Src Dependent Pancreatic Acinar Injury Can Be Initiated Independent of an Increase in Cytosolic Calcium

Several deleterious intra-acinar phenomena are simultaneously triggered on initiating acute pancreatitis. These culminate in acinar injury or inflammatory mediator generation in vitro and parenchymal damage in vivo. Supraphysiologic caerulein is one such initiator which simultaneously activates numerous signaling pathways including non-receptor tyrosine kinases such as of the Src family. It also causes a sustained increase in cytosolic calcium- a player thought to be crucial in regulating deleterious phenomena. We have shown Src to be involved in caerulein induced actin remodeling, and caerulein induced changes in the Golgi and post-Golgi trafficking to be involved in trypsinogen activation, which initiates acinar cell injury. However, it remains unclear whether an increase in cytosolic calcium is necessary to initiate acinar injury or if injury can be initiated at basal cytosolic calcium levels by an alternate pathway. To study the interplay between tyrosine kinase signaling and calcium, we treated mouse pancreatic acinar cells with the tyrosine phosphatase inhibitor pervanadate. We studied the effect of the clinically used Src inhibitor Dasatinib (BMS-354825) on pervanadate or caerulein induced changes in Src activation, trypsinogen activation, cell injury, upstream cytosolic calcium, actin and Golgi morphology. Pervanadate, like supraphysiologic caerulein, induced Src activation, redistribution of the F-actin from its normal location in the sub-apical area to the basolateral areas, and caused antegrade fragmentation of the Golgi. These changes, like those induced by supraphysiologic caerulein, were associated with trypsinogen activation and acinar injury, all of which were prevented by Dasatinib. Interestingly, however, pervanadate did not cause an increase in cytosolic calcium, and the caerulein induced increase in cytosolic calcium was not affected by Dasatinib. These findings suggest that intra-acinar deleterious phenomena may be initiated independent of an increase in cytosolic calcium. Other players resulting in acinar injury along with the Src family of tyrosine kinases remain to be explored. © 2013 Mishra et al

Role of Spirituality in Mental Health Practice

Background: Most modern medical disciplines adopt biomedical and positivistic corners while viewing andinterpreting various events and phenomena related to living and physical worlds. But in case of mental health thedimension is much complicated and full of abstract elements and relativism; all these areas can be expressed orenumerated what can be possible in other steams of physical and biological sciences. Factors like socio-cultural andhuman factors, spirituality and religiosity have some definite association with various aspects of mental health andillness. Spirituality in recent times has been entertained as a major factor in determining the course of mental healthand illness; it drew the attention of mental health clinicians and researchers to find out its temporal relationship withmental illness and psychological wellbeing. Many authentic literatures came up with the view that positivespirituality does have some potentialities to enhance as well as protect the positive mental health and psychologicalwell-being of the people. Spirituality can also lower the distress level and increase the positive coping ability ofpeople. The aim of this article is to explore the role of spirituality in mental health in terms of evolution ofpsychopathology, understanding of the illness and finally, its role in treatment of the psychiatric settings. This articlealso aims to sensitize mental health clinicians to remain positive towards the religious and spiritual beliefs of patientsand to use those things in the therapeutic process

The effectiveness of e-& mHealth interventions to promote physical activity and healthy diets in developing countries: a systematic review

