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Abstract Background Despite serious health and social consequences, effective intervention strategies for habitual alcohol binge drinking are lacking. The development of novel therapeutic and preventative approaches is highly desirable. Accumulating evidence in the past several years has established associations between the gut microbiome and microbial metabolites with drinking behavior, but druggable targets and their underlying mechanism of action are understudied. Results Here, using a drink-in-the-dark mouse model, we identified a microbiome metabolite-based novel treatment (sodium valerate) that can reduce excessive alcohol drinking. Sodium valerate is a sodium salt of valeric acid short-chain fatty acid with a similar structure as γ-aminobutyric acid (GABA). Ten days of oral sodium valerate supplementation attenuates excessive alcohol drinking by 40%, reduces blood ethanol concentration by 53%, and improves anxiety-like or approach-avoidance behavior in male mice, without affecting overall food and water intake. Mechanistically, sodium valerate supplementation increases GABA levels across stool, blood, and amygdala. It also significantly increases H4 acetylation in the amygdala of mice. Transcriptomics analysis of the amygdala revealed that sodium valerate supplementation led to changes in gene expression associated with functional pathways including potassium voltage-gated channels, inflammation, glutamate degradation, L-DOPA degradation, and psychological behaviors. 16S microbiome profiling showed that sodium valerate supplementation shifts the gut microbiome composition and decreases microbiome-derived neuroactive compounds through GABA degradation in the gut microbiome. Conclusion Our findings suggest that sodium valerate holds promise as an innovative therapeutic avenue for the reduction of habitual binge drinking, potentially through multifaceted mechanisms. Video Abstract

The extent and magnitude of the mental health stigma are enormous, with substantial clinical and social implications. There is a complex relationship between mental health stigma and mental health professionals (MHPs); MHPs can be anti-stigma crusaders, victims of stigma, and even a source of stigma. Unfortunately, literature is scarce talking about the relationship between stigma and MHPs. Hence, the current review aims to bridge the existing gap in the literature on various aspects of stigma and the role of MHPs. For the current review, we ran a search in PubMed and Google Scholar databases; we restricted our study to records focusing on the interplay of mental health stigma and the MHPs, published during 2012–2022, in English, and having a full text available. We found that MHPs (psychiatrists, psychologists, and psychiatric nurses) can also be the recipients of the stigma. The stigma faced by the MHPs is determined by the negative stereotypes set by the media, or medical students, or other health professionals; the marginal position of psychiatry in the health system; difficult-to-treat mental disorders; MHPs’ own experience of stigma; and the attitude or beliefs of various caders of the MHPs, their professional experience, and expertise in managing various mental health conditions. Notably, MHPs can also be a source of stigma (stigmatizers). MHPs need to be sensitized concerning this, and the anti-stigma interventions must incorporate this aspect of stigma. Novel interventions, such as digital-based programs, should be used instead of traditional anti-stigma programs in order to decrease stigma around mental health issues and make anti-stigma initiatives more appealing and scalable. To address the issues of stigma, there has to be more communication between MHPs, other health professionals, service users, and policymakers.

Pregnancy can exacerbate or prompt the onset of stress-related disorders, such as post-traumatic stress disorder (PTSD). PTSD is associated with heightened stress responsivity and emotional dysregulation, as well as increased risk of chronic disorders and mortality. Further, maternal PTSD is associated with gestational epigenetic age acceleration in newborns, implicating the prenatal period as a developmental time period for the transmission of effects across generations. Here, we evaluated the associations between PTSD symptoms, maternal epigenetic age acceleration, and infant gestational epigenetic age acceleration in 89 maternal-neonatal dyads. Trauma-related experiences and PTSD symptoms in mothers were assessed during the third trimester of pregnancy. The MethylationEPIC array was used to generate DNA methylation data from maternal and neonatal saliva samples collected within 24 h of infant birth. Maternal epigenetic age acceleration was calculated using Horvath’s multi-tissue clock, PhenoAge and GrimAge. Gestational epigenetic age was estimated using the Haftorn clock. Maternal cumulative past-year stress (GrimAge: p = 3.23e-04, PhenoAge: p = 9.92e-03), PTSD symptoms (GrimAge: p = 0.019), and difficulties in emotion regulation (GrimAge: p = 0.028) were associated with accelerated epigenetic age in mothers. Maternal PTSD symptoms were associated with lower gestational epigenetic age acceleration in neonates (p = 0.032). Overall, our results suggest that maternal cumulative past-year stress exposure and trauma-related symptoms may increase the risk for age-related problems in mothers and developmental problems in their newborns.

