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Obesity and prostate cancer-specific mortality after radical prostatectomy: results from the Shared Equal Access Regional Cancer Hospital (SEARCH) database.
BackgroundAt the population level, obesity is associated with prostate cancer (PC) mortality. However, few studies analyzed the associations between obesity and long-term PC-specific outcomes after initial treatment.MethodsWe conducted a retrospective analysis of 4268 radical prostatectomy patients within the Shared Equal Access Regional Cancer Hospital (SEARCH) database. Cox models accounting for known risk factors were used to examine the associations between body mass index (BMI) and PC-specific mortality (PCSM; primary outcome). Secondary outcomes included biochemical recurrence (BCR) and castration-resistant PC (CRPC). BMI was used as a continuous and categorical variable (normal <25 kg/m2, overweight 25-29.9 kg/m2 and obese ⩾30 kg/m2). Median follow-up among all men who were alive at last follow-up was 6.8 years (interquartile range=3.5-11.0). During this time, 1384 men developed BCR, 117 developed CRPC and 84 died from PC. Hazard ratios were analyzed using competing-risks regression analysis accounting for non-PC death as a competing risk.ResultsOn crude analysis, higher BMI was not associated with risk of PCSM (P=0.112), BCR (0.259) and CRPC (P=0.277). However, when BMI was categorized, overweight (hazard ratio (HR) 1.99, P=0.034) and obesity (HR 1.97, P=0.048) were significantly associated with PCSM. Obesity and overweight were not associated with BCR or CRPC (all P⩾0.189). On multivariable analysis adjusting for both clinical and pathological features, results were little changed in that obesity (HR=2.05, P=0.039) and overweight (HR=1.88, P=0.061) were associated with higher risk of PCSM, but not with BCR or CRPC (all P⩾0.114) with the exception that the association for overweight was no longer statistical significant.ConclusionsOverweight and obesity were associated with increased risk of PCSM after radical prostatectomy. If validated in larger studies with longer follow-up, obesity may be established as a potentially modifiable risk factor for PCSM
Lowered cameras reveal hidden behaviors of Antarctic krill
Antarctic krill (Euphausia superba, hereafter ‘krill’) exemplify the methodological challenges of studying small, mobile, aggregating pelagic organisms.1 Krill are a central species in the Southern Ocean food web, provide important biogeochemical functions and support a valuable commercial fishery.2 Most of what we know about krill has been derived from acoustic surveys and net samples, the former being essential for estimating krill biomass and catch limits. However, understanding krill behavior, particularly in the poorly-studied autumn–winter seasons, is key for management and conservation. Here, we used seasonal video observations collected with a profiling camera system of krill along the Western Antarctic Peninsula to reveal krill vertical distribution, aggregation density and individual behaviors that have remained hidden from traditional sampling methods.
Erosion of Trust in the Medical Profession in India : Time for Doctors to Act
In India, over the last decade, a series of stewardship failures in the health system, particularly in the medical profession, have led to a massive erosion of trust in these institutions. In many low- and middle-income countries (LMICs), the situation is similar and has reached crisis proportions; this crisis requires urgent attention. This paper draws on the insights from the recent developments in India, to argue that a purely control-based regulatory response to this crisis in the medical profession, as is being currently envisaged by the Parliament and the Supreme Court of India, runs the risk of undermining the trusting interpersonal relations between doctors and their patients. A more balanced approach which takes into account the differences between system and interpersonal forms of trust and distrust is warranted. Such an approach should on one hand strongly regulate the institutions mandated with the stewardship and qualities of care functions, and simultaneously on the other hand, initiate measures to nurture the trusting interpersonal relations between doctors and patients. The paper concludes by calling for doctors, and those mandated with the stewardship of the profession, to individually and collectively, critically self-reflect upon the state of their profession, its priorities and its future direction
Lipidomics Reveals Early Metabolic Changes in Subjects with Schizophrenia: Effects of Atypical Antipsychotics
There is a critical need for mapping early metabolic changes in schizophrenia to capture failures in regulation of biochemical pathways and networks. This information could provide valuable insights about disease mechanisms, trajectory of disease progression, and diagnostic biomarkers. We used a lipidomics platform to measure individual lipid species in 20 drug-naïve patients with a first episode of schizophrenia (FE group), 20 patients with chronic schizophrenia that had not adhered to prescribed medications (RE group), and 29 race-matched control subjects without schizophrenia. Lipid metabolic profiles were evaluated and compared between study groups and within groups before and after treatment with atypical antipsychotics, risperidone and aripiprazole. Finally, we mapped lipid profiles to n3 and n6 fatty acid synthesis pathways to elucidate which enzymes might be affected by disease and treatment. Compared to controls, the FE group showed significant down-regulation of several n3 polyunsaturated fatty acids (PUFAs), including 20:5n3, 22:5n3, and 22:6n3 