions, while the fruit texture was dissected with a TAXT-AED texture analyzer. The array of volatile compounds was classed into seven major groups and used in a genome-wide association analysis carried out with 9142 single nucleotide polymorphisms (SNPs). Marker-trait associations were identified on seven chromosomes co-locating with important candidate genes for aroma, such as MdAAT1 and MdIGS. The integration of volatilome and fruit texture data conducted with a multiple factor analysis unraveled contrasting behavior, underlying opposite regulation of the two fruit quality aspects. The association analysis using the first two principal components identified two QTLs located on chromosomes 10 and 2, respectively. The distinction of the apple accessions on the basis of the allelic configuration of two functional markers, MdPG1 and MdACO1, shed light on the type of interplay existing between fruit texture and the production of volatile organic compounds. © The Author 2017. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Differential Parenting and Risk for Psychopathology: A Monozygotic Twin Difference Approach

PubMed Central

Long, E.C.; Aggen, S. H.; Gardner, C.; Kendler, K. S.

2015-01-01

Purpose Consistent and non-specific associations have been found between parenting style and major depression, anxiety disorders, and externalizing behavior. Although often considered part of twins’ shared environment, parenting can also be conceptualized as non-shared environment. Non-shared environmental influences have important effects on development but are difficult to test and sort out because of the possible confounding effects of gene-environment interactions and evocative gene-environment correlations. The MZ differences approach is one way to analytically investigate non-shared environment. Methods The aim of the present study is to use the MZ differences approach to investigate the relationship between differential parenting among 1,303 twin pairs (mean age 36.69 +/− 8.56) and differences in total symptom counts of major depression (MD), generalized anxiety disorder (GAD), conduct disorder (CD), and anti-social behavior (ASB) during adulthood. Results Although effect sizes tended to be small, a number of results were significantly different from zero. Perceived differences in parental coldness was positively associated with internalizing disorders. Differences in protectiveness were negatively associated with MD, GAD, and ASB. Differences in authoritarianism were positively associated with MD and CD, but negatively associated with ASB. Conclusions Perceived differences in parenting style are associated with differences in MD, GAD, CD, and ASB outcomes in a sample of MZ twins. Despite the lack of a basis for making causal inferences about parenting style and psychopathology, these results are suggestive of such a relationship and show that non-shared environmental influence of parenting does in some cases significantly predict adult psychopathology. PMID:25940788

Treatment of Oral Mucosal Lesions Associated With Overlapping Psychodermatologic Disorders.

PubMed

Alfaris, Sausan; France, Katherine; Sollecito, Thomas P; Stoopler, Eric T

2018-04-01

Delusional infestations are psychodermatologic disorders in which those affected have a false belief they are infested by parasites and/or "growing" inanimate objects from cutaneous surfaces. Individuals with delusional parasitosis (DP) believe parasites, bacteria, worms, mites, or other living organisms are the source of cutaneous symptoms, while those with Morgellons disease (MD) attribute their symptoms to growth of small fibers or inorganic material. In both DP and MD, self-inflicted, non-healing cutaneous lesions caused by scratching at the affected areas to alleviate symptoms are commonly observed. This report describes a case of oral mucosal lesions in a patient demonstrating overlapping symptoms of DP and MD. It is important for oral healthcare providers to recognize oral signs and symptoms that may be associated with psychodermatologic disorders.

Mediodorsal nucleus of the thalamus is critical for the expression of memory of methamphetamine-produced conditioned place preference in rats.

PubMed

Kuo, C-S; Chai, S-C; Chen, H-H

2011-03-31

Methamphetamine (MA) is a powerful and highly addictive psychostimulant. However, the neural substrate mediating MA-induced conditioned effects, an essential part of addiction, remain unclear. The present study investigated the involvement of the anterior cingulate cortex (ACC), the lateral nucleus of amygdala (LNA), and the mediodorsal nucleus of the thalamus (MD) in MA-conditioned place preference (CPP). Rats underwent bilateral radio-frequency lesions of the ACC, LNA, or MD followed by MA CPP training. Lesions of the MD, but not the ACC or LNA, disrupted MA CPP learning. To clarify the role of the MD on the different stages of the MA CPP memory process, bilateral microinfusions of lidocaine into the MD were performed 5 min prior to each conditioning trial, immediately after the conditioning trial, or 5 min before the testing phase. Pretesting, but not pre- or post-conditioning, infusions of lidocaine into the MD impaired MA CPP. Furthermore, a clear preference for the previously conditioned MA paired cues was expressed when the rats were tested again 24 h after infusions of lidocaine. These results are interpreted as indicating that the MD is specifically involved in the memory retrieval process of MA associated memory which suggests the MD could have an important role in relapse in individuals suffering from MA addiction. Copyright © 2011 IBRO. Published by Elsevier Ltd. All rights reserved.

Relationship between visual field progression and baseline refraction in primary open-angle glaucoma.

PubMed

Naito, Tomoko; Yoshikawa, Keiji; Mizoue, Shiro; Nanno, Mami; Kimura, Tairo; Suzumura, Hirotaka; Umeda, Yuzo; Shiraga, Fumio

2016-01-01

To analyze the relationship between visual field (VF) progression and baseline refraction in Japanese patients with primary open-angle glaucoma (POAG) including normal-tension glaucoma. In this retrospective study, the subjects were patients with POAG who had undergone VF tests at least ten times with a Humphrey Field Analyzer (Swedish interactive thresholding algorithm standard, Central 30-2 program). VF progression was defined as a significantly negative value of mean deviation (MD) slope at the final VF test. Multivariate logistic regression models were applied to detect an association between MD slope deterioration and baseline refraction. A total of 156 eyes of 156 patients were included in this analysis. Significant deterioration of MD slope was observed in 70 eyes of 70 patients (44.9%), whereas no significant deterioration was evident in 86 eyes of 86 patients (55.1%). The eyes with VF progression had significantly higher baseline refraction compared to those without apparent VF progression (-1.9±3.8 diopter [D] vs -3.5±3.4 D, P=0.0048) (mean ± standard deviation). When subject eyes were classified into four groups by the level of baseline refraction applying spherical equivalent (SE): no myopia (SE > -1D), mild myopia (-1D ≥ SE > -3D), moderate myopia (-3D ≥ SE > -6D), and severe myopia (-6D ≥ SE), the Cochran-Armitage trend analysis showed a decreasing trend in the proportion of MD slope deterioration with increasing severity of myopia (P=0.0002). The multivariate analysis revealed that baseline refraction (P=0.0108, odds ratio [OR]: 1.13, 95% confidence interval [CI]: 1.03-1.25) and intraocular pressure reduction rate (P=0.0150, OR: 0.97, 95% CI: 0.94-0.99) had a significant association with MD slope deterioration. In the current analysis of Japanese patients with POAG, baseline refraction was a factor significantly associated with MD slope deterioration as well as intraocular pressure reduction rate. When baseline refraction was classified into four groups, MD slope in myopia groups was less deteriorated as compared to those in the emmetropic/hyperopic group.

Mobile App-Based Interventions to Support Diabetes Self-Management: A Systematic Review of Randomized Controlled Trials to Identify Functions Associated with Glycemic Efficacy

PubMed Central

Wu, Yuan; Yao, Xun; Vespasiani, Giacomo; Nicolucci, Antonio; Dong, Yajie; Kwong, Joey; Li, Ling; Sun, Xin

2017-01-01

Background Mobile health apps for diabetes self-management have different functions. However, the efficacy and safety of each function are not well studied, and no classification is available for these functions. Objective The aims of this study were to (1) develop and validate a taxonomy of apps for diabetes self-management, (2) investigate the glycemic efficacy of mobile app-based interventions among adults with diabetes in a systematic review of randomized controlled trials (RCTs), and (3) explore the contribution of different function to the effectiveness of entire app-based interventions using the taxonomy. Methods We developed a 3-axis taxonomy with columns of clinical modules, rows of functional modules and cells of functions with risk assessments. This taxonomy was validated by reviewing and classifying commercially available diabetes apps. We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Chinese Biomedical Literature Database, and ClinicalTrials.gov from January 2007 to May 2016. We included RCTs of adult outpatients with diabetes that compared using mobile app-based interventions with usual care alone. The mean differences (MDs) in hemoglobin A1c (HbA1c) concentrations and risk ratios of adverse events were pooled using a random-effects meta-analysis. After taxonomic classification, we performed exploratory subgroup analyses of the presence or absence of each module across the included app-based interventions. Results Across 12 included trials involving 974 participants, using app-based interventions was associated with a clinically significant reduction of HbA1c (MD 0.48%, 95% CI 0.19%-0.78%) without excess adverse events. Larger HbA1c reductions were noted among patients with type 2 diabetes than those with type 1 diabetes (MD 0.67%, 95% CI 0.30%-1.03% vs MD 0.37%, 95% CI –0.12%-0.86%). Having a complication prevention module in app-based interventions was associated with a greater HbA1c reduction (with complication prevention: MD 1.31%, 95% CI 0.66%-1.96% vs without: MD 0.38%, 95% CI 0.09%-0.67%; intersubgroup P=.01), as was having a structured display (with structured display: MD 0.69%, 95% CI 0.32%-1.06% vs without: MD 0.69%, 95% CI –0.18%-0.53%; intersubgroup P=.03). However, having a clinical decision-making function was not associated with a larger HbA1c reduction (with clinical decision making: MD 0.19%, 95% CI –0.24%-0.63% vs without: MD 0.61%, 95% CI 0.27%-0.95%; intersubgroup P=.14). Conclusions The use of mobile app-based interventions yields a clinically significant HbA1c reduction among adult outpatients with diabetes, especially among those with type 2 diabetes. Our study suggests that the clinical decision-making function needs further improvement and evaluation before being added to apps. PMID:28292740

77 FR 23166 - Airworthiness Directives; The Boeing Company Airplanes

Federal Register 2010, 2011, 2012, 2013, 2014

2012-04-18

... Aircraft System Component (JASC)/Air Transport Association (ATA) of America Code 28, Fuel. (e) Unsafe...-30F, MD-11, and MD-11F airplanes. This proposed AD was prompted by fuel system reviews conducted by... for fuel tank systems. As a result of those findings, we issued a regulation titled ``Transport...

New Insights into the Comorbidity between ADHD and Major Depression in Adolescent and Young Adult Females

ERIC Educational Resources Information Center

Biederman, Joseph; Ball, Sarah W.; Monuteaux, Michael C.; Mick, Eric; Spencer, Thomas J.; McCreary, Michelle; Cote, Michelle; Faraone, Stephen V.

2008-01-01

The association between attention-deficit/hyperactivity disorder (ADHD) and major depression (MD) in adolescent and young adult females is evaluated. Findings indicate that MD emerging in the context of ADHD is an impairing and severe comorbidity that needs to be considered further clinically and scientifically.

Prehospital Air Medical Plasma (PAMPer) Trial

DTIC Science & Technology

2015-07-01

Defense, Washington Headquarters Services, Directorate for Information Operations and Reports (0704-0188), 1215 Jefferson Davis Highway, Suite 1204...Clifford Calloway MD, PhD, Associate Professor of Emergency Medicine, University of Pittsburgh Mark Yazer, MD, Medical Director Centralized...Transfusion Service; University of Pittsburgh Barbara Early, RN, BSN, CCRC, MACRO CRC Director , University of Pittsburgh C. Investigators at other

Novel plasmid conferring kanamycin and tetracycline resistance in turkey-derived Campylobacter jejuni strain 11601MD

USDA-ARS?s Scientific Manuscript database

In Campylobacter spp., resistance to the antibiotics kanamycin and tetracycline is frequently associated with plasmid-borne genes. However, relatively few plasmids of Campylobacter jejuni have been fully characterized to date. A novel plasmid (p11601MD; 44,095 bp.) harboring tet(O) was identified in...

Quantum coherence generating power, maximally abelian subalgebras, and Grassmannian geometry

NASA Astrophysics Data System (ADS)

Zanardi, Paolo; Campos Venuti, Lorenzo

2018-01-01

We establish a direct connection between the power of a unitary map in d-dimensions (d < ∞) to generate quantum coherence and the geometry of the set Md of maximally abelian subalgebras (of the quantum system full operator algebra). This set can be seen as a topologically non-trivial subset of the Grassmannian over linear operators. The natural distance over the Grassmannian induces a metric structure on Md, which quantifies the lack of commutativity between the pairs of subalgebras. Given a maximally abelian subalgebra, one can define, on physical grounds, an associated measure of quantum coherence. We show that the average quantum coherence generated by a unitary map acting on a uniform ensemble of quantum states in the algebra (the so-called coherence generating power of the map) is proportional to the distance between a pair of maximally abelian subalgebras in Md connected by the unitary transformation itself. By embedding the Grassmannian into a projective space, one can pull-back the standard Fubini-Study metric on Md and define in this way novel geometrical measures of quantum coherence generating power. We also briefly discuss the associated differential metric structures.

Deviant white matter structure in adults with attention-deficit/hyperactivity disorder points to aberrant myelination and affects neuropsychological performance.

PubMed

Onnink, A Marten H; Zwiers, Marcel P; Hoogman, Martine; Mostert, Jeanette C; Dammers, Janneke; Kan, Cornelis C; Vasquez, Alejandro Arias; Schene, Aart H; Buitelaar, Jan; Franke, Barbara

2015-12-03

Attention-deficit/hyperactivity disorder (ADHD) in childhood is characterized by gray and white matter abnormalities in several brain areas. Considerably less is known about white matter microstructure in adults with ADHD and its relation with clinical symptoms and cognitive performance. In 107 adult ADHD patients and 109 gender-, age- and IQ-matched controls, we used diffusion tensor imaging (DTI) with tract-based spatial statistics (TBSS) to investigate whole-skeleton changes of fractional anisotropy (FA) and mean, axial, and radial diffusivity (MD, AD, RD). Additionally, we studied the relation of FA and MD values with symptom severity and cognitive performance on tasks measuring working memory, attention, inhibition, and delay discounting. In comparison to controls, participants with ADHD showed reduced FA in corpus callosum, bilateral corona radiata, and thalamic radiation. Higher MD and RD were found in overlapping and even more widespread areas in both hemispheres, also encompassing internal and external capsule, sagittal stratum, fornix, and superior lateral fasciculus. Values of FA and MD were not associated with symptom severity. However, within some white matter clusters that distinguished patients from controls, worse inhibition performance was associated with reduced FA and more impulsive decision making was associated with increased MD. This study shows widespread differences in white matter integrity between adults with persistent ADHD and healthy individuals. Changes in RD suggest aberrant myelination as a pathophysiological factor in persistent ADHD. The microstructural differences in adult ADHD may contribute to poor inhibition and greater impulsivity but appear to be independent of disease severity. Copyright © 2015. Published by Elsevier Inc.

Mediterranean Diet and Changes in Sleep Duration and Indicators of Sleep Quality in Older Adults.

PubMed

Campanini, Marcela Z; Guallar-Castillón, Pilar; Rodríguez-Artalejo, Fernando; Lopez-Garcia, Esther

2017-03-01

To examine the association between adherence to a Mediterranean diet (MD) and changes in sleep duration and sleep quality in older adults. We used data from 1596 participants in the Seniors-ENRICA cohort aged ≥ 60 years. MD was evaluated in 2012 with the Mediterranean Diet Adherence Screener (MEDAS) score. Sleep duration (h) and indicators of poor sleep quality were assessed both in 2012 and 2015. Analyses were adjusted for sociodemographic, lifestyle and morbidity variables, and for sleep duration and the number of poor sleep indicators at baseline. Over a median follow-up of 2.8 years, 12.2% of individuals increased and 8.8% decreased their sleep duration by ≥2 h/night. Compared with those in the lowest tertile of adherence to the MD in 2012, those in the highest tertile showed both a lower risk of a ≥2 h/night increase in sleep duration (odds ratio [OR]: 0.54, 95% confidence interval [CI] 0.34-0.85, p-trend = .01) and of a ≥2 h/night decrease (OR: 0.58, 95% CI 0.35-0.95, p-trend = 0.02) from 2012 to 2015. Being in the highest tertile of MD in 2012 was also associated with lower risk of poor sleep quality at follow-up, the OR (95% CI) for having 2-3 indicators of poor sleep was 0.70 (0.51-0.97) and for ≥4 indicators was 0.68 (0.47-0.99, p-trend = .04). High adherence to the MD was also associated with 56% lower odds of having large changes in sleep duration and ≥2 indicators of poor sleep quality simultaneously (OR: 0.44, 95% CI 0.29-0.68, p trend < .001). Adherence to a MD pattern was associated with lower risk of changes in sleep duration and with better sleep quality in older adults. © Sleep Research Society 2016. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

MD-2 is required for disulfide HMGB1–dependent TLR4 signaling

PubMed Central

Wang, Haichao; Ju, Zhongliang; Ragab, Ahmed A.; Lundbäck, Peter; Long, Wei; Valdes-Ferrer, Sergio I.; He, Mingzhu; Pribis, John P.; Li, Jianhua; Lu, Ben; Gero, Domokos; Szabo, Csaba; Antoine, Daniel J.; Harris, Helena E.; Golenbock, Doug T.; Meng, Jianmin; Roth, Jesse; Chavan, Sangeeta S.; Andersson, Ulf; Billiar, Timothy R.; Al-Abed, Yousef

2015-01-01

Innate immune receptors for pathogen- and damage-associated molecular patterns (PAMPs and DAMPs) orchestrate inflammatory responses to infection and injury. Secreted by activated immune cells or passively released by damaged cells, HMGB1 is subjected to redox modification that distinctly influences its extracellular functions. Previously, it was unknown how the TLR4 signalosome distinguished between HMGB1 isoforms. Here we demonstrate that the extracellular TLR4 adaptor, myeloid differentiation factor 2 (MD-2), binds specifically to the cytokine-inducing disulfide isoform of HMGB1, to the exclusion of other isoforms. Using MD-2–deficient mice, as well as MD-2 silencing in macrophages, we show a requirement for HMGB1-dependent TLR4 signaling. By screening HMGB1 peptide libraries, we identified a tetramer (FSSE, designated P5779) as a specific MD-2 antagonist preventing MD-2–HMGB1 interaction and TLR4 signaling. P5779 does not interfere with lipopolysaccharide-induced cytokine/chemokine production, thus preserving PAMP-mediated TLR4–MD-2 responses. Furthermore, P5779 can protect mice against hepatic ischemia/reperfusion injury, chemical toxicity, and sepsis. These findings reveal a novel mechanism by which innate systems selectively recognize specific HMGB1 isoforms. The results may direct toward strategies aimed at attenuating DAMP-mediated inflammation while preserving antimicrobial immune responsiveness. PMID:25559892

The impact of altruistic behaviors for children and grandchildren on major depression among parents and grandparents in the United States: a prospective study.

PubMed

Fujiwara, Takeo; Lee, Cynthia K

2008-04-01

Although previous studies have suggested that altruistic behaviors are beneficial for mental health, few studies have examined the impact of altruistic behaviors for children and grandchildren (ABC) on the mental health of parents and grandparents using a longitudinal study design. It is needed to test whether paternal and maternal ABC prevent the development of mental health problems in later life. The association between three types of ABC (informal assistance, emotional support, financial support) in 1995-1996 and major depression (MD) in 1998 were examined using a nationally representative longitudinal study in the US (the National Survey of Midlife Development in the United States (MIDUS) in 1995-1996 and the MIDUS Psychological Experience Follow-Up study in 1998, N=724). Moderate amounts of informal assistance and financial support by fathers/grandfathers, but not by mothers/grandmothers, showed a protective effect on MD 2-3 years later, holding parents/grandparents and children covariates. Emotional support was not associated with MD for both sexes after adjusting for covariates. The sample size in this study was relatively small and not all possible covariates were adjusted. The effect of children's/grandchildren's responses for ABC on the development of parental MD was not examined. The impact of ABC on MD in 2-3 years varies depending on the types of ABC and the sex of parents/grandparents. Moderate amounts of informal assistance and financial support had a protective effect on MD in later life among fathers/grandfathers, but not among mothers/grandmothers.

In vivo imaging of saccular hydrops in humans reflects sensorineural hearing loss rather than Meniere's disease symptoms.

PubMed

Attyé, Arnaud; Eliezer, Michael; Medici, Maud; Tropres, Irène; Dumas, Georges; Krainik, Alexandre; Schmerber, Sébastien

2018-07-01

A case-controlled imaging study demonstrated that saccular hydrops was specific to Meniere's disease (MD), but only present in a subset of patients. Here, we compared patients with definite MD, vertigo and sensorineural hearing loss (SNHL) to elucidate the relationship between saccular hydrops and extent of SNHL. In this prospective study, we performed 3D-FLAIR sequences between 4.5 and 5.5 h after contrast media injection in patients with MD (n=20), SNHL (n=20), vertigo (n=20) and 30 healthy subjects. Two radiologists independently graded saccular hydrops. ROC analysis was performed to determine the hearing loss threshold to differentiate patients with saccular hydrops. Saccular hydrops was found in 11 of 20 MD patients, 10 of 20 SNHL patients and in none of the vertigo patients and healthy subjects. In SNHL patients, 45 dB was the threshold above which there was a significant association with saccular hydrops, with sensitivity of 100 % and specificity of 90 %. In MD patients, 40 dB was the threshold above which there was a significant association with saccular hydrops, with sensitivity of 100 % and specificity of 44 %. Our results indicate saccular hydrops as a feature of worse than moderate SNHL rather than MD itself. • MRI helps clinicians to assess patients with isolated low-tone sensorineural hearing loss. • Saccular hydrops correlates with sensorineural hearing loss at levels above 40 dB. • Vertigo patients without sensorineural hearing loss do not have saccular hydrops. • Saccular hydrops is described in patients without clinical diagnosis of Meniere's disease.

Atmospheric Pressure and Onset of Episodes of Menière's Disease - A Repeated Measures Study.

PubMed

Gürkov, Robert; Strobl, Ralf; Heinlin, Nina; Krause, Eike; Olzowy, Bernhard; Koppe, Christina; Grill, Eva

2016-01-01

External changes of air pressure are transmitted to the middle and inner ear and may be used therapeutically in Menière's disease, one of the most common vertigo disorders. We analyzed the possible relationship of atmospheric pressure and other meteorological parameters with the onset of MD vertigo episodes in order to determine whether atmospheric pressure changes play a role in the occurrence of MD episodes. Patients of a tertiary outpatient dizziness clinic diagnosed with MD were asked to keep a daily vertigo diary to document MD episodes (2004-2009). Local air pressure, absolute temperature and dew point temperature were acquired on an hourly basis. Change in meteorological parameters was conceptualized as the maximum difference in a 24 hour time frame preceding each day. Effects were estimated using additive mixed models with a random participant effect. We included lagged air parameters, age, sex, weekday and season in the model. A total of 56 persons (59% female) with mean age 54 years were included. Mean follow-up time was 267 days. Persons experienced on average 10.3 episodes during the observation period (median 8). Age and change in air pressure were significantly associated with vertigo onset risk (Odds Ratio = 0.979 and 1.010). We could not show an effect of sex, weekday, season, air temperature, and dew point temperature. Change in air pressure was significantly associated with onset of MD episodes, suggesting a potential triggering mechanism in the inner ear. MD patients may possibly use air pressure changes as an early warning system for vertigo attacks in the future.

Genome-wide Mechanosensitive MicroRNA (MechanomiR) Screen Uncovers Dysregulation of Their Regulatory Networks in the mdm Mouse Model of Muscular Dystrophy*

PubMed Central

Mohamed, Junaith S.; Hajira, Ameena; Lopez, Michael A.; Boriek, Aladin M.

2015-01-01

Muscular dystrophies (MDs) are a heterogeneous group of genetic and neuromuscular disorders, which result in severe loss of motor ability and skeletal muscle mass and function. Aberrant mechanotransduction and dysregulated-microRNA pathways are often associated with the progression of MD. Here, we hypothesized that dysregulation of mechanosensitive microRNAs (mechanomiRs) in dystrophic skeletal muscle plays a major role in the progression of MD. To test our hypothesis, we performed a genome-wide expression profile of anisotropically regulated mechanomiRs and bioinformatically analyzed their target gene networks. We assessed their functional roles in the advancement of MD using diaphragm muscles from mdm (MD with myositis) mice, an animal model of human tibial MD (titinopathy), and their wild-type littermates. We were able to show that ex vivo anisotropic mechanical stretch significantly alters the miRNA expression profile in diaphragm muscles from WT and mdm mice; as a result, some of the genes associated with MDs are dysregulated in mdm mice due to differential regulation of a distinct set of mechanomiRs. Interestingly, we found a contrasting expression pattern of the highly expressed let-7 family mechanomiRs, let-7e-5p and miR-98–5p, and their target genes associated with the extracellular matrix and TGF-β pathways, respectively, between WT and mdm mice. Gain- and loss-of-function analysis of let-7e-5p in myocytes isolated from the diaphragms of WT and mdm mice confirmed Col1a1, Col1a2, Col3a1, Col24a1, Col27a1, Itga1, Itga4, Scd1, and Thbs1 as target genes of let-7e-5p. Furthermore, we found that miR-98 negatively regulates myoblast differentiation. Our study therefore introduces additional biological players in the regulation of skeletal muscle structure and myogenesis that may contribute to unexplained disorders of MD. PMID:26272747

Energy availability and the female athlete triad in elite endurance athletes.

PubMed

Melin, A; Tornberg, Å B; Skouby, S; Møller, S S; Sundgot-Borgen, J; Faber, J; Sidelmann, J J; Aziz, M; Sjödin, A

2015-10-01

The female athlete triad (Triad), links low energy availability (EA), with menstrual dysfunction (MD), and impaired bone health. The aims of this study were to examine associations between EA/MD and energy metabolism and the prevalence of Triad-associated conditions in endurance athletes. Forty women [26.2 ± 5.5 years, body mass index (BMI) 20.6 ± 2.0 kg/m(2), body fat 20.0 ± 3.0%], exercising 11.4 ± 4.5 h/week, were recruited from national teams and competitive clubs. Protocol included gynecological examination; assessment of bone health; indirect respiratory calorimetry; diet and exercise measured 7 days to assess EA; eating disorder (ED) examination; blood analysis. Subjects with low/reduced EA (< 45 kcal/kg FFM/day), had lower resting metabolic rate (RMR) compared with those with optimal EA [28.4 ± 2.0 kcal/kg fat-free mass (FFM)/day vs 30.5 ± 2.2 kcal/kg FFM/day, P < 0.01], as did subjects with MD compared with eumenorrheic subjects (28.6 ± 2.4 kcal/kg FFM/day vs 30.2 ± 1.8 kcal/kg FFM/day, P < 0.05). 63% had low/reduced EA, 25% ED, 60% MD, 45% impaired bone health, and 23% had all three Triad conditions. 53% had low RMR, 25% hypercholesterolemia, and 38% hypoglycemia. Conclusively, athletes with low/reduced EA and/or MD had lowered RMR. Triad-associated conditions were common in this group of athletes, despite a normal BMI range. The high prevalence of ED, MD, and impaired bone health emphasizes the importance of prevention, early detection, and treatment of energy deficiency. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

E9-Im9 Colicin DNase−Immunity Protein Biomolecular Association in Water: A Multiple-Copy and Accelerated Molecular Dynamics Simulation Study

PubMed Central

2008-01-01

Protein−protein transient and dynamic interactions underlie all biological processes. The molecular dynamics (MD) of the E9 colicin DNase protein, its Im9 inhibitor protein, and their E9-Im9 recognition complex are investigated by combining multiple-copy (MC) MD and accelerated MD (aMD) explicit-solvent simulation approaches, after validation with crystalline-phase and solution experiments. Im9 shows higher flexibility than its E9 counterpart. Im9 displays a significant reduction of backbone flexibility and a remarkable increase in motional correlation upon E9 association. Im9 loops 23−31 and 54−64 open with respect to the E9-Im9 X-ray structure and show high conformational diversity. Upon association a large fraction (∼20 nm2) of E9 and Im9 protein surfaces become inaccessible to water. Numerous salt bridges transiently occurring throughout our six 50 ns long MC-MD simulations are not present in the X-ray model. Among these Im9 Glu31−E9 Arg96 and Im9 Glu41−Lys89 involve interface interactions. Through the use of 10 ns of Im9 aMD simulation, we reconcile the largest thermodynamic impact measured for Asp51Ala mutation with Im9 structure and dynamics. Lys57 acts as an essential molecular switch to shift Im9 surface loop towards an ideal configuration for E9 inhibition. This is achieved by switching Asp60−Lys57 and Asp62−Lys57 hydrogen bonds to Asp51−Lys57 salt bridge. E9-Im9 recognition involves shifts of conformational distributions, reorganization of intramolecular hydrogen bond patterns, and formation of new inter- and intramolecular interactions. The description of key transient biological interactions can be significantly enriched by the dynamic and atomic-level information provided by computer simulations. PMID:19053689

Properties of pattern standard deviation in open-angle glaucoma patients with hemi-optic neuropathy and bi-optic neuropathy.

PubMed

Heo, Dong Won; Kim, Kyoung Nam; Lee, Min Woo; Lee, Sung Bok; Kim, Chang-Sik

2017-01-01

To evaluate the properties of pattern standard deviation (PSD) according to localization of the glaucomatous optic neuropathy. We enrolled 242 eyes of 242 patients with primary open-angle glaucoma, with a best-corrected visual acuity ≥ 20/25, and no media opacity. Patients were examined via dilated fundus photography, spectral-domain optical coherence tomography, and Humphrey visual field examination, and divided into those with hemi-optic neuropathy (superior or inferior) and bi-optic neuropathy (both superior and inferior). We assessed the relationship between mean deviation (MD) and PSD. Using broken stick regression analysis, the tipping point was identified, i.e., the point at which MD became significantly associated with a paradoxical reversal of PSD. In 91 patients with hemi-optic neuropathy, PSD showed a strong correlation with MD (r = -0.973, β = -0.965, p < 0.001). The difference between MD and PSD ("-MD-PSD") was constant (mean, -0.32 dB; 95% confidence interval, -2.48~1.84 dB) regardless of visual field defect severity. However, in 151 patients with bi-optic neuropathy, a negative correlation was evident between "-MD-PSD" and MD (r2 = 0.907, p < 0.001). Overall, the MD tipping point was -14.0 dB, which was close to approximately 50% damage of the entire visual field (p < 0.001). Although a false decrease of PSD usually begins at approximately 50% visual field damage, in patients with hemi-optic neuropathy, the PSD shows no paradoxical decrease and shows a linear correlation with MD.

Factors that influence standard automated perimetry test results in glaucoma: test reliability, technician experience, time of day, and season.

PubMed

Junoy Montolio, Francisco G; Wesselink, Christiaan; Gordijn, Marijke; Jansonius, Nomdo M

2012-10-09

To determine the influence of several factors on standard automated perimetry test results in glaucoma. Longitudinal Humphrey field analyzer 30-2 Swedish interactive threshold algorithm data from 160 eyes of 160 glaucoma patients were used. The influence of technician experience, time of day, and season on the mean deviation (MD) was determined by performing linear regression analysis of MD against time on a series of visual fields and subsequently performing a multiple linear regression analysis with the MD residuals as dependent variable and the factors mentioned above as independent variables. Analyses were performed with and without adjustment for the test reliability (fixation losses and false-positive and false-negative answers) and with and without stratification according to disease stage (baseline MD). Mean follow-up was 9.4 years, with on average 10.8 tests per patient. Technician experience, time of day, and season were associated with the MD. Approximately 0.2 dB lower MD values were found for inexperienced technicians (P < 0.001), tests performed after lunch (P < 0.001), and tests performed in the summer or autumn (P < 0.001). The effects of time of day and season appeared to depend on disease stage. Independent of these effects, the percentage of false-positive answers strongly influenced the MD with a 1 dB increase in MD per 10% increase in false-positive answers. Technician experience, time of day, season, and the percentage of false-positive answers have a significant influence on the MD of standard automated perimetry.

Association of a MAOA gene variant with generalized anxiety disorder, but not with panic disorder or major depression.

PubMed

Tadic, A; Rujescu, D; Szegedi, A; Giegling, I; Singer, P; Möller, H-J; Dahmen, N

2003-02-01

This study was conducted to detect a possible association of a T941G single nucleotide polymorphism (SNP) in the monoamine oxidase A (MAOA) gene with generalized anxiety disorder (GAD), panic disorder (PD), or major depression (MD). Fifty GAD patients (34 females and 16 males), 38 PD patients (21 females and 17 males), and 108 MD patients (80 females and 28 males) were included. The comparison group consisted of 276 (132 females and 144 males) unrelated healthy individuals. The 941T allele was over-represented in patients suffering from GAD (chi(2) = 6.757; df = 1; P < 0.01, not corrected for multiple testing) when compared to healthy volunteers. No association was observed in MD or PD. This is the first study specifically analyzing the MAOA G941T polymorphism in GAD and thus needs to be replicated in an independent sample. However, the results are in line with previous data suggesting an association between the MAOA locus and regulation of complex human behavior. Copyright 2003 Wiley-Liss, Inc.

Epigenetic regulation of MdMYB1 is associated with paper bagging-induced red pigmentation of apples.

PubMed

Bai, Songling; Tuan, Pham Anh; Saito, Takanori; Honda, Chikako; Hatsuyama, Yoshimichi; Ito, Akiko; Moriguchi, Takaya

2016-09-01

Paper-bagging treatment can transform non-transcribed MdMYB1 - 2 and MdMYB1 - 3 alleles into transcribed alleles through epigenetic regulations, resulting in the red pigmentation of a normally non-red apple cultivar 'Mutsu.' Anthocyanin biosynthesis in apples is regulated by MdMYB1/A/10, an R2R3-Type MYB gene. 'Mutsu,' a triploid apple cultivar harboring non-transcribed MdMYB1-2 and MdMYB1-3 alleles, retains green skin color under field conditions. However, it can show red/pink pigmentation under natural or artificial ultraviolet-B (UV-B) light exposure after paper-bagging and bag removal treatment. In the present study, we found that in 'Mutsu,' paper bagging-induced red pigmentation was due to the activation of non-transcribed MdMYB1-2/-3 alleles, which triggered the expression of downstream anthocyanin biosynthesis genes in a UV-B-dependent manner. By monitoring the epigenetic changes during UV-B-induced pigmentation, no significant differences in DNA methylation and histone modifications in the 5' upstream region of MdMYB1-2/-3 were recorded between the UV-B-treated fruit skin (red) and the fruit skin treated only by white light (green). In contrast, bag treatment lowered the DNA methylation in this region of MdMYB1-2/-3 alleles. Similarly, higher levels of histone H3 acetylation and trimethylation of H3 tail at lysine 4, and lower level of trimethylation of H3 tail at lysine 27 were observed in the 5' upstream region of MdMYB1-2/-3 in the skin of the fruit immediately after bag removal. These results suggest that bagging treatment can induce epigenetic changes, facilitating the binding of trans factor(s) to MdMYB1-2/-3 alleles, resulting in the activation of these MYBs after bag removal.

Mediterranean Diet and Prevention of Chronic Diseases

PubMed Central

Romagnolo, Donato F.; Selmin, Ornella I.

2017-01-01

A large body of research data suggests that traditional dietary habits and lifestyle unique to the Mediterranean region (Mediterranean diet, MD) lower the incidence of chronic diseases and improve longevity. These data contrast with troubling statistics in the United States and other high income countries pointing to an increase in the incidence of chronic diseases and the projected explosion in cost of medical care associated with an aging population. In 2013, the MD was inscribed by UNESCO in the “Representative List of the Intangible Cultural Heritage of Humanity.” The 2015–2020 Dietary Guidelines for Americans included the MD as a healthy dietary pattern. Therefore, specific objectives of this article are to provide an overview of the nutritional basis of this healthful diet, its metabolic benefits, and its role in multiple aspects of disease prevention and healthy aging. Whereas recommendations about the MD often focus on specific foods or bioactive compounds, we suggest that the eating pattern as a whole likely contributes to the health promoting effects of the MD. PMID:29051674

Giant Meckel’s diverticulum: An exceptional cause of intestinal obstruction

PubMed Central

Akbulut, Sami; Yagmur, Yusuf

2014-01-01

Meckel’s diverticulum (MD) results from incomplete involution of the proximal portion of the vitelline (also known as the omphalomesenteric) duct during weeks 5-7 of foetal development. Although MD is the most commonly diagnosed congenital gastrointestinal anomaly, it is estimated to affect only 2% of the population worldwide. Most cases are asymptomatic, and diagnosis is often made following investigation of unexplained gastrointestinal bleeding, perforation, inflammation or obstruction that prompt clinic presentation. While MD range in size from 1-10 cm, cases of giant MD (≥ 5 cm) are relatively rare and associated with more severe forms of the complications, especially for obstruction. Herein, we report a case of giant MD with secondary small bowel obstruction in an adult male that was successfully managed by surgical resection and anastomosis created with endoscopic stapler device (80 mm, endo-GIA stapler). Patient was discharged on post-operative day 6 without any complications. Histopathologic examination indicated Meckel’s diverticulitis without gastric or pancreatic metaplasia. PMID:24672650

Molecular dynamics coupled with a virtual system for effective conformational sampling.

PubMed

Hayami, Tomonori; Kasahara, Kota; Nakamura, Haruki; Higo, Junichi

2018-07-15

An enhanced conformational sampling method is proposed: virtual-system coupled canonical molecular dynamics (VcMD). Although VcMD enhances sampling along a reaction coordinate, this method is free from estimation of a canonical distribution function along the reaction coordinate. This method introduces a virtual system that does not necessarily obey a physical law. To enhance sampling the virtual system couples with a molecular system to be studied. Resultant snapshots produce a canonical ensemble. This method was applied to a system consisting of two short peptides in an explicit solvent. Conventional molecular dynamics simulation, which is ten times longer than VcMD, was performed along with adaptive umbrella sampling. Free-energy landscapes computed from the three simulations mutually converged well. The VcMD provided quicker association/dissociation motions of peptides than the conventional molecular dynamics did. The VcMD method is applicable to various complicated systems because of its methodological simplicity. © 2018 Wiley Periodicals, Inc. © 2018 Wiley Periodicals, Inc.

Adherence to the Mediterranean Diet and Circulating Levels of Sirtuin 4 in Obese Patients: A Novel Association

PubMed Central

Barrea, Luigi; Somma, Carolina Di; Muscogiuri, Giovanna; Macchia, Paolo Emidio; Falco, Andrea; Colao, Annamaria; Savastano, Silvia

2017-01-01

Purpose This study was aimed at evaluating sirtuin 4 (Sirt4) levels in obese individuals, in relation to their adherence to the Mediterranean diet (MD), a healthy dietary pattern characterized by high antioxidant capacity, and markers of visceral fat storage. Subjects/Methods Forty-three obese patients (44% males; BMI: 36.7–58.8 kg/m2) were consecutively included. PREvención con DIeta MEDiterránea (PREDIMED) and the 7-day food records were used to assess the adherence to MD and dietary pattern, respectively. Visceral adiposity index (VAI) was calculated. Sirt4 levels were detected by ELISA method. Results The majority of the obese participants (62.8%) had an average adherence to MD. Compared with average adherers, low adherers had higher BMI, energy intake, and percentage of energy from lipids, mainly saturated fat and polyunsaturated fatty acids (PUFA), and lower Sirt4 levels. After adjusting for BMI, Sirt4 levels remained negatively correlated with VAI. After adjusting for total energy intake, Sirt4 levels remained negatively associated with PREDIMED and consumption of n-3 PUFA, vitamins C and E. The threshold value of PREDIMED predicting the lowest decrease in Sirt4 levels was found at a score of 6. Conclusions Less reduced Sirt4 levels in obese patients adhering to MD suggest a further aspect of the antioxidant advantage of MD. PMID:28706576

Adherence to the Mediterranean Diet and Circulating Levels of Sirtuin 4 in Obese Patients: A Novel Association.

PubMed

Barrea, Luigi; Tarantino, Giovanni; Somma, Carolina Di; Muscogiuri, Giovanna; Macchia, Paolo Emidio; Falco, Andrea; Colao, Annamaria; Savastano, Silvia

2017-01-01

This study was aimed at evaluating sirtuin 4 (Sirt4) levels in obese individuals, in relation to their adherence to the Mediterranean diet (MD), a healthy dietary pattern characterized by high antioxidant capacity, and markers of visceral fat storage. Forty-three obese patients (44% males; BMI: 36.7-58.8 kg/m 2 ) were consecutively included. PREvención con DIeta MEDiterránea (PREDIMED) and the 7-day food records were used to assess the adherence to MD and dietary pattern, respectively. Visceral adiposity index (VAI) was calculated. Sirt4 levels were detected by ELISA method. The majority of the obese participants (62.8%) had an average adherence to MD. Compared with average adherers, low adherers had higher BMI, energy intake, and percentage of energy from lipids, mainly saturated fat and polyunsaturated fatty acids (PUFA), and lower Sirt4 levels. After adjusting for BMI, Sirt4 levels remained negatively correlated with VAI. After adjusting for total energy intake, Sirt4 levels remained negatively associated with PREDIMED and consumption of n-3 PUFA, vitamins C and E. The threshold value of PREDIMED predicting the lowest decrease in Sirt4 levels was found at a score of 6. Less reduced Sirt4 levels in obese patients adhering to MD suggest a further aspect of the antioxidant advantage of MD.

Soft tissue changes following extraction vs. nonextraction orthodontic fixed appliance treatment: a systematic review and meta-analysis.

PubMed

Konstantonis, Dimitrios; Vasileiou, Dimitrios; Papageorgiou, Spyridon N; Eliades, Theodore

2018-06-01

The aim of this systematic review was to assess the effect of systematic extraction protocols during orthodontic fixed appliance treatment on the soft tissue profile of human patients. Nine databases were searched until December 2016 for controlled clinical studies including premolar extraction or nonextraction treatment. After elimination of duplicate studies, data extraction, and risk-of-bias assessment according to the Cochrane guidelines, random-effects meta-analyses of mean differences (MD) or standardized mean differences (SMD) and their 95% CIs were performed, followed by subgroup, meta-regression, and sensitivity analyses. Extraction treatment was associated with increased lower lip retraction (24 studies; 1,456 patients; MD = 1.96 mm), upper lip retraction (21 studies; 1,149 patients; MD = 1.26 mm), nasolabial angle (21 studies; 1,089 patients; MD = 4.21°), soft-tissue profile convexity (six studies; 408 patients; MD = 1.24°), and profile pleasantness (three studies; 249 patients; SMD = 0.41). Patient age, extraction protocol, and amount of upper incisor retraction during treatment were significantly associated with the observed extraction effects, while the quality of evidence was very low in all cases due to risk of bias, baseline confounding, inconsistency, and imprecision. Although tooth extractions seem to affect patient profile, existing studies are heterogenous and no consistent predictions of profile response can be made. © 2018 Eur J Oral Sci.

[Dietetic factors associated with prostate cancer: protective effects of Mediterranean diet].

PubMed

Ferrís-Tortajada, J; Berbel-Tornero, O; García-Castell, J; Ortega-García, J A; López-Andreu, J A

2012-04-01

To review diet risk factors (RF) implied, more or less evidence-based, in the etiopathology of prostate carcinoma (PC), especially those that characterize the traditional Mediterranean diet (MD). Literature review of PC related diet RF in MedLine, CancerLit, Science Citation Index y Embase. Search profiles were "Dietetic Factors/Nutritional Factors/Mediterranean Diet/Primary Prevention", and "Prostate Cancer". Diet RF are associated with 35% of cancer mortality and 10-12% of PC mortality. The main diet RF, implied in the development of PC but with a protective effect, which are considered characteristic of MD are: high daily ingestion of vegetarian products (cereals, legumes, dried and fresh fruits, tubers, vegetables..); olive oil as main lipid source; low intake of animal saturated fat, processed red meat, milk and dairy products; regular consumption of small fish; and low alcohol intake (wine with meals). The MD contains many phytoactive compounds (lycopene, lupeol, quercetin, genistein, carnosol, resveratrol, catechins, vitamins..) with PC protective effects. Diet RF have a role on prostatic carcinogenesis. Further epidemiologic studies with better designs are needed to clarify PC related diet RF. PC risk is reduced in persons on MD compared with those on Western diet. The preventive effect of MD is due to the great number and quality of phytochemicals with antioxidant and antinflammatory properties that contains. Copyright © 2011 AEU. Published by Elsevier Espana. All rights reserved.

Association between central obesity and circadian parameters of blood pressure from the korean ambulatory blood pressure monitoring registry: Kor-ABP registry.

PubMed

Kang, In Sook; Pyun, Wook Bum; Shin, Jinho; Kim, Ju Han; Kim, Soon Gil; Shin, Gil Ja

2013-10-01

Central obesity has been reported as a risk for atherosclerosis and metabolic syndrome. The influence of central obesity on diurnal blood pressure (BP) has not been established. In this study, we investigated the influence of central obesity on the circadian parameters of BP by 24 hr ambulatory BP monitoring. Total 1,290 subjects were enrolled from the Korean Ambulatory BP registry. Central obesity was defined as having a waist circumference≥90 cm in males and ≥85 cm in females. The central-obese group had higher daytime systolic BP (SBP), nighttime SBP and diastolic BP (DBP) than the non-obese group (all, P<0.001). There were no differences in nocturnal dipping (ND) patterns between the groups. Female participants showed a higher BP mean difference (MD) than male participants with concerns of central obesity (daytime SBP MD 5.28 vs 4.27, nighttime SBP MD 6.48 vs 2.72) and wider pulse pressure (PP). Central obesity within the elderly (≥65 yr) also showed a higher BP MD than within the younger group (daytime SBP MD 8.23 vs 3.87, daytime DBP 4.10 vs 1.59). In conclusion, central obesity has no influence on nocturnal dipping patterns. However, higher SBP and wider PP are associated with central obesity, which is accentuated in women.

GEMS and New Pre-Accretionally Irradiated RELICT Grains in Interplanetary Dust - The Plot Thickens

NASA Astrophysics Data System (ADS)

Bradley, J.

1995-09-01

The hypothesis that GEMS (glass with embedded metal and sulfides) in interplanetary dust particles (IDPs) might be the long-sought interstellar silicate grains is undergoing close scrutiny [1-3]. GEMS are proposed to be interstellar because: (a) they are abundant in cometary IDPs; (b) they were irradiated prior to incorporation into IDPs; (c) both their size distribution and Oamorphous silicate" microstructures are consistent with those of interstellar silicates; (d) they contain nanometer-sized (superparamagnetic) alpha-iron inclusions, which provides a simple explanation for the observed interstellar grain alignment and polarization [4,5]. Challenges to the GEMS hypothesis include the following: (a) GEMS may have formed and been irradiated in the solar nebula rather than a presolar interstellar environment; (b) non-solar isotope abundances have yet to be measured in GEMS; (c) the irradiation regime required to produce the observed effects in GEMS might be incompatible with the interstellar medium; (b) relationships between GEMS and carbon (e.g. core/mantle) need clarification; (c) major element abundances in GEMS should be consistent with observed interstellar gas phase depletions [2,3]. GEMS may indeed have formed in the solar nebula, in which case they would be the oldest known solar nebula solids [2]. An interstellar origin for GEMS does not require detection of non-solar isotope abundances [6]. Irradiation experiments are in progress to simulate the properties of GEMS. The petrographic relationship between GEMS and carbon in IDPs is being investigated (by examining IDPs embedded and thin-sectioned in carbon-free media). Major element abundances in GEMS are being evaluated in terms on interstellar gas phase abundances. For example, sulfur is not highly depleted in the interstellar gas, implying that it must be significantly depleted in interstellar grains [3]. GEMS are significantly depleted in sulfur relative to solar abundances. Analytical electron microscopic studies of the local petrographic environment of GEMS in IDPs are continuing. There is evidence of a population of relict grains associated with GEMS. Some of these relict grains have distinctive compositions and they appear to have functioned as (pre-existing) depositional substrates while GEMS were being formed. Thus, it may be possible to begin to assign a chronology to the seemingly complex admixture of grains that make up the ultrafine-grained matrices of anhydrous chondritic IDPs. References: [1] Bradley J. P. (1994) Science, 265, 925-929. [2] Flynn G. J. (1994) Nature, 371, 287-288. [3] Martin P. G. (1995) Astrophys. J., 445, L63-L66. [4] Mathis J. S. (1986) Astrophys. J., 308, 281-287. [5] Mathis J. S. (1993) Rept. Prog. Phys., 56, 605-652. [6] Walker R. M. (1994) in Analysis of Interplanetary Dust (M. E. Zolensky et al., eds.), pp. 203-209, AIP Conf. Proc. 310.

Development of thalamocortical connections between the mediodorsal thalamus and the prefrontal cortex and its implication in cognition

PubMed Central

Ferguson, Brielle R.; Gao, Wen-Jun

2015-01-01

The mediodorsal thalamus (MD) represents a fundamental subcortical relay to the prefrontal cortex (PFC), and is thought to be highly implicated in modulation of cognitive performance. Additionally, it undergoes highly conserved developmental stages, which, when dysregulated, can have detrimental consequences. Embryonically, the MD experiences a tremendous surge in neurogenesis and differentiation, and disruption of this process may underlie the pathology in certain neurodevelopmental disorders. However, during the postnatal period, a vast amount of cell loss in the MD occurs. These together may represent an extended critical period for postnatal development, in which disturbances in the normal growth or reduction of the MD afferents to the PFC, can result in PFC-dependent cognitive, affective, or psychotic abnormalities. In this review, we explore the current knowledge supporting this hypothesis of a protracted critical period, and propose how developmental changes in the MD contribute to successful prefrontal cortical development and function. Specifically, we elaborate on the unique properties of MD-PFC connections compared with other thalamocortical afferents in sensory cortices, examine how MD-PFC innervation modulates synaptic transmission in the local prefrontal circuitry, and speculate on what occurs during postnatal development, particularly within the early neonatal stage, as well as juvenile and adolescent periods. Finally, we discuss the questions that remain and propose future experiments in order to provide perspective and novel insights into the cause of neuropsychiatric disorders associated with MD-PFC development. PMID:25620923

Intestinal permeability and Ménière's disease.

