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Retrospective age-of-onset and projected lifetime prevalence of psychiatric disorders among U.S. Army National Guard soldiers. - Journal of affective disorders
The study of military-related mental health has been disproportionately focused on current symptomology rather than potentially more informative life course mental health. Indeed, no study has assessed age-of-onset and projected lifetime prevalence of disorders among reservists.Age-of-onset and projected lifetime DSM-IV anxiety, mood, and substance use disorders were assessed in 671 Ohio Army National Guard soldiers aged 17-60 years. Between 2008 and 2012, face-to-face clinical assessments and surveys were conducted using the Structured Clinical Interview for DSM-IV and Clinician-Administered PTSD Scale.Lifetime prevalence of psychiatric disorders was 61%. Alcohol abuse/dependence (44%) and major depressive disorder (23%) were the most common disorders. The majority (64%) of participants reported disorders antedating enlistment. Median age-of-onset varied with anxiety disorders - particularly phobias and OCD - having the earliest (median=15 years) and mood disorders the latest median age-of-onset (median=21 years).The study was limited by both the retrospective investigation of age-of-onset and the location of our sample. As our sample may not represent the general military population, our findings need to be confirmed in additional samples.Each psychiatric disorder exhibited a distinct age-of-onset pattern, such that phobias and OCD onset earliest, substance use disorders onset during a short interval from late-adolescence to early-adulthood, and mood disorders onset the latest. Our finding that the majority of participants reported disorders antedating enlistment suggests that an assessment of lifetime psychopathology is essential to understanding the mental health burden of both current and former military personnel.Copyright Â© 2016 Elsevier B.V. All rights reserved.
CRISPR screens provide a comprehensive assessment of cancer vulnerabilities but generate false-positive hits for highly amplified genomic regions. - Cancer discovery
CRISPR/Cas9 has emerged as a powerful new tool to systematically probe gene function. In this study, we compare the performance of CRISPR to RNAi-based loss-of-function screens for the identification of cancer dependencies by performing parallel deep-coverage shRNA and CRISPR screens targeting 2722 genes across several cancer cell lines. CRISPR-based dropout screens identified more lethal genes compared to RNAi in all five cancer models, indicating that the identification of many cellular dependencies may require full gene inactivation, as induced by CRISPR but not RNAi. However, in two aneuploid cancer models we found that all genes within highly amplified regions, including non-expressed genes, scored as lethal by CRISPR, revealing an unanticipated class of false-positive hits in CRISPR-based screens. Using a CRISPR tiling array that encompassed all possible sgRNAs against the coding regions of 139 genes, we found that sgRNAs targeting essential domains provide the most robust dropout phenotypes, suggesting that this approach might be used to define the protein domains that are required for cancer dependence. Collectively, these findings demonstrate the utility of CRISPR-based screens in the identification of cancer-dependent genes, but also reveal the need to carefully control for false-positive results especially in chromosomally unstable cancer lines.Copyright Â©2016, American Association for Cancer Research.
Prospecting for Energy-Rich Renewable Raw Materials: Sorghum Stem Case Study. - PloS one
Sorghum vegetative tissues are becoming increasingly important for biofuel production. The composition of sorghum stem tissues is influenced by genotype, environment and photoperiod sensitivity, and varies widely between varieties and also between different stem tissues (outer rind vs inner pith). Here, the amount of cellulose, (1,3;1,4)-Î²-glucan, arabinose and xylose in the stems of twelve diverse sorghum varieties, including four photoperiod-sensitive varieties, was measured. At maturity, most photoperiod-insensitive lines had 1% w/w (1,3;1,4)-Î²-glucan in stem pith tissue whilst photoperiod-sensitive varieties remained in a vegetative stage and accumulated up to 6% w/w (1,3;1,4)-Î²-glucan in the same tissue. Three sorghum lines were chosen for further study: a cultivated grain variety (Sorghum bicolor BTx623), a sweet variety (S. bicolor Rio) and a photoperiod-sensitive wild line (S. bicolor ssp. verticilliflorum Arun). The Arun line accumulated 5.5% w/w (1,3;1,4)-Î²-glucan and had higher SbCslF6 and SbCslH3 transcript levels in pith tissues than did photoperiod-insensitive varieties Rio and BTx623 (<1% w/w pith (1,3;1,4)-Î²-glucan). To assess the digestibility of the three varieties, stem tissue was treated with either hydrolytic enzymes or dilute acid and the release of fermentable glucose was determined. Despite having the highest lignin content, Arun yielded significantly more glucose than the other varieties, and theoretical calculation of ethanol yields was 10 344 L ha-1 from this sorghum stem tissue. These data indicate that sorghum stem (1,3;1,4)-Î²-glucan content may have a significant effect on digestibility and bioethanol yields. This information opens new avenues of research to generate sorghum lines optimised for biofuel production.