The integrated dysbiosis of gut microbiota and altered host transcriptomics in irritable bowel syndrome (IBS) is yet to be known. This study investigated the associations among gut microbiota and host transcriptomics in young adults with IBS. Stool and peripheral blood samples from 20 IBS subjects and 21 healthy controls (HCs) collected at the baseline visit of an RCT were sequenced to depict the gut microbiota and transcriptomic profiles, respectively. The diversities, composition, and predicted metabolic pathways of gut microbiota significantly differed between IBS subjects and HCs. Nine genera were significantly abundant in IBS stool samples, including Akkermansia, Blautia, Coprococcus, Granulicatella, Holdemania, Oribacterium, Oscillospira, Parabacteroides, and Sutterella. There were 2264 DEGs found between IBS subjects and HCs; 768 were upregulated, and 1496 were downregulated in IBS participants compared with HCs. The enriched gene ontology included the immune system process and immune response. The pathway of antigen processing and presentation (hsa04612) in gut microbiota was also significantly different in the RNA-seq data. Akkermansia, Blautia, Holdemania, and Sutterella were significantly correlated with ANXA2P2 (upregulated, positive correlations), PCSK1N (downregulated, negative correlations), and GLTPD2 (downregulated, negative correlations). This study identified the dysregulated immune response and metabolism in IBS participants revealed by the altered gut microbiota and transcriptomic profiles.

Background: Rheumatoid arthritis (RA) is an inflammation of joints with increased cellularity of synovial tissue. Allopathic drugs possess several adverse effects, which have led to increase in the utilization of herbal medicines. Polyherbal emulgel resolves the bioavailability issue associated with hydrophobic drugs and can be used effectively in the treatment of RA. Objectives: The present study aimed at the formulation of polyherbal emulgel, and evaluation of in vitro anti-inflammatory activity and in vivo antiarthritic activity. Methods: Seven emulgels F-1 to F-7 were optimally formulated. In vitro anti-inflammatory activity was determined using protein denaturation method employing Diclofenac sodium as the standard. In antiarthritic study Complete Freund's Adjuvant (CFA) model was used. The various parameters were assessed, like paw volume, body weight, hematological parameters, antioxidant parameters, Rheumatic factor (RF), and histopathological study of ankle joint. Results: F-4 and F-7 were found to be optimized formulations as compared to other formulations. The in vitro anti-inflammatory activity was found to be highest in F-4 with IC50 7.74 and F-7 with IC50 8.87 in comparison with Diclofenac sodium having IC50 57.0. Both formulations F-7 and F-4 showed a significant reduction in paw volume and normalization of body weights. The formulation F-7 even showed more potent antiarthritic activity than F-4 by decreasing white blood cells (WBC), lymphocytes, increasing packed cell volume (PCV), neutrophils, superoxide dismutase (SOD), catalase and decreasing malondialdehyde (MDA) levels in serum. This was further confirmed by histopathological study. Conclusion: As an anti-inflammatory agent, this newly developed emulgel was found to possess more therapeutic efficacy than commercially available diclofenac sodium.

Introduction: The aging process and the pandemic have significantly affected the elderly population, resulting in a wide range of physiological and psychological changes. These changes have created a significant burden for the nation as the elderly is often overlooked. In response to this, the Government of India and AIIMS Bhopal developed a yoga-meditation-based intervention to help improve the mental health of the elderly (>60 years) during the pandemic. Methodology: A retrospective case − control study was conducted on the geriatric population aged over 60 years of both sexes from March 2021 to September 2021 at the All India Institute of Medical Sciences, Bhopal. The sample size was calculated to be 690 participants based on the prevalence of depression and anxiety in the elderly population and using the depression, anxiety, and stress scale 21 (DASS)-21. Participants were asked to fill out the DASS questionnaire, and those with mild to moderate depression, anxiety, or stress were randomly divided into two groups. The intervention group received a 6-week yoga-based mobile intervention, and the results were analyzed using the SPSS software version 27. Results: The between group analysis showed that MOMMY intervention was effective in reducing symptoms of depression (t=3.38, df=93, p