PubMed

Di Berardino, F; Zanetti, D; Ciusani, E; Caccia, C; Leoni, V; De Grazia, U; Filipponi, E; Elli, L

Ménière disease (MD) is a multifactorial chronic disabling condition characterized by episodic vertigo, ear fullness, and hearing loss. MD patients often complain of aspecific gastrointestinal symptoms associated with autonomic dysregulation, frequently outweighed by the otological manifestations. Dietary modifications have been reported to improve the typical MD symptoms in some cases. Our purpose was to test the urinary levels of lactulose and mannitol (double sugar test) and the fecal calprotectin, both markers of altered intestinal permeability, in subjects with definite MD in an active and inactive stage. Twenty-six with definite unilateral MD were studied: 14 patients were symptomatic for at least 3months with moderate to severe vertigo spells and a functional level ≥4; 12 patients had been asymptomatic (no vertigo spells) for at least 3months and had a functional level=1 at the time of testing. Twenty healthy volunteers were recruited as "control group". Lactulose and mannitol absorption was significantly increased in the symptomatic M patients compared to the asymptomatic group (p<0.02 and p<0.004, respectively) and to the controls. FC were also higher than normal only in the symptomatic group. (p<0.01). An altered intestinal permeability, according to the two assays, was found only in symptomatic MD patients. The rationale for a possible relationship between MD and intestinal permeability is forwarded. The double-sugar test and FC quantification might be implemented in the MD diagnostic workup. Copyright © 2017 Elsevier Inc. All rights reserved.

Very virulent plus strains of MDV induce acute form of transient paralysis in both susceptible and resistant chicken lines

USDA-ARS?s Scientific Manuscript database

Marek’s Disease (MD) is a lymphoproliferative disease of domestic chickens caused by a highly cell-associated alpha herpesvirus, Marek’s disease virus (MDV). Clinical signs of MD include depression, crippling, weight loss, and transient paralysis (TP). TP is a disease of the central nervous system...

Severe necrotic dermatitis in the combs of line 6-3 chickens is associated with Marek's disease virus-induced immunosuppression

USDA-ARS?s Scientific Manuscript database

Marek’s disease (MD), a lymphoproliferative disorder of domestic chickens is characterized by bursal–thymic atrophy and rapid onset of T-cell lymphomas that infiltrate lymphoid tissues, visceral organs, and peripheral nerves. Marek’s disease virus (MDV), the etiological agent of MD, is a highly cel...

Characterizing the molecular basis of attenuation of Marek’s disease virus via in vitro serial passage

USDA-ARS?s Scientific Manuscript database

Marek’s disease (MD) is a lymphoproliferative disease of chickens caused by the oncogenic Gallid herpesvirus 2, commonly known as Marek’s disease virus (MDV). MD vaccines, the primary control method, are often generated by repeated in vitro serial passage of this highly cell-associated virus to atte...

Nutrition and Osteoporosis: Preliminary data of Campania Region of European PERsonalised ICT Supported Service for Independent Living and Active Ageing

PubMed Central

Vuolo, L.; Barrea, L.; Savanelli, MC; Savastano, S.; Rubino, M.; Scarano, E.; Soprano, M.; Illario, M.; Colao, A.; Di Somma, C.

2015-01-01

Background: Bone impairment and malnutrition are associated with significant disability and mortality. PERSSILAA is an European project developing health services to detect and prevent frailty in older adults by addressing cognitive, physical and nutritional. Methods: Subjects underwent anthropometric measurements, calcaneal quantitative ultrasound (QUS) scan and PREDIMED (PREvención con DIeta MEDiterránea) questionnaire. Aim: To investigate the association between adherence to the Mediterranean Diet (MD) and bone health. Results: 87 subjects (4 males and 83 females) 70.1±4.9 aged, were examined. Mean Body Mass Index (BMI) was 28.7±4.7(kg/m2): in particular 28 subjects (32.2%) resulted obese, 42 (48.3%) overweight, and only 17 (19.5%) with normal weight. Mean T score was −1.2±1.2: in particular 13 subjects (14.9%) resulted osteoporotic; 43 (49.5%) osteopenic; and 31 (35.6%) with normal bone mineral density. Regarding adherence to MD, 9 subjects (10.3%) were poorly adherent; 41 (47.2%) average adherent; 37 (42.5%) highly adherent. T-score was associated with PREDIMED score and osteoporotic subjects presented the lowest PREDIMED score (5.8±2.2). Conclusions: These preliminary data show a significant correlation between the adherence to the MD and bone health parameters. The association between MD and bone health highlights the potential beneficial effects of nutritional interventions promoting a Mediterranean food pattern, as safe adjuvant treatment in ageing. PMID:27042428

Nutrition and Osteoporosis: Preliminary data of Campania Region of European PERsonalised ICT Supported Service for Independent Living and Active Ageing.

PubMed

Vuolo, L; Barrea, L; Savanelli, M C; Savastano, S; Rubino, M; Scarano, E; Soprano, M; Illario, M; Colao, A; Di Somma, C

2015-12-01

Bone impairment and malnutrition are associated with significant disability and mortality. PERSSILAA is an European project developing health services to detect and prevent frailty in older adults by addressing cognitive, physical and nutritional. Subjects underwent anthropometric measurements, calcaneal quantitative ultrasound (QUS) scan and PREDIMED (PREvención con DIeta MEDiterránea) questionnaire. To investigate the association between adherence to the Mediterranean Diet (MD) and bone health. 87 subjects (4 males and 83 females) 70.1±4.9 aged, were examined. Mean Body Mass Index (BMI) was 28.7±4.7(kg/m(2)): in particular 28 subjects (32.2%) resulted obese, 42 (48.3%) overweight, and only 17 (19.5%) with normal weight. Mean T score was -1.2±1.2: in particular 13 subjects (14.9%) resulted osteoporotic; 43 (49.5%) osteopenic; and 31 (35.6%) with normal bone mineral density. Regarding adherence to MD, 9 subjects (10.3%) were poorly adherent; 41 (47.2%) average adherent; 37 (42.5%) highly adherent. T-score was associated with PREDIMED score and osteoporotic subjects presented the lowest PREDIMED score (5.8±2.2). These preliminary data show a significant correlation between the adherence to the MD and bone health parameters. The association between MD and bone health highlights the potential beneficial effects of nutritional interventions promoting a Mediterranean food pattern, as safe adjuvant treatment in ageing.

Aspirin use is associated with lower mammographic density in a large screening cohort.

PubMed

Wood, Marie E; Sprague, Brian L; Oustimov, Andrew; Synnstvedt, Marie B; Cuke, Melissa; Conant, Emily F; Kontos, Despina

2017-04-01

Observational and biologic studies suggest that aspirin is a promising prevention therapy for breast cancer. However, clinical trials to date have not corroborated this evidence, potentially due to study design. We evaluated the effect of aspirin on mammographic density (MD), an established modifiable risk factor for breast cancer. Electronic medical records from the University of Pennsylvania were evaluated for women who underwent screening mammography, saw their primary care provider, and had a confirmed list of medications during 2012-2013. Logistic regression was performed to test for associations between clinically recorded MD and aspirin use, after adjusting for age, body mass index (BMI), and ethnicity. We identified 26,000 eligible women. Mean age was 57.3, mean BMI was 28.9 kg/m 2 , 41% were African American, and 19.7% reported current aspirin use. Aspirin users were significantly older and had higher BMI. There was an independent, inverse association between aspirin use and MD (P trend  < 0.001). Women with extremely dense breasts were less likely to be aspirin users than women with scattered fibroglandular density (OR 0.73; 95% CI 0.57-0.93). This association was stronger for younger women (P = 0.0002) and for African Americans (P = 0.011). The likelihood of having dense breasts decreased with aspirin dose (P trend  = 0.007), suggesting a dose response. We demonstrate an independent association between aspirin use and lower MD in a large, diverse screening cohort. This association was stronger for younger and African American women: two groups at greater risk for ER- breast cancer. These results contribute to the importance of investigating aspirin for breast cancer prevention.

A ‘modified de Gramont’ regimen of fluorouracil, alone and with oxaliplatin, for advanced colorectal cancer

PubMed Central

Cheeseman, S L; Joel, S P; Chester, J D; Wilson, G; Dent, J T; Richards, F J; Seymour, M T

2002-01-01

The standard de Gramont (dG) regimen of fortnightly leucovorin, bolus fluorouracil and 22-h infusion of fluorouracil, d1+2, and the same regimen plus oxaliplatin, are effective but also cumbersome. We therefore present simplified ‘Modified de Gramont’ (MdG) regimens. Forty-six advanced gastrointestinal cancer patients entered a dose-exploring study of MdG, including an expanded cohort of colorectal cancer patients at optimum dose. Treatment (fortnightly) comprised: 2-h i.v.i. leucovorin (350 mg d,l-LV or 175 mg l-LV, not adjusted for patient surface area); bolus fluorouracil (400 mg m−2), then ambulatory 46-h fluorouracil infusion (2000–3600 mg m−2, cohort escalation). Subsequently, 62 colorectal patients (25 unpretreated; 37 fluorouracil-resistant) received MdG plus oxaliplatin (OxMdG) 85 mg m−2. Fluorouracil pharmacokinetics during MdG were compared with dG. The optimum fluorouracil doses for MdG alone were determined as 400 mg m−2 bolus + 2800 mg m−2 46-h infusion. A lower dose of 400 mg m−2 bolus + 2400 mg m−2 infusion which, like dG produces minimal toxicity, was chosen for the OxMdG combination. Fluorouracil exposure (AUC0–48 h) at this lower dose is equivalent to dG. With OxMdG, grade 3–4 toxicity was rare (neutropenia 2.8% cycles; vomiting or diarrhoea <1% cycles), but despite this there were two infection-associated deaths. Oxaliplatin was omitted for cumulative neurotoxicity in 17 out of 62 patients. Objective responses in colorectal cancer patients were: 1st-line MdG (22 assessable): PR=36%, NC=32%, PD=32%. 1st-line OxMdG (24 assessable): CR/PR=72%; NC=20%; PD=8%; 2nd line OxMdG (34 assessable): PR=12%; NC=38%; PD=50%. MdG and OxMdG are convenient and well-tolerated. OxMdG was particularly active as 1st-line treatment of advanced colorectal cancer. Both regimens are being further evaluated in the current UK MRC phase III trial. British Journal of Cancer (2002) 87, 393–399. doi:10.1038/sj.bjc.6600467 www.bjcancer.com © 2002 Cancer Research UK PMID:12177775

PuReMD-GPU: A reactive molecular dynamics simulation package for GPUs

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

Kylasa, S.B., E-mail: skylasa@purdue.edu; Aktulga, H.M., E-mail: hmaktulga@lbl.gov; Grama, A.Y., E-mail: ayg@cs.purdue.edu

2014-09-01

We present an efficient and highly accurate GP-GPU implementation of our community code, PuReMD, for reactive molecular dynamics simulations using the ReaxFF force field. PuReMD and its incorporation into LAMMPS (Reax/C) is used by a large number of research groups worldwide for simulating diverse systems ranging from biomembranes to explosives (RDX) at atomistic level of detail. The sub-femtosecond time-steps associated with ReaxFF strongly motivate significant improvements to per-timestep simulation time through effective use of GPUs. This paper presents, in detail, the design and implementation of PuReMD-GPU, which enables ReaxFF simulations on GPUs, as well as various performance optimization techniques wemore » developed to obtain high performance on state-of-the-art hardware. Comprehensive experiments on model systems (bulk water and amorphous silica) are presented to quantify the performance improvements achieved by PuReMD-GPU and to verify its accuracy. In particular, our experiments show up to 16× improvement in runtime compared to our highly optimized CPU-only single-core ReaxFF implementation. PuReMD-GPU is a unique production code, and is currently available on request from the authors.« less

Marginal analysis in assessing factors contributing time to physician in the Emergency Department using operations data.

PubMed

Pathan, Sameer A; Bhutta, Zain A; Moinudheen, Jibin; Jenkins, Dominic; Silva, Ashwin D; Sharma, Yogdutt; Saleh, Warda A; Khudabakhsh, Zeenat; Irfan, Furqan B; Thomas, Stephen H

2016-01-01

Background: Standard Emergency Department (ED) operations goals include minimization of the time interval (tMD) between patients' initial ED presentation and initial physician evaluation. This study assessed factors known (or suspected) to influence tMD with a two-step goal. The first step was generation of a multivariate model identifying parameters associated with prolongation of tMD at a single study center. The second step was the use of a study center-specific multivariate tMD model as a basis for predictive marginal probability analysis; the marginal model allowed for prediction of the degree of ED operations benefit that would be affected with specific ED operations improvements. Methods: The study was conducted using one month (May 2015) of data obtained from an ED administrative database (EDAD) in an urban academic tertiary ED with an annual census of approximately 500,000; during the study month, the ED saw 39,593 cases. The EDAD data were used to generate a multivariate linear regression model assessing the various demographic and operational covariates' effects on the dependent variable tMD. Predictive marginal probability analysis was used to calculate the relative contributions of key covariates as well as demonstrate the likely tMD impact on modifying those covariates with operational improvements. Analyses were conducted with Stata 14MP, with significance defined at p  < 0.05 and confidence intervals (CIs) reported at the 95% level. Results: In an acceptable linear regression model that accounted for just over half of the overall variance in tMD (adjusted r 2 0.51), important contributors to tMD included shift census ( p  = 0.008), shift time of day ( p  = 0.002), and physician coverage n ( p  = 0.004). These strong associations remained even after adjusting for each other and other covariates. Marginal predictive probability analysis was used to predict the overall tMD impact (improvement from 50 to 43 minutes, p  < 0.001) of consistent staffing with 22 physicians. Conclusions: The analysis identified expected variables contributing to tMD with regression demonstrating significance and effect magnitude of alterations in covariates including patient census, shift time of day, and number of physicians. Marginal analysis provided operationally useful demonstration of the need to adjust physician coverage numbers, prompting changes at the study ED. The methods used in this analysis may prove useful in other EDs wishing to analyze operations information with the goal of predicting which interventions may have the most benefit.

Ad libitum Mediterranean and Low Fat Diets both Significantly Reduce Hepatic Steatosis: a Randomized Controlled Trial.

PubMed

Properzi, Catherine; O'Sullivan, Therese A; Sherriff, Jill L; Ching, Helena L; Jeffrey, Garry P; Buckley, Rachel F; Tibballs, Jonathan; MacQuillan, Gerry C; Garas, George; Adams, Leon A

2018-05-05

Although diet induced weight loss is first-line treatment for patients with non-alcoholic fatty liver disease (NAFLD), long-term maintenance is difficult. The optimal diet for either improvement in NAFLD or associated cardio-metabolic risk factors regardless of weight loss, is unknown. We examined the effect of two ad libitum isocaloric diets [Mediterranean (MD) or Low Fat (LF)] on hepatic steatosis and cardio-metabolic risk factors. Subjects with NAFLD were randomized to a 12-week blinded dietary intervention (MD vs LF). Hepatic steatosis was determined via magnetic resonance spectroscopy (MRS). From a total of 56 subjects enrolled, 49 subjects completed the intervention and 48 were included for analysis. During the intervention, subjects on the MD had significantly higher total and monounsaturated fat but lower carbohydrate and sodium intakes compared to LF subjects (p<0.01). At week 12, hepatic steatosis had reduced significantly in both groups (p<0.01) and there was no difference in liver fat reduction between the groups (p=0.32), with mean (SD) relative reductions of 25.0% (±25.3%) in LF and 32.4% (±25.5%) in MD. Liver enzymes also improved significantly in both groups. Weight loss was minimal and not different between groups [-1.6 (±2.1)kg in LF vs -2.1 (±2.5)kg in MD, (p=0.52)]. Within-group improvements in the Framingham risk score, total cholesterol, serum triglyceride, and HbA1c were observed in the MD (all p<0.05) but not with the LF diet. Adherence was higher for the MD compared to LF (88% vs. 64%, p=0.048). Ad libitum low fat and Mediterranean diets both improve hepatic steatosis to a similar degree. This article is protected by copyright. All rights reserved. © 2018 by the American Association for the Study of Liver Diseases.

History of the First-Generation Marek's Disease Vaccines: The Science and Little-Known Facts.

PubMed

Schat, Karel A

2016-12-01

Shortly after the isolation of Marek's disease (MD) herpesvirus (MDV) in the late 1960s vaccines were developed in England, the United States, and The Netherlands. Biggs and associates at the Houghton Poultry Research Station (HPRS) in England attenuated HPRS-16, the first cell-culture-isolated MDV strain, by passaging HPRS-16 in chick kidney cells. Although HPRS-16/Att was the first commercially available vaccine, it never became widely used and was soon replaced by the FC126 strain of herpesvirus of turkeys (HVT) vaccine developed by Witter and associates at the Regional Poultry Research Laboratory (now Avian Disease and Oncology Laboratory [ADOL]) in East Lansing, MI. Ironically, Kawamura et al. isolated a herpesvirus from kidney cell cultures from turkeys in 1969 but never realized its potential as a vaccine against MD. Rispens of the Central Veterinary Institute (CVI) developed the third vaccine. His associate, Maas, had found commercial flocks of chickens with MDV antibodies but without MD. Subsequently, Rispens isolated a very low pathogenic strain from hen number 988 from his MD antibody-positive flock, which was free of avian leukosis virus and clinical MD. This isolate became the CVI-988 vaccine used mostly in The Netherlands. During the late 1970s, HVT was no longer fully protective against some new emerging field strains. The addition of SB-1, isolated by Schat and Calnek, to HVT improved protection against the emerging very virulent strains. In the 1990s CVI-988 became the worldwide vaccine gold standard. This review will present data from published papers and personal communications providing additional information about the exciting 15-yr period after the isolation of MDV to the development of the different vaccines.

Maternal death in the emergency department from trauma.

PubMed

Brookfield, Kathleen F; Gonzalez-Quintero, Victor H; Davis, James S; Schulman, Carl I

2013-09-01

Trauma during pregnancy is among leading causes of non-pregnancy-related maternal death (MD). This study describes risk factors for MD from trauma during pregnancy in a large urban population. We queried an urban Level One Trauma Center registry for the medical records of pregnant women suffering trauma from 1990 to 2007. Associations were examined between maternal demographics, injury mode details, injury characteristics, and risk of maternal death upon arrival to the emergency room. Overall, 351 patients were identified. Most traumas was caused by motor vehicle collision (71.8 %), accounting for 78.9 % of MD, followed by gun shot wound (10.3 %), stabbing (8.5 %), falls (4.3 %), and assaults (4 %). Abdominal and head injuries were more frequent in cases of MD compared with patients admitted to the hospital (33.3 vs. 25.1 % abdominal, 55.6 vs. 29.4 % head; p < 0.001). A greater proportion of MDs were characterized by lack of restraint use (66.7 %) compared to women admitted to the hospital (47.7 %) and women discharged after observation (43.1 %); p = 0.014. ER deaths had more negative base excess scores than women who were admitted or discharged (-14 vs. -3 vs. -2; p < 0.001), lower blood pH values (6.96 vs. 7.40 vs. 7.44; p < 0.001), greater Injury Severity Scores (ISS) (44.4 vs. 11.49 vs. 2.66; p < 0.001), and lower Revised Trauma Scores (RTS) (0.5 vs. 7.49 vs. 7.83; p < 0.001). Lack of restraint use in the pregnant population is associated with increased MD. Although not validated in the pregnant population, the ISS and RTS were associated with maternal mortality outcomes.

Adherence to the Mediterranean diet and risk of bladder cancer in the EPIC cohort study.

PubMed

Buckland, G; Ros, M M; Roswall, N; Bueno-de-Mesquita, H B; Travier, N; Tjonneland, A; Kiemeney, L A; Sacerdote, C; Tumino, R; Ljungberg, B; Gram, I T; Weiderpass, E; Skeie, G; Malm, J; Ehrnström, R; Chang-Claude, J; Mattiello, A; Agnoli, C; Peeters, P H; Boutron-Ruault, M C; Fagherazzi, G; Clavel-Chapelon, F; Nilsson, L M; Amiano, P; Trichopoulou, A; Oikonomou, E; Tsiotas, K; Sánchez, M J; Overvad, K; Quirós, J R; Chirlaque, M D; Barricarte, A; Key, T J; Allen, N E; Khaw, K T; Wareham, N; Riboli, E; Kaaks, R; Boeing, H; Palli, D; Romieu, I; Romaguera, D; Gonzalez, C A

2014-05-15

There is growing evidence of the protective role of the Mediterranean diet (MD) on cancer. However, to date no epidemiological study has investigated the influence of the MD on bladder cancer. We evaluated the association between adherence to the MD and risk of urothelial cell bladder cancer (UCC), according to tumor aggressiveness, in the European Prospective Investigation into Cancer and Nutrition (EPIC). The analysis included 477,312 participants, recruited from ten European countries between 1991 and 2000. Information from validated dietary questionnaires was used to develop a relative Mediterranean diet score (rMED), including nine dietary components. Cox regression models were used to assess the effect of the rMED on UCC risk, while adjusting for dietary energy and tobacco smoking of any kind. Stratified analyses were performed by sex, BMI, smoking status, European region and age at diagnosis. During an average follow-up of 11 years, 1,425 participants (70.9% male) were diagnosed with a first primary UCC. There was a negative but non-significant association between a high versus low rMED score and risk of UCC overall (HR: 0.84 [95% CI 0.69, 1.03]) and risk of aggressive (HR: 0.88 [95% CI 0.61, 1.28]) and non-aggressive tumors (HR: 0.78 [95% CI 0.54, 1.14]). Although there was no effect modification in the stratified analyses, there was a significant 34% (p = 0.043) decreased risk of UCC in current smokers with a high rMED score. In EPIC, the MD was not significantly associated with risk of UCC, although we cannot exclude that a MD may reduce risk in current smokers. © 2013 UICC.

Thalamic white matter in multiple sclerosis: A combined diffusion-tensor imaging and quantitative susceptibility mapping study.

PubMed

Bergsland, Niels; Schweser, Ferdinand; Dwyer, Michael G; Weinstock-Guttman, Bianca; Benedict, Ralph H B; Zivadinov, Robert

2018-06-19

Thalamic white matter (WM) injury in multiple sclerosis (MS) remains relatively poorly understood. Combining multiple imaging modalities, sensitive to different tissue properties, may aid in further characterizing thalamic damage. Forty-five MS patients and 17 demographically-matched healthy controls (HC) were scanned with 3T MRI to obtain quantitative measures of diffusivity and magnetic susceptibility. Participants underwent cognitive evaluation with the Brief International Cognitive Assessment for Multiple Sclerosis battery. Tract-based spatial statistics identified thalamic WM. Non-parametric combination (NPC) analysis was used to perform joint inference on fractional anisotropy (FA), mean diffusivity (MD) and magnetic susceptibility measures. The association of surrounding WM lesions and thalamic WM pathology was investigated with lesion probability mapping. Compared to HCs, the greatest extent of thalamic WM damage was reflected by the combination of increased MD and decreased magnetic susceptibility (63.0% of thalamic WM, peak p = .001). Controlling for thalamic volume resulted in decreased FA and magnetic susceptibility (34.1%, peak p = .004) as showing the greatest extent. In MS patients, the most widespread association with information processing speed was found with the combination of MD and magnetic susceptibility (67.6%, peak p = .0005), although this was not evident after controlling for thalamic volume. For memory measures, MD alone yielded the most widespread associations (45.9%, peak p = .012 or 76.7%, peak p = .001), even after considering thalamic volume, albeit with smaller percentages. White matter lesions were related to decreased FA (peak p = .0063) and increased MD (peak p = .007), but not magnetic susceptibility, of thalamic WM. Our study highlights the complex nature of thalamic pathology in MS. © 2018 Wiley Periodicals, Inc.

Herpes virus and Ménière's disease.

PubMed

Gartner, M; Bossart, W; Linder, T

2008-01-01

The main goal of this study was to examine the vestibular ganglia from patients with intractable classic Ménière's disease (MD) for the presence or absence of DNA from three neurotropic viruses herpes simplex virus 1 and 2 (HSV1, HSV2) and varicella zoster virus (VZV) and to investigate the hypothesis that MD is associated with virus reactivation within Scarpa's ganglion. Polymerase chain reaction (PCR) was performed with nested primer sets specific for viral genomic DNA of HSV1, HSV2 and VZV in biopsies of the ganglion scarpae of patients with MD who underwent vestibular neurectomy. Included were patients with MD classified as definite MD according to American Academy of Otolaryngology/Head and Neck Surgery criteria. The ganglion scarpae and ganglion geniculi harvested at autopsy from patients without history of MD or facial palsy served as control specimens. No viral DNA was detected in the vestibular ganglion of 7 patients with definite MD. In 34% of the vestibular ganglia of the control group we detected either HSV1 or VZV. Only one Scarpa's ganglion had both viruses present at the same time. Thirty-two out of 34 ganglia from the geniculate segment of the facial nerve contained either HSV1 and/or VZV genomic DNA. Eight specimens contained both viruses simultaneously. Altogether viral DNA was found in 94% of ganglia. Viral genomic DNA of HSV2 was not detected. Although HSV and VZV appear to be present in many ganglion cells throughout the human body, we were unable to find genomic DNA of these viruses in patients with definite MD and disabling vertigo, who underwent vestibular neurectomy. Based on these results, reactivation of HSV1 and VZV in the vestibular ganglion does not seem to play a role in the pathogenesis of MD. (c) 2008 S. Karger AG, Basel

Does psychosis increase the risk of suicide in patients with major depression? A systematic review.

PubMed

Zalpuri, Isheeta; Rothschild, Anthony J

2016-07-01

Over the years studies have shown conflicting results about the risk of suicide in psychotic depression (MD-psych). To understand this association, we undertook a comprehensive review of the literature to ascertain whether individuals with MD-psych have higher rates of completed suicides, suicide attempts or suicidal ideation compared to those with non-psychotic depression (MD-nonpsych). We searched Pubmed, PsycINFO and Ovid in English language, from 1946-October 2015. Studies were included if suicidal ideation, attempts or completed suicides were assessed. During the acute episode of depression, patients with MD-psych have higher rates of suicide, suicide attempts, and suicidal ideation than patients with MD-nonpsych, especially when the patient is hospitalized on an inpatient psychiatric unit. Studies done after the acute episode has resolved are less likely to show this difference, likely due to patients having received treatment. Diagnostic interviews were not conducted in all studies. Many studies did not report whether psychotic symptoms in MD-psych patients were mood-congruent or mood-incongruent; hence it is unclear whether the type of delusion increases suicide risk. Studies did not describe whether MD-psych patients experienced command hallucinations encouraging them to engage in suicidal behavior. Only 24 studies met inclusion criteria; several of them had small sample size and a quality score of zero, hence impacting validity. This review indicates that the seemingly conflicting data in suicide risk between MD-psych and MD-nonpsych in previous studies appears to be related to whether one looks at differences during the acute episode or over the long-term. Copyright © 2016 Elsevier B.V. All rights reserved.

Structural insights into pharmacophore-assisted in silico identification of protein-protein interaction inhibitors for inhibition of human toll-like receptor 4 - myeloid differentiation factor-2 (hTLR4-MD-2) complex.

PubMed

Mishra, Vinita; Pathak, Chandramani

2018-05-29

Toll-like receptor 4 (TLR4) is a member of Toll-Like Receptors (TLRs) family that serves as a receptor for bacterial lipopolysaccharide (LPS). TLR4 alone cannot recognize LPS without aid of co-receptor myeloid differentiation factor-2 (MD-2). Binding of LPS with TLR4 forms a LPS-TLR4-MD-2 complex and directs downstream signaling for activation of immune response, inflammation and NF-κB activation. Activation of TLR4 signaling is associated with various pathophysiological consequences. Therefore, targeting protein-protein interaction (PPI) in TLR4-MD-2 complex formation could be an attractive therapeutic approach for targeting inflammatory disorders. The aim of present study was directed to identify small molecule PPI inhibitors (SMPPIIs) using pharmacophore mapping-based approach of computational drug discovery. Here, we had retrieved the information about the hot spot residues and their pharmacophoric features at both primary (TLR4-MD-2) and dimerization (MD-2-TLR4*) protein-protein interaction interfaces in TLR4-MD-2 homo-dimer complex using in silico methods. Promising candidates were identified after virtual screening, which may restrict TLR4-MD-2 protein-protein interaction. In silico off-target profiling over the virtually screened compounds revealed other possible molecular targets. Two of the virtually screened compounds (C11 and C15) were predicted to have an inhibitory concentration in μM range after HYDE assessment. Molecular dynamics simulation study performed for these two compounds in complex with target protein confirms the stability of the complex. After virtual high throughput screening we found selective hTLR4-MD-2 inhibitors, which may have therapeutic potential to target chronic inflammatory diseases.

Motion Tree Delineates Hierarchical Structure of Protein Dynamics Observed in Molecular Dynamics Simulation

PubMed Central

Moritsugu, Kei; Koike, Ryotaro; Yamada, Kouki; Kato, Hiroaki; Kidera, Akinori

2015-01-01

Molecular dynamics (MD) simulations of proteins provide important information to understand their functional mechanisms, which are, however, likely to be hidden behind their complicated motions with a wide range of spatial and temporal scales. A straightforward and intuitive analysis of protein dynamics observed in MD simulation trajectories is therefore of growing significance with the large increase in both the simulation time and system size. In this study, we propose a novel description of protein motions based on the hierarchical clustering of fluctuations in the inter-atomic distances calculated from an MD trajectory, which constructs a single tree diagram, named a “Motion Tree”, to determine a set of rigid-domain pairs hierarchically along with associated inter-domain fluctuations. The method was first applied to the MD trajectory of substrate-free adenylate kinase to clarify the usefulness of the Motion Tree, which illustrated a clear-cut dynamics picture of the inter-domain motions involving the ATP/AMP lid and the core domain together with the associated amplitudes and correlations. The comparison of two Motion Trees calculated from MD simulations of ligand-free and -bound glutamine binding proteins clarified changes in inherent dynamics upon ligand binding appeared in both large domains and a small loop that stabilized ligand molecule. Another application to a huge protein, a multidrug ATP binding cassette (ABC) transporter, captured significant increases of fluctuations upon binding a drug molecule observed in both large scale inter-subunit motions and a motion localized at a transmembrane helix, which may be a trigger to the subsequent structural change from inward-open to outward-open states to transport the drug molecule. These applications demonstrated the capabilities of Motion Trees to provide an at-a-glance view of various sizes of functional motions inherent in the complicated MD trajectory. PMID:26148295

Atmospheric Pressure and Onset of Episodes of Menière’s Disease - A Repeated Measures Study

PubMed Central

Strobl, Ralf; Heinlin, Nina; Krause, Eike; Olzowy, Bernhard; Koppe, Christina; Grill, Eva

2016-01-01

Background External changes of air pressure are transmitted to the middle and inner ear and may be used therapeutically in Menière’s disease, one of the most common vertigo disorders. We analyzed the possible relationship of atmospheric pressure and other meteorological parameters with the onset of MD vertigo episodes in order to determine whether atmospheric pressure changes play a role in the occurrence of MD episodes. Methods Patients of a tertiary outpatient dizziness clinic diagnosed with MD were asked to keep a daily vertigo diary to document MD episodes (2004–2009). Local air pressure, absolute temperature and dew point temperature were acquired on an hourly basis. Change in meteorological parameters was conceptualized as the maximum difference in a 24 hour time frame preceding each day. Effects were estimated using additive mixed models with a random participant effect. We included lagged air parameters, age, sex, weekday and season in the model. Results A total of 56 persons (59% female) with mean age 54 years were included. Mean follow-up time was 267 days. Persons experienced on average 10.3 episodes during the observation period (median 8). Age and change in air pressure were significantly associated with vertigo onset risk (Odds Ratio = 0.979 and 1.010). We could not show an effect of sex, weekday, season, air temperature, and dew point temperature. Conclusions Change in air pressure was significantly associated with onset of MD episodes, suggesting a potential triggering mechanism in the inner ear. MD patients may possibly use air pressure changes as an early warning system for vertigo attacks in the future. PMID:27096752

Prevalence of Body Dysmorphic Disorder and Muscle Dysmorphia Among Entry-Level Military Personnel.

PubMed

Campagna, John D A; Bowsher, Barbara

2016-05-01

To determine the prevalence of body dysmorphic disorder (BDD) and muscle dysmorphia (MD) in enlisted U.S. military personnel; and secondarily, to determine supplement use and relationship with BDD and MD. A survey of advanced individual training of tri-service personnel at Fort Sam Houston, Texas, was performed combining the dysmorphia concern questionnaire, the MD symptom questionnaire, a supplement questionnaire, and demographic factors. Of the 1,320 service members approached, 1,150 (87.1%) completed the survey. The majority of participants were male, 62.8% (n = 722) and Army soldiers 59.0% (n = 679). The prevalence rate of BDD was 13.0% in males and 21.7% in females. The prevalence of MD was 12.7% in males and 4.2% in females. There was a strong correlation between having BDD and using supplements to get thinner (odds ratio 5.1; 95% confidence interval 3.4-7.8; p < 0.001) and MD to get more muscular (odds ratio 5.4; 95% confidence interval 3.5-8.3; p < 0.001). Our study shows a higher than expected prevalence rate of BDD and MD in service members. This indicates a need for increased awareness of dysmorphias in mental health providers, primary care providers, and commanders and justifies further military specific BDD and MD research. Reprint & Copyright © 2016 Association of Military Surgeons of the U.S.

Urinary N-terminal fragment of titin is a marker to diagnose muscular dystrophy in patients with cardiomyopathy.

PubMed

Yoshihisa, Akiomi; Kiko, Takatoyo; Sato, Takamasa; Oikawa, Masayoshi; Kobayashi, Atsushi; Takeishi, Yasuchika

2018-06-02

The differential diagnosis of cardiomyopathy is important. It has been recently reported that urinary titin N (U-TN) is increased in patients with muscular dystrophy (MD), and is associated with muscular damage. We aimed to clarify whether U-TN is useful as a diagnostic tool for distinguishing MD from various cardiomyopathies [e.g. dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM)]. We measured and compared the U-TN/creatinine ratio (U-TN/Cr; pmol/mg/dl) in 278 control subjects and 331 patients with various cardiomyopathies (DCM, n = 199; sarcoidosis, n = 18; HCM, n = 86; amyloidosis, n = 15; Fabry disease, n = 6; MD, n = 7). The U-TN/Cr was significantly higher in MD patients than in patients with various cardiomyopathies and the control subjects (P < 0.001). From the ROC analysis, the U-TN/Cr (with a cut-off value of 8.7) identified MD with 100% sensitivity, 82% specificity, and an area under the curve (AUC) of 0.92 (95% CI 0.87-0.98, P < 0.001). The AUC of the U-TN/Cr that was able to predict MD was superior to those of U-TN, creatinine kinase, B-type natriuretic peptide, and troponin I. Urinary Titin-N is a novel marker to diagnose MD. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Occupational exposures and mammographic density in Spanish women.

PubMed

Lope, Virginia; García-Pérez, Javier; Pérez-Gómez, Beatriz; Pedraza-Flechas, Ana María; Alguacil, Juan; González-Galarzo, Mª Carmen; Alba, Miguel Angel; van der Haar, Rudolf; Cortés-Barragán, Rosa Ana; Pedraz-Pingarrón, Carmen; Moreo, Pilar; Santamariña, Carmen; Ederra, María; Vidal, Carmen; Salas-Trejo, Dolores; Sánchez-Contador, Carmen; Llobet, Rafael; Pollán, Marina

2018-02-01

The association between occupational exposures and mammographic density (MD), a marker of breast cancer risk, has not been previously explored. Our objective was to investigate the influence of occupational exposure to chemical, physical and microbiological agents on MD in adult women. This is a population-based cross-sectional study based on 1476 female workers aged 45-65 years from seven Spanish breast cancer screening programmes. Occupational history was surveyed by trained staff. Exposure to occupational agents was assessed using the Spanish job-exposure matrix MatEmESp. Percentage of MD was measured by two radiologists using a semiautomatic computer tool. The association was estimated using mixed log-linear regression models adjusting for age, education, body mass index, menopausal status, parity, smoking, alcohol intake, type of mammography, family history of breast cancer and hormonal therapy use, and including screening centre and professional reader as random effects terms. Although no association was found with most of the agents, women occupationally exposed to perchloroethylene (e β =1.51; 95% CI 1.04 to 2.19), ionising radiation (e β =1.23; 95% CI 0.99 to 1.52) and mould spores (e β =1.44; 95% CI 1.01 to 2.04) tended to have higher MD. The percentage of density increased 12% for every 5 years exposure to perchloroethylene or mould spores, 11% for every 5 years exposure to aliphatic/alicyclic hydrocarbon solvents and 3% for each 5 years exposure to ionising radiation. Exposure to perchloroethylene, ionising radiation, mould spores or aliphatic/alicyclic hydrocarbon solvents in occupational settings could be associated with higher MD. Further studies are needed to clarify the accuracy and the reasons for these findings. © 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.

Disease-Related Microstructural Differences in the Brain in Women With Provoked Vestibulodynia.

PubMed

Gupta, Arpana; Woodworth, Davis C; Ellingson, Benjamin M; Rapkin, Andrea J; Naliboff, Bruce; Kilpatrick, Lisa A; Stains, Jean; Masghati, Salome; Tillisch, Kirsten; Mayer, Emeran A; Labus, Jennifer S

2018-05-01

Provoked vestibulodynia (PVD) is a chronic pelvic pain disorder affecting 16% of the female population. Neuroimaging studies have highlighted central abnormalities in PVD, similar to other chronic pelvic pain disorders, including brain regions involved in sensory processing and modulation of pain. The aim of the study was to determine alterations in the subvoxel, microstructural organization within tissues in PVD compared with healthy control participants (HCs) and a disease control group (irritable bowel syndrome [IBS]). Diffusion tensor imaging magnetic resonance imaging was conducted in 87 age-matched premenopausal women (29 PVD, 29 HCs, 29 IBS). Statistical parameter mapping of fractional anisotropy (FA) and mean diffusivity (MD) maps were used to identify microstructural difference in the brain specific to PVD or shared with IBS. PVD alterations in microstructural organization of the brain were predominantly observed in fibers associated with sensorimotor integration and pain processing that relay information between the thalamus, basal ganglia, sensorimotor, and insular cortex. PVD, compared with HCs, showed extensive increases in the FA of somatosensory and basal ganglia regions. In contrast, PVD and IBS subjects did not show any FA-related group differences. PVD subjects showed greater MD in the basal ganglia compared with HCs (higher MD in the internal capsule and pallidum) and IBS (higher MD in the putamen and pallidum). Increases in MD were associated with increased vaginal muscle tenderness and vulvar pain. The current findings highlight possible shared mechanisms between 2 different pelvic pain disorders, but also highlight the widespread alterations observed specifically in PVD compared with HCs. Alterations in microstructure in PVD were observed in fibers associated with sensorimotor integration and pain processing, which were also associated with increased vaginal muscle tenderness and vulvar pain. These alterations may be contributing to increased pain sensitivity and tenderness, highlighting the need for new therapies targeting the central nervous system. Copyright © 2018 The American Pain Society. Published by Elsevier Inc. All rights reserved.

Fatigue and cognitive function in systemic lupus erythematosus: associations with white matter microstructural damage. A diffusion tensor MRI study and meta-analysis.

PubMed

Wiseman, S J; Bastin, M E; Hamilton, I F; Hunt, D; Ritchie, S J; Amft, E N; Thomson, S; Belch, J F F; Ralston, S H; Wardlaw, J M

2017-05-01

Objective The objective of this study was to investigate fatigue and cognitive impairments in systemic lupus erythematous (SLE) in relation to diffuse white matter microstructural brain damage. Methods Diffusion tensor MRI, used to generate biomarkers of brain white matter microstructural integrity, was obtained in patients with SLE and age-matched controls. Fatigue and cognitive function were assessed and related to SLE activity, clinical data and plasma biomarkers of inflammation and endothelial dysfunction. Results Fifty-one patients with SLE (mean age 48.8 ± 14.3 years) were included. Mean diffusivity (MD) was significantly higher in all white matter fibre tracts in SLE patients versus age-matched healthy controls ( p < 0.0001). Fatigue in SLE was higher than a normal reference range ( p < 0.0001) and associated with lower MD ( ß = -0.61, p = 0.02), depression ( ß = 0.17, p = 0.001), anxiety ( ß = 0.13, p = 0.006) and higher body mass index ( ß = 0.10, p = 0.004) in adjusted analyses. Poorer cognitive function was associated with longer SLE disease duration ( p = 0.003) and higher MD ( p = 0.03) and, in adjusted analysis, higher levels of IL-6 ( ß = -0.15, p = 0.02) but not with MD. Meta-analysis (10 studies, n = 261, including the present study) confirmed that patients with SLE have higher MD than controls. Conclusion Patients with SLE have more microstructural brain white matter damage for age than the general population, but this does not explain increased fatigue or lower cognition in SLE. The association between raised IL-6 and worse current cognitive function in SLE should be explored in larger datasets.

Mobile App-Based Interventions to Support Diabetes Self-Management: A Systematic Review of Randomized Controlled Trials to Identify Functions Associated with Glycemic Efficacy.

PubMed

Wu, Yuan; Yao, Xun; Vespasiani, Giacomo; Nicolucci, Antonio; Dong, Yajie; Kwong, Joey; Li, Ling; Sun, Xin; Tian, Haoming; Li, Sheyu

2017-03-14

Mobile health apps for diabetes self-management have different functions. However, the efficacy and safety of each function are not well studied, and no classification is available for these functions. The aims of this study were to (1) develop and validate a taxonomy of apps for diabetes self-management, (2) investigate the glycemic efficacy of mobile app-based interventions among adults with diabetes in a systematic review of randomized controlled trials (RCTs), and (3) explore the contribution of different function to the effectiveness of entire app-based interventions using the taxonomy. We developed a 3-axis taxonomy with columns of clinical modules, rows of functional modules and cells of functions with risk assessments. This taxonomy was validated by reviewing and classifying commercially available diabetes apps. We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Chinese Biomedical Literature Database, and ClinicalTrials.gov from January 2007 to May 2016. We included RCTs of adult outpatients with diabetes that compared using mobile app-based interventions with usual care alone. The mean differences (MDs) in hemoglobin A 1c (HbA 1c ) concentrations and risk ratios of adverse events were pooled using a random-effects meta-analysis. After taxonomic classification, we performed exploratory subgroup analyses of the presence or absence of each module across the included app-based interventions. Across 12 included trials involving 974 participants, using app-based interventions was associated with a clinically significant reduction of HbA 1c (MD 0.48%, 95% CI 0.19%-0.77%) without excess adverse events. Larger HbA 1c reductions were noted among patients with type 2 diabetes than those with type 1 diabetes (MD 0.67%, 95% CI 0.30%-1.03% vs MD 0.36%, 95% CI 0.08%-0.81%). Having a complication prevention module in app-based interventions was associated with a greater HbA 1c reduction (with complication prevention: MD 1.31%, 95% CI 0.66%-1.96% vs without: MD 0.38%, 95% CI 0.09%-0.67%; intersubgroup P=.01), as was having a structured display (with structured display: MD 0.69%, 95% CI 0.32%-1.06% vs without: MD 0.16%, 95% CI 0.16%-0.48%; intersubgroup P=.03). However, having a clinical decision-making function was not associated with a larger HbA 1c reduction (with clinical decision making: MD 0.18%, 95% CI 0.21%-0.56% vs without: MD 0.61%, 95% CI 0.27%-0.95%; intersubgroup P=.10). The use of mobile app-based interventions yields a clinically significant HbA 1c reduction among adult outpatients with diabetes, especially among those with type 2 diabetes. Our study suggests that the clinical decision-making function needs further improvement and evaluation before being added to apps. ©Yuan Wu, Xun Yao, Giacomo Vespasiani, Antonio Nicolucci, Yajie Dong, Joey Kwong, Ling Li, Xin Sun, Haoming Tian, Sheyu Li. Originally published in JMIR Mhealth and Uhealth (http://mhealth.jmir.org), 14.03.2017.

European National Society Cardiovascular Journals

PubMed Central

Alfonso, F.; Ambrosio, G.; Pinto, F.J.; van der Wall, E.E.

2008-01-01

Anesti Kondili MD, Djamaleddine Nibouche MD, Karlen Adamyan MD, Kurt Huber MD, Hugo Ector MD, Izet Masic MD, Rumiana Tarnovska MD, Mario Ivanusa MD, Vladimír Stane˘k MD, Jørgen Videbæk MD, Mohamed Hamed MD, Alexandras Laucevicius MD, Pirjo Mustonen MD, Jean-Yves Artigou MD, Ariel Cohen MD, Mamanti Rogava MD, Michael Böhm MD, Eckart Fleck MD, Gerd Heusch MD, Rainer Klawki MD, Panos Vardas MD, Christodoulos Stefanadis MD, József Tenczer MD, Massimo Chiariello MD, Aleksandras Laucevicius MD, Joseph Elias MD, Halima Benjelloun MD, Olaf Rødevand MD, Piotr Kul/akowski MD, Edvard Apetrei MD, Victor A. Lusov MD, Rafael G. Oganov MD, Velibor Obradovic MD, Gabriel Kamensky MD, Miran F. Kenda MD, Christer Höglund MD, Thomas F. Lüscher MD, René Lerch MD, Moufid Jokhadar MD, Habib Haouala MD, Vedat Sansoy MD, Valentin Shumakov MD, Adam Timmis MD. (European National Society Cardiovascular Journals Editors, see Appendix for complete affiliations) PMID:18665206

DNMT gene expression and methylome in Marek’s disease resistant and susceptible chickens prior to and following infection by MDV

USDA-ARS?s Scientific Manuscript database

Marek’s disease (MD) is characterized as a T cell lymphoma induced by a cell-associated a-herpesvirus, Marek’s disease virus type 1 (MDV1). As with many viral infectious diseases, DNA methylation variations were observed in the progression of MD; these variations are thought to play an important rol...

Progress on Identifying Specific Genetic Changes in the Marek's Disease Virus Genome Associated With Attenuation Induced by Repeated In Vitro Passages

USDA-ARS?s Scientific Manuscript database

Marek’s disease (MD) vaccines have been successfully used for decades to control tumor formation induced by Marek’s disease virus (MDV), the causative agent and an oncogenic alphaherpesvirus. However, there is still a need for improved MD vaccines as none are sterilizing, and unpredictable vaccine b...

From Workstation to Classroom with the Click of a Mouse

ERIC Educational Resources Information Center

Gay, Rick

2009-01-01

Since July 2007, members of the Association of School Business Officials of Maryland and the District of Columbia have been able to shop for school and curriculum-related supplies through the ASBO MD/DC Web-based shopping platform. This shopping platform comprises 35 catalogs with more than 450,000 line items offered by 225 vendors. ASBO MD/DC's…

LRRTM4-C538Y novel gene mutation is associated with hereditary macular degeneration with novel dysfunction of ON-type bipolar cells.

PubMed

Kawamura, Yuichi; Suga, Akiko; Fujimaki, Takuro; Yoshitake, Kazutoshi; Tsunoda, Kazushige; Murakami, Akira; Iwata, Takeshi

2018-05-14

The macula is a unique structure in higher primates, where cone and rod photoreceptors show highest density in the fovea and the surrounding area, respectively. The hereditary macular dystrophies represent a heterozygous group of rare disorders characterized by central visual loss and atrophy of the macula and surrounding retina. Here we report an atypical absence of ON-type bipolar cell response in a Japanese patient with autosomal dominant macular dystrophy (adMD). To identify a causal genetic mutation for the adMD, we performed whole-exome sequencing (WES) on four affected and four-non affected members of the family for three generations, and identified a novel p.C538Y mutation in a post-synaptic gene, LRRTM4. WES analysis revealed seven rare genetic variations in patients. We further referred to our in-house WES data from 1360 families with inherited retinal diseases, and found that only p.C538Y mutation in LRRTM4 was associated with adMD-affected patients. Combinatorial filtration using public database of single-nucleotide polymorphism frequency and genotype-phenotype annotated database identified novel mutation in atypical adMD.

The brain and the biology of belief: An interview with Andrew Newberg, MD. Interview by Nancy Nachman-Hunt.

PubMed

Newberg, Andrew

2009-01-01

Andrew Newberg, MD, is an associate professor in the Department of Radiology, Division of Nuclear Medicine, at the Hospital of the University of Pennsylvania, Philadelphia, with secondary appointments in the Departments of Psychiatry and Religious Studies. He is actively involved in neuroimaging research projects, including the study of the neurophysiological correlates of meditation and other types of complementary therapies. Dr Newberg's research now largely focuses on how brain function is associated with various mental states, in particular, the relationship between brain function and mystical or religious experiences. He has authored several books, including Why God Won't Go Away: Brain Science and the Biology of Belief (Ballantine/Random House, 2001) and coauthor with Eugene G. d'Aquili, MD, of The Mystical Mind: Probing the Biology of Religious Experience (Fortress Press, 1999). His most recent book is How God Changes Your Brain, with coauthor Mark Waldman (Ballantine Books, 2009).

Cognitive control dysfunction in emotion dysregulation and psychopathology of major depression (MD): Evidence from transcranial brain stimulation of the dorsolateral prefrontal cortex (DLPFC).

PubMed

Salehinejad, Mohammad Ali; Ghanavai, Elham; Rostami, Reza; Nejati, Vahid

2017-03-01

Previous studies showed that MD is associated with a variety of cognitive deficits and executive dysfunctions which can persist even in remitted states. However, the role of cognitive impairments in MD psychopathology and treatment is not fully understood. This article aims to discuss how executive functions central components (e.g., Working memory and attention) mediate MD psychopathology considering the role of dorsolateral prefrontal cortex (dLPFC) and present findings of a brain stimulation experiment to support this notion. The effect of transcranial direct current stimulation (tDCS) of the dLPFC on enhancing cognitive control functions was investigated. Twenty-four patients with MD (Experimental group=12, Control group=12) received 10 sessions of tDCS (2mA for 30min) over 10 consecutive days. The experimental group received active stimulation and the control group received sham stimulation. Participant's performance on cognitive functions (PAL, SRM, RVP and CRT from CANTAB) and their depression scores were assessed before and after tDCS. Results showed that brain stimulation of the dLPFC improved executive dysfunction in patients and a significant improvement on depression scores was also observed suggesting that cognitive control dysfunction may be a mediator in emotional dysregulation and psychopathology of MD. No follow-up investigation was done in this study which does not allow to infer long-term effect of tDCS. Low-focality of tDCS might have stimulated adjacent areas too. Cognitive components, namely cognitive control dysfunction, play role in MD psychopathology as they are involved in emotion dysregulation in MD. The amount of contribution of cognitive components in MD psychopathology is however, an open question. tDCS can be used as an intervention to improve cognitive dysfunction in MD. Copyright © 2017 Elsevier B.V. All rights reserved.

Ligand Binding Pathways and Conformational Transitions of the HIV Protease.