Background: Promoting physical activity and healthy eating is important to combat the unprecedented rise in NCDs in many developing countries. Using modern information-and communication technologies to deliver physical activity and diet interventions is particularly promising considering the increased proliferation of such technologies in many developing countries. The objective of this systematic review is to investigate the effectiveness of e-& mHealth interventions to promote physical activity and healthy diets in developing countries.Methods: Major databases and grey literature sources were searched to retrieve studies that quantitatively examined the effectiveness of e-& mHealth interventions on physical activity and diet outcomes in developing countries. Additional studies were retrieved through citation alerts and scientific social media allowing study inclusion until August 2016. The CONSORT checklist was used to assess the risk of bias of the included studies.Results: A total of 15 studies conducted in 13 developing countries in Europe, Africa, Latin-and South America and Asia were included in the review. The majority of studies enrolled adults who were healthy or at risk of diabetes or hypertension. The average intervention length was 6.4 months, and text messages and the Internet were the most frequently used intervention delivery channels. Risk of bias across the studies was moderate (55.7 % of the criteria fulfilled). Eleven studies reported significant positive effects of an e-& mHealth intervention on physical activity and/or diet behaviour. Respectively, 50 % and 70 % of the interventions were effective in promoting physical activity and healthy diets.Conclusions: The majority of studies demonstrated that e-& mHealth interventions were effective in promoting physical activity and healthy diets in developing countries. Future interventions should use more rigorous study designs, investigate the cost-effectiveness and reach of interventions, and focus on emerging technologies, such as smart phone apps and wearable activity trackers.Trial registration: The review protocol can be retrieved from the PROSPERO database (Registration ID: CRD42015029240)

Prevalence and clustering of cardiovascular disease risk factors in rural Nepalese population aged 40-80 years

Abstract Background Cardiovascular diseases (CVD) are the main cause of mortality in low- and middle-income countries like Nepal. Different risk factors usually cluster and interact multiplicatively to increase the risk of developing acute cardiovascular events; however, information related to clustering of CVD risk factors is scarce in Nepal. Therefore, we aimed to determine the prevalence of CVD risk factors with a focus on their clustering pattern in a rural Nepalese population. Methods A community-based cross-sectional study was conducted among residents aged 40 to 80 years in Lamjung District of Nepal in 2014. A clustered sampling technique was used in steps. At first, four out of 18 wards were chosen at random. Then, one person per household was selected randomly (n = 388). WHO STEPS questionnaires (version 2.2) were used to collect data. Chi-square and independent t-test were used to test significance at the level of p < 0.05. Results A total 345 samples with complete data were analyzed. Smoking [24.1% (95% CI: 19.5–28.6)], harmful use of alcohol [10.7% (7.4–13.9)], insufficient intake of fruit and vegetable [72% (67.1–76.6)], low physical activity [10.1% (6.9–13.2)], overweight and obesity [59.4% (54.2–64.5)], hypertension [42.9% (37.6–48.1)], diabetes [16.2% (14.0–18.3)], and dyslipidemia [56.0% (53.0–58.7)] were common risk factors among the study population. Overall, 98.2% had at least one risk factor, while 2.0% exhibited six risk factors. Overall, more than a half (63.4%) of participants had at least three risk factors (male: 69.4%, female: 58.5%). Age [OR: 2.3 (95% CI: 1.13–4.72)] and caste/ethnicity [2.0 (95% CI: 1.28–3.43)] were significantly associated with clustering of at least three risk factors. Conclusions Cardiovascular risk factors and their clustering were common in the rural population of Nepal. Therefore, comprehensive interventions against all risk factors should be immediately planned and implemented to reduce the future burden of CVD in the rural population of Nepal

Total cardiovascular risk for next 10 years among rural population of Nepal using WHO/ISH risk prediction chart

BACKGROUND: Cardiovascular diseases (CVD) are the leading cause of morbidity and mortality globally. Primary prevention of CVD based on total CVD risk approach using WHO/ISH risk prediction chart would be more effective to stratify population under different risk levels, prioritize and utilize the scarce resources of low and middle-income countries. This study estimated total 10-year CVD risk and determined the proportion of population who need immediate drug therapy among the rural population of Nepal. METHODS: A community based cross-sectional study conducted among 345 participants aged 40–80 years in rural villages of Lamjung District of Nepal. They were selected randomly from total eighteen wards. Data were collected using WHO STEPS questionnaires. WHO/ISH risk prediction chart for SEAR D was used to estimate total cardiovascular risk. Chi-square and independent t-test were used to test significance at the level of p < 0.05 in SPSS version 16.0. RESULTS: Of the total participants, 55.4% were female. The mean age (standard deviation) of the participants was 53.5 ± 10.1 years. According to WHO/ISH chart proportions of low, moderate and high CVD risk were 86.4%, 9.3%, and 4.3%, respectively. Eleven percent of participants were in need of immediate pharmacotherapy. Age (p = 0.001), level of education (p = 0.01) and occupation (p = 0.001) were significantly associated with elevated CVD risk. CONCLUSION: A large proportion of Nepalese rural population is at moderate and high CVD risk. Immediate pharmacological interventions are warranted for at least one in every ten individuals along with lifestyle interventions. Both population-wise and high-risk approaches are required to minimize CVD burden in the future