Routine Cyst Fluid Cytology Is Not Indicated in the Evaluation of Pancreatic Cystic Lesions. - Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract
The work-up of cystic lesions of the pancreas often involves endoscopic ultrasound (EUS) with fine needle aspiration (FNA). In addition to CEA and amylase measurement, fluid is routinely sent for cytologic examination. We evaluated the utility of cytologic findings in clinical decision-making.Records of patients who underwent EUS-guided pancreatic cyst aspiration were reviewed. Findings from axial imaging and EUS were compared to cyst fluid cytology as well as fluid amylase and CEA. All results were then compared to final diagnosis, determined by clinical analysis for those patients not resected, and surgical pathology report for those who underwent resection.A total of 167 patients were reviewed. Of 48 patients with suspicious findings on imaging, cytology yielded diagnostic information in 89.6Â % of cases (43 patients). However, in the 119 patients where no suspicious components were revealed on imaging, fluid cytology yielded no significant diagnostic results in any case. In all cases where mucin was noted on cytologic review, thick fluid was also seen at the time of aspiration.In our cohort of patients with cystic pancreatic lesions, cytologic analysis of pancreatic cyst fluid yielded no diagnostic benefit over radiologic findings alone. In such cases where fluid is to be aspirated, specimens that would otherwise be sent for cytologic evaluation would be better served for other purposes, such as molecular analysis or banking for future research.
Understanding Inpatient Perceptions of Indwelling Urinary Catheters Using the Health Belief Model. - Infection control and hospital epidemiology
Patient interviews using the Health Belief Model framework identified thematic patient perceptions of indwelling urinary catheters and catheter-associated urinary tract infections. Generally, patients perceived catheters as convenient and were unaware of catheter alternatives and risks for infection. Better patient education is needed to reduce urinary catheter use and infections. Infect Control Hosp Epidemiol 2016;1-3.
CD66 and CD49f expressing cells are associated with distinct neoplastic phenotypes and progression in human cervical cancer. - European journal of cancer (Oxford, England : 1990)
In this study, building on our recent work identifying a subset of CD66+ve cells with distinctive tumourigenic properties in human cervical cancers, we examine patterns of expression and function of these cells; to generate insights into the process of metastasis.Our broad approach in this study has been to compare the expression and function of two subsets marked by CD66 and CD49f. We use a combination of histopathology, immunostaining and flow cytometry, functional analysis of an established cervical cancer cell line and a retrospective analysis of a cohort of cervical cancer.We noted CD66 expression associated with clusters of cells which are spindle shaped, SMA+ve, podoplanin+ve, phalloidin high, fibronectin high, plakoglobin low, ki67-ve and CK10+ve at the migratory phase along with features of partial EMT. Further, TGFÎ²1 a well known regulator of EMT, positively correlated with CD66 expression. The additional CD49f+ve subset at the leading invading front of migration was SMA-ve, phalloidin low, fibronectin low, plakoglobin high, Ki67+ve and CK14+ve. These data are consistent with a role for CD66 cells in metastatic invasion with a collective cell migration process co-opting the CD49f subset. Our retrospective analysis of a cohort is consistent with a role for CD66 in metastasis. However, the broad analysis of CD66, CD49f and TGFÎ²1 expression with patterns of overall survival points to a possible protective effect particularly for local recurrences. Hence, future studies focussing on potential heterogeneity within the CD66 subsetÂ along with the possible role of isoforms and intra-cellular roles would be essential.Copyright Â© 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.
Fine scale patterns of genetic partitioning in the rediscovered African crocodile, Crocodylus suchus (Saint-Hilaire 1807). - PeerJ
Landscape heterogeneity, phylogenetic history, and stochasticity all influence patterns of geneflow and connectivity in wild vertebrates. Fine-scale patterns of genetic partitioning may be particularly important for the sustainable management of widespread species in trade, such as crocodiles. We examined genetic variation within the rediscovered African crocodile, Crocodylus suchus, across its distribution in West and Central Africa. We genotyped 109 individuals at nine microsatellite loci from 16 sampling localities and used three Bayesian clustering techniques and an analysis of contemporary gene flow to identify population structure across the landscape. We identified up to eight genetic clusters that largely correspond to populations isolated in coastal wetland systems and across large distances. Crocodile population clusters from the interior were readily distinguished from coastal areas, which were further subdivided by distance and drainage basin. Migration analyses indicated contemporary migration only between closely positioned coastal populations. These findings indicate high levels of population structure throughout the range of C. suchus and we use our results to suggest a role for molecular tools in identifying crocodile conservation units for this species. Further research, including additional sampling throughout the Congo and Niger drainages, would clarify both the landscape connectivity and management of this species.