PubMed

Miao, Yinglong; Huang, Yu-Ming M; Walker, Ross C; McCammon, J Andrew; Chang, Chia-En A

2018-03-06

It is important to determine the binding pathways and mechanisms of ligand molecules to target proteins to effectively design therapeutic drugs. Molecular dynamics (MD) is a promising computational tool that allows us to simulate protein-drug binding at an atomistic level. However, the gap between the time scales of current simulations and those of many drug binding processes has limited the usage of conventional MD, which has been reflected in studies of the HIV protease. Here, we have applied a robust enhanced simulation method, Gaussian accelerated molecular dynamics (GaMD), to sample binding pathways of the XK263 ligand and associated protein conformational changes in the HIV protease. During two of 10 independent GaMD simulations performed over 500-2500 ns, the ligand was observed to successfully bind to the protein active site. Although GaMD-derived free energy profiles were not fully converged because of insufficient sampling of the complex system, the simulations still allowed us to identify relatively low-energy intermediate conformational states during binding of the ligand to the HIV protease. Relative to the X-ray crystal structure, the XK263 ligand reached a minimum root-mean-square deviation (RMSD) of 2.26 Å during 2.5 μs of GaMD simulation. In comparison, the ligand RMSD reached a minimum of only ∼5.73 Å during an earlier 14 μs conventional MD simulation. This work highlights the enhanced sampling power of the GaMD approach and demonstrates its wide applicability to studies of drug-receptor interactions for the HIV protease and by extension many other target proteins.

Fast recovery of free energy landscapes via diffusion-map-directed molecular dynamics.

PubMed

Preto, Jordane; Clementi, Cecilia

2014-09-28

The reaction pathways characterizing macromolecular systems of biological interest are associated with high free energy barriers. Resorting to the standard all-atom molecular dynamics (MD) to explore such critical regions may be inappropriate as the time needed to observe the relevant transitions can be remarkably long. In this paper, we present a new method called Extended Diffusion-Map-directed Molecular Dynamics (extended DM-d-MD) used to enhance the sampling of MD trajectories in such a way as to rapidly cover all important regions of the free energy landscape including deep metastable states and critical transition paths. Moreover, extended DM-d-MD was combined with a reweighting scheme enabling to save on-the-fly information about the Boltzmann distribution. Our algorithm was successfully applied to two systems, alanine dipeptide and alanine-12. Due to the enhanced sampling, the Boltzmann distribution is recovered much faster than in plain MD simulations. For alanine dipeptide, we report a speedup of one order of magnitude with respect to plain MD simulations. For alanine-12, our algorithm allows us to highlight all important unfolded basins in several days of computation when one single misfolded event is barely observable within the same amount of computational time by plain MD simulations. Our method is reaction coordinate free, shows little dependence on the a priori knowledge of the system, and can be implemented in such a way that the biased steps are not computationally expensive with respect to MD simulations thus making our approach well adapted for larger complex systems from which little information is known.

Lipid droplet-associated gene expression and chromatin remodelling in LIPASE 5'-upstream region from beginning- to mid-endodormant bud in 'Fuji' apple.

PubMed

Saito, Takanori; Wang, Shanshan; Ohkawa, Katsuya; Ohara, Hitoshi; Ikeura, Hiromi; Ogawa, Yukiharu; Kondo, Satoru

2017-11-01

We found that lipid accumulation in the meristem region and the expression of MdLIP2A, which appears to be regulated by chromatin remodeling, coincided with endodormancy induction in the 'Fuji' apple. In deciduous trees, including apples (Malus × domestica Borkh.), lipid accumulation in the meristem region towards endodormancy induction has been thought to be an important process for the acquisition of cold tolerance. In this study, we conducted histological staining of crude lipids in the meristem region of 'Fuji' apples and found that lipid accumulation coincided with endodormancy induction. Since a major component of lipid bodies (triacylglycerol) is esterified fatty acids, we analysed fatty acid-derived volatile compounds and genes encoding fatty acid-modifying enzymes (MdLOX1A and MdHPL2A); the reduction of lipid breakdown also coincided with endodormancy induction. We then characterised the expression patterns of lipid body-regulatory genes MdOLE1 and MdLIP2A during endodormancy induction and found that the expression of MdLIP2A correlated well with lipid accumulation towards endodormancy induction. Based on these results, we conducted chromatin remodelling studies and localized the cis-element in the 5'-upstream region of MdLIP2A to clarify its regulatory mechanism. Finally, we revealed that chromatin was concentrated - 764 to - 862 bp of the 5'-upstream region of MdLIP2A, which harbours the GARE [gibberellin responsive MYB transcription factor binding site] and CArG [MADS-box transcription factor binding site] motifs-meristem development-related protein-binding sites.

Association between ambient particulate matter and disorders of vestibular function.

PubMed

Han, Changwoo; Lim, Youn-Hee; Jung, Kweon; Hong, Yun-Chul

2017-05-01

Exposure to environmental chemicals has been suggested to alter the physiologic state of the inner and middle ear. However, it is unknown if particulate matter exposure is associated with acute vestibular dysfunction. To estimate the effects of particulate matter exposure on the number of hospital visits related to three major diseases of vestibular dysfunction, Meniere's disease (MD), benign paroxysmal positional vertigo (BPPV), and vestibular neuronitis (VN). Our study subject is from Korean National Health Insurance Service-National Sample Cohort, which is dynamic cohort consist of 1 million participants representing the Korean population. Among total cohort participants, we used the hospital visit data of 210,000 individuals who resided in Seoul from 2007 to 2010. Time series analysis using the Poisson generalized additive model and case-crossover analysis using conditional logistic regression were used to investigate the association between daily particulate matter levels (PM 2.5 , particulate matter <2.5μg/m 3 ; PM 10 , particulate matter <10μg/m 3 ; PM 10-2.5 , PM 10 - PM 2.5 ) and number of MD, BPPV, and VN hospital visits. Time series analysis showed that an interquartile range (IQR) increase in PM 10 and PM 10-2.5 on lag day 1 was associated with an increased risk of MD hospital visits [relative risk (RR), 95% confidence interval (CI), PM 10 : 1.09 (1.02-1.15); PM 10-2.5 : 1.06 (1.02-1.10)]. In addition, elderly individuals (≥60 years old) showed an increased risk of MD hospital visits after particulate matter exposure when compared to younger individuals. An IQR increase in particulate matter on lag day 1 was associated with a marginally significant increase in VN hospital visits [RR (95%CI), PM 2.5 : 1.11 (0.98-1.25); PM 10 : 1.07 (0.99-1.15); PM 10-2.5 : 1.04 (0.99-1.09)]. However, no association between particulate matter exposure and BPPV hospital visits was noted. Case-crossover analyses showed similar results to the time-series analysis across all three diseases. MD hospital visits were associated with ambient particulate matter exposure. Elderly individuals, in particular, were more susceptible to particulate matter exposure than younger individuals. Copyright © 2017 Elsevier Inc. All rights reserved.

Molecular Imaging and Precision Medicine in Dementia and Movement Disorders.

PubMed

Mallik, Atul K; Drzezga, Alexander; Minoshima, Satoshi

2017-01-01

Precision medicine (PM) has been defined as "prevention and treatment strategies that take individual variability into account." Molecular imaging (MI) is an ideally suited tool for PM approaches to neurodegenerative dementia and movement disorders (MD). Here we review PM approaches and discuss how they may be applied to other associated neurodegenerative dementia and MD. With ongoing major therapeutic research initiatives that include the use of molecular imaging, we look forward to established interventions targeted to specific molecular pathophysiology and expect the potential benefit of MI PM approaches in neurodegenerative dementia and MD will only increase. Copyright © 2016 Elsevier Inc. All rights reserved.

[Genetic Variability and Structure of SNP Haplotypes in the DMPK Gene in Yakuts and Other Ethnic Groups of Northern Eurasia in Relation to Myotonic Dystrophy].

PubMed

Swarovskaya, M G; Stepanova, S K; Marussin, A V; Sukhomyasova, A L; Maximova, N R; Stepanov, V A

2015-06-01

The genetic variability of the DMPK locus has been studied in relation to six SNP markers (rs2070736, rs572634, rs1799894, rs527221, rs915915, and rs10415988) in Yakuts with myotonic dystrophy (MD) in the Yakut population and in populations of northern Eurasia. Significant differences were observed in the allele frequencies between patients and a population sample of Yakuts for three SNP loci (rs915915, rs1799894, and rs10415988) associated with a high chance of disease manifestation. The odds ratios (OR) of MD development in representatives of the Yakut population for these three loci were 2.59 (95% CI, p = 0,004), 4.99 (95% CI, p = 0.000), and 3.15 (95% CI, p = 0.01), respectively. Haplotype TTTCTC, which is associated with MD, and haplotype GTCCTT, which was observed only in Yakut MD patients (never in MD patients of non-Yakut origin), were revealed. A low level of variability in the locus of DMRK gene in Yakuts (H(e) = 0.283) compared with other examined populations was noted. An analysis of pairwise genetic relationships between populations revealed their significant differentiation for all the examined loci. In addition, a low level of differentiation in territorial groups of Yakut populations (F(ST) = 0.79%), which was related to the high subdivision of the northern Eurasian population (F(ST) = 11.83%), was observed.

The relationship of community activities with cognitive impairment and depressive mood independent of mobility disorder in Japanese older adults.

PubMed

Okura, Mika; Ogita, Mihoko; Yamamoto, Miki; Nakai, Toshimi; Numata, Tomoko; Arai, Hidenori

This study aimed to examine the relationship of participating in community activities (CA) with cognitive impairment and depressive mood independent of mobility disorder (MD) among older Japanese people. Elderly residents in institutions or those requiring long-term care insurance services were excluded; questionnaires were mailed to 5401 older adults in 2013. The response rate was 94.3% (n=5094). We used multiple imputation to manage missing data. The questionnaire addressed physical fitness, memory, mood, and CA. Participants were divided into two groups (good and bad) based on the median scores for physical fitness, memory, and mood. We identified items related to periodically performed CA, cognitive impairment, and depressive mood, and examined correlations between scores on these sets of items. The mean age was 75.9 years; 58.4% of participants were women. The following CA significantly predicted reduced cognitive impairment and depressive mood independent of MD: volunteer activity, community activity, visiting friends at home, pursuing hobbies, paid work, farm work, and daily shopping. These results were corrected for age, sex, and response method (mail or home-visit). Higher CA scores were associated with lower cognitive impairment and lower depressive mood independent of MD. CA is negatively associated with cognitive impairment and depressive mood among community-dwelling elderly independent of MD; promoting CA may protect against cognitive impairment and depressive mood in this population. However, MD, cognitive impairment, and depressive mood may lead to reduced CA. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Remote thalamic microstructural abnormalities related to cognitive function in ischemic stroke patients.

PubMed

Fernández-Andújar, Marina; Doornink, Fleur; Dacosta-Aguayo, Rosalía; Soriano-Raya, Juan José; Miralbell, Júlia; Bargalló, Núria; López-Cancio, Elena; Pérez de la Ossa, Natalia; Gomis, Meritxell; Millán, Mònica; Barrios, Maite; Cáceres, Cynthia; Pera, Guillem; Forés, Rosa; Clemente, Imma; Dávalos, Antoni; Mataró, Maria

2014-11-01

Ischemic stroke can lead to a continuum of cognitive sequelae, ranging from mild vascular cognitive impairment to vascular dementia. These cognitive deficits can be influenced by the disruption of cortico-subcortical circuits. We sought to explore remote thalamic microstructural abnormalities and their association with cognitive function after ischemic stroke. Seventeen patients with right hemispheric ischemic stroke and 17 controls matched for age, sex, and years of education were included. All participants underwent neurological, neuropsychological, and diffusion tensor image examination. Patients were assessed 3 months poststroke. Voxel-wise analysis was used to study thalamic diffusion differences between groups. Mean fractional anisotropy (FA) and mean diffusivity (MD) values in significant thalamic areas were calculated for each subject and correlated with cognitive performance. Stroke patients showed lower FA values and higher MD values in specific areas of both the left and right thalamus compared with controls. In patients, decreased FA values were associated with lower verbal fluency performance in the right thalamus (R(2) = 0.45, β = 0.74) and the left thalamus (R(2) = 0.57, β = 0.77) after adjusting for diabetes mellitus. Moreover, increased MD values were associated with lower verbal fluency performance in the right thalamus (R(2) = 0.27, β = -0.54) after adjusting for diabetes mellitus. In controls, thalamic FA and MD values were not related to any cognitive function. Our findings support the hypothesis that ischemic stroke lesions are associated with remote thalamic diffusion abnormalities, and that these abnormalities can contribute to cognitive dysfunction 3 months after a cerebrovascular event. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Thermal Conductivities in Solids from First Principles: Accurate Computations and Rapid Estimates

NASA Astrophysics Data System (ADS)

Carbogno, Christian; Scheffler, Matthias

In spite of significant research efforts, a first-principles determination of the thermal conductivity κ at high temperatures has remained elusive. Boltzmann transport techniques that account for anharmonicity perturbatively become inaccurate under such conditions. Ab initio molecular dynamics (MD) techniques using the Green-Kubo (GK) formalism capture the full anharmonicity, but can become prohibitively costly to converge in time and size. We developed a formalism that accelerates such GK simulations by several orders of magnitude and that thus enables its application within the limited time and length scales accessible in ab initio MD. For this purpose, we determine the effective harmonic potential occurring during the MD, the associated temperature-dependent phonon properties and lifetimes. Interpolation in reciprocal and frequency space then allows to extrapolate to the macroscopic scale. For both force-field and ab initio MD, we validate this approach by computing κ for Si and ZrO2, two materials known for their particularly harmonic and anharmonic character. Eventually, we demonstrate how these techniques facilitate reasonable estimates of κ from existing MD calculations at virtually no additional computational cost.

Quality of life in age-related macular degeneration: a review of the literature

PubMed Central

Mitchell, Jan; Bradley, Clare

2006-01-01

Background The Age-related Macular Degeneration Alliance International commissioned a review of the literature on quality of life (QoL) in macular degeneration (MD) with a view to increasing awareness of MD, reducing its impact and improving services for people with MD worldwide. Method A systematic review was conducted using electronic databases, conference proceedings and key journal hand search checks. The resulting 'White Paper' was posted on the AMD Alliance website and is reproduced here. Review MD is a chronic, largely untreatable eye condition which leads to loss of central vision needed for tasks such as reading, watching TV, driving, recognising faces. It is the most common cause of blindness in the Western world. Shock of diagnosis, coupled with lack of information and support are a common experience. Incidence of depression is twice that found in the community-dwelling elderly, fuelled by functional decline and loss of leisure activities. Some people feel suicidal. MD threatens independence, especially when comorbidity exacerbates functional limitations. Rehabilitation, including low vision aid (LVA) provision and training, peer support and education, can improve functional and psychological outcomes but many people do not receive services likely to benefit them. Medical treatments, suitable for only a small minority of people with MD, can improve vision but most limit progress of MD, at least for a time, rather than cure. The White Paper considers difficulties associated with inappropriate use of health status measures and misinterpretation of utility values as QoL measures: evidence suggests they have poor validity in MD. Conclusion There is considerable evidence for the major damage done to QoL by MD which is underestimated by health status and utility measures. Medical treatments are limited to a small proportion of people. However, much can be done to improve QoL by early diagnosis of MD with good communication of prognosis and continuing support. Support could include provision of LVAs, peer support, education and effective help in adjusting to MD. It is vital that appropriate measures of visual function and QoL be used in building a sound evidence base for the effectiveness of rehabilitation and treatment. PMID:17184527

Distinct Facial Processing Related Negative Cognitive Bias in First-Episode and Recurrent Major Depression: Evidence from the N170 ERP Component

PubMed Central

Chen, Jiu; Ma, Wentao; Zhang, Yan; Wu, Xingqu; Wei, Dunhong; Liu, Guangxiong; Deng, Zihe; Yang, Laiqi; Zhang, Zhijun

2014-01-01

Background States of depression are associated with increased sensitivity to negative events. For this novel study, we have assessed the relationship between the number of depressive episodes and the dysfunctional processing of emotional facial expressions. Methodology/Principal Findings We used a visual emotional oddball paradigm to manipulate the processing of emotional information while event-related brain potentials were recorded in 45 patients with first episode major depression (F-MD), 40 patients with recurrent major depression (R-MD), and 46 healthy controls (HC). Compared with the HC group, F-MD patients had lower N170 amplitudes when identifying happy, neutral, and sad faces; R-MD patients had lower N170 amplitudes when identifying happy and neutral faces, but higher N170 amplitudes when identifying sad faces. F-MD patients had longer N170 latencies when identifying happy, neutral, and sad faces relative to the HC group, and R-MD patients had longer N170 latencies when identifying happy and neutral faces, but shorter N170 latencies when identifying sad faces compared with F-MD patients. Interestingly, a negative relationship was observed between N170 amplitude and the depressive severity score for identification of happy faces in R-MD patients while N170 amplitude was positively correlated with the depressive severity score for identification of sad faces in F-MD and R-MD patients. Additionally, the deficits of N170 amplitude for sad faces positively correlated with the number of depressive episodes in R-MD patients. Conclusion/Significance These results provide new evidence that having more recurrent depressive episodes and serious depressive states are likely to aggravate the already abnormal processing of emotional facial expressions in patients with depression. Moreover, it further suggests that the impaired processing as indexed by N170 amplitude for positive face identification may be a potentially useful biomarker for predicting propagation of depression while N170 amplitude for negative face identification could be a potential biomarker for depression recurrence. PMID:25314024

Commentary on: Muscle dysmorphia: Could it be classified as an addiction to body image?

PubMed Central

2015-01-01

Background The article titled ‘Muscle dysmorphia: Could it be classified as an addiction to body image?’ used Griffiths (2005) addiction components model as the framework in which to define muscle dysmorphia (MD) as an addiction. The authors (Foster, Shorter & Griffiths, 2014) proposed that MD could be re-classified as an addiction to body image. Method and aim In response to the original article, the author of this commentary reflected on the ‘Addiction to body image’ model and the components of addiction as described in the context of MD. This invited commentary aimed to provide opposing viewpoints in order to give a balanced overview on the topic. Results It appears as if the components of addictions can be used as a framework in which to define MD. However, systematic empirical evidence had not been provided for the withdrawal symptoms associated with this behavioral addiction. An opposing viewpoint is provided in response to Foster et al.’s (2014) statement that MD is different from other body dysmorphic disorders in regards to cognitive dysfunction, and therefore cannot be explained in the same way. Conclusions Based on the little systematic empirical evidence to date, it may be a bit premature to re-classify MD as an addiction to body image. PMID:25592217

History of Morgellons disease: from delusion to definition

PubMed Central

Middelveen, Marianne J; Fesler, Melissa C

2018-01-01

Morgellons disease (MD) is a skin condition characterized by the presence of multicolored filaments that lie under, are embedded in, or project from skin. Although the condition may have a longer history, disease matching the above description was first reported in the US in 2002. Since that time, the condition that we know as MD has become a polemic topic. Because individuals afflicted with the disease may have crawling or stinging sensations and sometimes believe they have an insect or parasite infestation, most medical practitioners consider MD a purely delusional disorder. Clinical studies supporting the hypothesis that MD is exclusively delusional in origin have considerable methodological flaws and often neglect the fact that mental disorders can result from underlying somatic illness. In contrast, rigorous experimental investigations show that this skin affliction results from a physiological response to the presence of an infectious agent. Recent studies from that point of view show an association between MD and spirochetal infection in humans, cattle, and dogs. These investigations have determined that the cutaneous filaments are not implanted textile fibers, but are composed of the cellular proteins keratin and collagen and result from overproduction of these filaments in response to spirochetal infection. Further studies of the genetics, pathogenesis, and treatment of MD are warranted. PMID:29467580

History of Morgellons disease: from delusion to definition.

PubMed

Middelveen, Marianne J; Fesler, Melissa C; Stricker, Raphael B

2018-01-01

Morgellons disease (MD) is a skin condition characterized by the presence of multicolored filaments that lie under, are embedded in, or project from skin. Although the condition may have a longer history, disease matching the above description was first reported in the US in 2002. Since that time, the condition that we know as MD has become a polemic topic. Because individuals afflicted with the disease may have crawling or stinging sensations and sometimes believe they have an insect or parasite infestation, most medical practitioners consider MD a purely delusional disorder. Clinical studies supporting the hypothesis that MD is exclusively delusional in origin have considerable methodological flaws and often neglect the fact that mental disorders can result from underlying somatic illness. In contrast, rigorous experimental investigations show that this skin affliction results from a physiological response to the presence of an infectious agent. Recent studies from that point of view show an association between MD and spirochetal infection in humans, cattle, and dogs. These investigations have determined that the cutaneous filaments are not implanted textile fibers, but are composed of the cellular proteins keratin and collagen and result from overproduction of these filaments in response to spirochetal infection. Further studies of the genetics, pathogenesis, and treatment of MD are warranted.

Microstructural Changes to the Brain of Mice after Methamphetamine Exposure as Identified with Diffusion Tensor Imaging

PubMed Central

McKenna, Benjamin S.; Brown, Gregory G.; Archibald, Sarah; Scadeng, Miriam; Bussell, Robert; Kesby, James P.; Markou, Athina; Soontornniyomkij, Virawudh; Achim, Cristian; Semenova, Svetlana

2016-01-01

Methamphetamine (METH) is an addictive psychostimulant inducing neurotoxicity. Human magnetic resonance imaging and diffusion tensor imaging (DTI) of METH-dependent participants find various structural abnormities. Animal studies demonstrate immunohistochemical changes in multiple cellular pathways after METH exposure. Here, we characterized the long-term effects of METH on brain microstructure in mice exposed to an escalating METH binge regimen using in vivo DTI, a methodology directly translatable across species. Results revealed four patterns of differential fractional anisotropy (FA) and mean diffusivity (MD) response when comparing METH-exposed (n=14) to saline-treated mice (n=13). Compared to the saline group, METH-exposed mice demonstrated: 1) decreased FA with no change in MD [corpus callosum (posterior forceps), internal capsule (left), thalamus (medial aspects), midbrain], 2) increased MD with no change in FA [posterior isocortical regions, caudate-putamen, hypothalamus, cerebral peduncle, internal capsule (right)], 3) increased FA with decreased MD [frontal isocortex, corpus callosum (genu)], and 4) increased FA with no change or increased MD [hippocampi, amygdala, lateral thalamus]. MD was negatively associated with calbindin-1 in hippocampi and positively with dopamine transporter in caudate-putamen. These findings highlight distributed and differential METH effects within the brain suggesting several distinct mechanisms. Such mechanisms likely change brain tissue differentially dependent upon neural location. PMID:27000304

Mediterranean food consumption patterns: low environmental impacts and significant health-nutrition benefits.

PubMed

Aboussaleh, Y; Capone, R; Bilali, H El

2017-11-01

The Mediterranean dietary patterns comply better with recommended nutrient and micronutrient intakes. The Mediterranean diet (MD) was associated with reduced mortality and lower risk for metabolic chronic diseases. It has also low ecological, carbon and water footprints due to its high share of plant-based foods. In fact, the share of plant-based dietary energy is higher in the Mediterranean than in Northern Europe. The Mediterranean hotspot is a major centre of plant and crop diversity. Mediterranean people gather and consume about 2300 plant species. This review paper aims at highlighting the nutrition-health benefits of the MD and analysing the main environmental impacts of the Mediterranean food consumption patterns. There is a growing body of scientific evidence that the MD has significant health-nutrition benefits and low environmental footprints, so there is urgent need to reverse the ongoing erosion of the MD heritage and to promote it as a sustainable diets model.

Mediodorsal thalamus is required for discrete phases of goal-directed behavior in macaques.

PubMed

Wicker, Evan; Turchi, Janita; Malkova, Ludise; Forcelli, Patrick Alexander

2018-05-31

Reward contingencies are dynamic: outcomes that were valued at one point may subsequently lose value. Action selection in the face of dynamic reward associations requires several cognitive processes: registering a change in value of the primary reinforcer, adjusting the value of secondary reinforcers to reflect the new value of the primary reinforcer, and guiding action selection to optimal choices. Flexible responding has been evaluated extensively using reinforcer devaluation tasks. Performance on this task relies upon amygdala, Areas 11 and 13 of orbitofrontal cortex (OFC), and mediodorsal thalamus (MD). Differential contributions of amygdala and Areas 11 and 13 of OFC to specific sub-processes have been established, but the role of MD in these sub-processes is unknown. Pharmacological inactivation of the macaque MD during specific phases of this task revealed that MD is required for reward valuation and action selection. This profile is unique, differing from both amygdala and subregions of the OFC.

Role of Molecular Dynamics and Related Methods in Drug Discovery.

PubMed

De Vivo, Marco; Masetti, Matteo; Bottegoni, Giovanni; Cavalli, Andrea

2016-05-12

Molecular dynamics (MD) and related methods are close to becoming routine computational tools for drug discovery. Their main advantage is in explicitly treating structural flexibility and entropic effects. This allows a more accurate estimate of the thermodynamics and kinetics associated with drug-target recognition and binding, as better algorithms and hardware architectures increase their use. Here, we review the theoretical background of MD and enhanced sampling methods, focusing on free-energy perturbation, metadynamics, steered MD, and other methods most consistently used to study drug-target binding. We discuss unbiased MD simulations that nowadays allow the observation of unsupervised ligand-target binding, assessing how these approaches help optimizing target affinity and drug residence time toward improved drug efficacy. Further issues discussed include allosteric modulation and the role of water molecules in ligand binding and optimization. We conclude by calling for more prospective studies to attest to these methods' utility in discovering novel drug candidates.

Medical Robotic and Telesurgical Simulation and Education Research

DTIC Science & Technology

2013-09-01

Hospital Nicholson Center 601 E Rollins St Orlando, FL 32803 9. SPONSORING / MONITORING AGENCY NAME( S ) AND ADDRESS(ES) 10. SPONSOR/MONITOR’S...Principal Investigators: R.M. Satava, University of Washington School of Medicine, Seattle , WA R.D. Smith, Florida Hospital Nicholson Center...Blalock 1210 Baltimore, MD 21287 USA Thomas S . Lendvay, MD, FACS Associate Professor Co-Director, Seattle Children’s Robotics Surgery Center

The Medial Dorsal Thalamic Nucleus and the Medial Prefrontal Cortex of the Rat Function Together to Support Associative Recognition and Recency but Not Item Recognition

ERIC Educational Resources Information Center

Cross, Laura; Brown, Malcolm W.; Aggleton, John P.; Warburton, E. Clea

2013-01-01

In humans recognition memory deficits, a typical feature of diencephalic amnesia, have been tentatively linked to mediodorsal thalamic nucleus (MD) damage. Animal studies have occasionally investigated the role of the MD in single-item recognition, but have not systematically analyzed its involvement in other recognition memory processes. In…

Clinical Investigation Program Report.

DTIC Science & Technology

1983-10-01

metastatic to liver. (0) H-83-63. Double-blind, randomized parallel comparison of two different dosage regimens of naproxen sodium in patients with...different dosage regimens of naproxen sodium in patients with bone pain due to m etastatic cancer. Start Date: May 83 Est Comp Date: Indefinite Principal...Investigator: Facility: LTC D Gandara, MD LAMC CPT R Mansour, MD D ept/Svc: Associate Investigators: Hematology-Oncology Key Words: naproxen sodium

Genetic mapping of QTLs associated with seed macronutrients accumulation in 'MD96-5722' by 'Spencer' recombinant inbred lines of soybean

USDA-ARS?s Scientific Manuscript database

Research of genetic mapping of QTLs for macronutrient accumulation in soybean seed is limited. Therefore, the objective of this research was to identify QTLs related to macronutrients (N, C, S, P, K, Ca, and Mg) in seeds in 92 F5:7 recombinant inbred lines developed from a cross between MD 96-5722 (...

Does RBC Storage Age Effect Inflammation, Immune Function and Susceptibility to Transfusion Associated Microchimerism in Critically Ill Patients? Adverse Effects of RBC Storage in Critically Ill Patients

DTIC Science & Technology

2013-12-01

PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Philip Spinella, M.D. 5d. PROJECT NUMBER Philip J. Norris , M.D.; Avani Shah, MPH 5e. TASK NUMBER Email...dysfunction syndrome , serious thrombotic events and nosocomial infections, and ICU and hospital length of stay. Prospective clinical studies investigating

Why Does Disaster Recovery Work Influence Mental Health?: Pathways through Physical Health and Household Income.

PubMed

Lowe, Sarah R; Kwok, Richard K; Payne, Julianne; Engel, Lawrence S; Galea, Sandro; Sandler, Dale P

2016-12-01

Disaster recovery work increases risk for mental health problems, yet the mechanisms underlying this association are unclear. We explored links from recovery work to post-traumatic stress (PTS), major depression (MD), and generalized anxiety disorder (GAD) symptoms through physical health symptoms and household income in the aftermath of the Deepwater Horizon oil spill. As part of the NIEHS GuLF STUDY, participants (N = 10,141) reported on cleanup work activities, spill-related physical health symptoms, and household income at baseline, and mental health symptoms an average of 14.69 weeks (SD = 16.79) thereafter. Cleanup work participation was associated with higher physical health symptoms, which in turn were associated with higher PTS, MD, and GAD symptoms. Similar pattern of results were found in models including workers only and investigating the influence of longer work duration and higher work-related oil exposure on mental health symptoms. In addition, longer worker duration and higher work-related oil exposure were associated with higher household income, which in turn was associated with lower MD and GAD symptoms. These findings suggest that physical health symptoms contribute to workers' risk for mental health symptoms, while higher household income, potentially from more extensive work, might mitigate risk. © Society for Community Research and Action 2016.

Genome-wide Mechanosensitive MicroRNA (MechanomiR) Screen Uncovers Dysregulation of Their Regulatory Networks in the mdm Mouse Model of Muscular Dystrophy.

PubMed

Mohamed, Junaith S; Hajira, Ameena; Lopez, Michael A; Boriek, Aladin M

2015-10-09

Muscular dystrophies (MDs) are a heterogeneous group of genetic and neuromuscular disorders, which result in severe loss of motor ability and skeletal muscle mass and function. Aberrant mechanotransduction and dysregulated-microRNA pathways are often associated with the progression of MD. Here, we hypothesized that dysregulation of mechanosensitive microRNAs (mechanomiRs) in dystrophic skeletal muscle plays a major role in the progression of MD. To test our hypothesis, we performed a genome-wide expression profile of anisotropically regulated mechanomiRs and bioinformatically analyzed their target gene networks. We assessed their functional roles in the advancement of MD using diaphragm muscles from mdm (MD with myositis) mice, an animal model of human tibial MD (titinopathy), and their wild-type littermates. We were able to show that ex vivo anisotropic mechanical stretch significantly alters the miRNA expression profile in diaphragm muscles from WT and mdm mice; as a result, some of the genes associated with MDs are dysregulated in mdm mice due to differential regulation of a distinct set of mechanomiRs. Interestingly, we found a contrasting expression pattern of the highly expressed let-7 family mechanomiRs, let-7e-5p and miR-98-5p, and their target genes associated with the extracellular matrix and TGF-β pathways, respectively, between WT and mdm mice. Gain- and loss-of-function analysis of let-7e-5p in myocytes isolated from the diaphragms of WT and mdm mice confirmed Col1a1, Col1a2, Col3a1, Col24a1, Col27a1, Itga1, Itga4, Scd1, and Thbs1 as target genes of let-7e-5p. Furthermore, we found that miR-98 negatively regulates myoblast differentiation. Our study therefore introduces additional biological players in the regulation of skeletal muscle structure and myogenesis that may contribute to unexplained disorders of MD. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Preliminary results demonstrating the impact of Mediterranean diet on bone health.

PubMed

Savanelli, Maria Cristina; Barrea, Luigi; Macchia, Paolo Emidio; Savastano, Silvia; Falco, Andrea; Renzullo, Andrea; Scarano, Elisabetta; Nettore, Immacolata Cristina; Colao, Annamaria; Di Somma, Carolina

2017-04-24

Nutrition is an environmental factor affecting bone health. Nutrition is considered essential to achieve and maintain optimal bone mass. Mediterranean diet (MD) has shown to prevent bone disease. Aim of this study is to investigate the relationship between bone health status and adherence the MD. Four-hundred eighteen healthy people (105 males and 313 females, age 50 ± 14 years) were recruited in the outdoor hospital of the "Campus Salute Onlus" held in Piazza del Plebiscito in Naples, October 17-20th 2013 and 09-11th October 2014. All subjects underwent clinical assessment, calcaneal quantitative ultrasound (QUS) scanner and PREvención con DIeta MEDiterránea (PREDIMED) questionnaire. Globally, prevalence of osteoporosis and osteopenia were 7.7 and 46.0%, respectively. The majority of subjects (60.5%) had an average score (score 6-9) of adherence to MD. The T-score showed positive correlation with PREDIMED score (r = 0.250, p < 0.001). The higher T-scores were positively associated with a higher consumption of extra-virgin olive oil (EVOO), vegetables, fruits, legumes, and fish and negatively associated with consumption of red meat. The higher T-scores were positively associated with the highest odds of PREDIMED scores (higher adherence) (OR 6.91, IC 6.27-7.61, p < 0.001). Multiple regression analysis models indicated that, among the single food items investigated, high T-score can be predicted by consumption of EVOO (p < 0.001), fish (p < 0.001) and fruit (p = 0.002) intake. A PREDIMED score of 3 was found to be predictive for a low T-score (α = 0.05, R-squared index = 0.417). The results demonstrate a positive correlation between bone health status and adherence to MD, suggesting that a high adherence to MD promotes bone health. The observations here reported confirmed that a specific dietary approach, such as MD, can represent a modifiable environmental factor for osteoporosis' prevention.

Properties of acid gels made from sodium caseinate-maltodextrin conjugates prepared by a wet heating method.

PubMed

Zhang, Shuwen; Gong, Yuansheng; Khanal, Som; Lu, Yanjie; Lucey, John A

2017-11-01

Covalent attachment of polysaccharides to proteins (conjugation) via the Maillard reaction has been extensively studied. Conjugation can lead to a significant improvement in protein functionality (e.g., solubility, emulsification, and heat stability). Caseins have previously been successfully conjugated with maltodextrin (Md), but the effect on the detailed acid gelation properties has not been examined. We studied the effect of conjugating sodium caseinate (NaCN) with 3 different sized Md samples via the Maillard reaction in aqueous solutions. The Md samples had dextrose equivalents of 4 to 7, 9 to 12, and 20 to 23 for Md40, Md100, and Md200, respectively. The conjugation reaction was performed in mixtures with 5% NaCN and 5% Md, which were heated at 90°C for 10 h. The degree of conjugation was estimated from the reduction in free amino groups as well as color changes. Sodium dodecyl sulfate-PAGE analysis was performed to confirm conjugation by employing staining of both protein and carbohydrate bands. The molar mass of samples was determined by size-exclusion chromatography coupled with multi-angle laser light scattering. After the conjugation reaction, samples were then gelled by the addition of 0.63% (wt/vol) glucono-δ-lactone at 30°C, such that samples reached pH 4.6 after about 13 h. The rheological properties of samples during acidification was monitored by small-strain dynamic oscillatory rheology. The microstructure of acid gels at pH 4.6 was examined by fluorescence microscopy. Conjugation resulted in a loss of 10.8, 8.8, and 11.9% of the available amino groups in the protein for the NaCN-Md40 conjugates (C40), NaCN-Md100 conjugates (C100), and NaCN-Md100 conjugates (C200), respectively. With a decrease in the size of the type of Md, an increase occurred in the molar mass of the resultant conjugate. The weight average molar masses of NaCN-Md samples were 340, 368, and 425 kDa for the conjugates C40, C100, and C200, respectively. Addition of Md to NaCN dispersion resulted in slightly shorter acid gelation times even without the conjugation reaction. The storage modulus (G') of acid gels was significantly lower in conjugated samples compared with the corresponding (unreacted) mixtures of Md and NaCN. The sample with the lowest G' value at pH 4.6 was the C40 conjugate. Fluorescence microscopy showed that gels made by conjugates had slightly larger pores. These results indicate that conjugation of casein modified its acid gelation properties, presumably by the Md polysaccharide moiety hindering aggregation and rearrangements of the casein network. Copyright © 2017 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Effects of Obesity and Leptin Deficiency on Morphine Pharmacokinetics in a Mouse Model.

PubMed

Dalesio, Nicholas M; Hendrix, Craig W; McMichael, Douglas Hale; Thompson, Carol B; Lee, Carlton K K; Pho, Huy; Arias, Rafael S; Lynn, Rachael Rzasa; Galinkin, Jeffrey; Yaster, Myron; Brown, Robert H; Schwartz, Alan R

2016-12-01

Obesity causes multiorgan dysfunction, specifically metabolic abnormalities in the liver. Obese patients are opioid-sensitive and have high rates of respiratory complications after surgery. Obesity also has been shown to cause resistance to leptin, an adipose-derived hormone that is key in regulating hunger, metabolism, and respiratory stimulation. We hypothesized that obesity and leptin deficiency impair opioid pharmacokinetics (PK) independently of one another. Morphine PK were characterized in C57BL/6J wild-type (WT), diet-induced obese (DIO), and leptin-deficient (ob/ob) mice, and in ob/ob mice given leptin-replacement (LR) therapy. WT mice received several dosing regimens of morphine. Obese mice (30 g) received one 80 mg/kg bolus of morphine. Blood was collected at fixed times after morphine injection for quantification of plasma morphine and morphine 3-glucuronide (M3G) levels. PK parameters used to evaluate morphine metabolism included area-under the curve (AUC150), maximal morphine concentration (CMAX), and M3G-to-morphine ratio, and drug elimination was determined by clearance (Cl/F), volume of distribution, and half-life (T1/2). PK parameters were compared between mouse groups by the use of 1-way analysis of variance, with P values less than .05 considered significant. DIO compared with WT mice had significantly decreased morphine metabolism with lower M3G-to-morphine ratio (mean difference [MD]: -4.9; 95% confidence interval [CI]: -8.8 to -0.9) as well as a decreased Cl/F (MD: -4.0; 95% CI: -8.9 to -0.03) Ob/ob compared with WT mice had a large increase in morphine exposure with a greater AUC150 (MD: 980.4; 95% CI: 630.1-1330.6), CMAX (MD: 6.8; 95% CI: 2.7-10.9), and longer T1/2 (MD: 23.1; 95% CI: 10.5-35.6), as well as a decreased Cl/F (MD: -7.0; 95% CI: -11.6 to -2.7). Several PK parameters were significantly greater in ob/ob compared with DIO mice, including AUC150 (MD: 636.4; 95% CI: 207.4-1065.4), CMAX (MD: 5.3; 95% CI: 3.2-10.3), and T1/2 (MD: 18.3; 95% CI: 2.8-33.7). When leptin was replaced in ob/ob mice, PK parameters began to approach DIO and WT levels. LR compared with ob/ob mice had significant decreases in AUC150 (MD: -779.9; 95% CI: -1229.8 to -330), CMAX (MD: -6.1; 95% CI: -11.4 to -0.9), and T1/2 (MD: -19; 95% CI: -35.1 to -2.8). Metabolism increased with LR, with LR mice having a greater M3G-to-morphine ratio compared with DIO (MD: 5.3; 95% CI: 0.3-10.4). Systemic effects associated with obesity decrease morphine metabolism and excretion. A previous study from our laboratory demonstrated that obesity and leptin deficiency decrease the sensitivity of central respiratory control centers to carbon dioxide. Obesity and leptin deficiency substantially decreased morphine metabolism and clearance, and replacing leptin attenuated the PK changes associated with leptin deficiency, suggesting leptin has a direct role in morphine metabolism.

Empathic and Self-Regulatory Processes Governing Doping Behavior

PubMed Central

Boardley, Ian D.; Smith, Alan L.; Mills, John P.; Grix, Jonathan; Wynne, Ceri

2017-01-01

Evidence associating doping behavior with moral disengagement (MD) has accumulated over recent years. However, to date, research examining links between MD and doping has not considered key theoretically grounded influences and outcomes of MD. As such, there is a need for quantitative research in relevant populations that purposefully examines the explanatory pathways through which MD is thought to operate. Toward this end, the current study examined a conceptually grounded model of doping behavior that incorporated empathy, doping self-regulatory efficacy (SRE), doping MD, anticipated guilt and self-reported doping/doping susceptibility. Participants were specifically recruited to represent four key physical-activity contexts and consisted of team- (n = 195) and individual- (n = 169) sport athletes and hardcore- (n = 125) and corporate- (n = 121) gym exercisers representing both genders (nmale = 371; nfemale = 239); self-reported lifetime prevalence of doping across the sample was 13.6%. Each participant completed questionnaires assessing the aforementioned variables. Structural equation modeling indicated strong support for all study hypotheses. Specifically, we established: (a) empathy and doping SRE negatively predicted reported doping; (b) the predictive effects of empathy and doping SRE on reported doping were mediated by doping MD and anticipated guilt; (c) doping MD positively predicted reported doping; (d) the predictive effects of doping MD on reported doping were partially mediated by anticipated guilt. Substituting self-reported doping for doping susceptibility, multisample analyses then demonstrated these predictive effects were largely invariant between males and females and across the four physical-activity contexts represented. These findings extend current knowledge on a number of levels, and in doing so aid our understanding of key psychosocial processes that may govern doping behavior across key physical-activity contexts. PMID:29018370

Reduced levels of skeletal muscle Na+K+ -ATPase in McArdle disease

NASA Technical Reports Server (NTRS)

Haller, R. G.; Clausen, T.; Vissing, J.; Blomqvist, C. G. (Principal Investigator)

1998-01-01

We evaluated the hypothesis that impaired sarcolemmal function associated with exaggerated potassium release, impaired potassium uptake, or both may contribute to exertional fatigue and abnormal circulatory responses to exercise in McArdle disease (MD). The cellular mechanism of exertional fatigue and muscle injury in MD is unknown but likely involves impaired function of the ATPases that couple ATP hydrolysis to cellular work, including the muscle sodium potassium pump (Na+K+-ATPase). However, the concentration of muscle Na+K+ pumps in MD is not known, and no studies have related exercise increases in blood potassium concentrations to muscle Na+K+ pump levels. We measured muscle Na+K+ pumps (3H-ouabain binding) and plasma K+ in response to 20 minutes of cycle exercise in six patients with MD and in six sex-, age-, and weight-matched sedentary individuals. MD patients had lower levels of 3H-ouabain binding (231 +/- 18 pmol/g w.w., mean +/- SD, range, 210 to 251) than control subjects (317 +/- 37, range, 266 to 371, p < 0.0004), higher peak increases in plasma potassium in response to 45 +/- 7 W cycle exercise (MD, 1.00 +/- 0.15 mmol/L; control subjects, 0.48 +/- 0.09; p < 0.0001), and mean exercise heart rate responses to exercise that were 45 +/- 12 bpm greater than control subjects. Our results indicate that Na+K+ pump levels are low in MD patients compared with healthy subjects and identify a limitation of potassium reuptake that could result in sarcolemmal failure during peak rates of membrane activation and may promote exaggerated potassium-activated circulatory responses to submaximal exercise. The mechanism of the low Na+K+ pump concentrations in MD is unknown but may relate to deconditioning or to disruption of a close functional relationship between membrane ion transport and glycolysis.

Decreased serum L-arginine and L-citrulline levels in major depression.

PubMed

Hess, S; Baker, G; Gyenes, G; Tsuyuki, R; Newman, S; Le Melledo, Jean-Michel

2017-11-01

It has been suggested that endothelial dysfunction caused by a decreased endothelial production of nitric oxide (NO) may contribute to the consistently observed increased risk of developing cardiovascular disease (CVD) in physically healthy patients suffering from major depression (MD). NO is a gas synthesized from Larginine (a conditionally essential amino acid) and oxygen by endothelial nitric oxide synthase (eNOS). The end products of NO production include both NO and L-citrulline. NO is rapidly reduced to the anions nitrite and nitrate, classically referred to as NO metabolites. Their measurement has been used as a surrogate measurement for endothelial NO production. We and others have shown decreased levels of NO metabolites in the serum of MD patients. The mechanism of this decreased production of NO by the endothelium has not yet been elucidated. The purpose of this study is to assess serum levels of L-arginine and L-citrulline in patients with MD. Levels of L-arginine and L-citrulline were measured in 35 unmedicated physically healthy MD patients and 36 healthy controls (HCs). L-arginine and L-citrulline concentrations were significantly lower in MD patients than in healthy controls (L-arginine, 73.54 + 21.53 μmol/L and 84.89 + 25.16, p = 0.04 μmol/L and L-citrulline 31.58 + 6.05 μmol/L and 35.19 + 6.85 μmol/L, p = 0.03, respectively). The decrease in L-arginine levels in MD patients is a possible explanation for the decrease in NO metabolites in MD patients and therefore may contribute, through endothelial dysfunction, to the increased CV risk associated with MD.

N-Terminal pro-brain natriuretic peptide levels in dichorionic diamniotic twins with selective intrauterine growth restriction.

PubMed

Fujioka, Kazumichi; Mizobuchi, Masami; Sakai, Hitomi; Iwatani, Sota; Wada, Keiko; Yoshimoto, Seiji; Nakao, Hideto

2014-03-04

Monochorionic diamniotic (MD) twins with selective intrauterine growth restriction (sIUGR) have known associations with cardiac complications. However, the cardiac load of dichorionic diamniotic (DD) twins with sIUGR (DD-sIUGR) remains unclear. N-terminal pro-brain natriuretic peptide (NT-pro BNP) is a convenient marker of cardiac dysfunction in neonates, and is elevated in MD twins with sIUGR (MD-sIUGR). However, there are no reports assessing serum NT-pro BNP levels in DD-sIUGR. Here, we aimed to clarify serum NT-pro BNP levels at birth in DD-sIUGR, and to compare them with those of MD-sIUGR. Forty-one DD twin pairs admitted to our center between October 2007 and January 2013 were enrolled in this study and separated into two groups: nine twins with sIUGR (DD-sIUGR group) and 32 twins without sIUGR (DD without sIUGR group). Sixteen MD twins with sIUGR (MD-sIUGR group) served as positive controls. Serum NT-pro BNP levels at birth in DD-sIUGR [median 2,115 pg/ml (range, 443-6,590 pg/ml)] were significantly higher than in DD without sIUGR [1,080 pg/ml (range, 313-3,470 pg/ml); p=0.001], and significantly lower than in MD twins with sIUGR [4,520 pg/ml (range, 529-62,400 pg/ml); p=0.04]. Serum NT-pro BNP levels between larger and smaller DD co-twins were significantly correlated (r = 0.582; p<0.0001). In conclusion, serum NT-pro BNP levels at birth in DD twins with sIUGR were higher than those without, and lower than in MD twins with sIUGR.

Empathic and Self-Regulatory Processes Governing Doping Behavior.

PubMed

Boardley, Ian D; Smith, Alan L; Mills, John P; Grix, Jonathan; Wynne, Ceri

2017-01-01

Evidence associating doping behavior with moral disengagement (MD) has accumulated over recent years. However, to date, research examining links between MD and doping has not considered key theoretically grounded influences and outcomes of MD. As such, there is a need for quantitative research in relevant populations that purposefully examines the explanatory pathways through which MD is thought to operate. Toward this end, the current study examined a conceptually grounded model of doping behavior that incorporated empathy, doping self-regulatory efficacy (SRE), doping MD, anticipated guilt and self-reported doping/doping susceptibility. Participants were specifically recruited to represent four key physical-activity contexts and consisted of team- ( n = 195) and individual- ( n = 169) sport athletes and hardcore- ( n = 125) and corporate- ( n = 121) gym exercisers representing both genders ( n male = 371; n female = 239); self-reported lifetime prevalence of doping across the sample was 13.6%. Each participant completed questionnaires assessing the aforementioned variables. Structural equation modeling indicated strong support for all study hypotheses. Specifically, we established: (a) empathy and doping SRE negatively predicted reported doping; (b) the predictive effects of empathy and doping SRE on reported doping were mediated by doping MD and anticipated guilt; (c) doping MD positively predicted reported doping; (d) the predictive effects of doping MD on reported doping were partially mediated by anticipated guilt. Substituting self-reported doping for doping susceptibility, multisample analyses then demonstrated these predictive effects were largely invariant between males and females and across the four physical-activity contexts represented. These findings extend current knowledge on a number of levels, and in doing so aid our understanding of key psychosocial processes that may govern doping behavior across key physical-activity contexts.

Different Preclimacteric Events in Apple Cultivars with Modified Ripening Physiology

PubMed Central

Singh, Vikram; Weksler, Asya; Friedman, Haya

2017-01-01

“Anna” is an early season apple cultivar exhibiting a fast softening and juiciness loss during storage, in comparison to two mid-late season cultivars “Galaxy” and “GD.” The poor storage capacity of “Anna” was correlated with high lipid oxidation-related autoluminescence, high respiration and ethylene production rates, associated with high expression of MdACO1, 2, 4, 7, and MdACS1. All cultivars at harvest responded to exogenous ethylene by enhancing ethylene production, typical of system-II. The contribution of pre-climacteric events to the poor storage capacity of “Anna” was examined by comparing respiration and ethylene production rates, response to exogenous ethylene, expression of genes responsible for ethylene biosynthesis and response, and developmental regulators in the three cultivars throughout fruit development. In contrast to the “Galaxy” and “GD,” “Anna” showed higher ethylene production and respiration rates during fruit development, and exhibited auto-stimulatory (system II-like) effect in response to exogenous ethylene. The higher ethylene production rate in “Anna” was correlated with higher expression of ethylene biosynthesis genes, MdACS3a MdACO2, 4, and 7 during early fruit development. The expression of negative regulators of ripening (AP2/ERF) and ethylene response pathway, (MdETR1,2 and MdCTR1) was lower in “Anna” in comparison to the other two cultivars throughout development and ripening. Similar pattern of gene expression was found for SQUAMOSA promoter binding protein (SBP)-box genes, including MdCNR and for MdFUL. Taken together, this study provides new understanding on pre-climacteric events in “Anna” that might affect its ripening behavior and physiology following storage. PMID:28928755

Biochemical characterisation of MdCXE1, a carboxylesterase from apple that is expressed during fruit ripening.

PubMed

Souleyre, Edwige J F; Marshall, Sean D G; Oakeshott, John G; Russell, Robyn J; Plummer, Kim M; Newcomb, Richard D

2011-05-01

Esters are an important component of apple (Malus×domestica) flavour. Their biosynthesis increases in response to the ripening hormone ethylene, but their metabolism by carboxylesterases (CXEs) is poorly understood. We have identified 16 members of the CXE multigene family from the commercial apple cultivar, 'Royal Gala', that contain all the conserved features associated with CXE members of the α/β hydrolase fold superfamily. The expression of two genes, MdCXE1 and MdCXE16 was characterised in an apple fruit development series and in a transgenic line of 'Royal Gala' (AO3) that is unable to synthesise ethylene in fruit. In wild-type MdCXE1 is expressed at low levels during early stages of fruit development, rising to a peak of expression in apple fruit at harvest maturity. It is not significantly up-regulated by ethylene in the skin of AO3 fruit. MdCXE16 is expressed constitutively in wild-type throughout fruit development, and is up-regulated by ethylene in skin of AO3 fruit. Semi-purified recombinant MdCXE1 was able to hydrolyse a range of 4-methyl umbelliferyl ester substrates that included those containing acyl moieties that are found in esters produced by apple fruit. Kinetic characterisation of MdCXE1 revealed that the enzyme could be inhibited by organophosphates and that its ability to hydrolyse esters showed increasing affinity (K(m)) but decreasing turnover (k(cat)) as substrate acyl carbon length increases from C2 to C16. Our results suggest that MdCXE1 may have an impact on apple flavour through its ability to hydrolyse relevant flavour esters in ripe apple fruit. Copyright © 2011 Elsevier Ltd. All rights reserved.