Farm-Level Risk Factors for Fish-Borne Zoonotic Trematode Infection in Integrated Small-Scale Fish Farms in Northern Vietnam

BACKGROUND: Northern Vietnam is an endemic region for fish-borne zoonotic trematodes (FZT), including liver and intestinal flukes. Humans acquire the FZT infection by eating raw or inadequately cooked fish. The production of FZT-free fish in aquaculture is a key component in establishing a sustainable program to prevent and control the FZT transmission to humans. Interventions in aquaculture should be based on knowledge of the main risk factors associated with FZT transmission. METHODOLOGY/PRINCIPAL FINDINGS: A longitudinal study was carried out from June 2006 to May 2007 in Nam Dinh province, Red River Delta to investigate the development and risk factors of FZT infections in freshwater cultured fish. A total of 3820 fish were sampled six times at two-month intervals from 96 fish farms. Logistic analysis with repeated measurements was used to evaluate potential risk factors based on information collected through questionnaire interviews with 61 fish farm owners. The results showed that the FZT infections significantly increased from first sampling in June to July 2006 (65%) to sixth sampling in April to May, 2007 (76%). The liver fluke, Clonorchis sinensis and different zoonotic intestinal flukes including Haplochis pumilio, H. taichui, H. yokogawai, Centrocestus formosanus and Procerovum varium were found in sampled fish. Duration of fish cultured (sampling times), mebendazole drug self-medication of household members, presence of snails in the pond, and feeding fish with green vegetation collected outside fish farms all had a significant effect on the development of FZT prevalence in the fish. CONCLUSIONS/SIGNIFICANCE: The FZT prevalence in fish increased by 11 percentage points during a one-year culture period and the risk factors for the development of infection were identified. Results also highlight that the young fish are already highly infected when stocked into the grow-out systems. This knowledge should be incorporated into control programs of FZT transmission in integrated small-scale aquaculture nursery and grow-out systems in Vietnam

The Transcriptome of Lutzomyia longipalpis (Diptera: Psychodidae) Male Reproductive Organs

BACKGROUND: It has been suggested that genes involved in the reproductive biology of insect disease vectors are potential targets for future alternative methods of control. Little is known about the molecular biology of reproduction in phlebotomine sand flies and there is no information available concerning genes that are expressed in male reproductive organs of Lutzomyia longipalpis, the main vector of American visceral leishmaniasis and a species complex. METHODS/PRINCIPAL FINDINGS: We generated 2678 high quality ESTs ("Expressed Sequence Tags") of L. longipalpis male reproductive organs that were grouped in 1391 non-redundant sequences (1136 singlets and 255 clusters). BLAST analysis revealed that only 57% of these sequences share similarity with a L. longipalpis female EST database. Although no more than 36% of the non-redundant sequences showed similarity to protein sequences deposited in databases, more than half of them presented the best-match hits with mosquito genes. Gene ontology analysis identified subsets of genes involved in biological processes such as protein biosynthesis and DNA replication, which are probably associated with spermatogenesis. A number of non-redundant sequences were also identified as putative male reproductive gland proteins (mRGPs), also known as male accessory gland protein genes (Acps). CONCLUSIONS: The transcriptome analysis of L. longipalpis male reproductive organs is one step further in the study of the molecular basis of the reproductive biology of this important species complex. It has allowed the identification of genes potentially involved in spermatogenesis as well as putative mRGPs sequences, which have been studied in many insect species because of their effects on female post-mating behavior and physiology and their potential role in sexual selection and speciation. These data open a number of new avenues for further research in the molecular and evolutionary reproductive biology of sand flies