Antibiotics are one of the most common drugs that can induce adverse drug reaction (ADR). A retrospective analysis was conducted using suspected antibiotic-related ADR data collected from the Ethiopian Pharmacovigilance Center over a 5-year period (2014-2019). There were a relatively large number of antibiotic-related ADRs (57.9%) containing 462 suspected drugs reported, with adults aged 18-64 (65.5%) and females (61.5%) predominating in the reported cases. Monotherapy and oral route administration were responsible for 85% and 83% of ADRs, respectively. Co-trimoxazole and amoxicillin were responsible for more than half of the reported ADRs and skin disorder was half of the affected system organ (SOC). Serious ADRs constituted 26% of all reported ADRs. The outcome of the patient showed that (44.7%) of patients were completely recovered after discontinuing the offending drug and additional intervention. The finding in this study suggests that antibiotic related ADRs are a significant health problem for patients in Ethiopia and further health facility based research is suggested.

Introduction: The COVID-19 pandemic has left an array of direct physical consequences unevenly on the elderly apart from leaving a wide range of indirect consequences of mental health problems on them. This study aims to understand the effect of a Yoga-Meditation based mobile phone application intervention to reduce the duress by mental health issues via a qualitative analysis. Methods: A phenomenological qualitative succession of an explanatory sequential design of a prior quantitative study followed by a Yoga-Meditation mobile phone based intervention, where 30 participants who had mild or moderate Depression, Anxiety or Stress as assessed by DASS-21 were chosen by random sampling and were asked to take part in an interview. The interview was transcribed, coded, patterns identified and themes were created to understand the perceptions. Results: Three major schools of thought were identified and explored to understand the general perception of Mental health, COVID-19 and the intervention: a) Knowledge Axis patterns of COVID-19, which included their prior knowledge about the disease, its consequences and their cues to action based on those beliefs, b) Mental Health and Strategies to Positivity, involves all their actions to promote, restore or propagate a positive mental attitude from religious activities to physical activities and c) Application related thoughts, involved their perceptions of the app, the barriers to use and suggestions to improve. Conclusion: This study gave deeper insight into the schools of thought which will be important in designing future interventions and yoga-meditation based programs in the future, essentially for geriatric populations as it serves as a feasible simple measure for the same.

Extant literature has established the effectiveness of various mental health promotion and prevention strategies, including novel interventions. However, comprehensive literature encompassing all these aspects and challenges and opportunities in implementing such interventions in different settings is still lacking. Therefore, in the current review, we aimed to synthesize existing literature on various mental health promotion and prevention interventions and their effectiveness. Additionally, we intend to highlight various novel approaches to mental health care and their implications across different resource settings and provide future directions. The review highlights the (1) concept of preventive psychiatry, including various mental health promotions and prevention approaches, (2) current level of evidence of various mental health preventive interventions, including the novel interventions, and (3) challenges and opportunities in implementing concepts of preventive psychiatry and related interventions across the settings. Although preventive psychiatry is a well-known concept, it is a poorly utilized public health strategy to address the population's mental health needs. It has wide-ranging implications for the wellbeing of society and individuals, including those suffering from chronic medical problems. The researchers and policymakers are increasingly realizing the potential of preventive psychiatry; however, its implementation is poor in low-resource settings. Utilizing novel interventions, such as mobile-and-internet-based interventions and blended and stepped-care models of care can address the vast mental health need of the population. Additionally, it provides mental health services in a less-stigmatizing and easily accessible, and flexible manner. Furthermore, employing decision support systems/algorithms for patient management and personalized care and utilizing the digital platform for the non-specialists' training in mental health care are valuable additions to the existing mental health support system. However, more research concerning this is required worldwide, especially in the low-and-middle-income countries.