Chloroquine inhibits autophagy and deteriorates the mitochondrial dysfunction and apoptosis in hypoxic rat neurons.

PubMed

Li, Peng; Hao, Lei; Guo, Yan-Yan; Yang, Guang-Lu; Mei, Hua; Li, Xiao-Hua; Zhai, Qiong-Xiang

2018-06-01

Mitochondrial dysfunction (MD) and apoptosis in the neurons are associated with neonatal hypoxic-ischemic (HI) encephalopathy (HIE). The present study was to explore the influence of autophagy on the induction of MD and apoptosis in the neurons in a neonatal HIE rats and in hypoxia-treated neurons in vitro. Ten-day-old HI rat pups were sacrificed for brain pathological examination and immunohistochemical analysis. The induction of autophagy, apoptosis and MD were also determined in the neurons under hypoxia, with or without autophagy inhibitor, chloroquine (CQ) treatment. HI treatment caused atrophy and apoptosis of neurons, with a significantly increased levels of apoptosis- and autophagy-associated proteins, such as cleaved caspase 3 and the B subunit of autophagy-related microtubule-associated protein 1 light chain 3 (LC3-B). in vitro experiments demonstrated that the hypoxia induced autophagy in neurons, as was inhibited by CQ. The hypoxia-induced cytochrome c release, cleaved caspase 3 and cleaved caspase 9 were aggravated by CQ. Moreover, there were higher levels of reactive oxygen species, more mitochondrial superoxide and less mitochondrial membrane potential in the CQ-treated neurons under hypoxia than in the neurons singularly under hypoxia. Apoptosis and autophagy were induced in HI neonatal rat neurons, autophagy inhibition deteriorates the hypoxia-induced neuron MD and apoptosis. It implies a neuroprotection of autophagy in the hypoxic-ischemic encephalopathy. Administration of autophagy inducer agents might be promising in HIE treatment. Copyright © 2018. Published by Elsevier Inc.

Recognition of Facial Emotional Expression in Amnestic Mild Cognitive Impairment

PubMed Central

Varjassyová, Alexandra; Hořínek, Daniel; Andel, Ross; Amlerova, Jana; Laczó, Jan; Sheardová, Kateřina; Magerová, Hana; Holmerová, Iva; Vyhnálek, Martin; Bradáč, Ondřej; Geda, Yonas E.; Hort, Jakub

2014-01-01

We examined whether recognition of facial emotional expression would be affected in amnestic mild cognitive impairment (aMCI). A total of 50 elderly persons met the initial inclusion criteria, 10 were subsequently excluded (Geriatric Depression Score >5). 22 subjects were classified with aMCI based on published criteria (single domain aMCI [SD-aMCI], n = 10; multiple domain aMCI [MD-aMCI], n = 12); 18 subjects were cognitively normal. All underwent standard neurological and neuropsychological evaluations as well as tests of facial emotion recognition (FER) and famous faces identification (FFI). Among normal controls, FFI was negatively correlated with MMSE and positively correlated with executive function. Among patients with aMCI, FER was correlated with attention/speed of processing. No other correlations were significant. In a multinomial logistic regression model adjusted for age, sex, and education, a poorer score on FER, but not on FFI, was associated with greater odds of being classified as MD-aMCI (odds ratio [OR], 3.82; 95% confidence interval [CI], 1.05–13.91; p = 0.042). This association was not explained by memory or global cognitive score. There was no association between FER or FFI and SD-aMCI (OR, 1.13; 95% CI, 0.36–3.57; p = 0.836). Therefore, FER, but not FFI, may be impaired in MD-aMCI. This implies that in MD-aMCI, the tasks of FER and FFI may involve segregated neurocognitive networks. PMID:22954669

Linear associations between clinically assessed upper motor neuron disease and diffusion tensor imaging metrics in amyotrophic lateral sclerosis.

PubMed

Woo, John H; Wang, Sumei; Melhem, Elias R; Gee, James C; Cucchiara, Andrew; McCluskey, Leo; Elman, Lauren

2014-01-01

To assess the relationship between clinically assessed Upper Motor Neuron (UMN) disease in Amyotrophic Lateral Sclerosis (ALS) and local diffusion alterations measured in the brain corticospinal tract (CST) by a tractography-driven template-space region-of-interest (ROI) analysis of Diffusion Tensor Imaging (DTI). This cross-sectional study included 34 patients with ALS, on whom DTI was performed. Clinical measures were separately obtained including the Penn UMN Score, a summary metric based upon standard clinical methods. After normalizing all DTI data to a population-specific template, tractography was performed to determine a region-of-interest (ROI) outlining the CST, in which average Mean Diffusivity (MD) and Fractional Anisotropy (FA) were estimated. Linear regression analyses were used to investigate associations of DTI metrics (MD, FA) with clinical measures (Penn UMN Score, ALSFRS-R, duration-of-disease), along with age, sex, handedness, and El Escorial category as covariates. For MD, the regression model was significant (p = 0.02), and the only significant predictors were the Penn UMN Score (p = 0.005) and age (p = 0.03). The FA regression model was also significant (p = 0.02); the only significant predictor was the Penn UMN Score (p = 0.003). Measured by the template-space ROI method, both MD and FA were linearly associated with the Penn UMN Score, supporting the hypothesis that DTI alterations reflect UMN pathology as assessed by the clinical examination.

[The Chilean Association of Biomedical Journal Editors].

PubMed

Reyes, H

2001-01-01

On September 29th, 2000, The Chilean Association of Biomedical Journal Editors was founded, sponsored by the "Comisión Nacional de Investigación Científica y Tecnológica (CONICYT)" (the Governmental Agency promoting and funding scientific research and technological development in Chile) and the "Sociedad Médica de Santiago" (Chilean Society of Internal Medicine). The Association adopted the goals of the World Association of Medical Editors (WAME) and therefore it will foster "cooperation and communication among Editors of Chilean biomedical journals; to improve editorial standards, to promote professionalism in medical editing through education, self-criticism and self-regulation; and to encourage research on the principles and practice of medical editing". Twenty nine journals covering a closely similar number of different biomedical sciences, medical specialties, veterinary, dentistry and nursing, became Founding Members of the Association. A Governing Board was elected: President: Humberto Reyes, M.D. (Editor, Revista Médica de Chile); Vice-President: Mariano del Sol, M.D. (Editor, Revista Chilena de Anatomía); Secretary: Anna María Prat (CONICYT); Councilors: Manuel Krauskopff, Ph.D. (Editor, Biological Research) and Maritza Rahal, M.D. (Editor, Revista de Otorrinolaringología y Cirugía de Cabeza y Cuello). The Association will organize a Symposium on Biomedical Journal Editing and will spread information stimulating Chilean biomedical journals to become indexed in international databases and in SciELO-Chile, the main Chilean scientific website (www.scielo.cl).

Physical perceptions and self-concept in athletes with muscle dysmorphia symptoms.

PubMed

González-Martí, Irene; Fernández Bustos, Juan Gregorio; Hernández-Martínez, Andrea; Contreras Jordán, Onofre Ricardo

2014-01-01

Individuals affected by Muscle Dysmorphia (MD; body image disorder based on the sub estimation of muscle size), practice weightlifting in order to alleviate their muscular dissatisfaction. Although physical activity is associated with increased physical self-perception, we assume that this was not reproduced in full in people with MD. The study sample consisted of 734 weightlifters and bodybuilders, 562 men and 172 women, who completed the Escala de Satisfacción Muscular, the Physical Self-Concept Questionnaire, and from whom measures of body fat and Fat -Free Mass Index (FFMI) were obtained. The results showed that people suffering from MD symptoms, overall, have poorer physical self-concept perceptions (F = 18.46 - 34.77, p < .01).

Driving an Industry: Medium and Heavy Duty Fuel Cell Electric Truck Component Sizing

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

Kast, James; Marcinkoski, Jason; Vijayagopal, Ram

Medium and heavy duty (MD and HD respectively) vehicles are responsible for 26 percent of the total U.S. transportation petroleum consumption [1]. Hydrogen fuel cells have demonstrated value as part of a portfolio of strategies for reducing petroleum use and emissions from MD and HD vehicles. [2] [3], but their performance and range capabilities, and associated component sizing remain less clear when compared to other powertrains. This paper examines the suitability of converting a representative sample of MD and HD diesel trucks into Fuel Cell Electric Trucks (FCETs), while ensuring the same truck performance, in terms of range, payload, acceleration,more » speed, gradeability and fuel economy.« less

Progression of White Matter Hyperintensities Preceded by Heterogeneous Decline of Microstructural Integrity.

PubMed

van Leijsen, Esther M C; Bergkamp, Mayra I; van Uden, Ingeborg W M; Ghafoorian, Mohsen; van der Holst, Helena M; Norris, David G; Platel, Bram; Tuladhar, Anil M; de Leeuw, Frank-Erik

2018-05-03

White matter hyperintensities (WMH) are frequently seen on neuroimaging of elderly and are associated with cognitive decline and the development of dementia. Yet, the temporal dynamics of conversion of normal-appearing white matter (NAWM) into WMH remains unknown. We examined whether and when progression of WMH was preceded by changes in fluid-attenuated inversion recovery and diffusion tensor imaging values, thereby taking into account differences between participants with mild versus severe baseline WMH. From 266 participants of the RUN DMC study (Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Imaging Cohort), we semiautomatically segmented WMH at 3 time points for 9 years. Images were registered to standard space through a subject template. We analyzed differences in baseline fluid-attenuated inversion recovery, fractional anisotropy, and mean diffusivity (MD) values and changes in MD values over time between 4 regions: (1) remaining NAWM, (2) NAWM converting into WMH in the second follow-up period, (3) NAWM converting into WMH in the first follow-up period, and (4) WMH. NAWM converting into WMH in the first or second time interval showed higher fluid-attenuated inversion recovery and MD values than remaining NAWM. MD values in NAWM converting into WMH in the first time interval were similar to MD values in WMH. When stratified by baseline WMH severity, participants with severe WMH had higher fluid-attenuated inversion recovery and MD and lower fractional anisotropy values than participants with mild WMH, in all areas including the NAWM. MD values in WMH and in NAWM that converted into WMH continuously increased over time. Impaired microstructural integrity preceded conversion into WMH and continuously declined over time, suggesting a continuous disease process of white matter integrity loss that can be detected using diffusion tensor imaging even years before WMH become visible on conventional neuroimaging. Differences in microstructural integrity between participants with mild versus severe WMH suggest heterogeneity of both NAWM and WMH, which might explain the clinical variability observed in patients with similar small vessel disease severity. © 2018 American Heart Association, Inc.

Blood Biomarker Profile of TBI Associated Cognitive Impairment Among Old and Young Veterans

DTIC Science & Technology

2016-10-01

INVESTIGATOR: Kristine Yaffe, MD CONTRACTING ORGANIZATION: Northern California Institute for Research and Education San Francisco, CA 94121 REPORT...MD 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Northern California Institute for Research and Education ...and Resiliency for Dementia: Comparison of Male and Female Veterans (Yaffe: PI) Time Commitment: 1.2 calendar months Supporting Agency: DOD

Effects of antiepileptic drugs on bone mineral density and bone metabolism in children: a meta-analysis*

PubMed Central

Zhang, Ying; Zheng, Yu-xin; Zhu, Jun-ming; Zhang, Jian-min; Zheng, Zhe

2015-01-01

Objective: The aim of our meta-analysis was to assess the effects of antiepileptic drugs on bone mineral density and bone metabolism in epileptic children. Methods: Searches of PubMed and Web of Science were undertaken to identify studies evaluating the association between antiepileptic drugs and bone mineral density and bone metabolism. Results: A total of 22 studies with 1492 subjects were included in our research. We identified: (1) a reduction in bone mineral density at lumbar spine (standardized mean difference (SMD)=−0.30, 95% confidence interval (CI) [−0.61, −0.05]), trochanter (mean difference (MD)=−0.07, 95% CI [−0.10, −0.05]), femoral neck (MD=−0.05, 95% CI [−0.09, −0.02]), and total body bone mineral density (MD=−0.33, 95% CI [−0.51, −0.15]); (2) a reduction in 25-hydroxyvitamin D (MD=−3.37, 95% CI [−5.94, −0.80]) and an increase in serum alkaline phosphatase (SMD=0.71, 95% CI [0.38, 1.05]); (3) no significant changes in serum parathyroid hormone, calcium, or phosphorus. Conclusions: Our meta-analysis suggests that treatment with antiepileptic drugs may be associated with decreased bone mineral density in epileptic children. PMID:26160719

Fluctuating hydrodynamics for multiscale modeling and simulation: energy and heat transfer in molecular fluids.

PubMed

Shang, Barry Z; Voulgarakis, Nikolaos K; Chu, Jhih-Wei

2012-07-28

This work illustrates that fluctuating hydrodynamics (FHD) simulations can be used to capture the thermodynamic and hydrodynamic responses of molecular fluids at the nanoscale, including those associated with energy and heat transfer. Using all-atom molecular dynamics (MD) trajectories as the reference data, the atomistic coordinates of each snapshot are mapped onto mass, momentum, and energy density fields on Eulerian grids to generate a corresponding field trajectory. The molecular length-scale associated with finite molecule size is explicitly imposed during this coarse-graining by requiring that the variances of density fields scale inversely with the grid volume. From the fluctuations of field variables, the response functions and transport coefficients encoded in the all-atom MD trajectory are computed. By using the extracted fluid properties in FHD simulations, we show that the fluctuations and relaxation of hydrodynamic fields quantitatively match with those observed in the reference all-atom MD trajectory, hence establishing compatibility between the atomistic and field representations. We also show that inclusion of energy transfer in the FHD equations can more accurately capture the thermodynamic and hydrodynamic responses of molecular fluids. The results indicate that the proposed MD-to-FHD mapping with explicit consideration of finite molecule size provides a robust framework for coarse-graining the solution phase of complex molecular systems.

Importance of frequency dependent magnetoresistance measurements in analysing the intrinsicality of magnetodielectric effect: A case study

NASA Astrophysics Data System (ADS)

Rai, Hari Mohan; Saxena, Shailendra K.; Mishra, Vikash; Kumar, Rajesh; Sagdeo, P. R.

2017-08-01

Magnetodielectric (MD) materials have attracted considerable attention due to their intriguing physics and potential future applications. However, the intrinsicality of the MD effect is always a major concern in such materials as the MD effect may arise also due to the MR (magnetoresistance) effect. In the present case study, we report an experimental approach to analyse and separate the intrinsic and MR dominated contributions of the MD phenomenon. For this purpose, polycrystalline samples of LaGa1-xAxO3 (A = Mn/Fe) have been prepared by solid state reaction method. The purity of their structural phase (orthorhombic) has been validated by refining the X-ray diffraction data. The RTMD (room temperature MD) response has been recorded over a frequency range of 20 Hz to 10 MHz. In order to analyse the intrinsicality of the MD effect, FDMR (frequency dependent MR) by means of IS (impedance spectroscopy) and dc MR measurements in four probe geometry have been carried out at RT. A significant RTMD effect has been observed in selected Mn/Fe doped LaGaO3 (LGO) compositions. The mechanism of MR free/intrinsic MD effect, observed in Mn/Fe doped LGO, has been understood speculatively in terms of modified cell volume associated with the reorientation/retransformation of spin-coupled Mn/Fe orbitals due to the application of magnetic field. The present analysis suggests that in order to justify the intrinsic/resistive origin of the MD phenomenon, FDMR measurements are more useful than measuring only dc MR or analysing the trends of magnetic field dependent change in the dielectric constant and tanδ. On the basis of the present case study, we propose that IS (FDMR) alone can be used as an effective experimental tool to detect and analyse the resistive and intrinsic parts contributing to the MD phenomenon.

Shared and Unique Risk Factors Underlying Mathematical Disability and Reading and Spelling Disability.

PubMed

Slot, Esther M; van Viersen, Sietske; de Bree, Elise H; Kroesbergen, Evelyn H

2016-01-01

High comorbidity rates have been reported between mathematical learning disabilities (MD) and reading and spelling disabilities (RSD). Research has identified skills related to math, such as number sense (NS) and visuospatial working memory (visuospatial WM), as well as to literacy, such as phonological awareness (PA), rapid automatized naming (RAN) and verbal short-term memory (Verbal STM). In order to explain the high comorbidity rates between MD and RSD, 7-11-year-old children were assessed on a range of cognitive abilities related to literacy (PA, RAN, Verbal STM) and mathematical ability (visuospatial WM, NS). The group of children consisted of typically developing (TD) children (n = 32), children with MD (n = 26), children with RSD (n = 29), and combined MD and RSD (n = 43). It was hypothesized that, in line with the multiple deficit view on learning disorders, at least one unique predictor for both MD and RSD and a possible shared cognitive risk factor would be found to account for the comorbidity between the symptom dimensions literacy and math. Secondly, our hypotheses were that (a) a probabilistic multi-factorial risk factor model would provide a better fit to the data than a deterministic single risk factor model and (b) that a shared risk factor model would provide a better fit than the specific multi-factorial model. All our hypotheses were confirmed. NS and visuospatial WM were identified as unique cognitive predictors for MD, whereas PA and RAN were both associated with RSD. Also, a shared risk factor model with PA as a cognitive predictor for both RSD and MD fitted the data best, indicating that MD and RSD might co-occur due to a shared underlying deficit in phonological processing. Possible explanations are discussed in the context of sample selection and composition. This study shows that different cognitive factors play a role in mathematics and literacy, and that a phonological processing deficit might play a role in the occurrence of MD and RSD.

A study of primary care physicians rating their immigrant patients' pain intensity.

PubMed

André, M; Löfvander, M

2013-01-01

Few studies focus on how physicians evaluate pain in foreign-born patients with varying cultural backgrounds. This study aimed to compare pain ratings [visual analogue scale (VAS) 0-100] done by Swedish primary care physicians and their patients, and to analyse which factors predicted physicians' higher ratings of pain in patients aged 18-45 years with long-standing disabling back pain. The two physicians jointly carried out the somatic and psychiatric diagnostic evaluations and alternated as consulting doctor or observer. One-third of the consultations were interpreted. Towards the end of the consultations, the patients rated their pain intensity 'right now' (patients' VAS). After the patient had left, the two physicians independently rated how much pain they thought the patient had, without looking at the patient's VAS score. The mean of the two doctors' VAS values (physicians' VAS) for each patient was used in the logistic regression calculations of odds ratios (OR) in main effect models for physicians' VAS above median (md) with patient's sex, education, origin, depression, psychosocial stress and pain sites as explanatory variables. Physicians' VAS values were significantly lower (md 15) than patients' VAS (md 66; women md 73, men md 52). The ratings showed no significant association with whether the physician was acting as consultant or observer. The higher physician VAS was only predicted by findings of multiple pain sites. Physicians appear to overlook psychological and emotional aspects when rating the pain of patients from other cultural backgrounds. This finding highlights a potential problem in multicultural care settings. © 2012 European Federation of International Association for the Study of Pain Chapters.

Tapering strategies in elite British endurance runners.

PubMed

Spilsbury, Kate L; Fudge, Barry W; Ingham, Stephen A; Faulkner, Steve H; Nimmo, Myra A

2015-01-01

The aim of the study was to explore pre-competition training practices of elite endurance runners. Training details from elite British middle distance (MD; 800 m and 1500 m), long distance (LD; 3000 m steeplechase to 10,000 m) and marathon (MAR) runners were collected by survey for 7 days in a regular training (RT) phase and throughout a pre-competition taper. Taper duration was [median (interquartile range)] 6 (3) days in MD, 6 (1) days in LD and 14 (8) days in MAR runners. Continuous running volume was reduced to 70 (16)%, 71 (24)% and 53 (12)% of regular levels in MD, LD and MAR runners, respectively (P < 0.05). Interval running volume was reduced compared to regular training (MD; 53 (45)%, LD; 67 (23)%, MAR; 64 (34)%, P < 0.05). During tapering, the peak interval training intensity was above race speed in LD and MAR runners (112 (27)% and 114 (3)%, respectively, P < 0.05), but not different in MD (100 (2)%). Higher weekly continuous running volume and frequency in RT were associated with greater corresponding reductions during the taper (R = -0.70 and R = -0.63, respectively, both P < 0.05). Running intensity during RT was positively associated with taper running intensity (continuous intensity; R = 0.97 and interval intensity; R = 0.81, both P < 0.05). Algorithms were generated to predict and potentially prescribe taper content based on the RT of elite runners. In conclusion, training undertaken prior to the taper in elite endurance runners is predictive of the tapering strategy implemented before competition.

Peer and cyber aggression in secondary school students: the role of moral disengagement, hostile attribution bias, and outcome expectancies.

PubMed

Pornari, Chrisa D; Wood, Jane

2010-01-01

This study investigated the relationship between cognitive mechanisms, applied by people to rationalize and justify harmful acts, and engagement in traditional peer and cyber aggression among school children. We examined the contribution of moral disengagement (MD), hostile attribution bias, and outcome expectancies, and we further explored the individual contribution of each MD mechanism. Our aim was to identify shared and unique cognitive factors of the two forms of aggression. Three hundred and thirty-nine secondary school children completed self-report measures that assessed MD, hostile attribution bias, outcome expectancies, and their roles and involvement in traditional and cyber aggression. We found that the MD total score positively related to both forms of peer-directed aggression. Furthermore, traditional peer aggression positively related to children's moral justification, euphemistic language, displacement of responsibility and outcome expectancies, and negatively associated with hostile attribution bias. Moral justification also related positively to cyber aggression. Cyber aggression and cyber victimization were associated with high levels of traditional peer aggression and victimization, respectively. The results suggest that MD is a common feature of both traditional and cyber peer aggression, but it seems that traditional forms of aggression demand a higher level of rationalization or justification. Moreover, the data suggest that the expectation of positive outcomes from harmful behavior facilitates engagement in traditional peer aggression. The differential contribution of specific cognitive mechanisms indicates the need for future research to elaborate on the current findings, in order to advance theory and inform existing and future school interventions tackling aggression and bullying. (c) 2009 Wiley-Liss, Inc.

Sport concussion assessment tool-Third edition normative reference values for professional Rugby Union players.

PubMed

Fuller, G W; Govind, O; Tucker, R; Raftery, M

2018-04-01

To establish normative reference data for the SCAT3 in professional Rugby Union players. A cross sectional study in professional Rugby Union players competing in national and international professional competitions between 2015 and 2016. The SCAT3 was administered pre-season or prior to tournaments. Data was collected electronically using a custom tablet application. SCAT3 subcomponents distributions were described and normative ranges determined using percentile cut-offs for average, unusually low/high, and extremely low/high scores. The association between player characteristics and performance in SCAT3 subcomponents was also investigated in exploratory analyses. A total of 3611 professional Rugby Union players were included. The most common baseline symptom was fatigue (14%). The symptom score median (md) was 0 (interquartile range (IQR)=0-1). Symptom severity md was 0 (IQR=0-1). The md of the SAC score was 28 (IQR=26-29). The md of the MBESS was 2 (IQR=0-4). The Tandem gait md was 11.1s (IQR=10.0-12.7s). Upper limb coordination was normal in 98.4%. Younger age and lower educational level were associated with worse performance on delayed recall and reverse month sub-components of the SCAT3 (p<0.0001). No statistically significant differences in SCAT3 subcomponents were evident across gender. Representative normative reference values for the SCAT3 among professional Rugby Union players are provided. Baseline performance on concentration and delayed recall tests may be lower in younger athletes or in those with lower educational level. Copyright © 2017. Published by Elsevier Ltd.

Authigenic 10Be/9Be ratio signatures of the cosmogenic nuclide production linked to geomagnetic dipole moment variation since the Brunhes/Matuyama boundary.

PubMed

Simon, Quentin; Thouveny, Nicolas; Bourlès, Didier L; Valet, Jean-Pierre; Bassinot, Franck; Ménabréaz, Lucie; Guillou, Valéry; Choy, Sandrine; Beaufort, Luc

2016-11-01

Geomagnetic dipole moment variations associated with polarity reversals and excursions are expressed by large changes of the cosmogenic nuclide beryllium-10 ( 10 Be) production rates. Authigenic 10 Be/ 9 Be ratios (proxy of atmospheric 10 Be production) from oceanic cores therefore complete the classical information derived from relative paleointensity (RPI) records. This study presents new authigenic 10 Be/ 9 Be ratio results obtained from cores MD05-2920 and MD05-2930 collected in the west equatorial Pacific Ocean. Be ratios from cores MD05-2920, MD05-2930 and MD90-0961 have been stacked and averaged. Variations of the authigenic 10 Be/ 9 Be ratio are analyzed and compared with the geomagnetic dipole low series reported from global RPI stacks. The largest 10 Be overproduction episodes are related to dipole field collapses (below a threshold of 2 × 10 22  Am 2 ) associated with the Brunhes/Matuyama reversal, the Laschamp (41 ka) excursion, and the Iceland Basin event (190 ka). Other significant 10 Be production peaks are correlated to geomagnetic excursions reported in literature. The record was then calibrated by using absolute dipole moment values drawn from the Geomagia and Pint paleointensity value databases. The 10 Be-derived geomagnetic dipole moment record, independent from sedimentary paleomagnetic data, covers the Brunhes-Matuyama transition and the whole Brunhes Chron. It provides new and complementary data on the amplitude and timing of millennial-scale geomagnetic dipole moment variations and particularly on dipole moment collapses triggering polarity instabilities.

Increased stress reactivity is associated with cognitive deficits and decreased hippocampal brain-derived neurotrophic factor in a mouse model of affective disorders.

PubMed

Knapman, A; Heinzmann, J-M; Hellweg, R; Holsboer, F; Landgraf, R; Touma, C

2010-07-01

Cognitive deficits are a common feature of major depression (MD), with largely unknown biological underpinnings. In addition to the affective and cognitive symptoms of MD, a dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is commonly observed in these patients. Increased plasma glucocorticoid levels are known to render the hippocampus susceptible to neuronal damage. This structure is important for learning and memory, creating a potential link between HPA axis dysregulation and cognitive deficits in depression. In order to further elucidate how altered stress responsiveness may contribute to the etiology of MD, three mouse lines with high (HR), intermediate (IR), or low (LR) stress reactivity were generated by selective breeding. The aim of the present study was to investigate whether increased stress reactivity is associated with deficits in hippocampus-dependent memory tests. To this end, we subjected mice from the HR, IR, and LR breeding lines to tests of recognition memory, spatial memory, and depression-like behavior. In addition, measurements of brain-derived neurotrophic factor (BDNF) in the hippocampus and plasma of these animals were conducted. Our results demonstrate that HR mice exhibit hippocampus-dependent memory deficits along with decreased hippocampal, but not plasma, BDNF levels. Thus, the stress reactivity mouse lines are a promising animal model of the cognitive deficits in MD with the unique feature of a genetic predisposition for an altered HPA axis reactivity, which provides the opportunity to explore the progression of the symptoms of MD, predisposing genetic factors as well as new treatment strategies. Copyright 2009 Elsevier Ltd. All rights reserved.

Complete protein-protein association kinetics in atomic detail revealed by molecular dynamics simulations and Markov modelling

NASA Astrophysics Data System (ADS)

Plattner, Nuria; Doerr, Stefan; de Fabritiis, Gianni; Noé, Frank

2017-10-01

Protein-protein association is fundamental to many life processes. However, a microscopic model describing the structures and kinetics during association and dissociation is lacking on account of the long lifetimes of associated states, which have prevented efficient sampling by direct molecular dynamics (MD) simulations. Here we demonstrate protein-protein association and dissociation in atomistic resolution for the ribonuclease barnase and its inhibitor barstar by combining adaptive high-throughput MD simulations and hidden Markov modelling. The model reveals experimentally consistent intermediate structures, energetics and kinetics on timescales from microseconds to hours. A variety of flexibly attached intermediates and misbound states funnel down to a transition state and a native basin consisting of the loosely bound near-native state and the tightly bound crystallographic state. These results offer a deeper level of insight into macromolecular recognition and our approach opens the door for understanding and manipulating a wide range of macromolecular association processes.

Hybrid Decompression Technique Versus Anterior Cervical Corpectomy and Fusion for Treating Multilevel Cervical Spondylotic Myelopathy: Which One Is Better?

PubMed

Liu, Jia-Ming; Peng, Hong-Wei; Liu, Zhi-Li; Long, Xin-Hua; Yu, Yan-Qing; Huang, Shan-Hu

2015-12-01

The hybrid decompression technique (corpectomy combined with discectomy) and anterior cervical corpectomy with fusion (ACCF) both provide good neurological recovery and disease stabilization for the treatment of multilevel cervical spondylotic myelopathy (CSM). However, no single study has been large enough to determine definitively which one is superior for this condition. A meta-analysis was conducted to compare the clinical efficacy and safety of the hybrid decompression technique versus ACCF for the treatment of multilevel CSM. Electronic databases such as PubMed, MEDLINE, EMBASE, Google Scholar, and the Cochrane Library were selected to search for potentially relevant trials up to April 2015 that compared the outcomes of the hybrid technique with ACCF for the treatment of multilevel CSM. Data extraction and quality assessment were performed according to Cochrane Collaboration guidelines. The outcome assessments were duration of surgery, blood loss, Cobb angle of C2-C7, segment angle, fusion rate, Japanese Orthopedics Association score, Neck Disability Index, and complications. The results were expressed as the odds ratio (OR) for dichotomous outcomes and the mean difference (MD) for continuous outcomes with a 95% confidence interval (CI). Five controlled clinical trials published between 2009 and 2013, involving 356 patients (hybrid, 196; ACCF, 160) with 3- or 4-level CSM were retrieved in this study. Overall, there were significant differences between the 2 treatment groups for blood loss (MD = -38.69, 95% CI = -54.62 to -22.76, P < 0.01), fusion rate (OR = 2.56, 95% CI = 1.11 to 5.93, P = 0.03), and complications (OR = 0.25, 95% CI = 0.15 to 0.43, P < 0.01). However, no significant differences were found for duration of surgery (MD = -4.50, 95% CI = -22.902 to 13.91, P = 0.63), Cobb angle of C2-C7 after surgery (MD = 3.32, 95% CI = -3.72 to 10.37, P = 0.35), segment angle after surgery (MD = 2.87, 95% CI = -2.47 to 8.21, P = 0.29), Japanese Orthopedics Association score (MD = -0.07, 95% CI = -0.36 to 0.22, P = 0.62), or Neck Disability Index (MD = -0.86, 95% CI = -3.26 to 1.54, P = 0.48). Based on this meta-analysis, both the hybrid technique and ACCF can achieve good results for CSM. However, the hybrid technique is associated with significantly less blood loss, complications, and a higher fusion rate than ACCF. Copyright © 2015 Elsevier Inc. All rights reserved.

Proteomics and SSH Analyses of ALA-Promoted Fruit Coloration and Evidence for the Involvement of a MADS-Box Gene, MdMADS1

PubMed Central

Feng, Xinxin; An, Yuyan; Zheng, Jie; Sun, Miao; Wang, Liangju

2016-01-01

Skin color is a key quality attribute of fruits and how to improve fruit coloration has long been a major concern. 5-Aminolevulinic acid (ALA), a natural plant growth regulator, can significantly increase anthocyanin accumulation in fruit skin and therefore effectively improve coloration of many fruits, including apple. However, the molecular mechanism how ALA stimulates anthocyanin accumulation in fruit skin remains unknown. Here, we investigated the impact of ALA on apple skin at the protein and mRNA levels. A total of 85 differentially expressed proteins in apple skins between ALA and water treatment (control) were identified by complementary gel-based and gel-free separation techniques. Most of these differentially expressed proteins were up-regulated by ALA. Function analysis suggested that 87.06% of the ALA-responsive proteins were associated with fruit ripening. To further screen ALA-responsive regulators, we constructed a subtracted cDNA library (tester: ALA treatment; driver: control) and obtained 104 differentially expressed unigenes, of which 38 unigenes were indicators for the fruit ripening-related genes. The differentially changed proteins and transcripts did not correspond well at an individual level, but showed similar regulated direction in function at the pathway level. Among the identified fruit ripening-related genes, the expression of MdMADS1, a developmental transcription regulator of fruit ripening, was positively correlated with expression of anthocyanin biosynthetic genes (MdCHS, MdDFR, MdLDOX, and MdUFGT) in apple skin under ALA treatment. Moreover, overexpression of MdMADS1 enhanced anthocyanin content in transformed apple calli, which was further enhanced by ALA. The anthocyanin content in MdMADS1-silenced calli was less than that in the control with ALA treatment, but higher than that without ALA treatment. These results indicated that MdMADS1 is involved in ALA-induced anthocyanin accumulation. In addition, anthocyanin-related verification in apple calli suggested that the regulation of MdMADS1 on anthocyanin biosynthesis was partially independent of fruit ripening process. Taken together, our findings provide insight into the mechanism how ALA regulates anthocyanin accumulation and add new information on transcriptase regulators of fruit coloration. PMID:27872628

Social, societal, and economic burden of mal de debarquement syndrome.

PubMed

Macke, Allison; LePorte, Andrew; Clark, Brian C

2012-07-01

Mal de debarquement syndrome (MdDS) is a disorder of phantom perception of self-motion of unknown cause. The purpose of this work was to describe the quality of life (QOL) of patients with MdDS and to estimate the economic costs associated with this disorder. A modified version of a QOL survey used for another neurological disease (multiple sclerosis; MSQOL-54) was used to assess the impact of MdDS on QOL in 101 patients. The estimated economic costs were based on self-reported direct and indirect costs of individuals living in the United States using Medicare reimbursement payment rates for 2011 in 79 patients. Patients with MdDS reported a poor overall QOL as indicated by a mean composite QOL score of 59.26 ± 1.89 (out of 100). The subcategories having the lowest QOL rating were role limitations due to physical problems (18.32 ± 3.20), energy (34.24 ± 1.47), and emotional problems (36.30 ± 4.00). The overall physical health composite score including balance was 49.40 ± 1.69, and the overall mental health composite score was 52.40 ± 1.83. The cost to obtain a diagnosis was $2,997 ± 337, which included requiring an average of 19 physician visits per patient. The direct cost of MdDS medical care was $826 ± 140 per patient per year, which mainly included diagnostic imaging and physician visits. The indirect costs (i.e., lost wages) were $9,781 ± 2,347 per patient per year. Among 65 patients who were gainfully employed when they acquired MdDS, the indirect costs were $11,888 ± 2,786 per patient per year. Thus, the total annual cost of the disorder ranged from $11,493 ± 2,341 to $13,561 ± 2,778 per patient per year depending on employment status prior to developing MdDS. MdDS negatively and dramatically impacts QOL, and also imposes a substantial economic burden on MdDS patients. These findings underscore the need for further basic and clinical research on MdDS.

Numerical Magnitude Representation in Children With Mathematical Difficulties With or Without Reading Difficulties.

PubMed

Tobia, Valentina; Fasola, Anna; Lupieri, Alice; Marzocchi, Gian Marco

2016-01-01

This study aimed to explore the spatial numerical association of response codes (SNARC), the flanker, and the numerical distance effects in children with mathematical difficulties. From a sample of 720 third, fourth, and fifth graders, 60 children were selected and divided into the following three groups: typically developing children (TD; n = 29), children with mathematical difficulties only (MD only; n = 21), and children with mathematical and reading difficulties (MD+RD; n = 10). Children were tested with a numerical Eriksen task that was built to assess SNARC, numerical distance, and flanker (first and second order congruency) effects. Children with MD only showed stronger SNARC and second order congruency effects than did TD children, whereas the numerical distance effects were similar across the three groups. Finally, the first order congruency effect was associated with reading difficulties. These results showed that children with mathematical difficulties with or without reading difficulties were globally more impaired when spatial incompatibilities were presented. © Hammill Institute on Disabilities 2014.

Application of multivariate statistics to vestibular testing: discriminating between Meniere's disease and migraine associated dizziness

NASA Technical Reports Server (NTRS)

Dimitri, P. S.; Wall, C. 3rd; Oas, J. G.; Rauch, S. D.

2001-01-01

Meniere's disease (MD) and migraine associated dizziness (MAD) are two disorders that can have similar symptomatologies, but differ vastly in treatment. Vestibular testing is sometimes used to help differentiate between these disorders, but the inefficiency of a human interpreter analyzing a multitude of variables independently decreases its utility. Our hypothesis was that we could objectively discriminate between patients with MD and those with MAD using select variables from the vestibular test battery. Sinusoidal harmonic acceleration test variables were reduced to three vestibulo-ocular reflex physiologic parameters: gain, time constant, and asymmetry. A combination of these parameters plus a measurement of reduced vestibular response from caloric testing allowed us to achieve a joint classification rate of 91%, independent quadratic classification algorithm. Data from posturography were not useful for this type of differentiation. Overall, our classification function can be used as an unbiased assistant to discriminate between MD and MAD and gave us insight into the pathophysiologic differences between the two disorders.

Adherence to the Mediterranean diet is inversely related to binge eating disorder in patients seeking a weight loss program.

PubMed

Bertoli, Simona; Spadafranca, Angela; Bes-Rastrollo, Maira; Martinez-Gonzalez, Miguel Angel; Ponissi, Veronica; Beggio, Valentina; Leone, Alessandro; Battezzati, Alberto

2015-02-01

The key factors influencing the development of Binge Eating Disorder (BED) are not well known. Adherence to the Mediterranean diet (MD) has been suspected to reduce the risk of several mental illnesses such as depression and anxiety. There are no existing studies that have examined the relationships between BED and MD. Cross-sectional study of 1472 participants (71.3% women; mean age: 44.8 ± 12.7) at high risk of BED. A MD score (MED-score) was derived from a validated food frequency questionnaire and BED by Binge Eating Scale questionnaire (BES). Body mass index, waist circumference and total body fat (%) were assessed by anthropometric measurements. 376 (25.5%) cases of self reported BED were identified. 11.1% of participants had a good adherence to MD (MED-score ≥ 9). After adjustments for age, gender, nutritional status, education, and physical activity level, high MED-score was associated with lower odds for BED (odds ratios and 95% confidence intervals of a BED disorder for successive levels of MED-score were 1 (reference), 0.77 (0.44, 1.36), 0.66 (0.37, 1.15), 0.50 (0.26, 0.96), and 0.45 (0.22, 0.55) (P for trend: <0.01). Olive oil and nut consumption were associated with low risk of BED development whereas butter, cream, sweets and commercial bakery/sweets/cakes consumption increased the risk. We did not find a cumulative effect of depression and anxiety on MED-score in binge eaters. These results demonstrate an inverse association between MD and the development of BED in a clinical setting among subjects at risk of BED. Therefore, we should be cautious about generalizing the results to the whole population, although reverse causality and confounding cannot be excluded as explanation. Further prospective studies are warranted. Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Mediterranean Diet: Prevention of Colorectal Cancer

PubMed Central

Donovan, Micah G.; Selmin, Ornella I.; Doetschman, Tom C.; Romagnolo, Donato F.

2017-01-01

Colorectal cancer (CRC) is the third most common cancer diagnosis and the second and third leading cause of cancer mortality in men and women, respectively. However, the majority of CRC cases are the result of sporadic tumorigenesis via the adenoma–carcinoma sequence. This process can take up to 20 years, suggesting an important window of opportunity exists for prevention such as switching toward healthier dietary patterns. The Mediterranean diet (MD) is a dietary pattern associated with various health benefits including protection against cardiovascular disease, diabetes, obesity, and various cancers. In this article, we review publications available in the PubMed database within the last 10 years that report on the impact of a MD eating pattern on prevention of CRC. To assist the reader with interpretation of the results and discussion, we first introduce indexes and scoring systems commonly used to experimentally determine adherence to a MD, followed by a brief introduction of the influence of the MD pattern on inflammatory bowel disease, which predisposes to CRC. Finally, we discuss key biological mechanisms through which specific bioactive food components commonly present in the MD are proposed to prevent or delay the development of CRC. We close with a discussion of future research frontiers in CRC prevention with particular reference to the role of epigenetic mechanisms and microbiome related to the MD eating pattern. PMID:29259973

Three-dimensional photography for the evaluation of facial profiles in obstructive sleep apnoea.

PubMed

Lin, Shih-Wei; Sutherland, Kate; Liao, Yu-Fang; Cistulli, Peter A; Chuang, Li-Pang; Chou, Yu-Ting; Chang, Chih-Hao; Lee, Chung-Shu; Li, Li-Fu; Chen, Ning-Hung

2018-06-01

Craniofacial structure is an important determinant of obstructive sleep apnoea (OSA) syndrome risk. Three-dimensional stereo-photogrammetry (3dMD) is a novel technique which allows quantification of the craniofacial profile. This study compares the facial images of OSA patients captured by 3dMD to three-dimensional computed tomography (3-D CT) and two-dimensional (2-D) digital photogrammetry. Measurements were correlated with indices of OSA severity. Thirty-eight patients diagnosed with OSA were included, and digital photogrammetry, 3dMD and 3-D CT were performed. Distances, areas, angles and volumes from the images captured by three methods were analysed. Almost all measurements captured by 3dMD showed strong agreement with 3-D CT measurements. Results from 2-D digital photogrammetry showed poor agreement with 3-D CT. Mandibular width, neck perimeter size and maxillary volume measurements correlated well with the severity of OSA using all three imaging methods. Mandibular length, facial width, binocular width, neck width, cranial base triangle area, cranial base area 1 and middle cranial fossa volume correlated well with OSA severity using 3dMD and 3-D CT, but not with 2-D digital photogrammetry. 3dMD provided accurate craniofacial measurements of OSA patients, which were highly concordant with those obtained by CT, while avoiding the radiation associated with CT. © 2018 Asian Pacific Society of Respirology.

Comparative phylogenetic analysis and transcriptional profiling of MADS-box gene family identified DAM and FLC-like genes in apple (Malusx domestica)

PubMed Central

Kumar, Gulshan; Arya, Preeti; Gupta, Khushboo; Randhawa, Vinay; Acharya, Vishal; Singh, Anil Kumar

2016-01-01

The MADS-box transcription factors play essential roles in various processes of plant growth and development. In the present study, phylogenetic analysis of 142 apple MADS-box proteins with that of other dicotyledonous species identified six putative Dormancy-Associated MADS-box (DAM) and four putative Flowering Locus C-like (FLC-like) proteins. In order to study the expression of apple MADS-box genes, RNA-seq analysis of 3 apical and 5 spur bud stages during dormancy, 6 flower stages and 7 fruit development stages was performed. The dramatic reduction in expression of two MdDAMs, MdMADS063 and MdMADS125 and two MdFLC-like genes, MdMADS135 and MdMADS136 during dormancy release suggests their role as flowering-repressors in apple. Apple orthologs of Arabidopsis genes, FLOWERING LOCUS T, FRIGIDA, SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 and LEAFY exhibit similar expression patterns as reported in Arabidopsis, suggesting functional conservation in floral signal integration and meristem determination pathways. Gene ontology enrichment analysis of predicted targets of DAM revealed their involvement in regulation of reproductive processes and meristematic activities, indicating functional conservation of SVP orthologs (DAM) in apple. This study provides valuable insights into the functions of MADS-box proteins during apple phenology, which may help in devising strategies to improve important traits in apple. PMID:26856238

Fluid Intelligence Predicts Novel Rule Implementation in a Distributed Frontoparietal Control Network.

PubMed

Tschentscher, Nadja; Mitchell, Daniel; Duncan, John

2017-05-03

Fluid intelligence has been associated with a distributed cognitive control or multiple-demand (MD) network, comprising regions of lateral frontal, insular, dorsomedial frontal, and parietal cortex. Human fluid intelligence is also intimately linked to task complexity, and the process of solving complex problems in a sequence of simpler, more focused parts. Here, a complex target detection task included multiple independent rules, applied one at a time in successive task epochs. Although only one rule was applied at a time, increasing task complexity (i.e., the number of rules) impaired performance in participants of lower fluid intelligence. Accompanying this loss of performance was reduced response to rule-critical events across the distributed MD network. The results link fluid intelligence and MD function to a process of attentional focus on the successive parts of complex behavior. SIGNIFICANCE STATEMENT Fluid intelligence is intimately linked to the ability to structure complex problems in a sequence of simpler, more focused parts. We examine the basis for this link in the functions of a distributed frontoparietal or multiple-demand (MD) network. With increased task complexity, participants of lower fluid intelligence showed reduced responses to task-critical events. Reduced responses in the MD system were accompanied by impaired behavioral performance. Low fluid intelligence is linked to poor foregrounding of task-critical information across a distributed MD system. Copyright © 2017 Tschentscher et al.

Microstructural changes to the brain of mice after methamphetamine exposure as identified with diffusion tensor imaging.

PubMed

McKenna, Benjamin S; Brown, Gregory G; Archibald, Sarah; Scadeng, Miriam; Bussell, Robert; Kesby, James P; Markou, Athina; Soontornniyomkij, Virawudh; Achim, Cristian; Semenova, Svetlana

2016-03-30

Methamphetamine (METH) is an addictive psychostimulant inducing neurotoxicity. Human magnetic resonance imaging and diffusion tensor imaging (DTI) of METH-dependent participants find various structural abnormities. Animal studies demonstrate immunohistochemical changes in multiple cellular pathways after METH exposure. Here, we characterized the long-term effects of METH on brain microstructure in mice exposed to an escalating METH binge regimen using in vivo DTI, a methodology directly translatable across species. Results revealed four patterns of differential fractional anisotropy (FA) and mean diffusivity (MD) response when comparing METH-exposed (n=14) to saline-treated mice (n=13). Compared to the saline group, METH-exposed mice demonstrated: 1) decreased FA with no change in MD [corpus callosum (posterior forceps), internal capsule (left), thalamus (medial aspects), midbrain], 2) increased MD with no change in FA [posterior isocortical regions, caudate-putamen, hypothalamus, cerebral peduncle, internal capsule (right)], 3) increased FA with decreased MD [frontal isocortex, corpus callosum (genu)], and 4) increased FA with no change or increased MD [hippocampi, amygdala, lateral thalamus]. MD was negatively associated with calbindin-1 in hippocampi and positively with dopamine transporter in caudate-putamen. These findings highlight distributed and differential METH effects within the brain suggesting several distinct mechanisms. Such mechanisms likely change brain tissue differentially dependent upon neural location. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Comparative phylogenetic analysis and transcriptional profiling of MADS-box gene family identified DAM and FLC-like genes in apple (Malusx domestica).

PubMed

Kumar, Gulshan; Arya, Preeti; Gupta, Khushboo; Randhawa, Vinay; Acharya, Vishal; Singh, Anil Kumar

2016-02-09

The MADS-box transcription factors play essential roles in various processes of plant growth and development. In the present study, phylogenetic analysis of 142 apple MADS-box proteins with that of other dicotyledonous species identified six putative Dormancy-Associated MADS-box (DAM) and four putative Flowering Locus C-like (FLC-like) proteins. In order to study the expression of apple MADS-box genes, RNA-seq analysis of 3 apical and 5 spur bud stages during dormancy, 6 flower stages and 7 fruit development stages was performed. The dramatic reduction in expression of two MdDAMs, MdMADS063 and MdMADS125 and two MdFLC-like genes, MdMADS135 and MdMADS136 during dormancy release suggests their role as flowering-repressors in apple. Apple orthologs of Arabidopsis genes, FLOWERING LOCUS T, FRIGIDA, SUPPRESSOR OF OVEREXPRESSION OF CONSTANS 1 and LEAFY exhibit similar expression patterns as reported in Arabidopsis, suggesting functional conservation in floral signal integration and meristem determination pathways. Gene ontology enrichment analysis of predicted targets of DAM revealed their involvement in regulation of reproductive processes and meristematic activities, indicating functional conservation of SVP orthologs (DAM) in apple. This study provides valuable insights into the functions of MADS-box proteins during apple phenology, which may help in devising strategies to improve important traits in apple.

An Assessment of the Oral Bioavailability of Three Ca-Channel Blockers Using a Cassette-Microdose Study: A New Strategy for Streamlining Oral Drug Development.

PubMed

Yamashita, Shinji; Kataoka, Makoto; Suzaki, Yuki; Imai, Hiromitsu; Morimoto, Takuya; Ohashi, Kyoichi; Inano, Akihiro; Togashi, Kazutaka; Mutaguchi, Kuninori; Sugiyama, Yuichi

2015-09-01

A cassette-microdose (MD) clinical study was performed to demonstrate its usefulness for identifying the most promising compound for oral use. Three Ca-channel blockers (nifedipine, nicardipine, and diltiazem) were chosen as model drugs. In the MD clinical study, a cassette-dose method was employed in which three model drugs were administered simultaneously. Both intravenous (i.v.) and oral (p.o.) administration studies were conducted to calculate the oral bioavailability (BA). For comparison, p.o. studies with therapeutic dose (ThD) levels were also performed. In all studies, blood concentrations of each drug were successfully determined using liquid chromatography-mass spectrometry with the lower limit of quantification of 0.2-2.0 pg/mL. Oral BA of nifedipine in the MD study was approximately 50% and in the same range with that obtained in the ThD study, whereas other two drugs showed significantly lower BA in the MD study, indicating a dose-dependent absorption. In addition, compared with the ThD study, absorption of nicardipine was delayed in the MD study. As a result, nifedipine was considered to be most promising for oral use. In conclusion, a cassette-MD clinical study is of advantage for oral drug development that enables to identify the candidate having desired properties for oral use. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

PARK7/DJ-1 dysregulation by oxidative stress leads to magnesium deficiency: implications in degenerative and chronic diseases.