within the phosphatidylcholine and phosphatidylethanolamine lipid classes. Differences between FE and controls were only observed in the n3 class PUFAs; no differences where noted in n6 class PUFAs. The RE group was not significantly different from controls, although some compositional differences within PUFAs were noted. Drug treatment was able to correct the aberrant PUFA levels noted in FE patients, but changes in re patients were not corrective. Treatment caused increases in both n3 and n6 class lipids. These results supported the hypothesis that phospholipid n3 fatty acid deficits are present early in the course of schizophrenia and tend not to persist throughout its course. These changes in lipid metabolism could indicate a metabolic vulnerability in patients with schizophrenia that occurs early in development of the disease. © 2013 McEvoy et al
Determination of Vitamin A and its Metabolites in Rat Testis: Possible Involvement of Vitamin A in Testicular Toxicity Caused by Molinate
This study was conducted to evaluate the effect of molinate on retinoids homeostasis in rat testis. Molinate was administrated to male Sprague–Dawley rats (200 mg kg−1 in corn oil, ip). Retinoid measurements were made at 6, 12, 48 and 168 h time points after administration. Testis levels of retinoic acid decreased (32 %) in a statistically significant manner at the 12 and 48 h time points. However, retinol and retinaldehyde were not significantly affected by molinate. These results suggest that molinate affects retinoic acid synthesis in testis and could contribute to understanding the molecular mechanism of molinate involved testicular toxicity
Measuring care of the elderly: psychometric testing and modification of the Time in Care instrument for measurement of care needs in nursing homes
<p>Abstract</p> <p>Background</p> <p>Aging entails not only a decrease in the ability to be active, but also a trend toward increased dependence to sustain basic life functions. An important aspect for appropriately elucidating the individual's care needs is the ability to measure them both simply and reliably. Since 2006 a new version of the Time in Care needs (TIC-n) instrument (19-item version) has been explored and used in one additional municipality with the same structure as the one described in an earlier study.</p> <p>Methods</p> <p>The TIC-n assessment was conducted on a total of 1282 care recipients. Factor analysis (principal component) was applied to explore the construct validity of the TIC-n. Cronbach's alpha was calculated to test reliability and for each of the items remaining in the instrument after factor analysis, an inter-rater comparison was carried out on all recipients in both municipalities. Independently of each other, a weighted Kappa (K<sub>w</sub>) was calculated. Results. The mean of each weighted Kappa (K<sub>w</sub>) for the dimensions in the two municipalities was 0.75 and 0.76, respectively. Factor analysis showed that all 19 items had a factor loading of ≥ 0.40. Three factors (General Care, Medical Care and Cognitive Care) were created.</p> <p>Conclusion</p> <p>The TIC-n instrument has now been tested for validity and reliability in two municipalities with satisfactory results. However, TIC-n can not yet be used as a golden standard, but it can be recommended for use of measurement of individual care needs in municipal elderly care.</p
Midgut microbiota of the malaria mosquito vector Anopheles gambiae and Interactions with plasmodium falciparum Infection
The susceptibility of Anopheles mosquitoes to Plasmodium infections relies on complex interactions between the insect vector and the malaria parasite. A number of studies have shown that the mosquito innate immune responses play an important role in controlling the malaria infection and that the strength of parasite clearance is under genetic control, but little is known about the influence of environmental factors on the transmission success. We present here evidence that the composition of the vector gut microbiota is one of the major components that determine the outcome of mosquito infections. A. gambiae mosquitoes collected in natural breeding sites from Cameroon were experimentally challenged with a wild P. falciparum isolate, and their gut bacterial content was submitted for pyrosequencing analysis. The meta-taxogenomic approach revealed a broader richness of the midgut bacterial flora than previously described. Unexpectedly, the majority of bacterial species were found in only a small proportion of mosquitoes, and only 20 genera were shared by 80% of individuals. We show that observed differences in gut bacterial flora of adult mosquitoes is a result of breeding in distinct sites, suggesting that the native aquatic source where larvae were grown determines the composition of the midgut microbiota. Importantly, the abundance of Enterobacteriaceae in the mosquito midgut correlates significantly with the Plasmodium infection status. This striking relationship highlights the role of natural gut environment in parasite transmission. Deciphering microbe-pathogen interactions offers new perspectives to control disease transmission.Institut de Recherche pour le Developpement (IRD); French Agence Nationale pour la Recherche [ANR-11-BSV7-009-01]; European Community [242095, 223601]info:eu-repo/semantics/publishedVersio
Individual working memory capacity is uniquely correlated with feature-based attention when combined with spatial attention