الملخص: أهداف البحث: في هذا العمل حاولنا فصل وتحديد تركيبة الزيت العطري والخصائص الدوائية لنوعين من ثمار حب الهيل الأسود المستوردة التي تم شراؤها من المتاجر المحلية الهندية والسعودية للتأكد من علاقة التركيب الكيميائي بالتأثيرات العلاجية. طرق البحث: لقد تم استخلاص الزيت العطري من عينات ثمار حب الهيل الأسود الهندية والسعودية باستخدام طريقة التقطير المائي، ثم تم تحديد تركيب الزيت العطري بواسطة جهاز مطياف الكتلة المرتبط بالكروماتوغرافيا الغازية. بعدها تم تقييم فاعلية تلك الزيوت كمضاد جرثومي ضد البكتيريا سالبة الجرام (الزائفة الزنجارية والإشريكية القولونية وأسينوباكتر بوماني) باستخدام طريقتي تحديد قيمة الحد الأدنى من التركيز المثبط وتحديد التركيز الأدنى القاتل للجراثيم. هذا بالإضافة إلى أنه قد تم تحديد الفاعلية المضادة للأكسدة باستخدام طريقة مكافحة الجذور الحرة التي يسببها مركب (٢,٢-ثنائي الفينيل ١- بيكريل الهيدرازيل) مع الفاعلية المضادة للالتهابات بواسطة فحص مثبطات الألبومين البقري وذلك لتقييم التأثيرات الدوائية لتلك الزيوت. النتائج: لقد أظهرت نتائج تحليل الزيوت العطرية المستخلصة بواسطة جهاز مطياف الكتلة المرتبط بالكروماتوغرافيا الغازية لكلتا العينتين وجود ٥٦ مكونا ذا فاعلية حيوية بنسب مختلفة حيث كانت المركبات الرئيسة في عينات الزيوت المستخلصة الهندية منها والسعودية هي: ١.٨- سينول (بتركيز ٤٤.٢٤٪ و٤٦.٢٢٪ على التوالي) ومركب الفا-تيربينول (بتركيز ٧.٤٧٪ و٧.٠٤٪ على التوالي) ومركب تيربينين-٤-ول (بتركيز ٥.٠١٪ و٤.٨٣٪ على التوالي) ومركب جرانيول د (بتركيز ٤.٠٥٪ و٣.٥٤٪ على التوالي) وبيتا-بينين (بتركيز ٣.٣٨٪ و٣.٩٨٪ على التوالي). كما لوحظ نشاط فائق مضاد للجراثيم ضد السلالات المختارة في كلتا العينتين بحد أدنى من التركيز المثبط الذي تراوح بين ٠.٥-١٪. كما كان التأثير المضاد للأكسدة ذو نشاط معتدل في كلتا العيّنتين. علاوةً على ذلك لقد أظهرت عينات السوق الهندي والسعودي قيمتي التأثير المضاد للالتهابات المعرفة بتركيز المادة الموافقة للتثبيط النصفي بنسبة ٥٣.١٢٪ و٥٥.٢٦ ميكروغرام/مل على التوالي في اختبار تثبيط تمسخ الألبومين. مما يشير إلى إمكانات مضادة للالتهابات مماثلة أو شبيهة لتأثير دواء الإيبوبروفين. الاستنتاجات: أن مكونات تركيبة الزيتين من كلتا العيّنتين متشابهتين نوعيا ولكن مع وجود بعض الاختلافات الكمية لكل مركب تم التعرف عليه. كما أنه لم يلحظ أي اختلافات كبيرة في الخصائص الدوائية لهما مما يتطلب إجراء المزيد من الدراسات لمزيد من التأكيد. Abstract: Objective: This work attempted to isolate, identify, and correlate the composition of essential oils (EOs) and pharmacological properties of two imported Amomum subulatum fruit samples. These samples were collected from Indian and KSA local supermarkets to ensure consistency in their therapeutic effects. Methods: EOs were extracted from Indian and KSA A. subulatum fruit samples using a hydro-distillation method and identified by gas chromatography-mass spectrometry (GC–MS). Antimicrobial activity against gram-negative bacteria (Pseudomonas aeruginosa, Escherichia coli, and Acinetobacter baumannii) was determined using minimum inhibitory (MIC) and minimum bactericidal concentration methods. Antioxidant and anti-inflammatory activities were determined using a 2,2-diphenyl-1-picrylhydrazyl-induced free radical assay, and a bovine albumin inhibitory assay, respectively. These analyses were performed to evaluate the pharmacological activities of the substances. Results: GC–MS retention times of both samples demonstrated 56 bioactive ingredients with different percentages. The principal bioactive compounds in the Indian and Saudi Arabian EO samples were 1,8-cineole (44.24% and 46.22%, respectively), α-terpineol (7.47% and 7.04%, respectively), terpinen-4-ol (5.01% and 4.83%, respectively), geraniol D (4.05% and 3.54%, respectively), and β-pinene (3.38% and 3.98%, respectively). Superior antimicrobial activity against the selected strains was observed for both samples, with an MIC range of 0.5%–1%. Antioxidant assays demonstrated moderate activity in both samples. Moreover, the Indian and Saudi Arabian samples exhibited IC50 values of 53.12% and 55.26 μg/mL, respectively, in albumin denaturation inhibition assays. This indicated an outstanding anti-inflammatory potential comparable to ibuprofen. Conclusions: The composition of EOs from both samples exhibited similar qualitative but different quantitative variability. No major variations in the pharmacological properties of EOs were observed. More studies are essential for further validation of our study findings.