PubMed

Kolisek, Martin; Montezano, Augusto C; Sponder, Gerhard; Anagnostopoulou, Aikaterini; Vormann, Juergen; Touyz, Rhian M; Aschenbach, Joerg R

2015-12-01

Disturbed magnesium (Mg(2+)) homoeostasis and increased levels of OS (oxidative stress) are associated with poor clinical outcomes in patients suffering from neurodegenerative, cardiovascular and metabolic diseases. Data from clinical and animal studies suggest that MD (Mg(2+) deficiency) is correlated with increased production of ROS (reactive oxygen species) in cells, but a straightforward causal relationship (including molecular mechanisms) between the two conditions is lacking. The multifactorial protein PARK7/DJ-1 is a major antioxidant protein, playing a key role in cellular redox homoeostasis, and is a positive regulator of AR (androgen receptor)-dependent transcription. SLC41A1 (solute carrier family 41 member 1), the gene encoding a ubiquitous cellular Mg(2+)E (Mg(2+)efflux) system, has been shown to be regulated by activated AR. We hypothesize that overexpression/up-regulation of PARK7/DJ-1, attributable to OS and related activation of AR, is an important event regulating the expression of SLC41A1 and consequently, modulating the Mg(2+)E capacity. This would involve changes in the transcriptional activity of PARK7/DJ-1, AR and SLC41A1, which may serve as biomarkers of intracellular MD and may have clinical relevance. Imipramine, in use as an antidepressant, has been shown to reduce the Mg(2+)E activity of SLC41A1 and OS. We therefore hypothesize further that administration of imipramine or related drugs will be beneficial in MD- and OS-associated diseases, especially when combined with Mg(2+) supplementation. If proved true, the OS-responsive functional axis, PARK7/DJ-1-AR-SLC41A1, may be a putative mechanism underlying intracellular MD secondary to OS caused by pro-oxidative stimuli, including extracellular MD. Furthermore, it will advance our understanding of the link between OS and MD. © 2015 Authors; published by Portland Press Limited.

Magnocellular-dorsal pathway and sub-lexical route in developmental dyslexia

PubMed Central

Gori, Simone; Cecchini, Paolo; Bigoni, Anna; Molteni, Massimo; Facoetti, Andrea

2014-01-01

Although developmental dyslexia (DD) is frequently associate with a phonological deficit, the underlying neurobiological cause remains undetermined. Recently, a new model, called “temporal sampling framework” (TSF), provided an innovative prospect in the DD study. TSF suggests that deficits in syllabic perception at a specific temporal frequencies are the critical basis for the poor reading performance in DD. This approach was presented as a possible neurobiological substrate of the phonological deficit of DD but the TSF can also easily be applied to the visual modality deficits. The deficit in the magnocellular-dorsal (M-D) pathway - often found in individuals with DD - fits well with a temporal oscillatory deficit specifically related to this visual pathway. This study investigated the visual M-D and parvocellular-ventral (P-V) pathways in dyslexic and in chronological age and IQ-matched normally reading children by measuring temporal (frequency doubling illusion) and static stimuli sensitivity, respectively. A specific deficit in M-D temporal oscillation was found. Importantly, the M-D deficit was selectively shown in poor phonological decoders. M-D deficit appears to be frequent because 75% of poor pseudo-word readers were at least 1 SD below the mean of the controls. Finally, a replication study by using a new group of poor phonological decoders and reading level controls suggested a crucial role of M-D deficit in DD. These results showed that a M-D deficit might impair the sub-lexical mechanisms that are critical for reading development. The possible link between these findings and TSF is discussed. PMID:25009484

[Autism, genetics and synaptic function alterations].

PubMed

Perche, O; Laumonnier, F; Baala, L; Ardourel, M-Y; Menuet, A; Robin, V; Mortaud, S; Montécot-Dubourg, C; Richard, O; Pichon, J; Briault, S

2010-10-01

Autism is a neurodevelopmental disorder characterized by a deficit of language and communication both associated with a restricted repertoire of activities and interests. The current prevalence of autistic disorder stricto sensu is estimated at 1/500 whereas autism spectrum disorders (ASD) increases up to 1/150 to 1/200. Mental deficiency (MD) and epilepsy are present in numerous autistic individuals. Consequently, autism is as a major public health issue. Autism was first considered as a non biological disease; however various rational approaches for analysing epidemiological data suggested the possibility of the influence of genetic factors. In 2003, this hypothesis was clearly illustrated by the characterization of genetic mutations transmitted through a mendelian manner. Subsequently, the glutamate synapse appeared as a preferential causal target in autism because the identified genes encoded proteins present in this structure. Strikingly, the findings that an identical genetic dysfunction of the synapse might also explain some MD suggested the possibility of a genetic comorbidity between these neurodevelopmental conditions. To date, various identified genes are considered indifferently as "autism" or "MD" genes. The characterization of mutations in the NLGN4X gene in patients with Asperger syndrome, autism without MD, or MD without autism, was the first example. It appears that a genetic continuum between ASD on one hand, and between autism and MD on the other hand, is present. Consequently, it is likely that genes already involved in MD will be found mutated in autistic patients and will represent future target for finding new factors in autism. Copyright © 2010 Elsevier Masson SAS. All rights reserved.

Moral distress in physicians and nurses: Impact on professional quality of life and turnover.

PubMed

Austin, Cindy L; Saylor, Robert; Finley, Phillip J

2017-07-01

The purpose of this study was to investigate moral distress (MD) and turnover intent as related to professional quality of life in physicians and nurses at a tertiary care hospital. Health care providers from a variety of hospital departments anonymously completed 2 validated questionnaires (Moral Distress Scale-Revised and Professional Quality of Life Scale). Compassion fatigue (as measured by secondary traumatic stress [STS] and burnout [BRN]) and compassion satisfaction are subscales which make up one's professional quality of life. Relationships between these constructs and clinicians' years in health care, critical care patient load, and professional discipline were explored. The findings (n = 329) demonstrated significant correlations between STS, BRN, and MD. Scores associated with intentions to leave or stay in a position were indicative of high verses low MD. We report highest scoring situations of MD as well as when physicians and nurses demonstrate to be most at risk for STS, BRN and MD. Both physicians and nurses identified the events contributing to the highest level of MD as being compelled to provide care that seems ineffective and working with a critical care patient load >50%. The results from this study of physicians and nurses suggest that the presence of MD significantly impacts turnover intent and professional quality of life. Therefore implementation of emotional wellness activities (e.g., empowerment, opportunity for open dialog regarding ethical dilemmas, policy making involvement) coupled with ongoing monitoring and routine assessment of these maladaptive characteristics is warranted. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Glucose Sensor MdHXK1 Phosphorylates and Stabilizes MdbHLH3 to Promote Anthocyanin Biosynthesis in Apple

PubMed Central

Hu, Da-Gang; Zhang, Quan-Yan; An, Jian-Ping; You, Chun-Xiang; Hao, Yu-Jin

2016-01-01

Glucose induces anthocyanin accumulation in many plant species; however, the molecular mechanism involved in this process remains largely unknown. Here, we found that apple hexokinase MdHXK1, a glucose sensor, was involved in sensing exogenous glucose and regulating anthocyanin biosynthesis. In vitro and in vivo assays suggested that MdHXK1 interacted directly with and phosphorylated an anthocyanin-associated bHLH transcription factor (TF) MdbHLH3 at its Ser361 site in response to glucose. Furthermore, both the hexokinase_2 domain and signal peptide are crucial for the MdHXK1-mediated phosphorylation of MdbHLH3. Moreover, phosphorylation modification stabilized MdbHLH3 protein and enhanced its transcription of the anthocyanin biosynthesis genes, thereby increasing anthocyanin biosynthesis. Finally, a series of transgenic analyses in apple calli and fruits demonstrated that MdHXK1 controlled glucose-induced anthocyanin accumulation at least partially, if not completely, via regulating MdbHLH3. Overall, our findings provide new insights into the mechanism of the glucose sensor HXK1 modulation of anthocyanin accumulation, which occur by directly regulating the anthocyanin-related bHLH TFs in response to a glucose signal in plants. PMID:27560976

The New Modern Mediterranean Diet Italian Pyramid.

PubMed

Vitiello, V; Germani, A; Capuzzo Dolcetta, E; Donini, L M; Del Balzo, V

2016-01-01

Epidemiological studies have established the health benefits associated with the adherence to the MD (Mediterranean Diet), mainly in relation to reducing the risk of developing the non communicable diseases. The MD is a sustainable diet model that respects the environment, promotes the bio-diversity, the local cultural heritages, the social interaction and economic aspects. The pyramid is a graphical representation designed to represent the frequencies of consumption and portion sizes of each food according to the Mediterranean model and tradition. The pyramid was developed taking into account the LARN (Reference Intake of nutrients and energy for Italian Population) and the Italian Guidelines for a healthy diet. The frequency of consumption and the portion size recommended are located at the different level of the pyramid. At the base of the pyramid there are the foods that should be consumed every meal and some concepts typical of the Mediterranean culture. In the middle there are foods that should be consumed daily and at the top of the pyramid the foods consumed on a weekly basis. The new modern MD Italian Pyramid is an important tool to promote the MD and improve the adherence to the MD dietary pattern.

Mediterranean diet as the diet of choice for patients with chronic kidney disease.

PubMed

Chauveau, Philippe; Aparicio, Michel; Bellizzi, Vincenzo; Campbell, Katrina; Hong, Xu; Johansson, Lina; Kolko, Anne; Molina, Pablo; Sezer, Siren; Wanner, Christoph; Ter Wee, Pieter M; Teta, Daniel; Fouque, Denis; Carrero, Juan J

2018-05-01

Traditional dietary management of chronic kidney disease (CKD) focuses on the quantity within the diet of energy and protein, and the restriction of single micronutrients, with little mention of dietary quality. Dietary patterns that are more plant-based, lower in meat (including processed meat), sodium and refined sugar, and have a higher content of grains and fibres are now included in multiple clinical guidelines for chronic disease prevention. The Mediterranean diet (MD) has been associated with reduced cardiovascular disease incidence in both observational and interventional studies. A wealth of evidence links MD with other beneficial effects on chronic diseases such as diabetes, obesity or cognitive health. This review examines each constituent of the classical MD and evaluates their suitability for the management of patients with CKD. We also evaluate the potential hyperkalaemia risk of increasing fruit and vegetable intake. Overall, a decrease in net endogenous acid production and increase in fibre may lead to a better control of metabolic acidosis. This, together with other putative favourable effects of MD on endothelial function, inflammation, lipid profile and blood pressure, provide mechanistic pathways to explain the observed reduced renal function decline and improved survival in CKD patients adhering to an MD.

Occupational exposure to mineral turpentine and heavy fuels: a possible risk factor for Alzheimer's disease.

PubMed

Helou, Rafik; Jaecker, Pierre

2014-05-01

The association between solvents and Alzheimer's disease (AD) has been the subject of several studies. Yet, only few studies have examined the various solvents separately, and the controls have rarely been monitored long enough. For these reasons and others, we believe that further studies are required. The objective of this study was to identify solvents associated with the clinicoradiological diagnostic of AD or mixed-type dementia (MD). A retrospective case-control study was performed in 156 patients followed up at the Memory Diagnostic Center of Bertinot Juel Hospital (France). The inclusion criteria were known occupation(s), a Mini-Mental State Examination (MMSE) score ≥10 at the first visit, a neuropsychological evaluation performed and a diagnosis established in our Memory Diagnostic Center. The diagnostics were crossed with 9 solvents belonging to two classes of solvents. Exposure was evaluated using French national job-exposure matrices. Certain petroleum-based solvents and fuels (i.e. mineral turpentine, diesel fuel, fuel oil and kerosene) were associated with a diagnosis of AD or MD. This association was still significant after adjustment for age, sex and education (adjusted OR: 6.5; 95% CI: 2-20). Occupational exposure to mineral turpentine and heavy fuels may be a risk factor for AD and MD.

Tractography of Association Fibers Associated with Language Processing.

PubMed

Egger, K; Yang, S; Reisert, M; Kaller, C; Mader, I; Beume, L; Weiller, C; Urbach, H

2015-10-01

Several major association fiber tracts are known to be part of the language processing system. There is evidence that high angular diffusion-based MRI is able to separate these fascicles in a constant way. In this study, we wanted to proof this thesis using a novel whole brain "global tracking" approach and to test for possible lateralization. Global tracking was performed in six healthy right-handed volunteers for the arcuate fascicle (AF), the medial longitudinal fascicle (MdLF), the inferior fronto-occipital fascicle (IFOF), and the inferior longitudinal fascicle (ILF). These fiber tracts were characterized quantitatively using the number of streamlines (SL) and the mean fractional anisotropy (FA). We were able to characterize the AF, the MdLF, the IFOF, and the ILF consistently in six healthy volunteers using global tracking. A left-sided dominance (LI > 0.2) for the AF was found in all participants. The MdLF showed a left-sided dominance in four participants (one female, three male). Regarding the FA, no lateralization (LI > 0.2) could be shown in any of the fascicles. Using a novel global tracking algorithm we confirmed that the courses of the primary language processing associated fascicles can consistently be differentiated. Additionally we were able to show a streamline-based left-sided lateralization in the AF of all right-handed healthy subjects.

Factors Associated with Increased Risk for Lethal Violence in Intimate Partner Relationships among Ethnically Diverse Black Women

PubMed Central

Sabri, Bushra; Stockman, Jamila K.; Campbell, Jacquelyn C.; O’Brien, Sharon; Campbell, Doris; Callwood, Gloria B.; Bertrand, Desiree; Sutton, Lorna W.; Hart-Hyndman, Greta

2014-01-01

The purpose of this study was to identify factors associated with increased risk for lethal violence among ethnically diverse Black women in Baltimore, Maryland (MD) and the US Virgin Islands (USVI). Women with abuse experiences (n=456) were recruited from primary care, prenatal or family planning clinics in Baltimore, MD and St. Thomas and St. Croix, USVI. Logistic regression was used to examine factors associated with the risk for lethal violence among abused women. Factors independently related to increased risk of lethal violence included fear of abusive partners, PTSD symptoms, and use of legal resources. These factors must be considered in assessing safety needs of Black women in abusive relationships. PMID:25429191

Cardiac involvement in female Duchenne and Becker muscular dystrophy carriers in comparison to their first-degree male relatives: a comparative cardiovascular magnetic resonance study.

PubMed

Florian, Anca; Rösch, Sabine; Bietenbeck, Michael; Engelen, Markus; Stypmann, Jörg; Waltenberger, Johannes; Sechtem, Udo; Yilmaz, Ali

2016-03-01

Duchenne (DMD) and Becker (BMD) muscular dystrophies are X-linked recessive disorders associated with both skeletal myopathy and progressive cardiomyopathy in males. Female DMD/BMD carriers (DMDc/BMDc) are mostly free of skeletal muscle symptoms, but they are also prone to cardiomyopathy. The aim of the current study was to characterize the frequency, pattern, and extent of cardiomyopathy in female DMD/BMD carriers (DMDc/BMDc) in comparison to their first-degree male MD relatives. Thirty-six (age 44 ± 14 years) female MD carriers (20 DMDc and 16 BMDc) constituted the 'MD carrier group' and were prospectively enrolled. All MD carriers underwent a complete CMR study comprising cine- and late gadolinium enhancement (LGE) imaging. In 22 of these women ('female MD carrier comparison group', 7 DMD and 15 BMD), at least one first-degree male relative with a previously established diagnosis of MD underwent the same CMR protocol and was assigned to the 'male MD comparison group' (n = 24, 6 DMD and 18 BMD). In the total MD carrier group, 17 (47%) MD carriers had at least one pathological CMR finding [5 (14%) with a reduced left ventricular ejection fraction (LV-EF) and 16 (44%) with the presence of LGE]. All LGE-positive patients (n = 16) showed non-ischaemic LGE with subepicardial involvement of the LV lateral free wall being the most frequent pattern (13/16, 81%). Compared with BMDc, DMDc demonstrated more frequently a pathological CMR result (65 vs. 19%; P = 0.008)--in spite of being significantly younger (40 ± 11 vs. 50 ± 16 years, P = 0.038). In the male MD comparison group, the same LGE pattern as in female carriers was seen, but with a significantly higher prevalence of cardiac abnormalities compared with their female carrier relatives constituting the female MD comparison group (75 vs. 27%; P = 0.003). Cardiac involvement is a frequent finding in female carriers of DMD, but less frequently observed in carriers of BMD. Those DMDc and BMDc with cardiac involvement demonstrate the same myocardial fibrosis pattern as their male counterparts with overt disease. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Personality, Socio-Economic Status and Inflammation: Cross-Sectional, Population-Based Study

PubMed Central

Millar, Keith; Lloyd, Suzanne M.; McLean, Jennifer S.; Batty, G. David; Burns, Harry; Cavanagh, Jonathan; Deans, Kevin A.; Ford, Ian; McConnachie, Alex; McGinty, Agnes; Mõttus, Réne; Packard, Chris J.; Sattar, Naveed; Shiels, Paul G.; Velupillai, Yoga N.; Tannahill, Carol

2013-01-01

Background Associations between socio-economic status (SES), personality and inflammation were examined to determine whether low SES subjects scoring high on neuroticism or hostility might suffer relatively higher levels of inflammation than affluent subjects. Methods In a cross-sectional design, 666 subjects were recruited from areas of high (most deprived – “MD”) and low (least deprived – “LD”) deprivation. IL-6, ICAM-1, CRP and fibrinogen were measured along with demographic and health-behaviour variables, and personality traits of neuroticism, extraversion and psychoticism (hostility). Regression models assessed the prediction of inflammation as a function of personality, deprivation and their interaction. Results Levels of CRP and IL-6 were an increasing function of neuroticism and extraversion only in LD subjects opposite trends were seen in MD subjects. The result was ascribed parsimoniously to an inflammatory ceiling effect or, more speculatively, to SES-related health-behaviour differences. Psychoticism was strongly associated with ICAM-1 in both MD and LD subjects. Conclusions The association between neuroticism, CRP and IL-6 may be reduced in MD subjects confirming speculation that the association differs across population sub-groups. The association between psychoticism and ICAM-1 supports evidence that hostility has adverse effects upon the endothelium, with consequences for cardiovascular health. Health interventions may be more effective by accounting for personality-related effects upon biological processes. PMID:23516457

Diffusion Tensor Tractography of the Cerebellar Peduncles in Prematurely Born 7-Year-Old Children.

PubMed

Shany, Eilon; Inder, Terrie E; Goshen, Sharon; Lee, Iris; Neil, Jeffrey J; Smyser, Christopher D; Doyle, Lex W; Anderson, Peter J; Shimony, Joshua S

2017-04-01

The objective of this study was to correlate neurodevelopmental outcome of preterm-born children and their perinatal clinical and imaging characteristics with diffusion magnetic resonance imaging (MRI) measures of the three cerebellar peduncles at age 7. Included in this prospective longitudinal study were 140 preterm-born children (<30 weeks gestation) who underwent neurodevelopmental assessment (IQ, motor, language, working memory) and diffusion-weighted imaging (DWI) at age 7 years. White matter tracts in the superior, middle, and inferior cerebellar peduncles were delineated using regions of interest drawn on T2-weighted images and fractional anisotropy (FA) maps. Diffusion measures (mean diffusivity (MD) and FA) and tract volumes were calculated. Linear regression was used to assess relationships with outcome. The severity of white matter injury in the neonatal period was associated with lower FA in the right superior cerebellar peduncle (SCP) and lower tract volumes of both SCPs and middle cerebellar peduncles (MCPs). In the MCP, higher IQ was associated with lower MD in the whole group and higher FA in right-handed children. In the SCP, lower motor scores were associated with higher MD and higher language scores were associated with higher FA. These associations remained significant in multivariable models. This study adds to the body of literature detailing the importance of cerebellar involvement in cognitive function related to reciprocal connections with supratentorial structures.

Anuran trypanosomes: phylogenetic evidence for new clades in Brazil.

PubMed

da S Ferreira, Juliana I G; da Costa, Andrea P; Ramirez, Diego; Roldan, Jairo A M; Saraiva, Danilo; da S Founier, Gislene F R; Sue, Ana; Zambelli, Erick R; Minervino, Antonio H H; Verdade, Vanessa K; Gennari, Solange M; Marcili, Arlei

2015-05-01

Trypanosomes of anurans and fish are grouped into the Aquatic Clade which includes species isolated from fish, amphibians, turtles and platypus, usually transmitted by leeches and phlebotomine sand flies. Trypanosomes from Brazilian frogs are grouped within the Aquatic Clade with other anuran trypanosome species, where there seems to be coevolutionary patterns with vertebrate hosts and association to Brazilian biomes (Atlantic Forest, Pantanal and Amazonia Rainforest). We characterised the anuran trypanosomes from two different areas of the Cerrado biome and examined their phylogenetic relationships based on the SSU rRNA gene. A total of 112 anurans of six species was analysed and trypanosome prevalence evaluated through haemoculture was found to be 7% (8 positive frogs). However, only three isolates (2.7%) from two anuran species were recovered and cryopreserved. Analysis including SSU rDNA sequences from previous studies segregated the anuran trypanosomes into six groups, the previously reported An01 to An04, and An05 and An06 reported herein. Clade An05 comprises the isolates from Leptodactylus latrans (Steffen) and Pristimantis sp. captured in the Cerrado biome and Trypanosoma chattoni Mathis & Leger, 1911. The inclusion of new isolates in the phylogenetic analyses provided evidence for a new group (An06) of parasites from phlebotomine hosts. Our results indicate that the diversity of trypanosome species is underestimated since studies conducted in Brazil and other regions of the world are still few.

Overexpression of a Novel Apple NAC Transcription Factor Gene, MdNAC1, Confers the Dwarf Phenotype in Transgenic Apple (Malus domestica)

PubMed Central

Jia, Dongfeng; Gong, Xiaoqing; Li, Mingjun; Li, Chao; Sun, Tingting

2018-01-01

Plant height is an important trait for fruit trees. The dwarf characteristic is commonly associated with highly efficient fruit production, a major objective when breeding for apple (Malus domestica). We studied the function of MdNAC1, a novel NAC transcription factor (TF) gene in apple related to plant dwarfing. Localized primarily to the nucleus, MdNAC1 has transcriptional activity in yeast cells. Overexpression of the gene results in a dwarf phenotype in transgenic apple plants. Their reduction in size is manifested by shorter, thinner stems and roots, and a smaller leaf area. The transgenics also have shorter internodes and fewer cells in the stems. Levels of endogenous abscisic acid (ABA) and brassinosteroid (BR) are lower in the transgenic plants, and expression is decreased for genes involved in the biosynthesis of those phytohormones. All of these findings demonstrate that MdNAC1 has a role in plants dwarfism, probably by regulating ABA and BR production. PMID:29702625

Rational design of novel TLR4 ligands by in silico screening and their functional and structural characterization in vitro.

PubMed

Honegr, Jan; Malinak, David; Dolezal, Rafael; Soukup, Ondrej; Benkova, Marketa; Hroch, Lukas; Benek, Ondrej; Janockova, Jana; Kuca, Kamil; Prymula, Roman

2018-02-25

The purpose of this study was to identify new small molecules that possess activity on human toll-like receptor 4 associated with the myeloid differentiation protein 2 (hTLR4/MD2). Following current rational drug design principles, we firstly performed a ligand and structure based virtual screening of more than 130 000 compounds to discover until now unknown class of hTLR4/MD2 modulators that could be used as novel type of immunologic adjuvants. The core of the in silico study was molecular docking of flexible ligands in a partially flexible hTLR4/MD2 receptor model using a peta-flops-scale supercomputer. The most promising substances resulting from this study, related to anthracene-succimide hybrids, were synthesized and tested. The best prepared candidate exhibited 80% of Monophosphoryl Lipid A in vitro agonistic activity in cell lines expressing hTLR4/MD2. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Sensory trick phenomenon improves motor control in pianists with dystonia: prognostic value of glove-effect

PubMed Central

Paulig, Jakobine; Jabusch, Hans-Christian; Großbach, Michael; Boullet, Laurent; Altenmüller, Eckart

2014-01-01

Musician’s dystonia (MD) is a task-specific movement disorder that causes loss of voluntary motor control while playing the instrument. A subgroup of patients displays the so-called sensory trick: alteration of somatosensory input, e.g., by wearing a latex glove, may result in short-term improvement of motor control. In this study, the glove-effect in pianists with MD was quantified and its potential association with MD-severity and outcome after treatment was investigated. Thirty affected pianists were included in the study. Music instrument digital interface-based scale analysis was used for assessment of fine motor control. Therapeutic options included botulinum toxin, pedagogical retraining and anticholinergic medication (trihexyphenidyl). 19% of patients showed significant improvement of fine motor control through wearing a glove. After treatment, outcome was significantly better in patients with a significant pre-treatment sensory trick. We conclude that the sensory trick may have a prognostic value for the outcome after treatment in pianists with MD. PMID:25295014

Self-reported inhibition predicts history of suicide attempts in bipolar disorder and major depression.

PubMed

Ponsoni, André; Branco, Laura Damiani; Cotrena, Charles; Shansis, Flávio Milman; Grassi-Oliveira, Rodrigo; Fonseca, Rochele Paz

2018-04-01

Studies have reliably identified an association between suicide attempts and executive functions such as decision making (DM) and inhibitory control (IC) in patients with mood disorders. As such, the present study aimed to investigate the association between inhibition, DM, impulsivity and the history of suicide attempts in individuals with bipolar (BD) or major depressive disorder (MDD), identifying which assessment instruments may be most strongly associated with suicide in clinical samples. The sample included 80 control subjects and two groups of patients with BD and MDD, matched by age and education (26 with a history of suicide attempts [MD+], and 26 with no such history [MD-]). Participants completed behavioral and self-report measures of DM and IC, which were compared between groups using ANCOVA, followed by logistic regression for patients with mood disorders only, and the presence or absence of a history of suicide as the outcome. Cognitive performance did not differ between groups. The MD+ group showed significantly higher motor and attentional impulsivity on the BIS-11 than the MD- and control groups. A regression analysis containing these scores showed that motor impulsivity was the only significant predictor of a history of suicide (OR = 1.14; 95%CI 1.00-1.30). Self-reported motor impulsivity was a significant predictor of suicide. These findings underscore the importance of self-report measures in neuropsychological assessment, and their contributions to the management and prognosis of patients with mood disorders. Lastly, they point to the role of impulsivity as a target for interventions and public policy on suicide prevention. Copyright © 2018 Elsevier Inc. All rights reserved.

Sex Differences in Financial Barriers and the Relationship to Recovery After Acute Myocardial Infarction.

PubMed

Beckman, Adam L; Bucholz, Emily M; Zhang, Weiwei; Xu, Xiao; Dreyer, Rachel P; Strait, Kelly M; Spertus, John A; Krumholz, Harlan M; Spatz, Erica S

2016-10-14

Financial barriers to health care are associated with worse outcomes following acute myocardial infarction (AMI). Yet, it is unknown whether the prevalence of financial barriers and their relationship with post-AMI outcomes vary by sex among young adults. We assessed sex differences in patient-reported financial barriers among adults aged <55 years with AMI using data from the Variation in Recovery: Role of Gender on Outcomes of Young AMI Patients study. We examined the prevalence of financial barriers and their association with health status 12 months post-AMI. Among 3437 patients, more women than men reported financial barriers to medications (22.3% vs 17.2%; P=0.001), but rates of financial barriers to services were similar (31.3% vs 28.9%; P=0.152). In multivariable linear regression models adjusting for baseline health, psychosocial status, and clinical characteristics, compared with no financial barriers, women and men with financial barriers to services and medications had worse mental functional status (Short Form-12 mental health score: mean difference [MD]=-3.28 and -3.35, respectively), greater depressive symptomatology (Patient Health Questionnaire-9: MD, 2.18 and 2.16), lower quality of life (Seattle Angina Questionnaire-Quality of Life: MD, -4.98 and -7.66), and higher perceived stress (Perceived Stress Score: MD, 3.76 and 3.90; all P<0.05). There was no interaction between sex and financial barriers. Financial barriers to care are common in young patients with AMI and associated with worse health outcomes 1 year post-AMI. Whereas women experienced more financial barriers than men, the association did not vary by sex. These findings emphasize the importance of addressing financial barriers to recovery post-AMI in young adults. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Mucoid Degeneration of the Anterior Cruciate Ligament: Characterization of Natural History, Femoral Notch Width Index, and Patient Reported Outcome Measures.

PubMed

Hotchen, Andrew J; Demetriou, Charis; Edwards, Dennis; Melton, Joel T K

2018-06-13

The presentation and clinical course of mucoid degeneration of the anterior cruciate ligament (MD-ACL) are poorly documented within the literature. Subsequently, it is under-diagnosed and the optimal management strategy remains ill-defined. Here, we characterize the syndrome associated with MD-ACL and compare the natural clinical course with the outcomes of arthroscopic management. Thirty-one patients with radiological features of MD-ACL over a 2-year period had their clinical notes retrospectively reviewed. Seven patients underwent arthroscopic debridement of the ACL for MD. These were followed up for a minimum of 2 years and an average of 2.8 years from surgery. The remainder were managed conservatively ( n  = 24) and were followed up for a minimum of 2 years and an average of 4.0 years. The notch width index (NWI) and associated pathology was noted. Primary outcome measures were presence of knee pain and use of analgesia. Secondary outcome measures were the Oxford and Lysholm knee scores. The most commonly reported symptoms were posterior knee pain (77.4%) and limitation of terminal flexion (58.1%). All patients who underwent arthroscopic debridement were pain and analgesia free at follow-up. Of the patients who did not undergo arthroscopic surgery, three patients had knee replacement surgery and three were lost to follow-up. The remaining patients, 14/18 (77.8%), reported knee pain and regular analgesia use at follow-up, which was significantly more than the arthroscopic debridement group ( p  < 0.01). The knee scores were significantly better in the arthroscopic debridement group at follow-up (Oxford knee score: 45 vs 34; Lysholm: 92 vs 67; p  < 0.01). Furthermore, the postoperative improvement in the Oxford knee and Lysholm scores compared with preoperatively was 12.1 and 31.8 points, respectively ( p  < 0.01). The NWI was increased in patients with mild-to-severe osteoarthritis (0.266 vs 0.273; p  < 0.05). MD-ACL should be considered in patients who report posterior knee pain, limitation of terminal flexion, and it can be associated with other knee pathologies. MD-ACL can be successfully managed with arthroscopic radio frequency debulking with improvement in quality of life at follow-up. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Effect of early institutionalization and foster care on long-term white matter development: a randomized clinical trial.

PubMed

Bick, Johanna; Zhu, Tong; Stamoulis, Catherine; Fox, Nathan A; Zeanah, Charles; Nelson, Charles A

2015-03-01

Severe neglect in early life is associated with compromises in brain development and associated behavioral functioning. Although early intervention has been shown to support more normative trajectories of brain development, specific improvements in the white matter pathways that underlie emotional and cognitive development are unknown. To examine associations among neglect in early life, early intervention, and the microstructural integrity of white matter pathways in middle childhood. The Bucharest Early Intervention Project is a randomized clinical trial of high-quality foster care as an intervention for institutionally reared children in Bucharest, Romania, from 2000 through the present. During infancy, children were randomly selected to remain in an institution or to be placed in foster care. Those who remained in institutions experienced neglect, including social, emotional, linguistic, and cognitive impoverishment. Developmental trajectories of these children were compared with a group of sociodemographically matched children reared in biological families at baseline and several points throughout development. At approximately 8 years of age, 69 of the original 136 children underwent structural magnetic resonance imaging scans. Four estimates of white matter integrity (fractional anisotropy [FA] and mean [MD], radial [RD], and axial [AD] diffusivity) for 48 white matter tracts throughout the brain were obtained through diffusion tensor imaging. Significant associations emerged between neglect in early life and microstructural integrity of the body of the corpus callosum (FA, β = 0.01 [P = .01]; RD, β = -0.02 [P = .005]; MD, β = -0.01 [P = .02]) and tracts involved in limbic circuitry (fornix crus [AD, β = 0.02 (P = .046)] and cingulum [RD, β = -0.01 (P = .02); MD, β = -0.01 (P = .049)]), frontostriatal circuitry (anterior [AD, β = -0.01 (P = .02)] and superior [AD, β = -0.02 (P = .02); MD, β = -0.01 (P = .03)] corona radiata and external capsule [right FA, β = 0.01 (P = .03); left FA, β = 0.01 (P = .03); RD, β = -0.01 (P = .01); MD, β = -0.01 (P = .03)]), and sensory processing (medial lemniscus [AD, β = -0.02 (P = .045); MD, β = -0.01 (P = .04)] and retrolenticular internal capsule [FA, β = -0.01 (P = .002); RD, β = 0.01 (P = .003); MD, β = 0.01 (P = .04)]). Follow-up analyses revealed that early intervention promoted more normative white matter development among previously neglected children who entered foster care. Results suggest that removal from conditions of neglect in early life and entry into a high-quality family environment can support more normative trajectories of white matter growth. Our findings have implications for public health and policy efforts designed to promote normative brain development among vulnerable children. clinicaltrials.gov Identifier: NCT00747396.

Authigenic 10Be/9Be ratio signatures of the cosmogenic nuclide production linked to geomagnetic dipole moment variation since the Brunhes/Matuyama boundary

PubMed Central

Thouveny, Nicolas; Bourlès, Didier L.; Valet, Jean‐Pierre; Bassinot, Franck; Ménabréaz, Lucie; Guillou, Valéry; Choy, Sandrine; Beaufort, Luc

2016-01-01

Abstract Geomagnetic dipole moment variations associated with polarity reversals and excursions are expressed by large changes of the cosmogenic nuclide beryllium‐10 (10Be) production rates. Authigenic 10Be/9Be ratios (proxy of atmospheric 10Be production) from oceanic cores therefore complete the classical information derived from relative paleointensity (RPI) records. This study presents new authigenic 10Be/9Be ratio results obtained from cores MD05‐2920 and MD05‐2930 collected in the west equatorial Pacific Ocean. Be ratios from cores MD05‐2920, MD05‐2930 and MD90‐0961 have been stacked and averaged. Variations of the authigenic 10Be/9Be ratio are analyzed and compared with the geomagnetic dipole low series reported from global RPI stacks. The largest 10Be overproduction episodes are related to dipole field collapses (below a threshold of 2 × 1022 Am2) associated with the Brunhes/Matuyama reversal, the Laschamp (41 ka) excursion, and the Iceland Basin event (190 ka). Other significant 10Be production peaks are correlated to geomagnetic excursions reported in literature. The record was then calibrated by using absolute dipole moment values drawn from the Geomagia and Pint paleointensity value databases. The 10Be‐derived geomagnetic dipole moment record, independent from sedimentary paleomagnetic data, covers the Brunhes‐Matuyama transition and the whole Brunhes Chron. It provides new and complementary data on the amplitude and timing of millennial‐scale geomagnetic dipole moment variations and particularly on dipole moment collapses triggering polarity instabilities. PMID:28163989

Association of 17-β Estradiol with Adipose-Derived Stem Cells: New Strategy to Produce Functional Myogenic Differentiated Cells with a Nano-Scaffold for Tissue Engineering.

PubMed

Feng, Chunxiang; Hu, Jinqian; Liu, Chang; Liu, Shiliang; Liao, Guiying; Song, Linjie; Zeng, Xiaoyong

2016-01-01

The increased incidence of stress urinary incontinence (SUI) in postmenopausal women has been proposed to be associated with a reduction in the level of 17-β estradiol (E2). E2 has also been shown to enhance the multi-differentiation ability of adipose-derived stem cells (ASCs) in vitro. However, studies on the potential value of E2 for tissue engineering in SUI treatment are rare. In the present study, we successfully fabricated myogenically differentiated ASCs (MD-ASCs), which were seeded onto a Poly(l-lactide)/Poly(e-caprolactone) electrospinning nano-scaffold, and incorporated E2 into the system, with the aim of improving the proliferation and myogenic differentiation of ASCs. ASCs were collected from the inguinal subcutaneous fat of rats. The proliferation and myogenic differentiation of ASCs, as well as the nano-scaffold biocompatibility of MD-ASCs, with or without E2 supplementation, were investigated. We demonstrated that E2 incorporation enhanced the proliferation of ASCs in vitro, and the most optimal concentration was 10-9 M. E2 also led to modulation of the MD-ASCs phenotype toward a concentrated type with smooth muscle-inductive medium. The expression of early (alpha-smooth muscle actin), mid (calponin), and late-stage (myosin heavy chain) contractile markers in MD-ASCs was enhanced by E2 during the different differentiation stages. Furthermore, the nano-scaffold was biocompatible with MD-ASCs, and cell proliferation was significantly enhanced by E2. Taken together, these results demonstrate that E2 can enhance the proliferation and myogenic differentiation of ASCs and can be used to construct a biocompatible cell/nano-scaffold. These scaffolds with desirable differentiation cells show promising applications for tissue engineering.

The Mediterranean dietary pattern as the diet of choice for non-alcoholic fatty liver disease: Evidence and plausible mechanisms.

PubMed

Zelber-Sagi, Shira; Salomone, Federico; Mlynarsky, Liat

2017-07-01

Non-alcoholic fatty liver disease (NAFLD) has become a major global health burden, leading to increased risk for cirrhosis, hepatocellular carcinoma, type-2 diabetes and cardiovascular disease. Lifestyle intervention aiming at weight reduction is the most established treatment. However, changing the dietary composition even without weight loss can also reduce steatosis and improve metabolic alterations as insulin resistance and lipid profile. The Mediterranean diet (MD) pattern has been proposed as appropriate for this goal, and was recommended as the diet of choice for the treatment of NAFLD by the EASL-EASD-EASO Clinical Practice Guidelines. The MD has an established superiority in long term weight reduction over low fat diet, but it improves metabolic status and steatosis even without it. However, the effect on liver inflammation and fibrosis was tested only in few observational studies with positive results. Furthermore, considering the strong association between NAFLD and diabetes and CVD, the MD has a highly established advantage in prevention of these diseases, demonstrated in randomized clinical trials. The individual components of the MD such as olive oil, fish, nuts, whole grains, fruits, and vegetables, have been shown to beneficially effect or negatively correlate with NAFLD, while consumption of components that characterize a Western dietary pattern as soft drinks, fructose, meat and saturated fatty acids have been shown to have detrimental association with NAFLD. In this review we will cover the epidemiological evidence and the plausible molecular mechanisms by which the MD as a whole and each of its components can be of benefit in NAFLD. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Petrophysics of Lower Silurian sandstones and integration with the tectonic-stratigraphic framework, Appalachian basin, United States

USGS Publications Warehouse

Castle, J.W.; Byrnes, A.P.

2005-01-01

Petrophysical properties were determined for six facies in Lower Silurian sandstones of the Appalachian basin: fluvial, estuarine, upper shoreface, lower shoreface, tidal channel, and tidal flat. Fluvial sandstones have the highest permeability for a given porosity and exhibit a wide range of porosity (2-18%) and permeability (0.002-450 md). With a transition-zone thickness of only 1-6 m (3-20 ft), fluvial sandstones with permeability greater than 5 md have irreducible water saturation (Siw) less than 20%, typical of many gas reservoirs. Upper shoreface sandstones exhibit good reservoir properties with high porosity (10-21%), high permeability (3-250 md), and low S iw (<20%). Lower shoreface sandstones, which are finer grained, have lower porosity (4-12%), lower permeability (0.0007-4 md), thicker transition zones (6-180 m [20-600 ft]), and higher S iw. In the tidal-channel, tidal-flat, and estuarine facies, low porosity (average < 6%), low permeability (average < 0.02 md), and small pore throats result in large transition zones (30-200 m; 100-650 ft) and high water saturations. The most favorable reservoir petrophysical properties and the best estimated production from the Lower Silurian sandstones are associated with fluvial and upper shoreface facies of incised-valley fills, which we interpret to have formed predominantly in areas of structural recesses that evolved from promontories along a collisional margin during the Taconic orogeny. Although the total thickness of the sandstone may not be as great in these areas, reservoir quality is better than in adjacent structural salients, which is attributed to higher energy depositional processes and shallower maximum burial depth in the recesses than in the salients. Copyright ??2005. The American Association of Petroleum Geologists. All rights reserved.

Comprehensive QTL mapping survey dissects the complex fruit texture physiology in apple (Malus x domestica Borkh.).

PubMed

Longhi, Sara; Moretto, Marco; Viola, Roberto; Velasco, Riccardo; Costa, Fabrizio

2012-02-01

Fruit ripening is a complex physiological process in plants whereby cell wall programmed changes occur mainly to promote seed dispersal. Cell wall modification also directly regulates the textural properties, a fundamental aspect of fruit quality. In this study, two full-sib populations of apple, with 'Fuji' as the common maternal parent, crossed with 'Delearly' and 'Pink Lady', were used to understand the control of fruit texture by QTL mapping and in silico gene mining. Texture was dissected with a novel high resolution phenomics strategy, simultaneously profiling both mechanical and acoustic fruit texture components. In 'Fuji × Delearly' nine linkage groups were associated with QTLs accounting from 15.6% to 49% of the total variance, and a highly significant QTL cluster for both textural components was mapped on chromosome 10 and co-located with Md-PG1, a polygalacturonase gene that, in apple, is known to be involved in cell wall metabolism processes. In addition, other candidate genes related to Md-NOR and Md-RIN transcription factors, Md-Pel (pectate lyase), and Md-ACS1 were mapped within statistical intervals. In 'Fuji × Pink Lady', a smaller set of linkage groups associated with the QTLs identified for fruit texture (15.9-34.6% variance) was observed. The analysis of the phenotypic variance over a two-dimensional PCA plot highlighted a transgressive segregation for this progeny, revealing two QTL sets distinctively related to both mechanical and acoustic texture components. The mining of the apple genome allowed the discovery of the gene inventory underlying each QTL, and functional profile assessment unravelled specific gene expression patterns of these candidate genes.

The Encapsidated Genome of Microplitis demolitor Bracovirus Integrates into the Host Pseudoplusia includens ▿ ‡

PubMed Central

Beck, Markus H.; Zhang, Shu; Bitra, Kavita; Burke, Gaelen R.; Strand, Michael R.

2011-01-01

Polydnaviruses (PDVs) are symbionts of parasitoid wasps that function as gene delivery vehicles in the insects (hosts) that the wasps parasitize. PDVs persist in wasps as integrated proviruses but are packaged as circularized and segmented double-stranded DNAs into the virions that wasps inject into hosts. In contrast, little is known about how PDV genomic DNAs persist in host cells. Microplitis demolitor carries Microplitis demolitor bracovirus (MdBV) and parasitizes the host Pseudoplusia includens. MdBV infects primarily host hemocytes and also infects a hemocyte-derived cell line from P. includens called CiE1 cells. Here we report that all 15 genomic segments of the MdBV encapsidated genome exhibited long-term persistence in CiE1 cells. Most MdBV genes expressed in hemocytes were persistently expressed in CiE1 cells, including members of the glc gene family whose products transformed CiE1 cells into a suspension culture. PCR-based integration assays combined with cloning and sequencing of host-virus junctions confirmed that genomic segments J and C persisted in CiE1 cells by integration. These genomic DNAs also rapidly integrated into parasitized P. includens. Sequence analysis of wasp-viral junction clones showed that the integration of proviral segments in M. demolitor was associated with a wasp excision/integration motif (WIM) known from other bracoviruses. However, integration into host cells occurred in association with a previously unknown domain that we named the host integration motif (HIM). The presence of HIMs in most MdBV genomic DNAs suggests that the integration of each genomic segment into host cells occurs through a shared mechanism. PMID:21880747

Interleukin-6 production and deregulation of the hypothalamic-pituitary-adrenal axis in patients with major depressive disorders.

PubMed

Humphreys, Derek; Schlesinger, Liana; Lopez, Marcelo; Araya, A Verónica

2006-12-01

The present study was designed to determine whether an association exists between HPA activity and cytokine production in major depression (MD). In 9 patients with MD and 11 control subjects of both sexes, all drug-free, activity of the HPA axis was evaluated by circadian rhythm of plasma cortisol, 24-h free urinary cortisol, an overnight 1 mg dexamethasone suppression test, and an oCRF stimulation test. Spontaneous and LPS-stimulated production of IL-1beta, IL-6, and TNFalpha by peripheral blood mononuclear cells were also determined. We found a significantly elevated spontaneous production of IL-6 in patients with MD (3541.2 +/- 726.8 vs 380.4 +/- 77.5 pg/mL in controls, p < 0.05), while LPS-stimulated production was significantly lower in patients than in control subjects (19,867.7 +/- 3649.2 vs 33,142.2 +/- 15,47.2 pg/mL, p < 0.05). The adrenocorticotropic hormone response to oCRF, evaluated as the area under the curve (AUCACTH) was significantly lower in patients than in control subjects (p = 0.02). A positive correlation between AUCACTH and LPS-stimulated IL-6 secretion was observed in patients with MD (r = 0.75, p < 0.05) but not in controls. These findings suggest that the activation of the inflammatory response described in depression might be associated with long-term hyperactivity of the HPA axis.

Relationship between slow visual processing and reading speed in people with macular degeneration

PubMed Central

Cheong, Allen MY; Legge, Gordon E; Lawrence, Mary G; Cheung, Sing-Hang; Ruff, Mary A

2007-01-01

Purpose People with macular degeneration (MD) often read slowly even with adequate magnification to compensate for acuity loss. Oculomotor deficits may affect reading in MD, but cannot fully explain the substantial reduction in reading speed. Central-field loss (CFL) is often a consequence of macular degeneration, necessitating the use of peripheral vision for reading. We hypothesized that slower temporal processing of visual patterns in peripheral vision is a factor contributing to slow reading performance in MD patients. Methods Fifteen subjects with MD, including 12 with CFL, and five age-matched control subjects were recruited. Maximum reading speed and critical print size were measured with RSVP (Rapid Serial Visual Presentation). Temporal processing speed was studied by measuring letter-recognition accuracy for strings of three randomly selected letters centered at fixation for a range of exposure times. Temporal threshold was defined as the exposure time yielding 80% recognition accuracy for the central letter. Results Temporal thresholds for the MD subjects ranged from 159 to 5881 ms, much longer than values for age-matched controls in central vision (13 ms, p<0.01). The mean temporal threshold for the 11 MD subjects who used eccentric fixation (1555.8 ± 1708.4 ms) was much longer than the mean temporal threshold (97.0 ms ± 34.2 ms, p<0.01) for the age-matched controls at 10° in the lower visual field. Individual temporal thresholds accounted for 30% of the variance in reading speed (p<0.05). Conclusion The significant association between increased temporal threshold for letter recognition and reduced reading speed is consistent with the hypothesis that slower visual processing of letter recognition is one of the factors limiting reading speed in MD subjects. PMID:17881032

Allelic Variation in Paralogs of GDP-l-Galactose Phosphorylase Is a Major Determinant of Vitamin C Concentrations in Apple Fruit1[C][W][OA

PubMed Central

Mellidou, Ifigeneia; Chagné, David; Laing, William A.; Keulemans, Johan; Davey, Mark W.

2012-01-01

To identify the genetic factors underlying the regulation of fruit vitamin C (l-ascorbic acid [AsA]) concentrations, quantitative trait loci (QTL) studies were carried out in an F1 progeny derived from a cross between the apple (Malus × domestica) cultivars Telamon and Braeburn over three years. QTL were identified for AsA, glutathione, total antioxidant activity in both flesh and skin tissues, and various quality traits, including flesh browning. Four regions on chromosomes 10, 11, 16, and 17 contained stable fruit AsA-QTL clusters. Mapping of AsA metabolic genes identified colocations between orthologs of GDP-l-galactose phosphorylase (GGP), dehydroascorbate reductase (DHAR), and nucleobase-ascorbate transporter within these QTL clusters. Of particular interest are the three paralogs of MdGGP, which all colocated within AsA-QTL clusters. Allelic variants of MdGGP1 and MdGGP3 derived from the cultivar Braeburn parent were also consistently associated with higher fruit total AsA concentrations both within the mapping population (up to 10-fold) and across a range of commercial apple germplasm (up to 6-fold). Striking differences in the expression of the cv Braeburn MdGGP1 allele between fruit from high- and low-AsA genotypes clearly indicate a key role for MdGGP1 in the regulation of fruit AsA concentrations, and this MdGGP allele-specific single-nucleotide polymorphism marker represents an excellent candidate for directed breeding for enhanced fruit AsA concentrations. Interestingly, colocations were also found between MdDHAR3-3 and a stable QTL for browning in the cv Telamon parent, highlighting links between the redox status of the AsA pool and susceptibility to flesh browning. PMID:23001142

Marfan syndrome associated aortic disease in neonates and children: a clinical-morphologic review.

PubMed

Ware, Adam L; Miller, Dylan V; Erickson, Lance K; Menon, Shaji C

2016-01-01

Marfan syndrome (MFS) is a multisystem connective tissue disorder that can lead to aortic dilation requiring aortic root replacement. Neonatal MFS (nMFS) is a rare and severe form of MFS compared to classic MFS (cMFS). Aortic root histology in MFS is thought to demonstrate predominantly medial degeneration (MD) of a translamellar mucoid extracellular matrix accumulation (MEMA-T) vs. the intralamellar mucoid extracellular matrix accumulation (MEMA-I) seen in other aortopathies. The objective of this study was to describe the clinical and histopathologic features of nMFS and cMFS patients undergoing aortic root replacement. Children with MFS who underwent aortic root replacement between 2000 and 2012 at a single institution were included. Medical records including clinical details, aortic dimensions (Z scores), and histology including MD type were obtained. Statistics were descriptive with univariate analysis of age at surgery and type of MD. Eleven patients, 3 (27%) with nMFS, were included. Root dilation at time of surgery was greater in nMFS compared to cMFS (Z=12.8 vs. 7.6, P=.005), and nMFS patients were younger at time of surgery (7.3 vs. 18.8 years, P=.002). Histology in the nMFS group demonstrated MEMA-I in one and no MD in two. In the cMFS group, there were three with MEMA-T, four with MEMA-I, and one with both types. In summary, nMFS has earlier root dilation often in the absence of MD. Both forms of MD were present in our cohort, and there was no correlation between age at surgery and type of MD. Copyright © 2016 Elsevier Inc. All rights reserved.

Down-staging (

PubMed

Beukers, Willemien; Meijer, Titia; Vissers, Cornelis J; Boormans, Joost L; Zwarthoff, Ellen C; van Leenders, Geert J L H

2012-08-01

Urothelial cell carcinoma (UCC) with musculus detrusor (MD) invasion is treated by cystectomy. Subsequent pathologic evaluation of cystectomies does not reveal MD invasion (

Positive predictive values by mammographic density and screening mode in the Norwegian Breast Cancer Screening Program.

PubMed

Moshina, Nataliia; Ursin, Giske; Roman, Marta; Sebuødegård, Sofie; Hofvind, Solveig

2016-01-01

To investigate the probability of breast cancer among women recalled due to abnormal findings on the screening mammograms (PPV-1) and among women who underwent an invasive procedure (PPV-2) by mammographic density (MD), screening mode and age. We used information about 28,826 recall examinations from 26,951 subsequently screened women in the Norwegian Breast Cancer Screening Program, 1996-2010. The radiologists who performed the recall examinations subjectively classified MD on the mammograms into three categories: fatty (<30% fibroglandular tissue); medium dense (30-70%) and dense (>70%). Screening mode was defined as screen-film mammography (SFM) and full-field digital mammography (FFDM). We examined trends of PPVs by MD, screening mode and age. We used logistic regression to estimate odds ratio (OR) of screen-detected breast cancer associated with MD among women recalled, adjusting for screening mode and age. PPV-1 and PPV-2 decreased by increasing MD, regardless of screening mode (p for trend <0.05 for both PPVs). PPV-1 and PPV-2 were statistically significantly higher for FFDM compared with SFM for women with fatty breasts. Among women recalled, the adjusted OR of breast cancer decreased with increasing MD. Compared with women with fatty breasts, the OR was 0.90 (95% CI: 0.84-0.96) for those with medium dense breasts and 0.85 (95% CI: 0.76-0.95) for those with dense breasts. PPVs decreased by increasing MD. Fewer women needed to be recalled or undergo an invasive procedure to detect one breast cancer among those with fatty versus dense breasts in the screening program in Norway, 1996-2010. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Once-daily versus multiple-daily mesalamine for patients with ulcerative colitis: a meta-analysis.