A growing literature suggests that working memory and attention are closely related constructs. Both involve the selection of task-relevant information, and both are characterized by capacity limits. Furthermore, studies using a variety of methodological approaches have demonstrated convergent working memory and attention-related processing at the individual, neural and behavioral level. Given the varieties of both constructs, the specific kinds of attention and WM must be considered. We find that individuals’ working memory capacity (WMC) uniquely interacts with feature-based attention when combined with spatial attention in a cuing paradigm (Posner, 1980). Our findings suggest a positive correlation between WM and feature-based attention only within the spotlight of spatial attention. This finding lends support to the controlled attention view of working memory by demonstrating that integrated feature-based expectancies are uniquely correlated with individual performance on a working memory task
Adjunctive long-acting risperidone in patients with bipolar disorder who relapse frequently and have active mood symptoms
<p>Abstract</p> <p>Background</p> <p>The objective of this exploratory analysis was to characterize efficacy and onset of action of a 3-month treatment period with risperidone long-acting injection (RLAI), adjunctive to an individual's treatment regimen, in subjects with symptomatic bipolar disorder who relapsed frequently and had significant symptoms of mania and/or depression.</p> <p>Methods</p> <p>Subjects with bipolar disorder with ≥4 mood episodes in the past 12 months entered the open-label stabilization phase preceding a placebo-controlled, double-blind study. Subjects with significant depressive or manic/mixed symptoms at baseline were analyzed. Significant depressive symptoms were defined as Montgomery-Åsberg Depression Rating Scale (MADRS) ≥16 and Young Mania Rating Scale (YMRS) < 16; manic/mixed symptoms were YMRS ≥16 with any MADRS score. Subjects received open-label RLAI (25-50 mg every 2 weeks) for 16 weeks, adjunctive to a subject's individualized treatment for bipolar disorder (mood stabilizers, antidepressants, and/or anxiolytics). Clinical status was evaluated with the Clinical Global Impressions of Bipolar Disorder-Severity (CGI-BP-S) scale and changes on the MADRS and YMRS scales. Within-group changes were evaluated using paired <it>t </it>tests; categorical differences were assessed using Fisher exact test. No adjustment was made for multiplicity.</p> <p>Results</p> <p>162 subjects who relapsed frequently met criteria for significant mood symptoms at open-label baseline; 59/162 (36.4%) had depressive symptoms, 103/162 (63.6%) had manic/mixed symptoms. Most subjects (89.5%) were receiving ≥1 medication for bipolar disorder before enrollment. Significant improvements were observed for the total population on the CGI-BP-S, MADRS, and YMRS scales (p < .001 vs. baseline, all variables). Eighty-two (53.3%) subjects achieved remission at the week 16 LOCF end point. The subpopulation with depressive symptoms at open-label baseline experienced significant improvement on the CGI-BP-S and MADRS scales (p < .001 vs. baseline, all variables). Subjects with manic/mixed symptoms at baseline had significant improvements on the CGI-BP-S and YMRS scales (p < .001 vs. baseline, all variables). No unexpected tolerability findings were observed.</p> <p>Conclusions</p> <p>Exploratory analysis of changes in overall clinical status and depression/mania symptoms in subjects with symptomatic bipolar disorder who relapse frequently showed improvements in each of these areas after treatment with RLAI, adjunctive to a subject's individualized treatment. Prospective controlled studies are needed to confirm these findings.</p
A survey of primary care physician practices in antibiotic prescribing for the treatment of uncomplicated male gonoccocal urethritis
<p>Abstract</p> <p>Background</p> <p>The development of resistance to antimicrobial therapy by <it>Neisseria gonorrhoeae </it>causes on-going problems for individual case management of gonorrhoea. Surveillance data about <it>N. gonorrhoeae </it>have indicated an increase in the incidence of gonorrhoea in France in 2006. As a consequence of the development of antibiotic resistance in <it>N. gonorrhoeae</it>, French guidelines excluded fluoroquinolones as a standard treatment for <it>N. gonorrhoeae</it>. Ceftriaxone became the recommended treatment, associated with azithromycin for <it>Clamydia trachomatis </it>infection. Our aim was to describe the practice patterns of general practitioners (GPs) in managing the antibiotic treatment of patients with symptoms suggestive of uncomplicated male urethritis.</p> <p>Methods</p> <p>We developed a clinical vignette describing a man with typical gonococcal urethritis symptoms to elicit questions about antibiotic treatment. We mailed the electronic questionnaire to a random sample of 1000 French GPs belonging to the <it>Sentinelles </it>Network.</p> <p>Results</p> <p>By the end of the survey period, 350 vignettes were received, yielding a response rate of 35%. Sixty-six GPs (20.2%) prescribed the recommended antibiotics for the simultaneous treatment of <it>N</it>. <it>gonorrhoeae </it>and <it>C. trachomatis </it>infections, while 132 GPs (40.4%) prescribed only non-recommended antibiotics, including ciprofloxacin in 69 cases (21.1%). General practitioners with less than 10 years in practice showed better compliance to guidelines than those with more years in practice (p < 0.05).</p> <p>Conclusions</p> <p>The results suggest a mismatch between the guidelines and the antibiotic treatment of male uncomplicated urethritis by French GPs, mostly among the subgroup of physicians who have been in practice longer. Educational approaches based on practice feedback need to be developed to improve these deficits in the quality of care.</p
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