The Caribbean reef shark (Carcharhinus perezi; Poey, 1876) is a medium to large-bodied coastal and reef-associated predator found throughout the subtropical and tropical waters of the Atlantic Ocean and Caribbean Sea, although its populations are increasingly threatened by overfishing. We describe the first mitochondrial genome sequence for this species, using Illumina MiSeq sequencing of an individual from The Bahamas. We report the mitogenome sequence of the Caribbean reef shark to be 16,709 bp and composed two rRNA genes, 22 tRNA genes, 13 protein-coding genes, 2 non-coding regions; the D-loop control region and the origin of light-strand replication. We discuss the implications of this new information on future monitoring efforts and conservation measures such as marine protected areas, and urge for greater application of mitochondrial studies of sharks in the Atlantic Ocean.

Summary: The ARID1A subunit of SWI/SNF chromatin remodeling complexes is a potent tumor suppressor. Here, a degron is applied to detect rapid loss of chromatin accessibility at thousands of loci where ARID1A acts to generate accessible minidomains of nucleosomes. Loss of ARID1A also results in the redistribution of the coactivator EP300. Co-incident EP300 dissociation and lost chromatin accessibility at enhancer elements are highly enriched adjacent to rapidly downregulated genes. In contrast, sites of gained EP300 occupancy are linked to genes that are transcriptionally upregulated. These chromatin changes are associated with a small number of genes that are differentially expressed in the first hours following loss of ARID1A. Indirect or adaptive changes dominate the transcriptome following growth for days after loss of ARID1A and result in strong engagement with cancer pathways. The identification of this hierarchy suggests sites for intervention in ARID1A-driven diseases.

Insulin resistance has been associated with depressive symptoms and depressive syndrome. Studies have attempted to assess the relationship between metabolic syndrome and depression and more specifically insulin resistance and depression. Studies have also been carried out to assess the direction of this relationship. This brief review is purported to present and discuss the currently available literature evidence about relationship of insulin resistance with depression and the treatment implications of this relationship. The presence of insulin resistance in an individual is positively associated with increased depressive symptoms and the presence of depressive symptoms is found to be associated with insulin resistance. However, a causal relationship could not be established. Prospective study designs can help to enhance our knowledge in finding a causal relationship. Intervention studies that will further help in treatment decisions are required.

The NR5A-family nuclear receptors are highly conserved and function within the somatic follicle cells of the ovary to regulate folliculogenesis and ovulation in mammals; however, their roles in Drosophila ovaries are largely unknown. Here, we discover that Ftz-f1, one of the NR5A nuclear receptors in Drosophila, is transiently induced in follicle cells in late stages of oogenesis via ecdysteroid signaling. Genetic disruption of Ftz-f1 expression prevents follicle cell differentiation into the final maturation stage, which leads to anovulation. In addition, we demonstrate that the bHLH/PAS transcription factor Single-minded (Sim) acts as a direct target of Ftz-f1 to promote follicle cell differentiation/maturation and that Ftz-f1’s role in regulating Sim expression and follicle cell differentiation can be replaced by its mouse homolog steroidogenic factor 1 (mSF-1). Our work provides new insight into the regulation of follicle maturation in Drosophila and the conserved role of NR5A nuclear receptors in regulating folliculogenesis and ovulation.

Earlier studies suggested that Mycobacterium tuberculosis (Mtb) proteins exported within the host macrophage play an essential role in tuberculosis pathogenesis. In fact, Mtb proteins interact with and deactivate key regulators of many macrophage functions such as phago-lysosome fusion and antigen presentation, resulting in the intracellular persistence of pathogenic mycobacteria. Cpn60.2 is an abundant Mtb chaperone protein, restricted to cell cytoplasm and surface, that was reported to be essential for bacterial growth. Here, we provide evidence that once Mtb is ingested by the macrophage, Cpn60.2 is able to detach from the bacterial surface and crosses the phagosomal membrane towards mitochondria organelles. Once there, Cpn60.2 interacts with host mortalin, a member of the HSP 70 gene family that contributes to apoptosis modulation. In this regard, we showed that Cpn60.2 blocks macrophage apoptosis, a phenotype that is reversed when cells are pretreated with a specific mortalin inhibitor. Our findings have extended the current knowledge of the Mtb Cpn60.2 functions to add a strong anti-apoptotic activity dependent on its interaction with mitochondrial mortalin, which otherwise promotes Mtb survival in the hostile macrophage environment.