PubMed

Tong, Jin Lu; Huang, Mei Lan; Xu, Xi Tao; Qiao, Yu Qi; Ran, Zhi Hua

2012-04-01

To systematically review the efficacy and safety of once-daily (OD) mesalamine for the treatment of ulcerative colitis (UC) compared with multiple-daily (MD) mesalamine. Electronic databases up to July 2011 were searched for related studies evaluating the efficacy of OD vs MD for treatment of UC. Only randomized controlled trials (RCTs) were considered eligible. Remission rates or relapse rates were analyzed using intention-to-treat (ITT) and per-protocol (PP) analysis. Pooled relative risk (RR) and 95% confidence interval (CI) were calculated. Publication bias was assessed with a funnel plot. Overall 10 RCTs including 9 full-text manuscripts and one abstract met the inclusion criteria. OD dosing of mesalamine was shown to be as effective as MD dosing for the maintenance of clinical remission in patients with quiescent UC (RR = 1.00, 95% CI 0.89-1.12) by ITT analysis. For active UC, a mild but significant benefit was achieved by OD dosing compared with MD dosing (RR = 0.80, 95% CI 0.64-0.99). Total adverse events were similar using OD and MD mesalamine in quiescent UC (RR = 1.06, 95% CI 0.93-1.20). Compliance with OD was slightly better than with MD (RR = 0.92, 95% CI 0.82-1.03). OD mesalamine is as effective and has a comparable safety profile as MD regimens for the maintenance treatment of UC, and is even more effective for inducing remission in active UC. © 2012 The Authors. Journal of Digestive Diseases © 2012 Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and Blackwell Publishing Asia Pty Ltd.

Relationship between symptoms of attention-deficit/hyperactivity disorder and family functioning: a community-based study.

PubMed

Cussen, Alexandra; Sciberras, Emma; Ukoumunne, Obioha C; Efron, Daryl

2012-02-01

This study examined the relationship between family functioning and attention-deficit/hyperactivity disorder (ADHD) symptoms in an Australian community-based sample. Children were screened for ADHD in their second year of formal schooling. Two hundred and two (202) primary caregivers completed validated measures of family quality of life (QoL), parent mental health, parenting styles and parental relationship quality. Compared with controls, parents of children screening positive for ADHD reported poorer family QoL in the domains of emotional impact (mean difference [MD] -20.1; 95% CI -38.2 to -1.9, p = 0.03) and impact on family activities (MD -17.2; 95% CI -27.9 to -6.5, p = 0.002), less parental warmth (MD -3.4; 95% CI -6.0 to -0.9, p = 0.01) and higher parental depression (MD 6.8; 95% CI 1.8 to 11.7, p = 0.009) and anxiety (MD 6.2; 95% CI 1.7 to 10.6, p = 0.008) after adjusting for socio-demographic characteristics and child conduct symptoms. Parents of children screening positive for ADHD reported higher stress (MD 4.5; 95% CI 1.2 to 7.1, p = 0.007) and more inconsistent (MD 3.0; 95% CI 1.2 to 4.8, p = 0.002) and hostile (MD = 2.2; 95% CI 1.0 to 3.4, p = 0.001) parenting after adjusting for socio-demographic factors only. No difference in parental relationship quality and parental inductive reasoning was identified. These findings suggest a strong association between poor family functioning and ADHD symptoms and carry implications for comprehensive ADHD management and the importance of seeing the child within the family context.

Transcriptome analysis of an apple (Malus × domestica) yellow fruit somatic mutation identifies a gene network module highly associated with anthocyanin and epigenetic regulation.

PubMed

El-Sharkawy, Islam; Liang, Dong; Xu, Kenong

2015-12-01

Using RNA-seq, this study analysed an apple (Malus×domestica) anthocyanin-deficient yellow-skin somatic mutant 'Blondee' (BLO) and its red-skin parent 'Kidd's D-8' (KID), the original name of 'Gala', to understand the molecular mechanisms underlying the mutation. A total of 3299 differentially expressed genes (DEGs) were identified between BLO and KID at four developmental stages and/or between two adjacent stages within BLO and/or KID. A weighted gene co-expression network analysis (WGCNA) of the DEGs uncovered a network module of 34 genes highly correlated (r=0.95, P=9.0×10(-13)) with anthocyanin contents. Although 12 of the 34 genes in the WGCNA module were characterized and known of roles in anthocyanin, the remainder 22 appear to be novel. Examining the expression of ten representative genes in the module in 14 diverse apples revealed that at least eight were significantly correlated with anthocyanin variation. MdMYB10 (MDP0000259614) and MdGST (MDP0000252292) were among the most suppressed module member genes in BLO despite being undistinguishable in their corresponding sequences between BLO and KID. Methylation assay of MdMYB10 and MdGST in fruit skin revealed that two regions (MR3 and MR7) in the MdMYB10 promoter exhibited remarkable differences between BLO and KID. In particular, methylation was high and progressively increased alongside fruit development in BLO while was correspondingly low and constant in KID. The methylation levels in both MR3 and MR7 were negatively correlated with anthocyanin content as well as the expression of MdMYB10 and MdGST. Clearly, the collective repression of the 34 genes explains the loss-of-colour in BLO while the methylation in MdMYB10 promoter is likely causal for the mutation. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

Living with myotonic dystrophy; what can be learned from couples? a qualitative study

PubMed Central

2011-01-01

Background Myotonic dystrophy type 1 (MD1) is one of the most prevalent neuromuscular diseases, yet very little is known about how MD1 affects the lives of couples and how they themselves manage individually and together. To better match health care to their problems, concerns and needs, it is important to understand their perspective of living with this hereditary, systemic disease. Methods A qualitative study was carried out with a purposive sample of five middle-aged couples, including three men and two women with MD1 and their partners. Fifteen in-depth interviews with persons with MD1, with their partners and with both of them as a couple took place in the homes of the couples in two cities and three villages in the Netherlands in 2009. Results People with MD1 associate this progressive, neuromuscular condition with decreasing abilities, describing physical, cognitive and psychosocial barriers to everyday activities and social participation. Partners highlighted the increasing care giving burden, giving directions and using reminders to compensate for the lack of initiative and avoidant behaviour due to MD1. Couples portrayed the dilemmas and frustrations of renegotiating roles and responsibilities; stressing the importance of achieving a balance between individual and shared activities. All participants experienced a lack of understanding from relatives, friends, and society, including health care, leading to withdrawal and isolation. Health care was perceived as fragmentary, with specialists focusing on specific aspects of the disease rather than seeking to understand the implications of the systemic disorder on daily life. Conclusions Learning from these couples has resulted in recommendations that challenge the tendency to treat MD1 as a condition with primarily physical impairments. It is vital to listen to couples, to elicit the impact of MD1, as a multisystem disorder that influences every aspect of their life together. Couple management, supporting the self-management skills of both partners is proposed as a way of reducing the mismatch between health services and health needs. PMID:21752270

InforMD: a new initiative to raise public awareness about breast density

PubMed Central

Hugo, Honor J; Zysk, Aneta; Dasari, Pallave; Britt, Kara; Hopper, John L; Stone, Jennifer; Thompson, Erik W; Ingman, Wendy V

2018-01-01

On a mammogram, breast density (also known as mammographic density) is shown as white and bright regions and is associated with reduced sensitivity in cancer detection and increased breast cancer risk. However, many Australian women are unaware of the significance of breast density as it is not routinely reported or discussed. In order to address this lack of knowledge, Australian breast cancer researchers with expertise in mammographic density formed the InforMD alliance (INformation FORum on Mammographic Density) in 2016. The alliance is working to raise awareness of breast density with the goal of improving breast cancer diagnosis and health outcomes for women. The InforMD website (www.InforMD.org.au) was launched in October 2016, coinciding with a major nationwide public awareness campaign by the alliance during breast cancer awareness month. The website contains unbiased, accurate, updated information on breast density. The website also provides summaries of major research articles in layperson language, recent news items related to breast density, links to relevant information for health professionals, events, and feature articles. Members of the public and health professionals can also subscribe for news updates. The interactive online Forum section facilitates discussion between health professionals, scientists and members of the public. To increase online traffic to the website, Facebook (www.facebook.com/BeInforMD) and Twitter (https://twitter.com/BeInforMD_) pages were launched in December 2016. Since its launch, InforMD has generated considerable interest. The public awareness campaign reached over 7 million Australians through a combination of newspaper, TV, radio, and online news. The website has attracted 13,058 unique visitors and 30,353 page views (data as of 19/12/2017). Breast cancer researchers have a significant role to play in disseminating information to the public on breast density. A combination of mainstream and social media, together with a well-informed and updated website, has laid the groundwork for the InforMD alliance to reach a wide audience. PMID:29492101

InforMD: a new initiative to raise public awareness about breast density.

PubMed

Hugo, Honor J; Zysk, Aneta; Dasari, Pallave; Britt, Kara; Hopper, John L; Stone, Jennifer; Thompson, Erik W; Ingman, Wendy V

2018-01-01

On a mammogram, breast density (also known as mammographic density) is shown as white and bright regions and is associated with reduced sensitivity in cancer detection and increased breast cancer risk. However, many Australian women are unaware of the significance of breast density as it is not routinely reported or discussed. In order to address this lack of knowledge, Australian breast cancer researchers with expertise in mammographic density formed the InforMD alliance (INformation FORum on Mammographic Density) in 2016. The alliance is working to raise awareness of breast density with the goal of improving breast cancer diagnosis and health outcomes for women. The InforMD website (www.InforMD.org.au) was launched in October 2016, coinciding with a major nationwide public awareness campaign by the alliance during breast cancer awareness month. The website contains unbiased, accurate, updated information on breast density. The website also provides summaries of major research articles in layperson language, recent news items related to breast density, links to relevant information for health professionals, events, and feature articles. Members of the public and health professionals can also subscribe for news updates. The interactive online Forum section facilitates discussion between health professionals, scientists and members of the public. To increase online traffic to the website, Facebook (www.facebook.com/BeInforMD) and Twitter (https://twitter.com/BeInforMD_) pages were launched in December 2016. Since its launch, InforMD has generated considerable interest. The public awareness campaign reached over 7 million Australians through a combination of newspaper, TV, radio, and online news. The website has attracted 13,058 unique visitors and 30,353 page views (data as of 19/12/2017). Breast cancer researchers have a significant role to play in disseminating information to the public on breast density. A combination of mainstream and social media, together with a well-informed and updated website, has laid the groundwork for the InforMD alliance to reach a wide audience.

Transcriptome analysis of an apple (Malus × domestica) yellow fruit somatic mutation identifies a gene network module highly associated with anthocyanin and epigenetic regulation

PubMed Central

El-Sharkawy, Islam; Liang, Dong; Xu, Kenong

2015-01-01

Using RNA-seq, this study analysed an apple (Malus×domestica) anthocyanin-deficient yellow-skin somatic mutant ‘Blondee’ (BLO) and its red-skin parent ‘Kidd’s D-8’ (KID), the original name of ‘Gala’, to understand the molecular mechanisms underlying the mutation. A total of 3299 differentially expressed genes (DEGs) were identified between BLO and KID at four developmental stages and/or between two adjacent stages within BLO and/or KID. A weighted gene co-expression network analysis (WGCNA) of the DEGs uncovered a network module of 34 genes highly correlated (r=0.95, P=9.0×10–13) with anthocyanin contents. Although 12 of the 34 genes in the WGCNA module were characterized and known of roles in anthocyanin, the remainder 22 appear to be novel. Examining the expression of ten representative genes in the module in 14 diverse apples revealed that at least eight were significantly correlated with anthocyanin variation. MdMYB10 (MDP0000259614) and MdGST (MDP0000252292) were among the most suppressed module member genes in BLO despite being undistinguishable in their corresponding sequences between BLO and KID. Methylation assay of MdMYB10 and MdGST in fruit skin revealed that two regions (MR3 and MR7) in the MdMYB10 promoter exhibited remarkable differences between BLO and KID. In particular, methylation was high and progressively increased alongside fruit development in BLO while was correspondingly low and constant in KID. The methylation levels in both MR3 and MR7 were negatively correlated with anthocyanin content as well as the expression of MdMYB10 and MdGST. Clearly, the collective repression of the 34 genes explains the loss-of-colour in BLO while the methylation in MdMYB10 promoter is likely causal for the mutation. PMID:26417021

Cognitive and emotional processing of pleasant and unpleasant experiences in major depression: A matter of vantage point?

PubMed

Pfaltz, Monique C; Wu, Gwyneth W Y; Liu, Guanyu; Tankersley, Amelia P; Stilley, Ashley M; Plichta, Michael M; McNally, Richard J

2017-03-01

In nonclinical populations, adopting a third-person perspective as opposed to a first-person perspective while analyzing negative emotional experiences fosters understanding of these experiences and reduces negative emotional reactivity. We assessed whether this generalizes to people with major depression (MD). Additionally, we assessed whether the emotion-reducing effects of adopting a third-person perspective also occur when subjects with MD and HC subjects analyze positive experiences. Seventy-two MD subjects and 82 HC subjects analyzed a happy and a negative experience from either a first-person or a third-person perspective. Unexpectedly, we found no emotion-reducing effects of third-person perspective in either group thinking about negative events. However, across groups, third-person perspective was associated with less recounting of negative experiences and with a clearer, more coherent understanding of them. Negative affect decreased and positive affect increased in both groups analyzing happy experiences. In MD subjects, decreases in depressive affect were stronger for the third-person perspective. In both groups, positive affect increased and negative affect decreased more strongly for the third-person perspective. While reflecting on their positive memory, MD subjects adopted their assigned perspective for a shorter amount of time (70%) than HC subjects (78%). However, percentage of time participants adopted their assigned perspective was unrelated to the significant effects we found. Both people suffering from MD and healthy individuals may benefit from processing pleasant experiences, especially when adopting a self-distant perspective. Copyright © 2016 Elsevier Ltd. All rights reserved.

Childhood trauma and neighborhood-level crime interact in predicting adult posttraumatic stress and major depression symptoms.

PubMed

Lowe, Sarah R; Quinn, James W; Richards, Catherine A; Pothen, John; Rundle, Andrew; Galea, Sandro; Ressler, Kerry J; Koenen, Karestan C; Bradley, Bekh

2016-01-01

Previous research has identified several individual-level factors that modify the risk of childhood trauma on adult psychiatric symptoms, including symptoms of major depression (MD) and posttraumatic stress (PTS). Neighborhood-level factors also influence the impact of individual-level exposures on adult psychopathology. However, no prior studies to our knowledge have explored cross-level interactions between childhood trauma and neighborhood-level factors on MD and PTS symptoms. The purpose of this study was therefore to explore cross-level interactions between a neighborhood-level factor - neighborhood-level crime - and childhood trauma on MD and PTS symptoms. Participants in this study (N=3192) were recruited from a large public hospital, and completed self-report inventories of childhood trauma and MD and PTS symptoms. Participant addresses were mapped onto 2010 census tracts, and data on crime within each tract were collected. Multilevel models found a significant cross-level interaction between childhood trauma and neighborhood crime on MD symptoms, such that the influence of high levels of childhood trauma on MD symptoms was enhanced for participants living in high-crime neighborhoods. Supplementary analyses found variation in the strength of cross-level interaction terms by types of childhood trauma and crime, with the strongest associations including emotional neglect paired with personal and property crime. The results provide preliminary support for interventions that help childhood trauma survivors find housing in less vulnerable neighborhoods and build skills to cope with neighborhood crime. Copyright © 2015 Elsevier Ltd. All rights reserved.

Mediterranean diet adherence and synergy with acute myocardial infarction and its determinants: A multicenter case-control study in Italy.

PubMed

La Torre, Giuseppe; Saulle, Rosella; Di Murro, Francesca; Siliquini, Roberta; Firenze, Alberto; Maurici, Massimo; Mannocci, Alice; Colamesta, Vittoria; Barillà, Francesco; Ferrante, Fabio; Agati, Luciano

2018-01-01

Cardiovascular diseases are the leading causes of mortality and morbidity in Western countries. The possible synergistic effect of poor adherence to a Mediterranean diet (MD) and other risk factors for acute myocardial infarction (AMI) such as hypertension, cholesterol, ever smoker, BMI> 25, diabetes, has not been deeply studied. Case-control study. Patients with first AMI and controls from four tertiary referral Italian centers were screened for enrolment. Dietary information was collected through a questionnaire and a MD adherence score was calculated. Physical activity and smoking habits were also registered. The Synergy Index was calculated according to Rothman. 127 cases and 173 controls were enrolled. The analysis was conducted using a dichotomous variable for the MD score with values ≥7 representing good adherence. Multivariate analysis showed the following variables associated to AMI: ever smoker (OR = 2.08), diabetes (OR = 1.42), hypertension (OR = 2.08), hypercholesterolemia (OR = 2.47), BMI> 25 (OR = 1.99), while a protective effect emerged both in subjects scoring > 7 on the MD score (OR = 0.55) and in subjects resident of Southern Italy (OR = 0.38). A synergistic effect does exist between poor adherence to the MD and the following risk factors: hypertension, hypercholesterolemia, BMI >25, diabetes and being a resident in central and northern Italy. Synergy between heart disease risk factors and MD underlines the need to enlarge the list of known modifiable cardiovascular risk factors to include and promote adherence to Mediterranean dietary habits.

The Effects of Music on Pain: A Meta-Analysis.

PubMed

Lee, Jin Hyung

2016-01-01

Numerous meta-analyses have been conducted on the topic of music and pain, with the latest comprehensive study published in 2006. Since that time, more than 70 randomized controlled trials (RCTs) have been published, necessitating a new and comprehensive review. The aim of this meta-analysis was to examine published RCT studies investigating the effect of music on pain. The present study included RCTs published between 1995 and 2014. Studies were obtained by searching 12 databases and hand-searching related journals and reference lists. Main outcomes were pain intensity, emotional distress from pain, vital signs, and amount of analgesic intake. Study quality was evaluated according to the Cochrane Collaboration guidelines. Analysis of the 97 included studies revealed that music interventions had statistically significant effects in decreasing pain on 0-10 pain scales (MD = -1.13), other pain scales (SMD = -0.39), emotional distress from pain (MD = -10.83), anesthetic use (SMD = -0.56), opioid intake (SMD = -0.24), non-opioid intake (SMD = -0.54), heart rate (MD = -4.25), systolic blood pressure (MD = -3.34), diastolic blood pressure (MD = -1.18), and respiration rate (MD = -1.46). Subgroup and moderator analyses yielded additional clinically informative outcomes. Considering all the possible benefits, music interventions may provide an effective complementary approach for the relief of acute, procedural, and cancer/chronic pain in the medical setting. © the American Music Therapy Association 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Brain microstructural correlates of visuospatial choice reaction time in children.

PubMed

Madsen, Kathrine Skak; Baaré, William F C; Skimminge, Arnold; Vestergaard, Martin; Siebner, Hartwig R; Jernigan, Terry L

2011-10-15

The corticospinal tracts and the basal ganglia continue to develop during childhood and adolescence, and indices of their maturation can be obtained using diffusion-weighted imaging. Here we show that a simple measure of visuomotor function is correlated with diffusion parameters in the corticospinal tracts and neostriatum. In a cohort of 75 typically-developing children aged 7 to 13years, mean 5-choice reaction times (RTs) were assessed. We hypothesised that children with faster choice RTs would show lower mean diffusivity (MD) in the corticospinal tracts and neostriatum and higher fractional anisotropy (FA) in the corticospinal tracts, after controlling for age, gender, and handedness. Mean MD and/or FA were extracted from the right and left corticospinal tracts, putamen, and caudate nuclei. As predicted, faster 5-choice RTs were associated with lower MD in the corticospinal tracts, putamen, and caudate. MD effects on RT were bilateral in the corticospinal tracts and putamen, whilst right caudate MD was more strongly related to performance than was left caudate MD. Our results suggest a link between motor performance variability in children and diffusivity in the motor system, which may be related to: individual differences in the phase of fibre tract and neostriatal maturation in children of similar age, individual differences in motor experience during childhood (i.e., use-dependent plasticity), and/or more stable individual differences in the architecture of the motor system. Copyright © 2011 Elsevier Inc. All rights reserved.

Childhood Trauma and Neighborhood-Level Crime Interact in Predicting Adult Posttraumatic Stress and Major Depression Symptoms

PubMed Central

Lowe, Sarah R.; Quinn, James W.; Richards, Catherine A.; Pothen, John; Rundle, Andrew; Galea, Sandro; Ressler, Kerry J.; Koenen, Karestan C.; Bradley, Bekh

2015-01-01

Previous research has identified several individual-level factors that modify the risk of childhood trauma on adult psychiatric symptoms, including symptoms of major depression (MD) and posttraumatic stress (PTS). Neighborhood-level factors also influence the impact of individual-level exposures on adult psychopathology. However, no prior studies to our knowledge have explored cross-level interactions between childhood trauma and neighborhood-level factors on MD and PTS symptoms. The purpose of this study was therefore to explore cross-level interactions between a neighborhood-level factor – neighborhood-level crime – and childhood trauma on MD and PTS symptoms. Participants in this study (N = 3,192) were recruited from a large public hospital, and completed self-report inventories of childhood trauma and MD and PTS symptoms. Participant addresses were mapped onto 2010 census tracts, and data on crime within each tract was collected. Multilevel models found a significant cross-level interaction between childhood trauma and neighborhood crime on MD symptoms, such that the influence of high levels of childhood trauma on MD symptoms was enhanced for participants living in high-crime neighborhoods. Supplementary analyses found variation in the strength of cross-level interaction terms by types of childhood trauma and crime, with the strongest associations including emotional neglect paired with personal and property crime. The results provide preliminary support for interventions that help childhood trauma survivors find housing in less vulnerable neighborhoods and build skills to cope with neighborhood crime. PMID:26499372

75 FR 6162 - Airworthiness Directives; McDonnell Douglas Corporation Model DC-9-81 (MD-81), DC-9-82 (MD-82...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-02-08

... Corporation Model DC- 9-81 (MD-81), DC-9-82 (MD-82), DC-9-83 (MD-83), DC-9-87 (MD-87), and MD-88 Airplanes... Model DC-9-81 (MD-81), DC-9-82 (MD-82), DC-9-83 (MD-83), DC-9-87 (MD-87), and MD-88 airplanes. This...., Washington, DC 20590, between 9 a.m. and 5 p.m., Monday through Friday, except Federal holidays. For service...

Pneumonia

MedlinePlus

... 2015 Updated by: Denis Hadjiliadis, MD, MHS, Associate Professor of Medicine, Pulmonary, Allergy, and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA. Internal ...

Assessment of virtual reality robotic simulation performance by urology resident trainees.

PubMed

Ruparel, Raaj K; Taylor, Abby S; Patel, Janil; Patel, Vipul R; Heckman, Michael G; Rawal, Bhupendra; Leveillee, Raymond J; Thiel, David D

2014-01-01

To examine resident performance on the Mimic dV-Trainer (MdVT; Mimic Technologies, Inc., Seattle, WA) for correlation with resident trainee level (postgraduate year [PGY]), console experience (CE), and simulator exposure in their training program to assess for internal bias with the simulator. Residents from programs of the Southeastern Section of the American Urologic Association participated. Each resident was scored on 4 simulator tasks (peg board, camera targeting, energy dissection [ED], and needle targeting) with 3 different outcomes (final score, economy of motion score, and time to complete exercise) measured for each task. These scores were evaluated for association with PGY, CE, and simulator exposure. Robotic skills training laboratory. A total of 27 residents from 14 programs of the Southeastern Section of the American Urologic Association participated. Time to complete the ED exercise was significantly shorter for residents who had logged live robotic console compared with those who had not (p = 0.003). There were no other associations with live robotic console time that approached significance (all p ≥ 0.21). The only measure that was significantly associated with PGY was time to complete ED exercise (p = 0.009). No associations with previous utilization of a robotic simulator in the resident's home training program were statistically significant. The ED exercise on the MdVT is most associated with CE and PGY compared with other exercises. Exposure of trainees to the MdVT in training programs does not appear to alter performance scores compared with trainees who do not have the simulator. © 2013 Published by Association of Program Directors in Surgery on behalf of Association of Program Directors in Surgery.

Experimental murine myopia induces collagen type Iα1 (COL1A1) DNA methylation and altered COL1A1 messenger RNA expression in sclera

PubMed Central

Zhou, Xiangtian; Ji, Fengtao; An, Jianhong; Zhao, Fuxin; Shi, Fanjun; Huang, Furong; Li, Yuan; Jiao, Shiming; Yan, Dongsheng; Chen, Xiaoyan; Chen, JiangFan

2012-01-01

Purpose To investigate whether myopia development is associated with changes of scleral DNA methylation in cytosine-phosphate-guanine (CpG) sites in the collagen 1A1 (COL1A1) promoter and messenger RNA (mRNA) levels following murine form deprivation myopia. Methods Fifty-seven C57BL/6 mice (postnatal day 23) were randomly assigned to four groups: (1) monocular form deprivation (MD) in which a diffuser lens was placed over one eye for 28 days; (2) normal controls without MD; (3) MD recovery in which the diffuser lens was removed for seven days; and (4) MD recovery normal controls. The DNA methylation pattern in COL1A1 promoter and exon 1 was determined by bisulfite DNA sequencing, and the COL1A1 mRNA level in sclera was determined by quantitative PCR. Results MD was found to induce myopia in the treated eyes. Six CpG sites in the promoter and exon 1 region of COL1A1 were methylated with significantly higher frequency in the treated eyes than normal control eyes (p<0.05), with CpG island methylation in MD-contralateral eyes being intermediate. Consistent with the CpG methylation, scleral COL1A1 mRNA was reduced by 57% in the MD-treated eyes compared to normal controls (p<0.05). After seven days of MD recovery, CpG methylation was significantly reduced (p=0.01). The methylation patterns returned to near normal level in five CpG sites, but the sixth was hypomethylated compared to normal controls. Conclusions In parallel with the development of myopia and the reduced COL1A1 mRNA, the frequency of methylation in CpG sites of the COL1A1 promoter/exon 1 increased during MD and returned to near normal during recovery. Thus, hypermethylation of CpG sites in the promoter/exon 1 of COL1A1 may underlie reduced collagen synthesis at the transcriptional level in myopic scleras. PMID:22690110

The neurophysiological features of myoclonus-dystonia and differentiation from other dystonias.

PubMed

Popa, Traian; Milani, Paolo; Richard, Aliénor; Hubsch, Cécile; Brochard, Vanessa; Tranchant, Christine; Sadnicka, Anna; Rothwell, John; Vidailhet, Marie; Meunier, Sabine; Roze, Emmanuel

2014-05-01

Myoclonus-dystonia (M-D) is a clinical syndrome characterized by a combination of myoclonic jerks and mild to moderate dystonia. The syndrome is related to ε-sarcoglycan (SGCE) gene mutations in about half the typical cases. Whether the M-D phenotype reflects a primary dysfunction of the cerebellothalamocortical pathway or of the striatopallidothalamocortical pathway is unclear. The exact role of an additional cortical dysfunction in the pathogenesis of M-D is also unknown. To clarify the neurophysiological features of M-D and discuss whether M-D due to SGCE deficiency differs from other primary dystonias. We studied a referred sample of 12 patients with M-D (mean [SD] age, 28.8 [6.2] years; age range, 19-38 years; 5 women) belonging to 11 unrelated families with a proven mutation or deletion of the SGCE gene and a group of 12 age- and sex-matched healthy control individuals. Every participant underwent 3 sessions exploring the excitability of the primary motor cortex, the response of the primary motor cortex to a plasticity-inducing protocol, and the cerebellar-dependent eye-blink classic conditioning (EBCC). The clinical evaluation of patients included the Unified Myoclonus Rating Scale and Burke-Fahn-Marsden Dystonia Rating Scale. Myoclonus-dystonia with a proven SGCE mutation. We measured resting and active motor thresholds, and short-interval intracortical inhibition and facilitation. The plasticity of the motor cortex was evaluated before and for 30 minutes after 600 pulses of rapid paired associative stimulation. The cerebellar functioning was evaluated with the number of conditioned responses during the 6 blocks of EBCC and 1 extinction block. All data were compared between the 2 groups. For patients, correlations were explored between electrophysiological data and clinical scores. We found lower membrane excitability of the corticocortical axons and normal intracortical γ-aminobutyric acid inhibition in contrast with what has been described in other forms of primary dystonia. Myoclonus-dystonia patients also shared some common pathophysiological features of dystonia, including enhanced responsiveness of the motor cortex to plasticity induction and abnormal response to cerebellar conditioning as tested by EBCC. Specific underlying dysfunctions are associated with the very particular clinical phenotype of M-D and make it a unique entity that stands apart from other primary dystonias.

Practical landmarks for visual field disability in glaucoma.

PubMed

Saunders, Luke J; Russell, Richard A; Crabb, David P

2012-09-01

To assess whether mean deviation (MD) from automated perimetry is related to the visual field (VF) component for legal fitness to drive (LFTD) in glaucoma patients. Monocular 24-2 VFs of 2604 patients with bilateral VF damage were retrospectively investigated. Integrated visual fields were calculated and used as a surrogate to assess LFTD according to current UK driving licence criteria. The better eye MD (BEMD), worse eye MD (WEMD) and a measure utilising MD of both eyes were compared, to assess respective diagnostic capabilities to predict LFTD (using the integrated visual field surrogate test as the gold standard) and a 'Probability of Failure' (PoF) for various defect levels was calculated. BEMD appears to be a good predictor of the VF component for a patient's LFTD (receiver operating characteristic area under the curve: 96.2%); MDs from both eyes offered no significant extra diagnostic power (area under the curve: 96.4%). PoF for BEMD thresholds of ≤-10 dB and ≤-14 dB were 70 (95% CI 66% to 74%) and 92% (87% to 95%), respectively. There is a strong relationship between BEMD and a patient's LFTD. PoF values for LFTD associated with readily available MD values provide practical landmarks for VF disability in glaucoma.

Viral pneumonia

MedlinePlus

... Hadjiliadis, MD, MHS, Paul F. Harron, Jr. Associate Professor of Medicine, Pulmonary, Allergy, and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA. Also ...

Meckel’s diverticulum: new solutions for an old problem?

PubMed Central

Chauhan, Abhishek; Suggett, Nigel; Guest, Peter; Goh, Jason

2016-01-01

Meckel's diverticulum (MD) is the most commonly encountered true diverticulum in the small bowel. Although overall a rare cause of gastrointestinal bleeding, it remains an important differential in a child/young adult presenting with lower gastrointestinal bleeding. We present two MD cases, one associated with brisk bleeding resulting in haemodynamic instability and the other in insidious blood loss causing symptoms of chronic iron deficiency. These cases illustrate the heterogeneous nature of the clinical picture associated with Meckel's diverticulae, a condition most gastroenterological and surgical units will encounter. We subsequently discuss the diagnostic and management dilemma Meckel's diverticulae pose and appraise the latest evidence and management strategies in this regard. PMID:28839845

Identification of single nucleotide polymorphisms in hematopoietic cell transplant patients affecting early recognition of, and response to, endotoxin.

PubMed

Guinan, Eva C; Palmer, Christine D; Mancuso, Christy J; Brennan, Lisa; Stoler-Barak, Liat; Kalish, Leslie A; Suter, Eugenie E; Gallington, Leighanne C; Huhtelin, David P; Mansilla, Maria; Schumann, Ralf R; Murray, Jeffrey C; Weiss, Jerrold; Levy, Ofer

2014-10-01

Hematopoietic cell transplant (HCT) is a life-saving therapy for many malignant and non-malignant bone marrow diseases. Associated morbidities are often due to transplant-related toxicities and infections, exacerbated by regimen-induced immune suppression and systemic incursion of bacterial products. Patients undergoing myeloablative conditioning for HCT become endotoxemic and display blood/plasma changes consistent with lipopolysaccharide (LPS)-induced systemic innate immune activation. Herein, we addressed whether patients scheduled for HCT display differences in recognition/response to LPS ex vivo traceable to specific single nucleotide polymorphisms (SNPs). Two SNPs of LPS binding protein (LBP) were associated with changes in plasma LBP levels, with one LBP SNP also associating with differences in efficiency of extraction and transfer of endotoxin to myeloid differentiation factor-2 (MD-2), a step needed for activation of TLR4. None of the examined SNPs of CD14, bactericidal/permeability-increasing protein (BPI), TLR4 or MD-2 were associated with corresponding protein plasma levels or endotoxin delivery to MD-2, but CD14 and BPI SNPs significantly associated with differences in LPS-induced TNF-α release ex vivo and infection frequency, respectively. These findings suggest that specific LBP, CD14 and BPI SNPs might be contributory assessments in studies where clinical outcome may be affected by host response to endotoxin and bacterial infection. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

IMPACT: Imaging and Molecular Markers for Patients with Lung Cancer: Approaches with Molecular Targets, Complementary/Innovative Treatments, and Therapeutic Modalities

DTIC Science & Technology

2014-02-01

DRP-1: Treatment of Malignant Pleural Effusion with ZD6474, a Novel VEGFR and EGFR TK Inhibitor (PI and co-PI: Roy Herbst, M.D., Ph.D., Carlos...Jimenez, M.D.) Recurrent malignant pleural effusion is a debilitating clinical problem that requires palliation with repeated therapeutic...thoracentesis or pleurodesis (Putnam, J Surg Clin North Am 2002). Malignant pleural effusions have been associated with high levels of VEGF. Treatment with a

Precision Medicine in NCI’s National Clinical Trials Network: Progress and Lessons Learned

Cancer.gov

NCI’s Jeff Abrams, M.D., Acting Director for Clinical Research in the Division of Cancer Treatment and Diagnosis (DCTD) and Associate Director of the Cancer Therapy Evaluation Program (CTEP) and Nita Seibel, M.D., Head of the Pediatric Solid Tumor Therapeutics in the Clinical Investigations Branch of CTEP, DCTD will host a Google Hangout on Air. The discussion will be moderated by Andrea Denicoff, R.N., N.P, Head, NCTN Clinical Trials Operations in the Investigational Drug Branch of CTEP, DCTD.

CD8 T Cells and Immunoediting of Breast Cancer

DTIC Science & Technology

2008-08-01

Reiman , C.J. Krco, I.T. Lamborn, and K.L. Knutson. CD8 T cells promote relapse of breast cancer by inducing epithelial to mesenchymal transition. J...Immunother 2006;29:682 (Abstract). 8 Santisteban, M., J.M. Reiman , M.K. Asiedu, M.D. Behrens, A. Nassar, K.R. Kalli, P. Haluska, J.N. Ingle, L.C...immune mechanisms, and their association with prognostic indicators. Surgery 2003;134(5):827-34. 3. Behrens, M.D., J. Reiman , C.J. Krco, I.T. Lamborn

Md-miR156ab and Md-miR395 Target WRKY Transcription Factors to Influence Apple Resistance to Leaf Spot Disease.

PubMed

Zhang, Qiulei; Li, Yang; Zhang, Yi; Wu, Chuanbao; Wang, Shengnan; Hao, Li; Wang, Shengyuan; Li, Tianzhong

2017-01-01

MicroRNAs (miRNAs) are key regulators of gene expression that post-transcriptionally regulate transcription factors involved in plant physiological activities. Little is known about the effects of miRNAs in disease resistance in apple ( Malus × domestica ). We globally profiled miRNAs in the apple cultivar Golden Delicious (GD) infected or not with the apple leaf spot fungus Alternaria alternaria f. sp. mali (ALT1), and identified 58 miRNAs that exhibited more than a 2-fold upregulation upon ALT1 infection. We identified a pair of miRNAs that target protein-coding genes involved in the defense response against fungal pathogens; Md-miR156ab targets a novel WRKY transcription factor, MdWRKYN1, which harbors a TIR and a WRKY domain. Md-miR395 targets another transcription factor, MdWRKY26, which contains two WRKY domains. Real-time PCR analysis showed that Md-miR156ab and Md-miR395 levels increased, while MdWRKYN1 and MdWRKY26 expression decreased in ALT1-inoculated GD leaves; furthermore, the overexpression of Md-miR156ab and Md-miR395 resulted in a significant reduction in MdWRKYN1 and MdWRKY26 expression. To investigate whether these miRNAs and their targets play a crucial role in plant defense, we overexpressed MdWRKYN1 or knocked down Md-miR156ab activity, which in both cases enhanced the disease resistance of the plants by upregulating the expression of the WRKY-regulated pathogenesis-related (PR) protein-encoding genes MdPR3-1, MdPR3-2, MdPR4, MdPR5, MdPR10-1 , and MdPR10-2 . In a similar analysis, we overexpressed MdWRKY26 or suppressed Md-miR395 activity, and found that many PR protein-encoding genes were also regulated by MdWRKY26 . In GD, ALT-induced Md-miR156ab and Md-miR395 suppress MdWRKYN1 and MdWRKY26 expression, thereby decreasing the expression of some PR genes, and resulting in susceptibility to ALT1.

Apple MdACS6 Regulates Ethylene Biosynthesis During Fruit Development Involving Ethylene-Responsive Factor.

PubMed

Li, Tong; Tan, Dongmei; Liu, Zhi; Jiang, Zhongyu; Wei, Yun; Zhang, Lichao; Li, Xinyue; Yuan, Hui; Wang, Aide

2015-10-01

Ethylene biosynthesis in plants involves different 1-aminocyclopropane-1-carboxylic acid synthase (ACS) genes. The regulation of each ACS gene during fruit development is unclear. Here, we characterized another apple (Malus×domestica) ACS gene, MdACS6. The transcript of MdACS6 was observed not only in fruits but also in other tissues. During fruit development, MdACS6 was initiated at a much earlier stage, whereas MdACS3a and MdACS1 began to be expressed at 35 d before harvest and immediateley after harvest, respectively. Moreover, the enzyme activity of MdACS6 was significantly lower than that of MdACS3a and MdACS1, accounting for the low ethylene biosynthesis in young fruits. Overexpression of MdACS6 (MdACS6-OE) by transient assay in apple showed enhanced ethylene production, and MdACS3a was induced in MdACS6-OE fruits but not in control fruits. In MdACS6 apple fruits silenced by the virus-induced gene silencing (VIGS) system (MdACS6-AN), neither ethylene production nor MdACS3a transcript was detectable. In order to explore the mechanism through which MdACS3a was induced in MdACS6-OE fruits, we investigated the expression of apple ethylene-responsive factor (ERF) genes. The results showed that the expression of MdERF2 was induced in MdACS6-OE fruits and inhibited in MdACS6-AN fruits. Yeast one-hybrid assay showed that MdERF2 protein could bind to the promoter of MdACS3a. Moreover, down-regulation of MdERF2 in apple flesh callus led to a decrease of MdACS3a expression, demonstrating the regulation of MdERF2 on MdACS3a. The mechanism through which MdACS6 regulates the action of MdACS3a was discussed. © The Author 2015. Published by Oxford University Press on behalf of Japanese Society of Plant Physiologists. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Vision-related Quality of Life in Korean Glaucoma Patients.

PubMed

Sung, Kyung Rim; Chun, Yeoun Sook; Park, Chan Kee; Kim, Hwang Ki; Yoo, Chungkwon; Kim, Yong Yeon; Park, Ki Ho; Kim, Chan Yun; Choi, Kyu-Ryong; Lee, Kyoo Won; Han, Seungbong; Kim, Chang-Sik

2017-02-01

The purpose of the study was to evaluate vision-related quality of life in Korean glaucoma patients and to explore the associated factors. A total of 907 glaucoma patients were recruited from the prospectively designed LIGHT (Life quality of the glaucoma patient who underwent treatment) study organized by the Korean Glaucoma Society. Basic questionnaire that included items related to socioeconomic status, comorbidity, and lifestyle, and the validated Korean version of the 25-item National Eye Institute Visual Function Questionnaire (NEI VFQ-25) were collected. The Rasch score, a logit-based interval scale estimate to summarizing the NEI VFQ-25 responses, was calculated. The univariate and multivariable regression models were used to evaluate associations between the Rasch score and variables. The mean patient age was 58.1±14.1 years, visual field mean deviation (VF MD) of the better and worse eyes was -4.92±6.14 and -9.77±8.31 dB, binocular-integrated VF (IVF) MD was -3.55±5.31 dB, respectively. The lower NEI VFQ-25 Rasch score showed a significant association with the presence of other ocular diseases (P=0.020), a high school level of education or less [vs. university (P=0.006), vs. graduate school or higher (P=0.019)], an anxious personality [vs. a moderate personality (P<0.001), vs. a relaxed personality (P<0.001)], the number of glaucoma medications in use (P=0.049), worse eye visual acuity (P<0.001), and IVF MD (P<0.001). Visual function parameters are important for the vision-related quality of life of Korean glaucoma patients, notably for worse eye visual acuity and IVF MD. However, social factors, self-assessed personality, and treatment-related issues are also substantial predictors of overall life quality.

Autonomic, functional, skeletal muscle, and cardiac abnormalities are associated with increased ergoreflex sensitivity in mitochondrial disease.

PubMed

Giannoni, Alberto; Aimo, Alberto; Mancuso, Michelangelo; Piepoli, Massimo Francesco; Orsucci, Daniele; Aquaro, Giovanni Donato; Barison, Andrea; De Marchi, Daniele; Taddei, Claudia; Cameli, Matteo; Raglianti, Valentina; Siciliano, Gabriele; Passino, Claudio; Emdin, Michele

2017-12-01

Mitochondrial disease (MD) is a genetic disorder affecting skeletal muscles, with possible myocardial disease. The ergoreflex, sensitive to skeletal muscle work, regulates ventilatory and autonomic responses to exercise. We hypothesized the presence of an increased ergoreflex sensitivity in MD patients, its association with abnormal ventilatory and autonomic responses, and possibly with subclinical cardiac involvement. Twenty-five MD patients (aged 46 ± 3 years, 32% male) with skeletal myopathy but without known cardiac disease, underwent a thorough evaluation including BNPs, galectin-3, soluble suppression of tumorigenesis 2 (sST2), high sensitivity troponin T/I, catecholamines, ECG, 24-h ECG recording, cardiopulmonary exercise testing, echocardiography, cardiac/muscle magnetic resonance (C/MMR), and ergoreflex assessment. Thirteen age- and sex-matched healthy controls were chosen. Among these myopathic patients, subclinical cardiac damage was detected in up to 80%, with 44% showing fibrosis at CMR. Ergoreflex sensitivity was markedly higher in patients than in controls (64% vs. 37%, P < 0.001), and correlated with muscle fat to water ratio and extracellular volume at MMR (both P < 0.05). Among patients, ergoreflex sensitivity was higher in those with cardiac involvement (P = 0.034). Patients showed a lower peak oxygen consumption (VO 2 /kg) than controls (P < 0.001), as well as ventilatory inefficiency (P = 0.024). Ergoreflex sensitivity correlated with reduced workload and peak VO 2 /kg (both P < 0.001), and several indicators of autonomic imbalance (P < 0.05). Plasma norepinephrine was the unique predictor of myocardial fibrosis at univariate analysis (P < 0.05). Skeletal myopathy in MD is characterized by enhanced ergoreflex sensitivity, which is associated with a higher incidence of cardiac involvement, exercise intolerance, and sympathetic activation. © 2017 The Authors. European Journal of Heart Failure © 2017 European Society of Cardiology.

A candidate gene based approach validates Md-PG1 as the main responsible for a QTL impacting fruit texture in apple (Malus x domestica Borkh).

PubMed

Longhi, Sara; Hamblin, Martha T; Trainotti, Livio; Peace, Cameron P; Velasco, Riccardo; Costa, Fabrizio

2013-03-04

Apple is a widely cultivated fruit crop for its quality properties and extended storability. Among the several quality factors, texture is the most important and appreciated, and within the apple variety panorama the cortex texture shows a broad range of variability. Anatomically these variations depend on degradation events occurring in both fruit primary cell wall and middle lamella. This physiological process is regulated by an enzymatic network generally encoded by large gene families, among which polygalacturonase is devoted to the depolymerization of pectin. In apple, Md-PG1, a key gene belonging to the polygalacturonase gene family, was mapped on chromosome 10 and co-localized within the statistical interval of a major hot spot QTL associated to several fruit texture sub-phenotypes. In this work, a QTL corresponding to the position of Md-PG1 was validated and new functional alleles associated to the fruit texture properties in 77 apple cultivars were discovered. 38 SNPs genotyped by gene full length resequencing and 2 SSR markers ad hoc targeted in the gene metacontig were employed. Out of this SNP set, eleven were used to define three significant haplotypes statistically associated to several texture components. The impact of Md-PG1 in the fruit cell wall disassembly was further confirmed by the cortex structure electron microscope scanning in two apple varieties characterized by opposite texture performance, such as 'Golden Delicious' and 'Granny Smith'. The results here presented step forward into the genetic dissection of fruit texture in apple. This new set of haplotypes, and microsatellite alleles, can represent a valuable toolbox for a more efficient parental selection as well as the identification of new apple accessions distinguished by superior fruit quality features.

Association of the duration of residence with obesity-related eating habits and dietary patterns among Latin-American immigrants in Spain.

PubMed

Marín-Guerrero, A C; Rodríguez-Artalejo, Fernando; Guallar-Castillón, P; López-García, Esther; Gutiérrez-Fisac, Juan L

2015-01-28

The dietary patterns of immigrants usually change with the duration of residence and progressively resemble those of the host country. However, very few studies have investigated individuals migrating to countries with a high-quality diet, such as the Mediterranean diet (MD), and none has yet focused on Latin-American immigrants. The present study examined the association of the duration of residence with obesity-related eating habits and dietary patterns among Latin-American immigrants residing in Spain. A cross-sectional study was conducted in 2008-10 in a representative sample of the adult population residing in Spain. Adherence to the MD was defined as a MD Adherence Screener score ≥ 9. Analyses were conducted by including 419 individuals aged 18-64 years born in Latin-American countries. Compared with immigrants residing in Spain for < 5 years, those residing for ≥ 10 years accounted for a lower percentage of individuals who habitually ate at fast-food restaurants and never trimmed visible fat from meat. Moreover, these immigrants were found to have a lower intake of sugary beverages and a higher intake of Na, saturated fat, fibre, olive oil, vegetables and fish and to more frequently strictly adhere to the MD. A longer duration of residence in Spain was found to be associated with both healthy and unhealthy changes in some eating habits and dietary patterns among Latin-American immigrants. Some of the healthy changes observed contrasted the 'Westernisation' of the diet reported in studies conducted in other Western countries. The results of the present study support the role of the food environment of the host country in the modification of the dietary patterns of immigrants.

Stimulant treatment history predicts frontal-striatal structural connectivity in adolescents with attention-deficit/hyperactivity disorder.

PubMed

Schweren, L J S; Hartman, C A; Zwiers, M P; Heslenfeld, D J; Franke, B; Oosterlaan, J; Buitelaar, J K; Hoekstra, P J

2016-04-01

Diffusion tensor imaging (DTI) has revealed white matter abnormalities in individuals with attention-deficit/hyperactivity disorder (ADHD). Stimulant treatment may affect such abnormalities. The current study investigated associations between long-term stimulant treatment and white matter integrity within the frontal-striatal and mesolimbic pathways, in a large sample of children, adolescents and young adults with ADHD. Participants with ADHD (N=172; mean age 17, range 9-26) underwent diffusion-weighted MRI scanning, along with an age- and gendermatched group of 96 control participants. Five study-specific white matter tract masks (orbitofrontal-striatal, orbitofrontal-amygdalar, amygdalar-striatal, dorsolateral-prefrontal-striatal and medialprefrontal-striatal) were created. First we analyzed case-control differences in fractional anisotropy (FA) and mean diffusivity (MD) within each tract. Second, FA and MD in each tract was predicted from cumulative stimulant intake within the ADHD group. After correction for multiple testing, participants with ADHD showed reduced FA in the orbitofrontal-striatal pathway (p=0.010, effect size=0.269). Within the ADHD group, higher cumulative stimulant intake was associated with lower MD in the same pathway (p=0.011, effect size=-0.164), but not with FA. The association between stimulant treatment and orbitofrontal-striatal MD was of modest effect size. It fell short of significance after adding ADHD severity or ADHD type to the model (p=0.036 and p=0.094, respectively), while the effect size changed little. Our findings are compatible with stimulant treatment enhancing orbitofrontal-striatal white matter connectivity, and emphasize the importance of the orbitofrontal cortex and its connections in ADHD. Longitudinal studies including a drug-naïve baseline assessment are needed to distinguish between-subject variability in ADHD severity from treatment effects. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Severity of Visual Field Loss and Health Related Quality of Life

PubMed Central

McKean-Cowdin, Roberta; Varma, Rohit; Wu, Joanne; Hays, Ron D.; Azen, Stanley P.

2009-01-01

Purpose To examine the association between severity of visual field loss (VFL) and self-reported health-related quality of life (HRQOL) in a population-based sample. Design Population-based cross-sectional study. Methods Participants in the Los Angeles Latino Eye Study underwent a comprehensive ophthalmic examination including visual field testing using the Humphrey Automated Field Analyzer II (SITA Standard 24-2). Mean Deviation (MD) scores were used to determine severity of VFL both as a continuous variable and stratified by severity: no VFL (MD≥ − 2 decibels [dB]), mild VFL (6dB

Primary alveolar hypoventilation

MedlinePlus

... Hadjiliadis, MD, MHS, Paul F. Harron, Jr. Associate Professor of Medicine, Pulmonary, Allergy, and Critical Care, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA. Also ...

Pharmacist and physician satisfaction and rates of switching to preferred medications associated with an instant prior authorization program for proton pump inhibitors in the North Carolina Medicaid program.