Higher incidence of perineal community acquired MRSA infections among toddlers

<p>Abstract</p> <p>Background</p> <p>A six-fold increase in pediatric MRSA infections, prompted us to examine the clinical profile of children with MRSA infections seen at Mercy Children's Hospital, Toledo, Ohio and to characterize the responsible strains.</p> <p>Methods</p> <p>Records were reviewed of pediatric patients who cultured positive for MRSA from June 1 to December 31, 2007. Strain typing by pulsed field gel electrophoresis (PFT) and DiversiLab, SCC<it>mec </it>typing, and PCR-based <it>lukSF-PV </it>gene (encodes Panton-Valentine leukocidin), arginine catabolic mobile element (ACME) and <it>cap</it>5 gene detection was performed.</p> <p>Results</p> <p>Chart review of 63 patients with MRSA infections revealed that 58(92%) were community acquired MRSA (CAMRSA). All CAMRSA were skin and soft tissue infections (SSTI). Twenty five (43%) patients were aged < 3 yrs, 19(33%) aged 4-12 and 14(24%) aged 13-18. Nineteen (76%) of those aged < 3 yrs had higher incidence of perineal infections compared to only 2(11%) of the 4-12 yrs and none of the 13-18 yrs of age. Infections in the extremities were more common in the older youth compared to the youngest children. Overall, there was a significant association between site of the infection and age group (Fisher's Exact p-value < 0.001). All CAMRSA were USA300 PFT, clindamycin susceptible, SCC<it>mec </it>type IVa and <it>lukSF-PV gene </it>positive. Nearly all contained ACME and about 80% were <it>cap</it>5 positive. Of the 58 USA300 strains by PFT, 55(95%) were also identified as USA300 via the automated repetitive sequence-based PCR method from DiversiLab.</p> <p>Conclusions</p> <p>CAMRSA SSTI of the perineum was significantly more common among toddlers and that of the extremities in older children. The infecting strains were all USA300 PFT. Further studies are needed to identify the unique virulence and colonization characteristics of USA300 strains in these infections.</p

Exacerbations of chronic obstructive pulmonary disease: when are antibiotics indicated? A systematic review

BACKGROUND: For decades, there is an unresolved debate about adequate prescription of antibiotics for patients suffering from exacerbations of chronic obstructive pulmonary disease (COPD). The aim of this systematic review was to analyse randomised controlled trials investigating the clinical benefit of antibiotics for COPD exacerbations. METHODS: We conducted a systematic review of randomised, placebo-controlled trials assessing the effects of antibiotics on clinically relevant outcomes in patients with an exacerbation. We searched bibliographic databases, scrutinized reference lists and conference proceedings and asked the pharmaceutical industry for unpublished data. We used fixed-effects models to pool results. The primary outcome was treatment failure of COPD exacerbation treatment. RESULTS: We included 13 trials (1557 patients) of moderate to good quality. For the effects of antibiotics on treatment failure there was much heterogeneity across all trials (I(2 )= 82%). Meta-regression revealed severity of exacerbation as significant explanation for this heterogeneity (p = 0.016): Antibiotics did not reduce treatment failures in outpatients with mild to moderate exacerbations (pooled odds ratio 1.09, 95% CI 0.75–1.59, I(2 )= 18%). Inpatients with severe exacerbations had a substantial benefit on treatment failure rates (pooled odds ratio of 0.25, 95% CI 0.16–0.39, I(2 )= 0%; number-needed to treat of 4, 95% CI 3–5) and on mortality (pooled odds ratio of 0.20, 95% CI 0.06–0.62, I(2 )= 0%; number-needed to treat of 14, 95% CI 12–30). CONCLUSION: Antibiotics effectively reduce treatment failure and mortality rates in COPD patients with severe exacerbations. For patients with mild to moderate exacerbations, antibiotics may not be generally indicated and further research is needed to guide antibiotic prescription in these patients