Aim: To study the Phytochemical constituents of dried aerial parts of Swertia chirata Linn (family Gentianaceae). Methods: The ethanolic extract of the aerial parts of plant S. chirata was subjected to column chromatography and was eluted with petroleum ether and chloroform of various concentrations to yield compound SC-1, 2 and 3 and their structures were elucidated on the basis of chemical methods and spectral techniques such as Ultraviolet (UV), Fourier Transform Infrared (FTIR), Hydrogen Nuclear Magnetic Resonance (1HNMR), Carbon Nuclear Magnetic Resonance (13CNMR), and Mass spectrometry (MS). Results: Three compounds were isolated and their structures were determined as (a) Olean-12-ene-18α H-3-one-9α-ol, (b) Olean-12-ene-18α H-3-one-19β-ol and (c) Olean-12-en-18α H-3-one. Conclusion: Chemical and spectral investigation of extract furnished three novel oleanenone triterpene glycosides from the genus Swertia for the first time.

Oligodendrocyte precursor cells (OPCs), also known as NG2 glia, arise from neural progenitor cells in the embryonic ganglionic eminences that also generate inhibitory neurons. They are ubiquitously distributed in the central nervous system, remain proliferative through life, and generate oligodendrocytes in both gray and white matter. OPCs exhibit some lineage plasticity, and attempts have been made to reprogram them into neurons, with varying degrees of success. However, little is known about how epigenetic mechanisms affect the ability of OPCs to undergo fate switch and whether OPCs have a unique chromatin environment around neuronal genes that might contribute to their lineage plasticity. Our bioinformatic analysis of histone posttranslational modifications at interneuron genes in OPCs revealed that OPCs had significantly fewer bivalent and repressive histone marks at interneuron genes compared to astrocytes or fibroblasts. Conversely, OPCs had a greater degree of deposition of active histone modifications at bivalently marked interneuron genes than other cell types, and this was correlated with higher expression levels of these genes in OPCs. Furthermore, a significantly higher proportion of interneuron genes in OPCs than in other cell types lacked the histone posttranslational modifications examined. These genes had a moderately high level of expression, suggesting that the “no mark” interneuron genes could be in a transcriptionally “poised” or “transitional” state. Thus, our findings suggest that OPCs have a unique histone code at their interneuron genes that may obviate the need for erasure of repressive marks during their fate switch to inhibitory neurons.

Aim: Ticks are obligate ectoparasites that have an impact on wide range of vertebrates and also act as a potential vector for the transmission of tropical theileriosis, babesiosis, etc., causing significant loss to livestock production worldwide. While feeding, they introduce their saliva containing different bioactive molecules into the host. These molecules have the capability to counteract the host hemostatic mechanism to suck host blood successfully. Therefore, the study was aimed to isolate anti-platelet aggregating peptides from salivary gland extract (SGE) of Hyalomma anatolicum ticks, a commonly available tick in India. Materials and Methods: Female H. anatolicum salivary glands were dissected out and SGE was prepared by homogenizing it in a suitable buffer under ice. Extract so obtained was fractionated by gel filtration chromatography using Sephacryl S-200 column. Total protein concentration in fractions was estimated and bovine platelets were isolated, stimulated with thrombin (positive control), treated with Gly-Pro-Arg-Pro amide (negative control) and with salivary gland fractions for identification of proteins/peptides having anti-platelet aggregating activities. Results: Proteins/peptides present in various salivary gland fractions inhibited the bovine platelet aggregation and the percent inhibition ranged between 33% and 35.8%. Conclusion: The results suggests that the fractions of H. anatolicum salivary glands possess thrombin-induced anti-platelet aggregating activity and which could be further exploited for raising anti-tick vaccine and also for therapeutic purpose.