PubMed

Jacobson Vann, Julie C; Christofferson, Stephanie; Humble, Charles G; Wegner, Steven E; Feaganes, John R; Trygstad, Troy K

2010-05-01

Proton pump inhibitors (PPIs) are among the highest expenditure drugs covered by health care plans. During fiscal year 2001-2002, Medicaid programs nationwide spent nearly $2 billion on PPIs. Although the costs of individual PPIs vary widely, there is little variation in therapeutic effectiveness. On June 1, 2007, the North Carolina Medicaid program implemented an "instant approval" option simultaneously with a prior authorization (PA) program for PPIs with the goal of managing costs and maintaining high-quality care. Preferred PPIs included generic omeprazole and Prilosec OTC. This instant approval process (IAP) was expected to impose less administrative burden than is typically associated with PA programs by permitting physician and nonphysician prescribers to either write the PA criteria directly on a prescription form or use "MD Easy," a preprinted form that could be faxed by the prescriber to the dispensing pharmacy. A previous study found that from the prescriber's perspective the IAP reduced practice-related administrative burden and was associated with a reduced gap in PPI therapy when compared with traditional PA. To evaluate the acceptability and effectiveness of this IAP for PPIs as assessed by the outcome measures of (a) pharmacist satisfaction with the IAP; (b) physician and pharmacist satisfaction with the MD Easy form; and (c) utilization rates for preferred PPIs, comparing medical practices that used the MD Easy form with practices that did not. A cross-sectional design was used to assess pharmacist and physician satisfaction. A stratified random sample of 240 pharmacies was selected from 1,561 North Carolina pharmacies with claims in the Medicaid claims data file during state fiscal year 2006. Additionally, a stratified random sample of 240 medical practices was selected from 1,045 primary care practices serving Medicaid beneficiaries during 2006. Surveys were administered to pharmacists using either in-person interviews or self-administered questionnaires and to physicians using a mailed questionnaire with follow-up to nonrespondents. An interrupted time series analysis was used to evaluate the effect of the MD Easy form on switching to preferred PPIs using paid Medicaid claims of surveyed practices from calendar year 2007. Practices that reported both using the IAP and receiving the MD Easy form were defined as MD Easy users. Monthly market share data were analyzed using log negative binomial regression models to account for autocorrelation in the time series data. The pharmacy survey was completed by 202 (84.2%) pharmacies selected for participation. Of 198 permanently employed pharmacists, 140 (70.7%) reported experience with the IAP for PPIs. More than two-thirds (68.6%) of the pharmacist respondents with IAP experience indicated that the IAP is better (34.3%) or much better (34.3%) than traditional PA with RESEARCH respect to overall administrative burden of phone calls, faxes, patient interactions, and doctor contacts. Surveys were completed by 171 (71.3%) of selected physician practices, of which 56 (32.7%) reported experience with the MD Easy forms. Of practices that recalled receiving the MD Easy forms, 52 of 56 (92.9%) reported that the forms "very much" or "somewhat" helped prevent gaps in PPI therapy; 54 of 55 (98.2%) reported that they helped identify patients affected by Medicaid PPI PA; and 100% reported that they helped physicians to follow PA requirements. Immediately after implementation of the IAP and MD Easy form, the observed market share of preferred PPIs increased by 4.1 times (95% CI = 3.57-4.62). From May to June 2007, the preferred PPI market share increased by 64.0 percentage points, from 19.3% to 83.3% (P < 0.001), for practices that reported using the IAP and receiving the MD Easy form (n = 56) and by 55.4 percentage points, from 21.8% to 77.2% (P < 0.001), for practices that either (a) reported not receiving the MD Easy form (n = 25) or (b) reported not using the IAP (n = 84) or (c) did not respond to the survey item asking about the MD Easy form (n = 4). The overall increase in preferred PPI market share after implementation of the IAP was 1.29 times higher for practices that used the MD Easy form than for those that did not based on negative binomial regression modeling; this difference approached statistical significance (95% CI = 1.00-1.68; P = 0.053). This study suggests that an IAP for PPIs using either handwritten prescriptions or a preprinted form is an effective alternative to traditional PA. The IAP was associated with an increase in market share for preferred PPIs and was perceived by pharmacists as less administratively burdensome than traditional PA. Additional studies are needed to determine sustainability and the applicability to other prescription drugs.

Meta-analysis of antecolic versus retrocolic gastric reconstruction after a pylorus-preserving pancreatoduodenectomy.

PubMed

Bell, Richard; Pandanaboyana, Sanjay; Shah, Nehal; Bartlett, Adam; Windsor, John A; Smith, Andrew M

2015-03-01

Delayed gastric emptying (DGE) is a common complication after a pylorus-preserving pancreatoduodenectomy (PPPD) and is associated with significant morbidity. This study determines whether DGE is affected by antecolic (AC) or retrocolic (RC) reconstruction after a PPPD. An electronic search was performed of the MEDLINE, EMBASE and PubMed databases to identify all articles related to this topic. Pooled risk ratios (RR) were calculated for categorical outcomes, and mean differences (MD) for secondary continuous outcomes using the fixed-effects and random-effects models for meta-analysis. Nine studies including 878 patients met the inclusion criteria. DGE was lower with an AC reconstruction RR 0.31 [0.12, 0.78] Z = 2.47 (P = 0.010). Length of stay (LOS) MD -4 days [-7.63, -1.14] Z = 2.65 (P = 0.008) and days to commence a solid diet MD -5 days [-6.63, -3.15] Z = 5.50 (P ≤ 0.000) were also significantly in favour of the AC group. There was no difference in the incidence of pancreatic fistula, intra-abdominal collection/bile leak or mortality between the two groups. AC reconstruction after PPPD is associated with a lower incidence of DGE. Time to oral intake was significantly shorter with AC reconstruction, with a reduced hospital stay. © 2014 International Hepato-Pancreato-Biliary Association.

Within-day energy deficiency and reproductive function in female endurance athletes.

PubMed

Fahrenholtz, I L; Sjödin, A; Benardot, D; Tornberg, Å B; Skouby, S; Faber, J; Sundgot-Borgen, J K; Melin, A K

2018-03-01

We aimed to estimate and compare within-day energy balance (WDEB) in athletes with eumenorrhea and menstrual dysfunction (MD) with similar 24-hour energy availability/energy balance (EA/EB). Furthermore, to investigate whether within-day energy deficiency is associated with resting metabolic rate (RMR), body composition, S-cortisol, estradiol, T 3 , and fasting blood glucose. We reanalyzed 7-day dietary intake and energy expenditure data in 25 elite endurance athletes with eumenorrhea (n = 10) and MD (n = 15) from a group of 45 subjects where those with disordered eating behaviors (n = 11), MD not related to low EA (n = 5), and low dietary record validity (n = 4) had been excluded. Besides gynecological examination and disordered eating evaluation, the protocol included RMR measurement; assessment of body composition by dual-energy X-ray absorptiometry, blood plasma analysis, and calculation of WDEB in 1-hour intervals. Subjects with MD spent more hours in a catabolic state compared to eumenorrheic athletes; WDEB < 0 kcal: 23.0 hour (20.8-23.4) vs 21.1 hour (4.7-22.3), P = .048; WDEB < -300 kcal: 21.8 hour (17.8-22.4) vs 17.6 hour (3.9-20.9), P = .043, although similar 24-hour EA: 35.6 (11.6) vs 41.3 (12.7) kcal/kg FFM/d, (P = .269), and EB: -659 (551) vs -313 (596) kcal/d, (P = .160). Hours with WDEB <0 kcal and <-300 kcal were inversely associated with RMR ratio (r = -.487, P = .013, r = -.472, P = .018), and estradiol (r = -.433, P = .034, r = -.516, P = .009), and positively associated with cortisol (r = .442, P = .027, r = .463, P = .019). In conclusion, although similar 24-hour EA/EB, the reanalysis revealed that MD athletes spent more time in a catabolic state compared to eumenorrheic athletes. Within-day energy deficiency was associated with clinical markers of metabolic disturbances. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Impact of Ménière's Disease on Significant Others' Health and Lives.

PubMed

Manchaiah, Vinaya; Pyykkő, Ilmari; Levo, Hilla; Kentala, Erna

2018-01-01

Ménière's disease (MD) is a chronic and, in part, intermittent illness that poses multiple challenges for both the physical and psychological well-being of patients, as well as on those around them. The patients face psychosocial consequences, which include disruptions to life goals, employment, income, relationships, leisure activities, and daily living activities that also influence their family members and friends. However, there is a limited understanding of the impact of MD on significant others (SOs). The current study was aimed at identifying how the SOs of patients with MD respond to different aspects of the impact of the disorder on health and life (i.e., psychological aspects, activities, participation, and positive aspects). The study employed a cross-sectional survey design. The study sample was 186 SOs of patients with MD who were recruited through Finnish Ménière's Federation. Participants completed a 25-item structured questionnaire focusing on different aspects of the impact of the disorder on health and life, and also provided some demographic information. Data were analyzed using Kruskal-Wallis test, Pearson's correlation, and K-means cluster analysis techniques. Examination of response patterns suggests that the disorder had, on average, a marginal effect on SOs' psychological aspects, activities, and participation as the SOs generally focused on complaints. Interestingly, SOs reported some positive consequences as a result of their partners' condition. The results show a limited association between SOs' demographic variables and response patterns. The Pearson's correlation suggested a strong association between the subscales psychological aspects, activity limitations, and participation restrictions. Also, a weak negative correlation was observed among positive aspects and participation restrictions. The cluster analysis resulted in three clusters, namely, (1) "nonengaged," (2) "supportive," and (3) "concerned." The current study results identify that the SOs' reaction to patients' condition varies and this may be from coping with victimization. Although the impact of MD on SOs is limited, some of the SOs may have more severe consequences and may require rehabilitation. The information gathered about SOs' coping and adjustment in this study can also help while developing management and/or rehabilitation plan for people with MD. American Academy of Audiology

Determinants and patterns of service utilization and recourse to professionals for mental health reasons

PubMed Central

2014-01-01

Background This study has a dual purpose: 1) identify determinants of healthcare service utilization for mental health reasons (MHR) in a Canadian (Montreal) catchment area; 2) determine the patterns of recourse to healthcare professionals in terms of frequency of visits and type of professionals consulted, and as it relates to the most prevalent mental disorders (MD) and psychological distress. Methods Data was collected from a random sample of 1,823 individuals interviewed after a two-year follow-up period. A regression analysis was performed to identify variables associated with service utilization and complementary analyses were carried out to better understand participants’ patterns of healthcare service utilization in relation to the most prevalent MD. Results Among 243 individuals diagnosed with a MD in the 12 months preceding an interview, 113 (46.5%) reported having used healthcare services for MHR. Determinants of service utilization were emotional and legal problems, number of MD, higher personal income, lower quality of life, inability of individuals to influence events occurring in their neighborhood, female gender and, marginally, lack of alcohol dependence in the past 12 months. Emotional problems were the most significant determinant of healthcare service utilization. Frequent visits with healthcare professionals were more likely associated with major depression and number of MD with or without dependence to alcohol or drugs. People suffering from major depression, psychological distress and social phobia were more likely to consult different professionals, while individuals with panic disorders relied on their family physician only. Concerning social phobia, panic disorders and psychological distress, more frequent visits with professionals did not translate into involvement of a higher number of professionals or vice-versa. Conclusions This study demonstrates the impact of emotional problems, neighborhood characteristics and legal problems in healthcare service utilization for MHR. Interventions based on inter-professional collaboration could be prioritized to increase the ability of healthcare services to take care especially of individuals suffering from social phobia, panic disorders and psychological distress. Others actions that could be prioritized are training of family physicians in the treatment of MD, use of psychiatric consultants, internet outreach, and reimbursement of psychological consultations for individuals with low income. PMID:24712834

Comparative Proteomics Analysis of Gastric Cancer Stem Cells

PubMed Central

Morisaki, Tamami; Yashiro, Masakazu; Kakehashi, Anna; Inagaki, Azusa; Kinoshita, Haruhito; Fukuoka, Tatsunari; Kasashima, Hiroaki; Masuda, Go; Sakurai, Katsunobu; Kubo, Naoshi; Muguruma, Kazuya; Ohira, Masaichi; Wanibuchi, Hideki; Hirakawa, Kosei

2014-01-01

Cancer stem cells (CSCs) are responsible for cancer progression, metastasis, and recurrence. To date, the specific markers of CSCs remain undiscovered. The aim of this study was to identify novel biomarkers of gastric CSCs for clinical diagnosis using proteomics technology. CSC-like SP cells, OCUM-12/SP cells, OCUM-2MD3/SP cells, and their parent OCUM-12 cells and OCUM-2MD3 cells were used in this study. Protein lysates from each cell line were analyzed using QSTAR Elite Liquid Chromatography with Tandem Mass Spectrometry, coupled with isobaric tags for relative and absolute quantitation technology. Candidate proteins detected by proteomics technology were validated by immunohistochemical analysis of 300 gastric cancers. Based on the results of LC-MS/MS, eight proteins, including RBBP6, GLG1, VPS13A, DCTPP1, HSPA9, HSPA4, ALDOA, and KRT18, were up-regulated in both OCUM-12/SP cells and OCUM-2MD3/SP cells when compared to their corresponding parent cells. RT-PCR analysis indicated that the expression level of RBBP6, HSPA4, DCTPP1, HSPA9, VPS13A, ALDOA, GLG1, and CK18 was high in OCUM-12/SP and OCUM-2MD3/SP, in compared with the control of parent OCUM-12 and OCUM-2MD3. These proteins were significantly associated with advanced invasion depth, lymph node metastasis, distant metastasis, or advanced clinical stage. RBBP6, DCTPP1, HSPA4, and ALDOA expression in particular were significantly associated with a poor prognosis in the 300 gastric cancer patients. RBBP6 was determined to be an independent prognostic factor. The motility-stimulating ability of OCUM-12/SP cells and OCUM-2MD3/SP cells was inhibited by RBBP6 siRNA. These findings might suggest that the eight proteins, RBBP6, GLG1, VPS13A, DCTPP1, HSPA9, HSPA4, ALDOA, and KRT18, utilizing comparative proteomics analysis, were perceived to be potential CSC markers of gastric cancer. Of the eight candidate proteins, RBBP6 was suggested to be a promising prognostic biomarker and a therapeutic target for gastric cancer. PMID:25379943

Primary Hyperparathyroidism and Hyperthyroidism in a Patient with Myotonic Dystrophy: A Case Report and Review of the Literature

PubMed Central

Alaya, Wafa; Berriche, Olfa; Younes, Samia; Sfar, Mohamed Habib

2015-01-01

Various endocrine manifestations are commonly described in myotonic dystrophy (MD), including primary hypogonadism, diabetes mellitus, and thyroid and parathyroid dysfunction. We describe a 46-year-old woman with a family history of MD with her son. She was diagnosed with cardiac arrhythmia and required the implantation of a pacemaker. She was noted to have a bilateral cataract. She complained of muscle weakness, diffuse myalgia, and palpitation. The electromyography (EMG) showed myotonic discharges. Laboratory tests showed high serum calcium 2.83 mmol/L, serum phosphate 1.2 mmol/L, parathormone 362.5 pg/mL, thyroid stimulating hormone TSH 0.02 mIU/L (normal range: 0.34–5.6 mIU/L), FT4 21.17 ng/mL, and negative anti-thyroperoxidase antibodies. Cervical ultrasound revealed a multinodular goiter. The 99mTc-MIBI scintigraphy localized a lower right parathyroid adenoma. The clinical data, the family history of MD, EMG data, and endocrine disturbances were strongly suggestive of MD associated with hyperthyroidism and primary hyperparathyroidism. PMID:26175917

[Methylmercury causes diffuse damage to the somatosensory cortex: how to diagnose Minamata disease].

PubMed

Ekino, Shigeo; Ninomiya, Tadashi; Imamura, Keiko; Susa, Mari

2007-01-01

The first acute case of methylmercury (MeHg) poisoning by the consumption of fish arose in Minamata, Japan, in 1953. It was officially recognized and called Minamata disease (MD) in 1956. There are still arguments about the definition of MD in terms of its associated clinical symptoms and lesions even 50 years after the initial recognition of MD. Studies on this MD epidemic are reviewed along with its historical background. Since MeHg dispersed from Minamata to the Shiranui Sea, residents living around the sea had been exposed to low-dose MeHg through fish consumption for about 20 years (at least from 1950 to 1968). These chronic MeHg poisoning patients complained of paresthesia at the distal parts of their extremities and around the lips even 30 years after the cessation of exposure to MeHg of anthropogenic origin. The persisting somatosensory disorders after the discontinuation of exposure to MeHg were induced by diffuse damage to the somatosensory cortex, but not by damage to the peripheral nervous system, as previously believed. Based on these findings, symptoms and lesions in MeHg poisoning are reappraised.

A Comparison of HAART Outcomes between the US Military HIV Natural History Study (NHS) and HIV Atlanta Veterans Affairs Cohort Study (HAVACS)

DTIC Science & Technology

2013-05-01

Acknowledgments The IDCRP HIV Working Group includes: Susan Banks, RN, CAPT Mary Bavaro, MD, Ionut Bebu, PhD, Helen Chun, MD, Nancy Crum- Cianflone, MD, MPH...Cathy Decker, MD, Conner Eggleston, LTC Tomas Ferguson, MD, COL Susan Fraser, MD, MAJ Joshua Hartzell, MD, MAJ Joshua Hawley, MD, LTC Gunther Hsue, MD

[Mediterranean diet in cancer patients and cancer free adult Arabs in Israel--a case-control study].

PubMed

Idilbi, Nasra Muhammad; Barchana, Micha; Milman, Uzi; Carel, Rafael S

2013-07-01

Although several studies have investigated the association of the Mediterranean diet (MD) with overall risk of specific cancers, data on overall cancer risk are sparse, especially in Arab populations. To compare between the score of MD in cancer patients and cancer-free adult Israeli Arabs in order to identify risk factors amenable to intervention. A case control study was conducted in northern Israel, involving 200 Arab subscribers of a regional Health Maintenance Organization (HMO). An inverse association was found (p = 0.000) between Mediterranean diet score and cancer, with OR = 0.4, 95% CI = 0.260-0.612. Greater adherence to Mediterranean diet is associated with lower prevalence of cancer. The adoption of this dietary pattern also seems to moderate the prevalence of obesity and risks of chronic diseases.

Androgens for the anaemia of chronic kidney disease in adults.

PubMed

Yang, Qianchun; Abudou, Minawaer; Xie, Xi Sheng; Wu, Taixiang

2014-10-09

Anaemia occurs when blood contains fewer red blood cells and lower haemoglobin levels than normal, and is a common complication among adults with chronic kidney disease (CKD). Although a number of approaches are applied to correct anaemia in adults with CKD, the use of androgen therapy is controversial. The aim of this review was to determine the benefits and harms of androgens for the treatment of anaemia in adult patients with CKD. We searched CENTRAL, the Cochrane Renal Group's Specialised Register, the Chinese Biomedicine Database (CBM), CNKI, VIP and reference lists of articles without language restriction. The most recent search was conducted in August 2014. All randomised controlled trials (RCTs) that assessed the use of androgens for treating anaemia of CKD in adults were eligible for inclusion. Two authors independently extracted data and assessed risk of bias in the included studies. Meta-analyses were performed using relative risk (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes, with 95% confidence intervals (CI). We included eight studies that reported data from 181 participants. Study quality was assessed as moderate in six studies, one was low quality, and one was high quality. The small number of included studies, and low participant numbers adversely influenced evidence quality overall.We found limited evidence (1 study, 24 participants) to indicate that oxymetholone can increase haemoglobin (Hb) (MD 1.90 g/dL, 95% CI 1.66 to 2.14), haematocrit (HCT) (MD 27.10%, 95% CI 26.49 to 27.71), change in albumin (MD 4.91 g/L, 95% CI 3.69 to 6.13), alanine aminotransferase (ALT) (MD 54.50 U/L, 95% CI 43.94 to 65.06), and aspartate aminotransferase (AST) (MD 47.33 U/L, 95% CI 37.69 to 56.97); and decrease high-density lipoprotein (HDL) (MD -15.66 mg/dL, 95% CI -24.84 to -6.48). We also found that compared with erythropoietin alone, nandrolone decanoate plus erythropoietin may increase HCT (3 studies, 73 participants: MD 2.54%, 95% Cl 0.96 to 4.12). Compared with erythropoietin (1 study, 27 participants), limited evidence was found to suggest that nandrolone decanoate can increase plasma total protein (MD 0.40 g/L, 95% CI 0.13 to 0.67), albumin (MD 0.20 g/L, 95% CI 0.01 to 0.39), and transferrin (MD 45.00 mg/dL, 95% CI 12.61 to 77.39) levels. Compared with no therapy (remnant kidney), evidence was found to suggest that nandrolone decanoate can increase Hb (2 studies, 33 participants: MD 1.04 g/dL, 95% Cl 0.66 to 1.41) and HCT (1 study, 24 participants: MD 3.70%, 95% Cl 0.68 to 6.72). Compared with no therapy (anephric), evidence was found (1 study, 5 participants) to suggest that nandrolone decanoate can increase Hb (MD 1.30 g/dL, 95% Cl 0.57 to 2.03), but nandrolone decanoate did not increase HCT (MD 2.00%, 95% Cl -0.85 to 4.85).However, oxymetholone was not found to reduce blood urea nitrogen (BUN), serum creatinine (SCr), cholesterol, or triglycerides; or increase plasma total protein, prealbumin, or transferrin. No evidence was found to indicate that nandrolone decanoate increased prealbumin or decreased BUN, SCr, AST, ALT, cholesterol, triglycerides, HDL or low-density lipoprotein (LDL). Adverse events associated with androgen therapy were reported infrequently. We found insufficient evidence to confirm that use of androgens for adults with CKD-related anaemia is beneficial.

The Jasmonate-Activated Transcription Factor MdMYC2 Regulates ETHYLENE RESPONSE FACTOR and Ethylene Biosynthetic Genes to Promote Ethylene Biosynthesis during Apple Fruit Ripening[OPEN

PubMed Central

Xu, Yaxiu; Zhang, Lichao; Ji, Yinglin; Tan, Dongmei; Yuan, Hui

2017-01-01

The plant hormone ethylene is critical for ripening in climacteric fruits, including apple (Malus domestica). Jasmonate (JA) promotes ethylene biosynthesis in apple fruit, but the underlying molecular mechanism is unclear. Here, we found that JA-induced ethylene production in apple fruit is dependent on the expression of MdACS1, an ACC synthase gene involved in ethylene biosynthesis. The expression of MdMYC2, encoding a transcription factor involved in the JA signaling pathway, was enhanced by MeJA treatment in apple fruits, and MdMYC2 directly bound to the promoters of both MdACS1 and the ACC oxidase gene MdACO1 and enhanced their transcription. Furthermore, MdMYC2 bound to the promoter of MdERF3, encoding a transcription factor involved in the ethylene-signaling pathway, thereby activating MdACS1 transcription. We also found that MdMYC2 interacted with MdERF2, a suppressor of MdERF3 and MdACS1. This protein interaction prevented MdERF2 from interacting with MdERF3 and from binding to the MdACS1 promoter, leading to increased transcription of MdACS1. Collectively, these results indicate that JA promotes ethylene biosynthesis through the regulation of MdERFs and ethylene biosynthetic genes by MdMYC2. PMID:28550149

The Jasmonate-Activated Transcription Factor MdMYC2 Regulates ETHYLENE RESPONSE FACTOR and Ethylene Biosynthetic Genes to Promote Ethylene Biosynthesis during Apple Fruit Ripening.

PubMed

Li, Tong; Xu, Yaxiu; Zhang, Lichao; Ji, Yinglin; Tan, Dongmei; Yuan, Hui; Wang, Aide

2017-06-01

The plant hormone ethylene is critical for ripening in climacteric fruits, including apple ( Malus domestica ). Jasmonate (JA) promotes ethylene biosynthesis in apple fruit, but the underlying molecular mechanism is unclear. Here, we found that JA-induced ethylene production in apple fruit is dependent on the expression of MdACS1 , an ACC synthase gene involved in ethylene biosynthesis. The expression of MdMYC2 , encoding a transcription factor involved in the JA signaling pathway, was enhanced by MeJA treatment in apple fruits, and MdMYC2 directly bound to the promoters of both MdACS1 and the ACC oxidase gene MdACO1 and enhanced their transcription. Furthermore, MdMYC2 bound to the promoter of MdERF3 , encoding a transcription factor involved in the ethylene-signaling pathway, thereby activating MdACS1 transcription. We also found that MdMYC2 interacted with MdERF2, a suppressor of MdERF3 and MdACS1 This protein interaction prevented MdERF2 from interacting with MdERF3 and from binding to the MdACS1 promoter, leading to increased transcription of MdACS1 Collectively, these results indicate that JA promotes ethylene biosynthesis through the regulation of MdERFs and ethylene biosynthetic genes by MdMYC2. © 2017 American Society of Plant Biologists. All rights reserved.

R-factor cointegrate formation in Salmonella typhimurium bacteriophage type 201 strains.

PubMed Central

Helmuth, R; Stephan, R; Bulling, E; van Leeuwen, W J; van Embden, J D; Guinée, P A; Portnoy, D; Falkow, S

1981-01-01

The genetic and molecular properties of the plasmids in Salmonella typhimurium phase type 201 isolated are described. Such strains are resistant to streptomycin, tetracycline, chloramphenicol, ampicillin, kanamycin, and several other antimicrobial drugs, and are highly pathogenic for calves. These strains have been encountered with increasing frequency since 1972 in West Germany and The Netherlands. We show that isolates of this phage type constitute a very homogeneous group with regard to their extrachromosomal elements. These bacteria carry three small plasmids: pRQ3, a 4.2-megadalton (Md) colicinogenic plasmid; pRQ4, 3.4-Md plasmid that interferes with the propagation of phages; and pRQ5, a 3.2-Md cryptic plasmid. Tetracycline resistance resides on a conjugative 120-MD plasmid pRQ1, belonging to the incompatibility class H2. Other antibiotic resistance determinants are encoded by a nonconjugative 108-Md plasmid pRQ2. Transfer of multiple-antibiotic resistance to appropriate recipient strains was associated with the appearance of a 230-Md plasmid, pRQ6. It appears that pRQ6 is a stable cointegrate of pRQ1 and pRQ2. This cointegrate plasmid was transferable with the same efficiency as pRQ1. Other conjugative plasmids could mobilize pRQ2, but stable cointegrates were not detected in the transconjugants. Phase type 201 strains carry a prophage, and we show that phage pattern 201 reflects the interference with propagation of typing phages effected by this prophage and plasmid pRQ4 in strains of phage type 201. Images PMID:7012128

Mediterranean diet adherence and synergy with acute myocardial infarction and its determinants: A multicenter case-control study in Italy

PubMed Central

Saulle, Rosella; Di Murro, Francesca; Siliquini, Roberta; Firenze, Alberto; Maurici, Massimo; Mannocci, Alice; Colamesta, Vittoria; Barillà, Francesco; Ferrante, Fabio; Agati, Luciano

2018-01-01

Background Cardiovascular diseases are the leading causes of mortality and morbidity in Western countries. The possible synergistic effect of poor adherence to a Mediterranean diet (MD) and other risk factors for acute myocardial infarction (AMI) such as hypertension, cholesterol, ever smoker, BMI> 25, diabetes, has not been deeply studied. Design Case-control study. Methods Patients with first AMI and controls from four tertiary referral Italian centers were screened for enrolment. Dietary information was collected through a questionnaire and a MD adherence score was calculated. Physical activity and smoking habits were also registered. The Synergy Index was calculated according to Rothman. Results 127 cases and 173 controls were enrolled. The analysis was conducted using a dichotomous variable for the MD score with values ≥7 representing good adherence. Multivariate analysis showed the following variables associated to AMI: ever smoker (OR = 2.08), diabetes (OR = 1.42), hypertension (OR = 2.08), hypercholesterolemia (OR = 2.47), BMI> 25 (OR = 1.99), while a protective effect emerged both in subjects scoring > 7 on the MD score (OR = 0.55) and in subjects resident of Southern Italy (OR = 0.38). A synergistic effect does exist between poor adherence to the MD and the following risk factors: hypertension, hypercholesterolemia, BMI >25, diabetes and being a resident in central and northern Italy. Conclusion Synergy between heart disease risk factors and MD underlines the need to enlarge the list of known modifiable cardiovascular risk factors to include and promote adherence to Mediterranean dietary habits. PMID:29543823

Novel glucokinase mutations in patients with monogenic diabetes - clinical outline of GCK-MD and potential for founder effect in Slavic population.

PubMed

Borowiec, M; Antosik, K; Fendler, W; Deja, G; Jarosz-Chobot, P; Mysliwiec, M; Zmyslowska, A; Malecki, M; Szadkowska, A; Mlynarski, W

2012-03-01

Glucokinase (GCK) gene mutations are the causative factor of GCK-MD (monogenic diabetes) characterized by a mild clinical phenotype and potential for insulin withdrawal. This study presents the results of a nationwide genetic screening for GCK-MD performed in Poland. A group of 194 patients with clinical suspicion of GCK-MD and 17 patients with neonatal diabetes were subjected to GCK sequencing. Patients negative for GCK mutations were subjected to multiplex ligation-dependent probe amplification (MLPA) to detect deletions or insertions. A total of 44 GCK heterozygous mutations were found in 68 probands (35%). Among those, 20 mutations were novel ones: A282fs, D198V, E158X, G246V, G249R, I348N, L165V, L315Q, M115I, N254S, P284fs, Q338P, R377L, R43C, R46S, S212fs, S212P, T255N, V406A and Y214D. No abnormalities were detected in MLPA analysis. Homozygous D278E mutation was found in one patient with neonatal diabetes. The most frequently observed combinations of symptoms typical for GCK-MD were mild diabetes and/or fasting hyperglycaemia (98.3%), positive C-peptide at diagnosis (76%) and dominant mode of inheritance (59%). This study outlines numerous novel mutations of the GCK gene present in white Caucasians of Slavic origin. Thorough clinical assessment of known factors associated with GCK-MD may facilitate patient selection. © 2011 John Wiley & Sons A/S.

Recall deficits in stroke patients with thalamic lesions covary with damage to the parvocellular mediodorsal nucleus of the thalamus.

PubMed

Pergola, Giulio; Güntürkün, Onur; Koch, Benno; Schwarz, Michael; Daum, Irene; Suchan, Boris

2012-08-01

The functional role of the mediodorsal thalamic nucleus (MD) and its cortical network in memory processes is discussed controversially. While Aggleton and Brown (1999) suggested a role for recognition and not recall, Van der Werf et al. (2003) suggested that this nucleus is functionally related to executive function and strategic retrieval, based on its connections to the prefrontal cortices (PFC). The present study used a lesion approach including patients with focal thalamic lesions to examine the functions of the MD, the intralaminar nuclei and the midline nuclei in memory processing. A newly designed pair association task was used, which allowed the assessment of recognition and cued recall performance. Volume loss in thalamic nuclei was estimated as a predictor for alterations in memory performance. Patients performed poorer than healthy controls on recognition accuracy and cued recall. Furthermore, patients responded slower than controls specifically on recognition trials followed by successful cued recall of the paired associate. Reduced recall of picture pairs and increased response times during recognition followed by cued recall covaried with the volume loss in the parvocellular MD. This pattern suggests a role of this thalamic region in recall and thus recollection, which does not fit the framework proposed by Aggleton and Brown (1999). The functional specialization of the parvocellular MD accords with its connectivity to the dorsolateral PFC, highlighting the role of this thalamocortical network in explicit memory (Van der Werf et al., 2003). Copyright © 2012 Elsevier Ltd. All rights reserved.

Systemic antibiotics in the treatment of aggressive periodontitis. A systematic review and a Bayesian Network meta-analysis.

PubMed

Rabelo, Cleverton Correa; Feres, Magda; Gonçalves, Cristiane; Figueiredo, Luciene C; Faveri, Marcelo; Tu, Yu-Kang; Chambrone, Leandro

2015-07-01

The aim of this study was to assess the effect of systemic antibiotic therapy on the treatment of aggressive periodontitis (AgP). This study was conducted and reported in accordance with the PRISMA statement. The MEDLINE, EMBASE and CENTRAL databases were searched up to June 2014 for randomized clinical trials comparing the treatment of subjects with AgP with either scaling and root planing (SRP) alone or associated with systemic antibiotics. Bayesian network meta-analysis was prepared using the Bayesian random-effects hierarchical models and the outcomes reported at 6-month post-treatment. Out of 350 papers identified, 14 studies were eligible. Greater gain in clinical attachment (CA) (mean difference [MD]: 1.08 mm; p < 0.0001) and reduction in probing depth (PD) (MD: 1.05 mm; p < 0.00001) were observed for SRP + metronidazole (Mtz), and for SRP + Mtz + amoxicillin (Amx) (MD: 0.45 mm, MD: 0.53 mm, respectively; p < 0.00001) than SRP alone/placebo. Bayesian network meta-analysis showed additional benefits in CA gain and PD reduction when SRP was associated with systemic antibiotics. SRP plus systemic antibiotics led to an additional clinical effect compared with SRP alone in the treatment of AgP. Of the antibiotic protocols available for inclusion into the Bayesian network meta-analysis, Mtz and Mtz/Amx provided to the most beneficial outcomes. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Generalized anxiety disorder, comorbid major depression and heart rate variability: a case-control study in taiwan.

PubMed

Chang, Hsin-An; Chang, Chuan-Chia; Tzeng, Nian-Sheng; Kuo, Terry B J; Lu, Ru-Band; Huang, San-Yuan

2013-12-01

Decreased heart rate variability (HRV) has been reported in generalized anxiety disorder (GAD), but the results are mixed. Little is known about the impact of comorbid major depression (MD) on HRV in GAD patients. Both issues necessitate further investigation. Twenty unmedicated, physically healthy GAD patients, 20 GAD patients with a secondary diagnosis of MD, 40 MD patients and 60 matched controls were recruited. We used the Hamilton Anxiety Rating Scale and the Hamilton Depression Rating Scale to assess anxiety and depression severity, respectively. Cardiac autonomic function was evaluated by measuring HRV parameters. Frequency-domain indices of HRV were obtained. Three patient groups had more anxiety and depression symptoms than control subjects, but heart rates (HRs) were significantly elevated only in GAD patients with comorbid depression. Relative to controls, GAD patients had reduced HRV while GAD patients with comorbid depression displayed the greatest reductions in HRV among three patients groups. Correlation analyses revealed anxiety/depression severity significantly associated with HRs, variance, LF-HRV and HF-HRV. However, separately analyzing among individual groups and adjusting for HRV-associated covariables rendered the correlations non-significant. Our results suggest that reduction in HRV is a psychophysiological marker of GAD and individuals with comorbid GAD and MD may be distinguished based on psychophysiological correlates (for example, HF-HRV) from non-comorbid GAD patients. Taken into account that comorbid depression may confer increased risks for cardiovascular events in GAD patients, this subgroup of GAD patients may benefit better from cardiovascular risk reduction strategies.

Developmental differences in white matter architecture between boys and girls.

PubMed

Schmithorst, Vincent J; Holland, Scott K; Dardzinski, Bernard J

2008-06-01

Previous studies have found developmental differences between males and females in brain structure. During childhood and adolescence, relative white matter volume increases faster in boys than in girls. Sex differences in the development of white matter microstructure were investigated in a cohort of normal children ages 5-18 in a cross-sectional diffusion tensor imaging (DTI) study. Greater fractional anisotropy (FA) in boys was shown in associative white matter regions (including the frontal lobes), while greater FA in girls was shown in the splenium of the corpus callosum. Greater mean diffusivity (MD) in boys was shown in the corticospinal tract and in frontal white matter in the right hemisphere; greater MD in girls was shown in occipito-parietal regions and the most superior aspect of the corticospinal tract in the right hemisphere. Significant sex-age interactions on FA and MD were also shown. Girls displayed a greater rate of fiber density increase with age when compared with boys in associative regions (reflected in MD values). However, girls displayed a trend toward increased organization with age (reflected in FA values) only in the right hemisphere, while boys displayed this trend only in the left hemisphere. These results indicate differing developmental trajectories in white matter for boys and girls and the importance of taking sex into account in developmental DTI studies. The results also may have implications for the study of the relationship of brain architecture with intelligence. Copyright 2007 Wiley-Liss, Inc.

Clinical and autonomic profile of patients with Alzheimer's disease and mixed dementia patients.

PubMed

Dias, Filipi Leles da Costa; Silva, Rose Mary Ferreira Lisboa da; Moraes, Edgar Nunes de; Caramelli, Paulo

2013-01-01

To analyze the clinical and autonomical profile of patients with Alzheimer's disease or mixed dementia (MD). Fifty-four patients with indication for cholinesterase inhibitors use were evaluated through clinical examination, rest electrocardiogram, and spectral analysis of heart rate (HR) variability through digital Holter system recordings. Overall, 61.1% of patients were female and were, on average, 77.1 years of age, 3.3 years of schooling and scored 16.4 points on the Mini Mental State Examination. The gap between symptom onset and diagnosis was 26.2 months. Almost all patients (90.7%) presented at least one clinical comorbidity, and each patient took, on average, 3.7 drugs to control them. Thirty-one patients had some alteration on the electrocardiogram and nine (16.6%) had orthostatic hypotension (OH). The latter was associated with the diagnosis of MD (p=0.001), with lower values of low (LF) and high (HF) frequency components of the spectral analysis in the supine position (p=0.000 and p=0.017, respectively) and with lower values of LF in the orthostatic position (p=0.006). Diagnosis of MD was associated with lower values of LF in both positions (p=0.003 and p=0.007). This sample of patients had frequent comorbidities, which resulted in the prescription of multiple drugs. Signs of autonomic dysfunction resulting in OH were found mainly in those with MD. Copyright © 2013 Elsevier Editora Ltda. All rights reserved.

Ectopic Cushing syndrome

MedlinePlus

... 7/2017 Updated by: Brent Wisse, MD, Associate Professor of Medicine, Division of Metabolism, Endocrinology & Nutrition, University of Washington School of Medicine, Seattle, WA. Also reviewed by David ...

A psychometric evaluation of the Rorschach comprehensive system's perceptual thinking index.

PubMed

Dao, Tam K; Prevatt, Frances

2006-04-01

In this study, we investigated evidence for reliability and validity of the Perceptual Thinking Index (PTI; Exner, 2000a, 2000b) among an adult inpatient population. We conducted reliability and validity analyses on 107 patients who met the Diagnostic and Statistical Manual of Mental Disorders (4th ed., text revision; American Psychiatric Association, 2000) criteria for a schizophrenia-spectrum disorder (SSD) or mood disorder with no psychotic features (MD). Results provided support for interrater reliability as well as internal consistency of the PTI. Furthermore, the PTI was an effective index in differentiating SSD patients from patients diagnosed with an MD. Finally, the PTI demonstrated adequate diagnostic statistics that can be useful in the classification of patients diagnosed with SSD and MD. We discuss methodological issues, implications for assessment practice, and directions for future research.

Application of molecular dynamics simulation to predict the compatability between water-insoluble drugs and self-associating poly(ethylene oxide)-b-poly(epsilon-caprolactone) block copolymers.

PubMed

Patel, Sarthak; Lavasanifar, Afsaneh; Choi, Phillip

2008-11-01

In the present work, molecular dynamics (MD) simulation was applied to study the solubility of two water-insoluble drugs, fenofibrate and nimodipine, in a series of micelle-forming PEO-b-PCL block copolymers with combinations of blocks having different molecular weights. The solubility predictions based on the MD results were then compared with those obtained from solubility experiments and by the commonly used group contribution method (GCM). The results showed that Flory-Huggins interaction parameters computed by the MD simulations are consistent with the solubility data of the drug/PEO-b-PCL systems, whereas those calculated by the GCM significantly deviate from the experimental observation. We have also accounted for the possibility of drug solubilization in the PEO block of PEO-b-PCL.

Discovering and Developing Successful Cardiovascular Therapeutics: A Conversation With James N. Topper, MD, PhD.

PubMed

Topper, James N; Rutherford, John D

2016-11-15

Dr James (also known as Jamie) N. Topper, MD, PhD, serves as Managing General Partner at Frazier Healthcare Partners, where he leads the Life Science Venture practice. In 2011, and 2016, he was named to the Midas List of leading venture capitalists, and, in 2013, he was recognized by Forbes as one of the top 10 healthcare investors. He has >25 years of experience working with entrepreneurs to found and build successful therapeutics-focused companies. Dr Topper holds a BS from the University of Michigan. He received an MD and PhD (in biophysics) from Stanford University School of Medicine. He completed postgraduate training in internal medicine and cardiovascular disease at the Brigham and Women's Hospital in Boston and is board certified in both disciplines. © 2016 American Heart Association, Inc.

Genetics Home Reference: PDGFRA-associated chronic eosinophilic leukemia

MedlinePlus

... area? Other Names for This Condition PDGFRA-associated myeloproliferative neoplasm Related Information How are genetic conditions and genes ... Disorders Hanns A. Pielenz Clinical Research Center for Myeloproliferative Neoplasia, MD Anderson Cancer Center ... ClinicalTrials.gov (1 link) ClinicalTrials.gov Scientific ...

Exploring intentions of physician-scientist trainees: factors influencing MD and MD/PhD interest in research careers.

PubMed

Kwan, Jennifer M; Daye, Dania; Schmidt, Mary Lou; Conlon, Claudia Morrissey; Kim, Hajwa; Gaonkar, Bilwaj; Payne, Aimee S; Riddle, Megan; Madera, Sharline; Adami, Alexander J; Winter, Kate Quinn

2017-07-11

Prior studies have described the career paths of physician-scientist candidates after graduation, but the factors that influence career choices at the candidate stage remain unclear. Additionally, previous work has focused on MD/PhDs, despite many physician-scientists being MDs. This study sought to identify career sector intentions, important factors in career selection, and experienced and predicted obstacles to career success that influence the career choices of MD candidates, MD candidates with research-intense career intentions (MD-RI), and MD/PhD candidates. A 70-question survey was administered to students at 5 academic medical centers with Medical Scientist Training Programs (MSTPs) and Clinical and Translational Science Awards (CTSA) from the NIH. Data were analyzed using bivariate or multivariate analyses. More MD/PhD and MD-RI candidates anticipated or had experienced obstacles related to balancing academic and family responsibilities and to balancing clinical, research, and education responsibilities, whereas more MD candidates indicated experienced and predicted obstacles related to loan repayment. MD/PhD candidates expressed higher interest in basic and translational research compared to MD-RI candidates, who indicated more interest in clinical research. Overall, MD-RI candidates displayed a profile distinct from both MD/PhD and MD candidates. MD/PhD and MD-RI candidates experience obstacles that influence their intentions to pursue academic medical careers from the earliest training stage, obstacles which differ from those of their MD peers. The differences between the aspirations of and challenges facing MD, MD-RI and MD/PhD candidates present opportunities for training programs to target curricula and support services to ensure the career development of successful physician-scientists.

Multiparameter MR imaging in the 6-OPRI variant of inherited prion disease.

PubMed

De Vita, E; Ridgway, G R; Scahill, R I; Caine, D; Rudge, P; Yousry, T A; Mead, S; Collinge, J; Jäger, H R; Thornton, J S; Hyare, H

2013-09-01

Inherited prion diseases represent over 15% of human prion cases and are a frequent cause of early onset dementia. The purpose of this study was to define the distribution of changes in cerebral volumetric and microstructural parenchymal tissues in a specific inherited human prion disease mutation combining VBM with VBA of cerebral MTR and MD. VBM and VBA of cerebral MTR and MD were performed in 16 healthy control participants and 9 patients with the 6-OPRI mutation. An analysis of covariance consisting of diagnostic grouping with age and total intracranial volume as covariates was performed. On VBM, there was a significant reduction in gray matter volume in patients compared with control participants in the basal ganglia, perisylvian cortex, lingual gyrus, and precuneus. Significant MTR reduction and MD increases were more anatomically extensive than volume differences on VBM in the same cortical areas, but MTR and MD changes were not seen in the basal ganglia. Gray matter and WM changes were seen in brain areas associated with motor and cognitive functions known to be impaired in patients with the 6-OPRI mutation. There were some differences in the anatomic distribution of MTR-VBA and MD-VBA changes compared with VBM, likely to reflect regional variations in the type and degree of the respective pathophysiologic substrates. Combined analysis of complementary multiparameter MR imaging data furthers our understanding of prion disease pathophysiology.

Orthodontic soft-tissue parameters: a comparison of cone-beam computed tomography and the 3dMD imaging system.

PubMed

Metzger, Tasha E; Kula, Katherine S; Eckert, George J; Ghoneima, Ahmed A

2013-11-01

Orthodontists rely heavily on soft-tissue analysis to determine facial esthetics and treatment stability. The aim of this retrospective study was to determine the equivalence of soft-tissue measurements between the 3dMD imaging system (3dMD, Atlanta, Ga) and the segmented skin surface images derived from cone-beam computed tomography. Seventy preexisting 3dMD facial photographs and cone-beam computed tomography scans taken within minutes of each other for the same subjects were registered in 3 dimensions and superimposed using Vultus (3dMD) software. After reliability studies, 28 soft-tissue measurements were recorded with both imaging modalities and compared to analyze their equivalence. Intraclass correlation coefficients and Bland-Altman plots were used to assess interexaminer and intraexaminer repeatability and agreement. Summary statistics were calculated for all measurements. To demonstrate equivalence of the 2 methods, the difference needed a 95% confidence interval contained entirely within the equivalence limits defined by the repeatability results. Statistically significant differences were reported for the vermilion height, mouth width, total facial width, mouth symmetry, soft-tissue lip thickness, and eye symmetry. There are areas of nonequivalence between the 2 imaging methods; however, the differences are clinically acceptable from the orthodontic point of view. Copyright © 2013 American Association of Orthodontists. Published by Mosby, Inc. All rights reserved.

Growth Failure in Children with Kidney Disease

MedlinePlus

... Ira Davis, M.D.; Ann Guillott, M.D.; Steve Alexander, M.D.; Deborah Kees-Folts, M.D.; Alicia Neu, M.D.; Steve Wassner, M.D.; John Brandt, M.D.; and ... Coordinating Committees Strategic Plans & Reports Research Areas FAQs Jobs at NIDDK Visit Us Contact Us News News ...

Vestibular syncope: A disorder associated with drop attack in Ménière's disease.

PubMed

Pyykkö, Ilmari; Manchaiah, Vinaya; Zou, Jing; Levo, Hilla; Kentala, Erna

2018-04-01

Experiments in humans and animals indicate that vestibular influx through vestibular sympathetic reflex is an important and vital part of the regulatory system of circulation. The otolith organ adjusts the circulatory responses through the vestibular sympathetic reflex during an upright stance and may trigger a vasovagal attack of syncope. The aim of the present study was to evaluate the prevalence and association of syncope attacks among patients with Ménière's disease (MD). Vestibular syncope was defined as a sudden and transient loss of consciousness, which subsides spontaneously in people with vestibular disorders and without localizing neurological deficit. During clinical interactions, we encountered 5 patients with syncope during a Tumarkin attack of MD. Thereafter we evaluated data from 952 patients collected with a questionnaire from the Finnish Ménière Association (FMA). The data contained case histories with special attention to Tumarkin attacks, participation restriction, migraines, and syncope attacks. The mean age of the subjects participating in the study was 60.6 years (range 25-75 years). The duration of the disease was on average 9.8 years (range 0.5-35 years). In the current study sample, attacks of syncope were reported by 38 patients (4%) in association with the vertigo attack. Syncope was associated with Tumarkin attacks (X 2 =16.7, p<0.001), migraine (X 2 =7.4, p<0.011), history of ischemic heart disease (X 2 =6.0, p<0.025), and history of cerebrovascular disease (X 2 =11.7, p<0.004). Duration of MD was correlated with syncope. Syncope was provoked by physical strain and environmental pressure, and was associated with impairment of the visual field (i.e., visual blurring). In logistic regression analysis, syncope was significantly associated with Tumarkin attacks (odds ratio 3.2), migraines (odds ratio 2.3) and nausea (odds ratio 1.3). The attack of syncope was experienced as frightening, and general health related quality of life (HRQoL) was significantly worsened. Also, the patients suffered more from fatigue. The current study indicates that patients with MD who suffer from Tumarkin attacks can suffer from syncope. It confirms the role of the otolith organ in controlling the circulatory homeostasis of the body. The actions are mediated through the vestibular sympathetic reflex. Copyright © 2017 Elsevier B.V. All rights reserved.

Usability testing of existing type 2 diabetes mellitus websites.

PubMed

Davis, Dorian; Jiang, Steven

2016-08-01

Given the significant increase in the use of the internet as an educational tool for diabetes, very little research has been published on the usability of healthcare websites, even though it is a determining factor for user satisfaction. The aim of this study is to evaluate and critique the interfaces of existing diabetes websites for usability concerns and provide design solutions for improvement. Emphasis is placed on Type 2 Diabetes Mellitus since it is the most common and life threatening form of diabetes. A usability test was performed on the interfaces of three existing diabetes websites, American Diabetes Association (www.diabetes.org), WebMD (www.webmd.com) and the National Diabetes Education Program (ndep.nih.gov). The goal was to collect qualitative and quantitative data to determine: (1) if participants are able to complete specified tasks successfully; (2) the length of time it takes participants to complete the specified tasks and; (3) participants' satisfaction with the three websites. Twenty adults, 18 years of age and older participated in the study. The results from the MANOVA test revealed a significant difference between the three websites for number of clicks, number of errors and completion time when analyzed simultaneously. The ANOVA tests revealed a significant difference for all three variables. The Student-Newman-Keuls (SNK) test shows a significant difference for completion time between American Diabetes Association and WebMD. A significant difference was found for the number of clicks for the National Diabetes Education Program compared to the American Diabetes Association and WebMD. However, no significant difference was found for the number of clicks between American Diabetes Association and WebMD. Lastly, a significant difference was found between each interface for number of errors. Although, the American Diabetes Association web-interface was most favorable, there were many positive design elements for each interface. On the other hand, the significant amount of information overload experienced for each website left participants feeling perplexed. Thus, innovative solutions are needed to reduce information overload and ensure users are engaged and empowered to make informed decisions about their healthcare. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

An apple MYB transcription factor, MdMYB3, is involved in regulation of anthocyanin biosynthesis and flower development

PubMed Central

2013-01-01

Background Red coloration of fruit is an important trait in apple, and it is mainly attributed to the accumulation of anthocyanins, a class of plant flavonoid metabolites. Anthocyanin biosynthesis is genetically determined by structural and regulatory genes. Plant tissue pigmentation patterns are mainly controlled by expression profiles of regulatory genes. Among these regulatory genes are MYB transcription factors (TFs), wherein the class of two-repeats (R2R3) is deemed the largest, and these are associated with the anthocyanin biosynthesis pathway. Although three MdMYB genes, almost identical in nucleotide sequences, have been identified in apple, it is likely that there are other R2R3 MYB TFs that are present in the apple genome that are also involved in the regulation of coloration of red color pigmentation of the skin of apple fruits. Results In this study, a novel R2R3 MYB gene has been isolated and characterized in apple. This MYB gene is closely related to the Arabidopsis thaliana AtMYB3, and has been designated as MdMYB3. This TF belongs to the subgroup 4 R2R3 family of plant MYB transcription factors. This apple MdMYB3 gene is mapped onto linkage group 15 of the integrated apple genetic map. Transcripts of MdMYB3 are detected in all analyzed tissues including leaves, flowers, and fruits. However, transcripts of MdMYB3 are higher in excocarp of red-skinned apple cultivars than that in yellowish-green skinned apple cultivars. When this gene is ectopically expressed in Nicotiana tabacum cv. Petite Havana SR1, flowers of transgenic tobacco lines carrying MdMYB3 have exhibited increased pigmentation and accumulate higher levels of anthocyanins and flavonols than wild-type flowers. Overexpression of MdMYB3 has resulted in transcriptional activation of several flavonoid pathway genes, including CHS, CHI, UFGT, and FLS. Moreover, peduncles of flowers and styles of pistils of transgenic plants overexpressing MdMYB3 are longer than those of wild-type plants, thus suggesting that this TF is involved in regulation of flower development. Conclusions This study has identified a novel MYB transcription factor in the apple genome. This TF, designated as MdMYB3, is involved in transcriptional activation of several flavonoid pathway genes. Moreover, this TF not only regulates the accumulation of anthocyanin in the skin of apple fruits, but it is also involved in the regulation of flower development, particularly that of pistil development. PMID:24199943

An apple MYB transcription factor, MdMYB3, is involved in regulation of anthocyanin biosynthesis and flower development.