Feasibility and patient satisfaction with smoking cessation interventions for prevention of healthcare-associated infections in inpatients. - Substance abuse treatment, prevention, and policy
Smoking increases hospitalization and healthcare-associated infection. Our primary aim of this pilot, randomized-controlled trial was to examine the feasibility and acceptability of a tobacco cessation intervention compared with usual care in inpatients. S. aureus carriage, healthcare-associated infections and infections post discharge were exploratory outcomes.Current inpatient smokers from a university hospital facility were randomized to usual care or a face to face tobacco cessation counseling session where patients' tobacco use and strategies for quitting were discussed. Patient engagement, satisfaction and withdrawal symptoms were measured at 1Â week and 12Â weeks post discharge. Nasal swabs were collected at enrollment and discharge and assessed for S. aureus colonization. P-values were calculated using Fisher's exact and t-tests were used to compare groups.For the study's primary outcome, participants reported the intervention as being generally acceptable and reported high overall levels of satisfaction, with a Likert scale score of at least 4/5 for all measures of satisfaction. No subjects utilized free tobacco cessation services after discharge. 83Â % of the intervention group and 93Â % of the control group smoked at least one cigarette after discharge. Secondary outcomes with regard to infections showed that, at discharge, 12Â % of the intervention group (nâ€‰=â€‰17) and 18Â % of the control group (nâ€‰=â€‰22) tested positive for S. aureus. After 3Â months, 9Â % of the intervention group developed infection, 41Â % visited an emergency room, and 24Â % were readmitted within 3Â months post-discharge, compared to 27, 32 and 36Â % of the control group respectively.With regards to the primary aim of this study, there were overall high levels of satisfaction with the intervention, indicating good feasibility and acceptance among patients. However, more intensive interventions in hospitalized patients and impact on healthcare-associated infections and post-discharge infections should be explored.
All-trans retinoic acid synergizes with FLT3 inhibition to eliminate FLT3/ITD+ leukemia stem cells in vitro and in vivo. - Blood
FMS-like tyrosine kinase 3 (FLT3)-mutant acute myeloid leukemia (AML) portends a poor prognosis, and ineffective targeting of the leukemic stem cell (LSC) population remains one of several obstacles in treating this disease. All-trans retinoic acid (ATRA) has been used in several clinical trials for the treatment of nonpromyelocytic AML with limited clinical activity observed. FLT3 tyrosine kinase inhibitors (TKIs) used as monotherapy also achieve limited clinical responses and are thus far unable to affect cure rates in AML patients. We explored the efficacy of combining ATRA and FLT3 TKIs to eliminate FLT3/internal tandem duplication (ITD)(+) LSCs. Our studies reveal highly synergistic drug activity, preferentially inducing apoptosis in FLT3/ITD(+) cell lines and patient samples. Colony-forming unit assays further demonstrate decreased clonogenicity of FLT3/ITD(+) cells upon treatment with ATRA and TKI. Most importantly, the drug combination depletes FLT3/ITD(+) LSCs in a genetic mouse model of AML, and prolongs survival of leukemic mice. Furthermore, engraftment of primary FLT3/ITD(+) patient samples is reduced in mice following treatment with FLT3 TKI and ATRA in combination, with evidence of cellular differentiation occurring in vivo. Mechanistically, we provide evidence that the synergism of ATRA and FLT3 TKIs is at least in part due to the observation that FLT3 TKI treatment upregulates the antiapoptotic protein Bcl6, limiting the drug's apoptotic effect. However, cotreatment with ATRA reduces Bcl6 expression to baseline levels through suppression of interleukin-6 receptor signaling. These studies provide evidence of the potential of this drug combination to eliminate FLT3/ITD(+) LSCs and reduce the rate of relapse in AML patients with FLT3 mutations.
Chelonitoxism in Andaman and Nicobar Island: A report on mass poisoning including a death of an adult. - Toxicon : official journal of the International Society on Toxinology
Chelonitoxism is a type of seafood poisoning which usually occurs due to consumption of certain marine turtle flesh. As the pharmacology or chemistry of the toxin is still unknown, antidote or treatment to chelonitoxism is unavailable. The symptoms can vary from common gastro-intestinal symptoms to neurological manifestations and even death. This case report of community poisoning following consumption of turtle meat includes the death of an adult male (56 yrs.) being reported for the first time in the Great Nicobar Island, Andaman and Nicobar (A&N) Islands, India in August 2012. The patient encountered common gastrointestinal symptoms after one day of ingestion of green turtle flesh and later, he developed neurological symptoms and did not respond to symptomatic treatment and expired after four days after the consumption. However, out of 30 villagers who took the same food, six others developed symptoms and recovered within a period of 3-7 days while two pets (a dog and a cat) died within 24 hours as they were fed with the same food. In spite of several existing wildlife protection acts, catching a turtle and making them a source of food-celebration is quite common in coastal areas of the Indian Ocean and the Bay of Bengal which includes A&N Islands. A proper monitoring and follow-up of the food-borne diseases along with a wide range of explorative health education protocol should be implemented especially for the people who are not reachable via media to avoid such incidents in future.Copyright Â© 2016 Elsevier Ltd. All rights reserved.
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