The yeast Chd1 protein acts to position nucleosomes across genomes. Here, we model the structure of the Chd1 protein in solution and when bound to nucleosomes. In the apo state, the DNA-binding domain contacts the edge of the nucleosome while in the presence of the non-hydrolyzable ATP analog, ADP-beryllium fluoride, we observe additional interactions between the ATPase domain and the adjacent DNA gyre 1.5 helical turns from the dyad axis of symmetry. Binding in this conformation involves unravelling the outer turn of nucleosomal DNA and requires substantial reorientation of the DNA-binding domain with respect to the ATPase domains. The orientation of the DNA-binding domain is mediated by sequences in the N-terminus and mutations to this part of the protein have positive and negative effects on Chd1 activity. These observations indicate that the unfavorable alignment of C-terminal DNA-binding region in solution contributes to an auto-inhibited state.

A study on heavy metals assessment in the water of Sahastradhara hill-stream was conducted with different five sites at significant differences. The present paper deals with the water quality status of Sahastradhara stream by the assessment of heavy metals. Heavy Metals were found in fluctuated trend from first upstream to last downstream. The values of almost all Heavy Metals were found in increasing manner especially after the fourth sampling site. After the third sampling station, a solid waste dumping site was found. So, there may be a relation between heavy metals in stream water and solid waste dumping site. Concentrations of all Heavy Metals at fourth and fifth sampling site were found very high. DOI: http://dx.doi.org/10.3126/ije.v3i3.11076 International Journal of Environment Vol.3(3) 2014: 164-172

Background: Attempted suicide is one of the major emergencies in psychiatry. Suicide attempts are considered to be the best predictors of an eventual completed suicide. Data of patients presenting with attempted suicide to the emergency settings at mental health institute settings is scanty in India. Aims: The study was carried out to assess the socio-demographic and clinical profile of the patients with suicidal attempt attending emergency services at a teaching Mental Health Institute in Northern India. Methods: Case records of all patients with attempted suicide attending emergency services at Institute of Human Behaviour and Allied Sciences (IHBAS) for one calendar year were reviewed. Socio-demographic and clinical details of the patients were retrieved on a Performa specifically designed for this study. Results: Of all the patients who attended emergency services during the study period, 56 patients had suicidal attempts. Majority of them were married (66%), males (57%), in the age group of 20-40 years (61%), were from nuclear families (80.4%) and had urban domicile (83.9%). Severe Mental Illnesses were found in about 70% of the cases with duration of illness more than 24 months in 39.2%. Thirty six (64.3%) patients had 1 suicide attempt while 18 (32.3%) had 2 or more attempts in preceding one month. In 70% - 80% of the cases, the lethality and intentionality of the index episode was found to be moderate to high. Most of the cases needed inpatient treatment. Conclusion: Assessment and management of patients presenting to emergency room with suicidal behavior is a key factor in preventing suicide. There is a pressing need to identify the socio-demographic and clinical factors affecting risk of suicide in a given case. Every case presenting with suicidal ideations or attempt should be evaluated in detail.

Aim: Catatonia is caused by a variety of psychiatric and organic conditions. The onset, clinical profile, and response to treatment may vary depending on the underlying cause. The study is an attempt to explore clinical profile, possible etiological correlates with neurotic/psychotic spectrum illnesses, and response to treatment and outcome in patients of catatonia. Materials and Methods: Retrospective chart analysis by using semistructured data sheet for the analysis of sociodemographic data, clinical profile, precipitating event, and response to treatment in patients with catatonic symptoms admitted to IHBAS (Institute of Human Behaviour and Allied Sciences, New Delhi, India) from January 2009 to December 2010 was undertaken. Results: Catatonia was commonly observed in patients with the following profile - late twenties, female, Hindu religion, urban background, and housewives. Psychotic spectrum disorder (57%, N=35) was the most commonly entertained diagnosis and affective disorder (18%, N=11) being the second common. Thirty four percent of the subjects responded to lorazepam treatment and rest required modified electroconvulsive therapy (MECT). Conclusion: Catatonia is more likely to be associated with Schizophrenia and Other Psychotic Disorders in Indian settings. Majority of patients responded to therapy either by lorazepam alone or to its augmentation with modified ECT. The study being a retrospective one, the sample being representative of the treatment seeking group only, and unavailability of the follow up data were the limitations of the study

Within the genomes of metazoans, nucleosomes are highly organised adjacent to the binding sites for a subset of transcription factors. Here we have sought to investigate which chromatin remodelling enzymes are responsible for this. We find that the ATP-dependent chromatin remodelling enzyme SNF2H plays a major role organising arrays of nucleosomes adjacent to the binding sites for the architectural transcription factor CTCF sites and acts to promote CTCF binding. At many other factor binding sites SNF2H and the related enzyme SNF2L contribute to nucleosome organisation. The action of SNF2H at CTCF sites is functionally important as depletion of CTCF or SNF2H affects transcription of a common group of genes. This suggests that chromatin remodelling ATPase's most closely related to the Drosophila ISWI protein contribute to the function of many human gene regulatory elements.