PubMed

Vimolmangkang, Sornkanok; Han, Yuepeng; Wei, Guochao; Korban, Schuyler S

2013-11-07

Red coloration of fruit is an important trait in apple, and it is mainly attributed to the accumulation of anthocyanins, a class of plant flavonoid metabolites. Anthocyanin biosynthesis is genetically determined by structural and regulatory genes. Plant tissue pigmentation patterns are mainly controlled by expression profiles of regulatory genes. Among these regulatory genes are MYB transcription factors (TFs), wherein the class of two-repeats (R2R3) is deemed the largest, and these are associated with the anthocyanin biosynthesis pathway. Although three MdMYB genes, almost identical in nucleotide sequences, have been identified in apple, it is likely that there are other R2R3 MYB TFs that are present in the apple genome that are also involved in the regulation of coloration of red color pigmentation of the skin of apple fruits. In this study, a novel R2R3 MYB gene has been isolated and characterized in apple. This MYB gene is closely related to the Arabidopsis thaliana AtMYB3, and has been designated as MdMYB3. This TF belongs to the subgroup 4 R2R3 family of plant MYB transcription factors. This apple MdMYB3 gene is mapped onto linkage group 15 of the integrated apple genetic map. Transcripts of MdMYB3 are detected in all analyzed tissues including leaves, flowers, and fruits. However, transcripts of MdMYB3 are higher in excocarp of red-skinned apple cultivars than that in yellowish-green skinned apple cultivars. When this gene is ectopically expressed in Nicotiana tabacum cv. Petite Havana SR1, flowers of transgenic tobacco lines carrying MdMYB3 have exhibited increased pigmentation and accumulate higher levels of anthocyanins and flavonols than wild-type flowers. Overexpression of MdMYB3 has resulted in transcriptional activation of several flavonoid pathway genes, including CHS, CHI, UFGT, and FLS. Moreover, peduncles of flowers and styles of pistils of transgenic plants overexpressing MdMYB3 are longer than those of wild-type plants, thus suggesting that this TF is involved in regulation of flower development. This study has identified a novel MYB transcription factor in the apple genome. This TF, designated as MdMYB3, is involved in transcriptional activation of several flavonoid pathway genes. Moreover, this TF not only regulates the accumulation of anthocyanin in the skin of apple fruits, but it is also involved in the regulation of flower development, particularly that of pistil development.

Low-Calorie Vegetarian Versus Mediterranean Diets for Reducing Body Weight and Improving Cardiovascular Risk Profile: CARDIVEG Study (Cardiovascular Prevention With Vegetarian Diet).

PubMed

Sofi, Francesco; Dinu, Monica; Pagliai, Giuditta; Cesari, Francesca; Gori, Anna Maria; Sereni, Alice; Becatti, Matteo; Fiorillo, Claudia; Marcucci, Rossella; Casini, Alessandro

2018-03-13

Only a few randomized dietary intervention studies that investigated the effects of lacto-ovo vegetarian diet (Vd) in clinically healthy omnivorous subjects are available. We randomly assigned to overweight omnivores with a low-to-moderate cardiovascular risk profile a low-calorie Vd compared with a low-calorie Mediterranean diet (MD), each lasting 3 months, with a crossover design. The primary outcome was the difference in body weight, body mass index, and fat mass changes between the 2 groups. Secondary outcomes were differences in circulating cardiovascular disease risk parameters changes between the 2 groups. One hundred eighteen subjects (mean age: 51.1 years, females: 78%) were enrolled. The total participation rate at the end of the study was 84.7%. No differences between the 2 diets in body weight were observed, as reported by similar and significant reductions obtained by both Vd (-1.88 kg) and MD (-1.77 kg). Similar results were observed for body mass index and fat mass. In contrast, significant differences between the 2 interventions were obtained for low-density lipoprotein cholesterol, triglycerides, and vitamin B 12 levels. The difference between the Vd and MD groups, in terms of end-of-diet values, was recorded at 9.10 mg/dL for low-density lipoprotein cholesterol ( P =0.01), 12.70 mg/dL for triglycerides ( P <0.01), and 32.32 pg/mL for vitamin B 12 ( P <0.01). Finally, no significant difference was found between Vd and MD interventions in oxidative stress markers and inflammatory cytokines, except for interleukin-17, which improved only in the MD group. Forty-six participants during the Vd period and 35 during the MD period reached the target values for ≥1 cardiovascular risk factor. Both Vd and MD were effective in reducing body weight, body mass index, and fat mass, with no significant differences between them. However, Vd was more effective in reducing low-density lipoprotein cholesterol levels, whereas MD led to a greater reduction in triglyceride levels. URL: https://www.clinicaltrials.gov. Unique identifier: NCT02641834. © 2018 American Heart Association, Inc.

National Proceedings: Forest and Conservation Nusery Associations - 1998

Treesearch

T.D. Landis; J.P. Barnett; [Technical Coordinators

1999-01-01

This proceedings is a compilation of 43 papers that were presented at the 3 regional nursery meetings in 1998.The Southern Forest Nursery Association Conference was held in Lafayette, LA, on July 13-16; the Northeastern Forest Nursery Association Conference was held in Annapolis, MD, on July 27-30; and the Combined Forest Nursery Association of British Comumbia/Western...

Insights into the transmembrane helix associations of kit ligand by molecular dynamics simulation and TOXCAT.

PubMed

Chai, Mengya; Liu, Bo; Sun, Fude; Wei, Peng; Chen, Peng; Xu, Lida; Luo, Shi-Zhong

2017-07-01

Kit ligand (KITL) plays important roles in cell proliferation, differentiation, and survival via interaction with its receptor Kit. The previous studies demonstrated that KITL formed a noncovalent homodimer through transmembrane (TM) domain; however, the undergoing mechanism of transmembrane association that determines KITL TM dimerization is still not clear. Herein, molecular dynamics (MD) simulation strategy and TOXCAT assay were combined to characterize the dimerization interface and structure of KITL TM in details. KITL TM formed a more energetically favorable noncovalent dimer through a conserved SxxxGxxxG motif in the MD simulation. Furthermore, the TOXCAT results demonstrated that KITL TM self-associated strongly in the bilayer membrane environment. Mutating any one of the small residues Ser11, Gly15 or Gly19 to Ile disrupted KITL TM dimerization dramatically, which further validated our MD simulation results. In addition, our results showed that Tyr22 could help to stabilize the TM interactions via interacting with the phosphoric group in the bilayer membrane. Pro7 did not induce helix kinks or swivel angles in KITL TM, but it was related with the pitch of the turn around this residue so as to affect the dimer formation. Combining the results of computer modeling and experimental mutagenesis studies on the KITL TM provide new insights for the transmembrane helix association of KITL dimerization. Proteins 2017; 85:1362-1370. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Age at onset of first signs or symptoms predicts age at loss of ambulation in Duchenne and Becker Muscular Dystrophy: Data from the MD STARnet.

PubMed

Ciafaloni, Emma; Kumar, Anil; Liu, Ke; Pandya, Shree; Westfield, Christina; Fox, Deborah J; Caspers Conway, Kristin M; Cunniff, Christopher; Mathews, Katherine; West, Nancy; Romitti, Paul A; McDermott, Michael P

2016-01-01

We investigated the prognostic utility of onset age at first signs and symptoms (SS) to predict onset age at loss of ambulation (LOA) for childhood-onset Duchenne and Becker Muscular Dystrophies (DBMD). Our cohort comprised male cases with DBMD ascertained by the population-based Muscular Dystrophy Surveillance, Tracking, and Research Network (MD STARnet). Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards models for associations between onset ages of first SS and LOA. Covariates controlled for were corticosteroid use, family history of DBMD, birth year, race/ethnicity, and MD STARnet site. Onset age at first SS was considered as a continuous and as a categorical variable. A one-year increase in onset age at first SS was significantly associated with a 10% reduction in annual risk of LOA (HR = 0.90, CI = 0.87-0.94). Treating onset age at first SS as a categorical variable yielded a similar association (≥ 5 years: referent; ≥ 3 to < 5 years: HR = 1.36, CI = 1.02-1.81; 18 months to < 3 years: HR = 1.72, CI = 1.31-2.26; < 18 months: HR = 1.52, CI = 1.14-2.02). Earlier onset age at first SS is associated with earlier onset age at LOA and may have clinical utility in differentiating childhood-onset Duchenne and Becker muscular dystrophies.

Coagulopathy and Shock on Admission is Associated with Mortality for Children with Traumatic Injuries at Combat Support Hospitals

DTIC Science & Technology

2012-01-01

Charles E . Wade, PhD; Lorne H. Blackbourne, MD; Philip C. Spinella, MD Trauma remains one of the most common causes of death in all age groups...the U.S. Government. The authors have not disclosed any potential conflicts of interest. For information regarding this article, E -mail: Jpatregnani...ELEMENT NUMBER 6. AUTHOR(S) Patregnani J. T., Borgman M. A., Maegele M., Wade C. E ., Blackbourne L. H., Spinella P. C., 5d. PROJECT NUMBER 5e. TASK

Measles, Mumps, and Rubella - Vaccine Use and Strategies for Elimination of Measles, Rubella, and Congenital Rubella Syndrome and Control of Mumps: Recommendations of the Advisory Committee on Immunization Practices (ACIP). Vol. 47/No. RR-8.

DTIC Science & Technology

1998-05-22

America William P. Glezen, M.D. Houston, Texas Mexico’s Health Secretariat Roberto Tapia Conyer, M.D. MEXICO National Medical Association Walter...were similar in two groups, one of which was administered MMR and varicella vaccines simultaneously at separate sites and the other of which received... Varicella prophylaxis (VZIG) Measles prophylaxis (IG) - Standard (i.e., nonimmuno- compromised) contact - Immunocompromised contact Blood

Association of Posttraumatic Stress Disorder with Somatic Symptoms, Health Care Visits, and Absenteeism among Iraq War Veterans

DTIC Science & Technology

2007-01-01

Health Care Visits, and Absenteeism Among Iraq War Veterans Charles W. Hoge, M.D. Artin Terhakopian, M.D. Carl A. Castro, Ph.D. Stephen C. Messer, Ph.D...Disorder With Somatic Symptoms, Health Care Visits, and Absenteeism Among Iraq War Veterans 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT...NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER 5e. TASK NUMBER 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) Walter Reed Army

A Conversation Among the IAS-USA Board of Directors: Hot Topics and Emerging Data in HIV Research and Care.

PubMed

Benson, Constance A; Currier, Judith S; Del Rio, Carlos; Gallant, Joel E; Gulick, Roy M; Marrazzo, Jeanne M; Richman, Douglas D; Saag, Michael S; Schooley, Robert T; Volberding, Paul A

The IAS-USA volunteer Board of Directors met in October 2016 for its annual meeting. For the second year, the Board conducted a live, hour-long, interactive, roundtable webinar covering current questions and issues in HIV research, prevention, and care. Important highlights from the Board's discussion, which was moderated by Paul A. Volberding, MD, are included below. Members of the IAS-USA volunteer Board of Directors are Constance A. Benson, MD; Judith S. Currier, MD; Carlos del Rio, MD; Joel E. Gallant, MD, MPH; Roy M. Gulick, MD, MPH; Jeanne M. Marrazzo, MD, MPH; Douglas D. Richman, MD; Michael S. Saag, MD; Robert T. Schooley, MD; and Paul A. Volberding, MD.

7 CFR 94.4 - Analytical methods.

Code of Federal Regulations, 2010 CFR

2010-01-01

..., Gaithersburg, MD 20877-2417. (d) Manual of Analytical Methods for the Analysis of Pesticide Residues in Human... Splittstoesser (Editors), American Public Health Association, 1015 Fifteenth Street, NW, Washington, DC 20005. (b... Examination of Dairy Products, American Public Health Association, 1015 Fifteenth Street, NW, Washington, DC...

7 CFR 94.4 - Analytical methods.

Code of Federal Regulations, 2011 CFR

2011-01-01

..., Gaithersburg, MD 20877-2417. (d) Manual of Analytical Methods for the Analysis of Pesticide Residues in Human... Splittstoesser (Editors), American Public Health Association, 1015 Fifteenth Street, NW, Washington, DC 20005. (b... Examination of Dairy Products, American Public Health Association, 1015 Fifteenth Street, NW, Washington, DC...

7 CFR 94.4 - Analytical methods.

Code of Federal Regulations, 2012 CFR

2012-01-01

..., Gaithersburg, MD 20877-2417. (d) Manual of Analytical Methods for the Analysis of Pesticide Residues in Human... Splittstoesser (Editors), American Public Health Association, 1015 Fifteenth Street, NW, Washington, DC 20005. (b... Examination of Dairy Products, American Public Health Association, 1015 Fifteenth Street, NW, Washington, DC...

7 CFR 94.4 - Analytical methods.

Code of Federal Regulations, 2013 CFR

2013-01-01

..., Gaithersburg, MD 20877-2417. (d) Manual of Analytical Methods for the Analysis of Pesticide Residues in Human... Splittstoesser (Editors), American Public Health Association, 1015 Fifteenth Street, NW, Washington, DC 20005. (b... Examination of Dairy Products, American Public Health Association, 1015 Fifteenth Street, NW, Washington, DC...

Microplitis demolitor bracovirus genome segments vary in abundance and are individually packaged in virions

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

Beck, Markus H.; Inman, Ross B.; Strand, Michael R.

2007-03-01

Polydnaviruses (PDVs) are distinguished by their unique association with parasitoid wasps and their segmented, double-stranded (ds) DNA genomes that are non-equimolar in abundance. Relatively little is actually known, however, about genome packaging or segment abundance of these viruses. Here, we conducted electron microscopy (EM) and real-time polymerase chain reaction (PCR) studies to characterize packaging and segment abundance of Microplitis demolitor bracovirus (MdBV). Like other PDVs, MdBV replicates in the ovaries of females where virions accumulate to form a suspension called calyx fluid. Wasps then inject a quantity of calyx fluid when ovipositing into hosts. The MdBV genome consists of 15more » segments that range from 3.6 (segment A) to 34.3 kb (segment O). EM analysis indicated that MdBV virions contain a single nucleocapsid that encapsidates one circular DNA of variable size. We developed a semi-quantitative real-time PCR assay using SYBR Green I. This assay indicated that five (J, O, H, N and B) segments of the MdBV genome accounted for more than 60% of the viral DNAs in calyx fluid. Estimates of relative segment abundance using our real-time PCR assay were also very similar to DNA size distributions determined from micrographs. Analysis of parasitized Pseudoplusia includens larvae indicated that copy number of MdBV segments C, B and J varied between hosts but their relative abundance within a host was virtually identical to their abundance in calyx fluid. Among-tissue assays indicated that each viral segment was most abundant in hemocytes and least abundant in salivary glands. However, the relative abundance of each segment to one another was similar in all tissues. We also found no clear relationship between MdBV segment and transcript abundance in hemocytes and fat body.« less

Standardization of a model to study revaccination against Marek's disease under laboratory conditions.

PubMed

Gimeno, Isabel M; Witter, Richard L; Cortes, Aneg L; Reddy, Sanjay M; Pandiri, Arun R

2012-01-01

Revaccination, the practice of administering Marek's disease (MD) vaccine a second time, has been used in commercial poultry flocks for many years. The rationale is largely anecdotal as the few published reports have failed to provide support for the value of the practice. In the present work, we have standardized a model to study MD revaccination under laboratory conditions. Nine bird experiments were conducted to evaluate homologous revaccination (same vaccine administered twice) and heterologous revaccination (administration of two different vaccines) with various challenge models. Our results demonstrated that heterologous revaccination (with a second vaccine more protective than the first vaccine) but not homologous revaccination provided a beneficial increase in protection. Administration of the first vaccine at 18 days of embryonation followed by a more protective second vaccine at hatch reproduced systematically the benefits of revaccination. In addition, our results show that revaccination protocols might aid in solving major drawbacks associated with various highly protective experimental MD vaccines; that is, lymphoid organ atrophy and residual virulence. Strain RM1 is one of the most protective vaccines against early challenge with highly virulent MD virus but it induces severe lymphoid atrophy in chickens lacking maternal antibodies against MD virus. In this study, strain RM1 did not induce lymphoid organ atrophy when administered as second vaccine in a revaccination protocol. Similarly, strain 648A100/BP5 maintains residual virulence in chickens lacking maternal antibodies against MD virus but did not induce any lesions when used as a second vaccine. Until now, arbitrary revaccination protocols have been occasionally proven useful to the poultry industry. The model developed in this study will allow for a better understanding of this phenomenon and its optimization. A more rational use of this practice will be of great help to control MD outbreaks until better vaccines are available.

The effective mitigation of greenhouse gas emissions from rice paddies without compromising yield by early-season drainage.

PubMed

Islam, Syed Faiz-Ul; van Groenigen, Jan Willem; Jensen, Lars Stoumann; Sander, Bjoern Ole; de Neergaard, Andreas

2018-01-15

Global rice production systems face two opposing challenges: the need to increase production to accommodate the world's growing population while simultaneously reducing greenhouse gas (GHG) emissions. Adaptations to drainage regimes are one of the most promising options for methane mitigation in rice production. Whereas several studies have focused on mid-season drainage (MD) to mitigate GHG emissions, early-season drainage (ED) varying in timing and duration has not been extensively studied. However, such ED periods could potentially be very effective since initial available C levels (and thereby the potential for methanogenesis) can be very high in paddy systems with rice straw incorporation. This study tested the effectiveness of seven drainage regimes varying in their timing and duration (combinations of ED and MD) to mitigate CH 4 and N 2 O emissions in a 101-day growth chamber experiment. Emissions were considerably reduced by early-season drainage compared to both conventional continuous flooding (CF) and the MD drainage regime. The results suggest that ED+MD drainage may have the potential to reduce CH 4 emissions and yield-scaled GWP by 85-90% compared to CF and by 75-77% compared to MD only. A combination of (short or long) ED drainage and one MD drainage episode was found to be the most effective in mitigating CH 4 emissions without negatively affecting yield. In particular, compared with CF, the long early-season drainage treatments LE+SM and LE+LM significantly (p<0.01) decreased yield-scaled GWP by 85% and 87% respectively. This was associated with carbon being stabilised early in the season, thereby reducing available C for methanogenesis. Overall N 2 O emissions were small and not significantly affected by ED. It is concluded that ED+MD drainage might be an effective low-tech option for small-scale farmers to reduce GHG emissions and save water while maintaining yield. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Genome-Wide Identification and Expression Analysis of the Tubby-Like Protein Family in the Malus domestica Genome

PubMed Central

Xu, Jia-Ning; Xing, Shan-Shan; Zhang, Zheng-Rong; Chen, Xue-Sen; Wang, Xiao-Yun

2016-01-01

Tubby-like proteins (TLPs), which have a highly conserved β barrel tubby domain, have been found to be associated with some animal-specific characteristics. In the plant kingdom, more than 10 TLP family members were identified in Arabidopsis, rice and maize, and they were found to be involved in responses to stress. The publication of the apple genome makes it feasible to systematically study the TLP family in apple. In this investigation, nine TLP encoding genes (TLPs for short) were identified. When combined with the TLPs from other plant species, the TLPs were divided into three groups (group A, B, and C). Most plant TLP members in group A contained an additional F-box domain at the N-terminus. However, no common domain was identified other than tubby domain either in group B or in group C. An analysis of the tubby domains of MdTLPs identified three types of conserved motifs. Motif 1 and 2, the signature motifs in the confirmed TLPs, were always present in MdTLPs, while motif 3 was absent from group B. Homology modeling indicated that the tubby domain of most MdTLPs had a closed β barrel, as in animal tubby domains. Expression profiling revealed that the MdTLP genes were expressed in multiple organs and were abundant in roots, stems, and leaves but low in flowers. An analysis of cis-acting elements showed that elements related to the stress response were prevalent in the promoter sequences of MdTLPs. Expression profiling by qRT-PCR indicated that almost all MdTLPs were up-regulated at some extent under abiotic stress, exogenous ABA and H2O2 treatments in leaves and roots, though different MdTLP members exhibited differently in leaves and roots. The results and information above may provide a basis for further investigation of TLP function in plants. PMID:27895653

Food insecurity and Mediterranean diet adherence among Greek university students.

PubMed

Theodoridis, X; Grammatikopoulou, M G; Gkiouras, K; Papadopoulou, S E; Agorastou, T; Gkika, I; Maraki, M I; Dardavessis, T; Chourdakis, M

2018-05-01

To assess Mediterranean diet (MD) adherence and food insecurity (FI) among university students in Greece. A non-probability sample of 236 students was recruited from Athens and Thessaloniki during 2016. FI was assessed with the Household Food Insecurity Access Scale and MD adherence with the MEDAS questionnaire. Mean MEDAS score of the sample was 6.4 ± 1.9, with women demonstrating greater MD adherence compared to men (p = 0.016) and Dietetics students exhibiting increased score compared to the rest (p ≤ 0.001). A low proportion of participants were food-secure (17.8%), 45.3% were severely food-insecure, 22.0% experienced moderate FI and the remaining 14.8% had low FI. Participants studying in the city they grew up exhibited lower FI compared to those studying in other cities (p = 0.009), while, additionally, a trend was noted for increased FI among students with an unemployed family member (p = 0.05). Students working night shifts had lower MD adherence and increased FI compared to the rest (p = 0.004 and p = 0.003, respectively). The same pattern was observed among participants who smoked (p = 0.003 for MD adherence and p = 0.009 for FI, respectively). Multivariate regression analyses did not reveal any connections between FI categories, waist circumference or BMI, but showed an inverse relationship between severe FI and MD adherence. The majority of the surveyed university students from Greece demonstrate some degree of FI, with a great proportion being severely food-insecure. Increased FI is inversely associated with MD adherence. Copyright © 2018 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.

Attentional biases toward body images in males at high risk of muscle dysmorphia

PubMed Central

Jin, Xinhong; Zhou, Shi; Chang, Shuzhi; Li, Hui

2018-01-01

Objective Although research on muscle dysmorphia (MD), a body dysmorphic disorder subtype, has recently increased, the causes and mechanisms underlying this disorder remain unclear. Results from studies examining disorders associated with body image suggest the involvement of self-schema in biasing attention toward specific body information. The present study examined whether individuals at higher risk of MD also display attentional biases toward specific types of body images. Methods The validated Chinese version of the Muscle Appearance Satisfaction Scale was used to distinguish men at higher and lower risk of MD. Sixty-five adult Chinese men at higher (HRMD, n = 33) and lower risk of MD (LRMD, n = 32) performed a visual probe task. Initially, an image of a bodybuilder with either larger or smaller musculature was presented on one side of a central point, with a neutral image of a car exterior presented on the other side along the horizontal plane for 2,000 ms. The paired images were removed, and a visual target (a dot) was displayed in the location of one of the previously shown images. Participants were asked to indicate the location of the target, and their eye movements were recorded during the entire visual presentation. Participant reaction time and three eye movement measurements (gaze direction, first saccade latency, and first fixation duration) were recorded for use in determining attentional bias. Results The HRMD group revealed biases in orienting and maintaining their attention on images of bodybuilders with larger musculatures. Participants in this group consequently had a shorter reaction time in identifying the target that appeared at the location in which an image of a bodybuilder with a larger musculature had been previously displayed. They also directed their initial gaze more frequently, had shorter saccade latency, and had longer first fixation duration on images of bodybuilders with larger musculatures (all p < .0001). In comparison, the LRMD group had longer reaction times, slower attention orientation toward body images, and shorter fixation duration for images of bodybuilders with larger musculatures (all p < .0001), indicating weaker or mixed responses. Discussion Adult Chinese men at higher risk of MD displayed biases in orienting and maintaining their visual attention toward images of bodybuilders with larger musculatures, and these biases facilitated their information processing. These results suggest that development of MD may be due in part to attentional biases associated with established negative self-schema of specific body information. These findings provide insight into understanding and identifying the cognitive characteristics of MD in an Asian population. PMID:29362698

Attentional biases toward body images in males at high risk of muscle dysmorphia.

PubMed

Jin, Xinhong; Jin, Yahong; Zhou, Shi; Yang, Shun-Nan; Chang, Shuzhi; Li, Hui

2018-01-01

Although research on muscle dysmorphia (MD), a body dysmorphic disorder subtype, has recently increased, the causes and mechanisms underlying this disorder remain unclear. Results from studies examining disorders associated with body image suggest the involvement of self-schema in biasing attention toward specific body information. The present study examined whether individuals at higher risk of MD also display attentional biases toward specific types of body images. The validated Chinese version of the Muscle Appearance Satisfaction Scale was used to distinguish men at higher and lower risk of MD. Sixty-five adult Chinese men at higher (HRMD, n  = 33) and lower risk of MD (LRMD, n  = 32) performed a visual probe task. Initially, an image of a bodybuilder with either larger or smaller musculature was presented on one side of a central point, with a neutral image of a car exterior presented on the other side along the horizontal plane for 2,000 ms. The paired images were removed, and a visual target (a dot) was displayed in the location of one of the previously shown images. Participants were asked to indicate the location of the target, and their eye movements were recorded during the entire visual presentation. Participant reaction time and three eye movement measurements (gaze direction, first saccade latency, and first fixation duration) were recorded for use in determining attentional bias. The HRMD group revealed biases in orienting and maintaining their attention on images of bodybuilders with larger musculatures. Participants in this group consequently had a shorter reaction time in identifying the target that appeared at the location in which an image of a bodybuilder with a larger musculature had been previously displayed. They also directed their initial gaze more frequently, had shorter saccade latency, and had longer first fixation duration on images of bodybuilders with larger musculatures (all p  < .0001). In comparison, the LRMD group had longer reaction times, slower attention orientation toward body images, and shorter fixation duration for images of bodybuilders with larger musculatures (all p  < .0001), indicating weaker or mixed responses. Adult Chinese men at higher risk of MD displayed biases in orienting and maintaining their visual attention toward images of bodybuilders with larger musculatures, and these biases facilitated their information processing. These results suggest that development of MD may be due in part to attentional biases associated with established negative self-schema of specific body information. These findings provide insight into understanding and identifying the cognitive characteristics of MD in an Asian population.

A new THz/Far-IR beamline at the Jefferson Lab ERL

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

Neil, George; Williams, Gwyn

2003-08-01

Multiparticle coherent synchrotron emitted by sub-picosecond bunches of electrons in an energy recovering linac, (ERL), at 75 MHz, yield average powers of ~ 100 watts, even for beam currents of 10 mA.This is 10,000 times higher than typical table-top systems.We describe a new ERL facility under construction at Jefferson Lab, and a new THz extraction system and beamline.We also present theoretical calculations.Potential applications of this exciting new source include driving new non-linear phenomena, performing pump-probe studies of dynamical properties of novel materials, and studying molecular vibrations and rotations, low frequency protein motions, phonons, superconductor bandgaps, electronic scattering, collective electronic excitationsmore » (e.g., charge density waves), and spintronics.This work was supported by the US Department of Energy, the Office of Naval Research and the Commonwealth of Virginia.G.L. Carr, M.C. Martin, W.R. McKinney, K. Jordan, G.R. Neil and G.P. Wi« less

Magnetic field geometries of two slowly rotating Ap/Bp stars: HD 12288 and HD 14437

NASA Astrophysics Data System (ADS)

Wade, G. A.; Kudryavtsev, D.; Romanyuk, I. I.; Landstreet, J. D.; Mathys, G.

2000-03-01

In this paper we report magnetic field models and basic physical parameters for the slowly rotating Ap/Bp stars HD 12288 and HD 14437. Using new and previously published mean longitudinal magnetic field, mean magnetic field modulus, and hipparcos photometric measurements, we have inferred the rotational periods of both stars (HD 12288: P_rot=34.9d +/- 0.2d HD 14437: P_rot=26.87d +/- 0.02d). From the magnetic measurements we have determined the best-fit decentred magnetic dipole configurations. For HD 12288, we find that the field geometry is consistent with a centred dipole, while for HD 14437 a large decentring parameter (a=0.23 R_*) is inferred. Both stars show one angle in the ambiguous (i,beta ) couplet which is smaller than about 20degr . This is consistent with the observation of Landstreet & Mathys (2000), who point out that almost all magnetic Ap stars with periods longer than about 30 days exhibit magnetic fields aligned with their rotational axis.

Macular degeneration affects eye movement behavior during visual search.

PubMed

Van der Stigchel, Stefan; Bethlehem, Richard A I; Klein, Barrie P; Berendschot, Tos T J M; Nijboer, Tanja C W; Dumoulin, Serge O

2013-01-01

Patients with a scotoma in their central vision (e.g., due to macular degeneration, MD) commonly adopt a strategy to direct the eyes such that the image falls onto a peripheral location on the retina. This location is referred to as the preferred retinal locus (PRL). Although previous research has investigated the characteristics of this PRL, it is unclear whether eye movement metrics are modulated by peripheral viewing with a PRL as measured during a visual search paradigm. To this end, we tested four MD patients in a visual search paradigm and contrasted their performance with a healthy control group and a healthy control group performing the same experiment with a simulated scotoma. The experiment contained two conditions. In the first condition the target was an unfilled circle hidden among c-shaped distractors (serial condition) and in the second condition the target was a filled circle (pop-out condition). Saccadic search latencies for the MD group were significantly longer in both conditions compared to both control groups. Results of a subsequent experiment indicated that this difference between the MD and the control groups could not be explained by a difference in target selection sensitivity. Furthermore, search behavior of MD patients was associated with saccades with smaller amplitudes toward the scotoma, an increased intersaccadic interval and an increased number of eye movements necessary to locate the target. Some of these characteristics, such as the increased intersaccadic interval, were also observed in the simulation group, which indicate that these characteristics are related to the peripheral viewing itself. We suggest that the combination of the central scotoma and peripheral viewing can explain the altered search behavior and no behavioral evidence was found for a possible reorganization of the visual system associated with the use of a PRL. Thus the switch from a fovea-based to a PRL-based reference frame impairs search efficiency.

Anosognosia for cognitive and behavioral symptoms in Parkinson's disease with mild dementia and mild cognitive impairment: Frequency and neuropsychological/neuropsychiatric correlates.

PubMed

Orfei, Maria Donata; Assogna, Francesca; Pellicano, Clelia; Pontieri, Francesco Ernesto; Caltagirone, Carlo; Pierantozzi, Mariangela; Stefani, Alessandro; Spalletta, Gianfranco

2018-04-17

Anosognosia is a multidimensional phenomenon with detrimental effects on patients' illness course, therapy compliance and quality of life. We aimed at investigating anosognosia for cognitive and behavioral symptoms in Parkinson's Disease (PD) with dementia (PDD) and, for the first time, in PD with Mild Cognitive Impairment (MCI-PD). Community dwelling subjects (47 mild PDD, 136 multidomain MCI-PD (mdMCI-PD), 5 single domain MCI-PD (sdMCI-PD), and 197 PD without cognitive impairment (noCI-PD) were enrolled in a cross-sectional design study. All the subjects were administered the Anosognosia Questionnaire for Dementia, the Mental Deterioration Battery and a number of neuropsychiatric inventories. A diagnosis of anosognosia was made in 36% of patients with mild PDD and 16% with mdMCI-PD, whether it was negligible in sdMCI-PD and noCI-PD. Higher severity of anosognosia for cognitive impairment was also found in PDD and in mdMCI-PD. SdMCI-PD had the lower severity of anosognosia for cognitive impairment. Higher anosognosia for cognitive impairment was associated to lower depression in noCI-PD (r = -0.227, p = 0.0013) and mdMCI-PD (r = -0.266, p = 0.0016), and to reduced hedonic tone in noCI-PD (r = -0.191, p = 0.0071). Greater anosognosia was associated to lower executive performances in PDD (r = 0.424, p = 0.0074). Anosognosia for non-motor symptoms is frequent in PD patients with mild dementia or mdMCI. Results confirm the role of neuropsychiatric characteristics in anosognosia also in PD, the high prevalence of anosognosia in neurodegenerative illnesses and suggest a common pathogenic path for anosognosia in different neurodegenerative and psychiatric disorders. Copyright © 2018 Elsevier Ltd. All rights reserved.

Glaucoma Patient-Reported Concerns and Associated Factors.

PubMed

Mogil, Rachel S; Tirsi, Andrew; Lee, Jung Min; Tello, Celso; Park, Sung Chul

2017-06-01

To assess the character and degree of concerns of glaucoma patients and identify demographic/clinical factors affecting the concerns. Prospective cross-sectional study. A questionnaire that addressed patients' concerns was administered to consecutive glaucoma patients. Severity of concern was scored with a scale of 0-5 in order of increasing severity. Age, sex, intraocular pressure, visual field (VF) mean deviation (MD), number of antiglaucoma medications, history of glaucoma surgery, and employment status were recorded. Questionnaire results of 152 patients (mean VF MD, -8.03 ± 7.86 dB [better eye] and -16.06 ± 10.22 dB [worse eye]; mean age, 69 ± 14 years) were analyzed. Severity of concern was greatest for general eyesight (2.92/5.00) and visual symptoms (2.78/5.00), followed by activities (2.20/5.00) and socioeconomic factors (2.13/5.00), and then ocular symptoms (1.69/5.00) (P < .001). The most common concerns within each domain were blurry vision (32%), reading small print (34%), medical costs (26%), and dryness (32%). Concern about visual symptoms correlated with VF MD of the better eye (r = -0.258; P = .001) and worse eye (r = -0.233; P = .004). Concern about activities correlated with history of glaucoma surgery (r = 0.148; P = .023) and VF MD of the better eye (r = -0.284; P < .001) and worse eye (r = -0.295; P < .001). Concern about socioeconomic factors correlated with VF MD of the better eye (r = -0.245; P = .003) and age (r = -0.260; P = .001). Glaucoma patients reported varied degrees of concern regarding items associated with quality of life. Certain items may be more concerning than others. Severity of some concerns increased with more severe VF loss, prior glaucoma surgery, or younger age. Copyright © 2017 Elsevier Inc. All rights reserved.

Left atrial booster pump function is an independent predictor of subsequent life-threatening ventricular arrhythmias in non-ischaemic cardiomyopathy.

PubMed

Negishi, Kazuaki; Negishi, Tomoko; Zardkoohi, Omeed; Ching, Elizabeth A; Basu, Nivedita; Wilkoff, Bruce L; Popović, Zoran B; Marwick, Thomas H

2016-10-01

Left atrial (LA) function helps to preserve cardiac output and to control pulmonary capillary wedge pressure in the setting of left ventricular (LV) impairment, but little is known about the contribution of the LA function to ventricular arrhythmia. We sought whether LA booster pump function was associated with arrhythmias in patients undergoing primary prevention implantable cardioverter-defibrillator (ICD) implantation for non-ischaemic dilated cardiomyopathy (NICM), independent of global longitudinal strain (GLS) and mechanical dispersion (MD). We identified 124 NICM patients (56 ± 13, 67 male) who underwent echocardiography pre-ICD implantation for primary prevention. The main outcome measure was appropriate ICD therapy (anti-tachycardia pacing or shock). The mitral A-wave was used as an LA functional marker. MD was defined as standard deviation of time to peak strain of each segment. Over a median follow-up of 3.8 ± 2.2 years, 36 patients had appropriate ICD therapy, including 23 shocks. Patients with appropriate ICD therapy had lower A-wave velocity (P < 0.001), larger LA volume (P < 0.001), and impaired circumferential MD (P = 0.006), but similar ejection fraction (EF) (P = 0.40) and GLS (P = 0.11). In sequential Cox proportional hazards models, A-wave, E/A ratio, and GLS were significantly associated with outcomes, independent of age, sex, and cardiac resynchronization therapy defibrillator or left bundle branch block. In nested Cox models, mitral A-wave had a prognostic value incremental to models with LV systolic (EF and GLS) and diastolic functional parameters (E/A, E/e', and LA volume) and MD. LA booster pump function was an independent and incremental predictor of arrhythmias in NICM over GLS and MD, and may aid better risk stratification in this population. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Using DTI to assess white matter microstructure in cerebral small vessel disease (SVD) in multicentre studies

PubMed Central

Croall, Iain D.; Lohner, Valerie; Moynihan, Barry; Khan, Usman; Hassan, Ahamad; O’Brien, John T.; Morris, Robin G.; Tozer, Daniel J.; Cambridge, Victoria C.; Harkness, Kirsty; Werring, David J.; Blamire, Andrew M.; Ford, Gary A.; Barrick, Thomas R.

2017-01-01

Diffusion tensor imaging (DTI) metrics such as fractional anisotropy (FA) and mean diffusivity (MD) have been proposed as clinical trial markers of cerebral small vessel disease (SVD) due to their associations with outcomes such as cognition. However, studies investigating this have been predominantly single-centre. As clinical trials are likely to be multisite, further studies are required to determine whether associations with cognition of similar strengths can be detected in a multicentre setting. One hundred and nine patients (mean age =68 years) with symptomatic lacunar infarction and confluent white matter hyperintensities (WMH) on MRI was recruited across six sites as part of the PRESERVE DTI substudy. After handling missing data, 3T-MRI scanning was available from five sites on five scanner models (Siemens and Philips), alongside neuropsychological and quality of life (QoL) assessments. FA median and MD peak height were extracted from DTI histogram analysis. Multiple linear regressions were performed, including normalized brain volume, WMH lesion load, and n° lacunes as covariates, to investigate the association of FA and MD with cognition and QoL. DTI metrics from all white matter were significantly associated with global cognition (standardized β =0.268), mental flexibility (β =0.306), verbal fluency (β =0.376), and Montreal Cognitive Assessment (MoCA) (β =0.273). The magnitudes of these associations were comparable with those previously reported from single-centre studies found in a systematic literature review. In this multicentre study, we confirmed associations between DTI parameters and cognition, which were similar in strength to those found in previous single-centre studies. The present study supports the use of DTI metrics as biomarkers of disease progression in multicentre studies. PMID:28487471

Cushing syndrome due to adrenal tumor

MedlinePlus

... 7/2017 Updated by: Brent Wisse, MD, Associate Professor of Medicine, Division of Metabolism, Endocrinology & Nutrition, University of Washington School of Medicine, Seattle, WA. Also reviewed by David ...

Apple (Malus domestica) MdERF2 negatively affects ethylene biosynthesis during fruit ripening by suppressing MdACS1 transcription.

PubMed

Li, Tong; Jiang, Zhongyu; Zhang, Lichao; Tan, Dongmei; Wei, Yun; Yuan, Hui; Li, Tianlai; Wang, Aide

2016-12-01

Ripening in climacteric fruit requires the gaseous phytohormone ethylene. Although ethylene signaling has been well studied, knowledge of the transcriptional regulation of ethylene biosynthesis is still limited. Here we show that an apple (Malus domestica) ethylene response factor, MdERF2, negatively affects ethylene biosynthesis and fruit ripening by suppressing the transcription of MdACS1, a gene that is critical for biosynthesis of ripening-related ethylene. Expression of MdERF2 was suppressed by ethylene during ripening of apple fruit, and we observed that MdERF2 bound to the promoter of MdACS1 and directly suppressed its transcription. Moreover, MdERF2 suppressed the activity of the promoter of MdERF3, a transcription factor that we found to bind to the MdACS1 promoter, thereby increasing MdACS1 transcription. We determined that the MdERF2 and MdERF3 proteins directly interact, and this interaction suppresses the binding of MdERF3 to the MdACS1 promoter. Moreover, apple fruit with transiently downregulated MdERF2 expression showed higher ethylene production and faster ripening. Our results indicate that MdERF2 negatively affects ethylene biosynthesis and fruit ripening in apple by suppressing the transcription of MdACS1 via multiple mechanisms, thereby acting as an antagonist of positive ripening regulators. Our findings offer a deep understanding of the transcriptional regulation of ethylene biosynthesis during climacteric fruit ripening. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

Evaluation of Ochratoxin Recognition by Peptides Using Explicit Solvent Molecular Dynamics

PubMed Central

Thyparambil, Aby A.; Bazin, Ingrid; Guiseppi-Elie, Anthony

2017-01-01

Biosensing platforms based on peptide recognition provide a cost-effective and stable alternative to antibody-based capture and discrimination of ochratoxin-A (OTA) vs. ochratoxin-B (OTB) in monitoring bioassays. Attempts to engineer peptides with improved recognition efficacy require thorough structural and thermodynamic characterization of the binding-competent conformations. Classical molecular dynamics (MD) approaches alone do not provide a thorough assessment of a peptide’s recognition efficacy. In this study, in-solution binding properties of four different peptides, a hexamer (SNLHPK), an octamer (CSIVEDGK), NFO4 (VYMNRKYYKCCK), and a 13-mer (GPAGIDGPAGIRC), which were previously generated for OTA-specific recognition, were evaluated using an advanced MD simulation approach involving accelerated configurational search and predictive modeling. Peptide configurations relevant to ochratoxin binding were initially generated using biased exchange metadynamics and the dynamic properties associated with the in-solution peptide–ochratoxin binding were derived from Markov State Models. Among the various peptides, NFO4 shows superior in-solution OTA sensing and also shows superior selectivity for OTA vs. OTB due to the lower penalty associated with solvating its bound complex. Advanced MD approaches provide structural and energetic insights critical to the hapten-specific recognition to aid the engineering of peptides with better sensing efficacies. PMID:28505090

Quantitative Susceptibility Mapping Reveals an Association between Brain Iron Load and Depression Severity

PubMed Central

Yao, Shun; Zhong, Yi; Xu, Yuhao; Qin, Jiasheng; Zhang, Ningning; Zhu, Xiaolan; Li, Yuefeng

2017-01-01

Previous studies have detected abnormal serum ferritin levels in patients with depression; however, the results have been inconsistent. This study used quantitative susceptibility mapping (QSM) for the first time to examine brain iron concentration in depressed patients and evaluated whether it is related to severity. We included three groups of age- and gender-matched participants: 30 patients with mild-moderate depression (MD), 14 patients with major depression disorder (MDD) and 20 control subjects. All participants underwent MR scans with a 3D gradient-echo sequence reconstructing for QSM and performed the 17-item Hamilton Depression Rating Scale (HDRS) test. In MDD, the susceptibility value in the bilateral putamen was significantly increased compared with MD or control subjects. In addition, a significant difference was also observed in the left thalamus in MDD patients compared with controls. However, the susceptibility values did not differ between MD patients and controls. The susceptibility values positively correlated with the severity of depression as indicated by the HDRS scores. Our results provide evidence that brain iron deposition may be associated with depression and may even be a biomarker for investigating the pathophysiological mechanism of depression. PMID:28900391

Ticagrelor vs prasugrel one-month maintenance therapy: impact on platelet reactivity and bleeding events.

PubMed

Alexopoulos, D; Stavrou, K; Koniari, I; Gkizas, V; Perperis, A; Kontoprias, K; Vogiatzi, C; Bampouri, T; Xanthopoulou, I

2014-09-02

Platelet reactivity (PR) and bleeding events following therapy with ticagrelor vs prasugrel have not been adequately studied. We aimed to compare PR and bleeding events in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) while on ticagrelor vs prasugrel for one month. Consecutive patients who were discharged either on ticagrelor 90 mg bid maintenance dose (MD) or prasugrel 10 mg MD were invited for PR assessment (VerifyNow, in PRU) at one month. High PR (HPR) was defined as >208 PRU. Bleeding events [Bleeding Academic Research Consortium (BARC) classification] were monitored. Out of 937 screened patients, 512 were analysed, 278 under ticagrelor MD and 234 under prasugrel MD. PR at 30 days (C-statistic of the propensity score model 0.63, 0.58-0.67 95% CI, p<0.001) was lower when on ticagrelor compared with prasugrel (33.3, 95% CI 29.3-37.3 vs 84.6, 95% CI 73.6-95.6, p<0.001). In the analysed population more BARC type 1 bleeding events were observed with ticagrelor compared to prasugrel (36.7% vs 28.2%, p=0.047). In 221 propensity score matched pairs, BARC type 1 bleeding rate was marginally higher in ticagrelor vs prasugrel treated patients (35.7% vs 27.1%, p=0.05). BARC type ≥2 events did not differ between groups 5 (2.3%) vs 5 (2.3%). HPR rate was higher for prasugrel-treated patients (5.4% vs 0%, p<0.001). In conclusion, in patients with ACS undergoing PCI, ticagrelor MD produces a significantly higher platelet inhibition compared to prasugrel MD. This pharmacodynamic difference might be associated with more nuisance bleeding events with ticagrelor use.

Study of conjunctival flora in anophthalmic patients: influence on the comfort of the socket.

PubMed

Toribio, Alvaro; Marrodán, Teresa; Fernández-Natal, Isabel; Martínez-Blanco, Honorina; Rodríguez-Aparicio, Leandro; Ferrero, Miguel Á

2017-08-01

To investigate the relationship between conjunctival flora and comfort of the socket in anophthalmic patients. A cross-sectional clinical study including 60 patients with unilateral anophthalmia who wear a prosthetic eye. From each patient three microbiological samples were taken from the lower conjunctival sac (healthy eye, pre-prosthesis, and retro-prosthesis space of socket). The 180 samples obtained were cultured. Samples from a randomized subgroup of 29 patients were measured by spectrophotometry at 540 nm after 48 h of growth, to determine their microbial density (MD). The grade of comfort of the socket (GCS) of each patient was established by a questionnaire. Epidemiological and clinical data of the anophthalmic socket and artificial eye care of each patient were also collected. MD decreased in healthy eyes (0.213 ± 0.201, P = 0.004) compared with the pre-prosthesis (0.402 ± 0.323) and retro-prosthesis (0.438 ± 0.268) samples. Pre-prosthesis MD correlated with retro-prosthesis MD (R = 0.401, P = 0.031) and healthy eye MD (R = 0.482, P = 0.008), and it was also related to poor GCS (P = 0.017). Aerobic Gram-negative bacteria in retro-prosthesis samples of patients with poor GCS was higher than in patients with good or fair GCS (P = 0.008). In the same samples, coagulase-negative staphylococci proportion (excluding S. epidermidis) increased in patients with good GCS (P = 0.030). Socket microflora is related to GCS. Increased pathogenic flora, especially Gram-negative bacteria, and high MD are related to discomfort, while coagulase-negative staphylococci (other than S. epidermidis) are associated with comfort.

Drosophila Nociceptors Mediate Larval Aversion to Dry Surface Environments Utilizing Both the Painless TRP Channel and the DEG/ENaC Subunit, PPK1

PubMed Central

Johnson, Wayne A.; Carder, Justin W.

2012-01-01

A subset of sensory neurons embedded within the Drosophila larval body wall have been characterized as high-threshold polymodal nociceptors capable of responding to noxious heat and noxious mechanical stimulation. They are also sensitized by UV-induced tissue damage leading to both thermal hyperalgesia and allodynia very similar to that observed in vertebrate nociceptors. We show that the class IV multiple-dendritic(mdIV) nociceptors are also required for a normal larval aversion to locomotion on to a dry surface environment. Drosophila melanogaster larvae are acutely susceptible to desiccation displaying a strong aversion to locomotion on dry surfaces severely limiting the distance of movement away from a moist food source. Transgenic inactivation of mdIV nociceptor neurons resulted in larvae moving inappropriately into regions of low humidity at the top of the vial reflected as an increased overall pupation height and larval desiccation. This larval lethal desiccation phenotype was not observed in wild-type controls and was completely suppressed by growth in conditions of high humidity. Transgenic hyperactivation of mdIV nociceptors caused a reciprocal hypersensitivity to dry surfaces resulting in drastically decreased pupation height but did not induce the writhing nocifensive response previously associated with mdIV nociceptor activation by noxious heat or harsh mechanical stimuli. Larvae carrying mutations in either the Drosophila TRP channel, Painless, or the degenerin/epithelial sodium channel subunit Pickpocket1(PPK1), both expressed in mdIV nociceptors, showed the same inappropriate increased pupation height and lethal desiccation observed with mdIV nociceptor inactivation. Larval aversion to dry surfaces appears to utilize the same or overlapping sensory transduction pathways activated by noxious heat and harsh mechanical stimulation but with strikingly different sensitivities and disparate physiological responses. PMID:22403719

Advertising of medical devices: foreign experience and Ukrainian practice.

PubMed

Pashkov, Vitalii; Harkusha, Andrii; Bytiak, Oleksii

Chosen European foreign policy vector for Ukraine establishes its obligation to enforce the process of adaptation of the EU law regulations in the internal legal policy. The approximation of Ukrainian law to the European Union (EU) "acquis communautaire" is not only the instrument for deepening our economic cooperation with the European Union, but also the important measure to enhance further development of Ukraine in general. National legislation, which regulate advertising and promotion of medical devices (MD), is not an exception. Some key points on legal regulation of abovementioned sphere is a base of this study. Ukrainian legislation, European Union`s Law Acts, EU's member-states law, WHO Acts and Recommendations, European Medical Technology Industry Association (EUCOMED) Acts. Article is based on dialectical, comparative, analytic, synthetic and comprehensive research methods. In accordance with Ukrainian legislation, there is no special law that concerns advertising on MD in Ukraine, this sphere is regulated by general law that named ≪About advertisement≫, but it doesn't take into account even main characteristics of such a special object as medical devices (MD). Moreover, the law ≪About advertisement≫ contain discrepancies in terms that are used, these contradictions, in our opinion, must be eliminated by appropriate law reforms. The advertising and promotion of MD in EU is regulated by a combination of EU and national legislation of EU Member States, national advertising and promotion of MD are not harmonized with the EU MDD for now, resulting in a fragmented legal landscape that differs from one EU Member State to the other. Practice of adopting different codes and guides that regulate advertising, including advertising of MD, is widespread in EU and EU Member States and thus must be used in Ukraine with appropriate reformation of national law.