A series of thiazolidin-4-one (2a–h; 3a–h), azetidin-2-one (4a–h) and 1,3,4-oxadiazole (5a–h) derivatives of isoninicotinic acid hydrazide (INH) were synthesized in order to obtain new compounds with potential anti-inflam­matory, analgesic, ulcerogenic and lipid peroxidation activities. The structures of the new compounds were supported by their IR, 1H-NMR and mass spectral data. All compounds were evaluated for their anti-inflammatory activity by the carrageenan-induced rat paw edema test method. Eleven of the new com­pounds, out of 32, showed very good anti-inflammatory activity in the carra­geenan-induced rat paw edema test, with significant analgesic activity in the tail immersion method together with negligible ulcerogenic action. The com­pounds, which showed less ulcerogenic action, also showed reduced malondial­dehyde content (MDA), which is one of the by-products of lipid peroxidation. The study showed that the compounds inhibited the induction of gastric mu­cosal lesions and it can be suggested from the results that their protective ef­fects may be related to inhibition of lipid peroxidation in the gastric mucosa.

In this study a series ofnew1-(2-aryl-5-phenethyl-1,3,4-oxadiazol-3(2H)-yl)ethanones 2a-e was synthesized by the cyclization of imines 1a-e using acetic anhydride. The products were evaluated for anti-bacterial and anti-fungal activity. Among the newly synthesized compounds, 1-(2-(4-(dimethylamino)phenyl)-5-phenethyl-1,3,4-oxadiazol-3(2H)-yl)ethanone (2a)and1-(2-(4-chlorophenyl)-5-phenethyl-1,3,4-oxadiazol-3(2H)-yl)ethanone (2b)were found to possess maximum activity against the tested strains of S. aureus and P. aeruginosa. It was concluded that para-substitution enhances the activity of synthesized oxadiazoles.

Mr. T, a 28-year-old unmarried male, a diagnosed case of Glucose-6 Phosphate Dehydrogenase (G6PD) deficiency since childhood, presented with 13 years of psychotic illness and disturbed biological functions. He showed poor response to antipsychotics and mood stabilizers and had three prior admissions to Psychiatry. There was a family history of psychotic illness. The General Physical Examination and Systemic Examination were unremarkable. Mental Status Examination revealed increased psychomotor activity, pressure of speech, euphoric affect, prolixity, delusion of persecution, delusion of grandiosity, delusion of control, thought withdrawal and thought insertion, and second and third person auditory hallucinations, with impaired judgment and insight. A diagnosis of schizophrenia paranoid type, with a differential diagnosis of schizoaffective disorder manic subtype, was made. This case is being reported for its rarity and atypicality of clinical presentation, as well as a course of psychotic illness in the G6PD Deficiency state,with its implications on management.

Defining the mechanisms of Mycobacterium tuberculosis (Mtb) persistence in the host macrophage and identifying mycobacterial factors responsible for it are keys to better understand tuberculosis pathogenesis. The emerging picture from ongoing studies of macrophage deactivation by Mtb suggests that ingested bacilli secrete various virulence determinants that alter phagosome biogenesis, leading to arrest of Mtb vacuole interaction with late endosomes and lysosomes. While most studies focused on Mtb interference with various regulators of the endosomal compartment, little attention was paid to mechanisms by which Mtb neutralizes early macrophage responses such as the NADPH oxidase (NOX2) dependent oxidative burst. Here we applied an antisense strategy to knock down Mtb nucleoside diphosphate kinase (Ndk) and obtained a stable mutant (Mtb Ndk-AS) that displayed attenuated intracellular survival along with reduced persistence in the lungs of infected mice. At the molecular level, pull-down experiments showed that Ndk binds to and inactivates the small GTPase Rac1 in the macrophage. This resulted in the exclusion of the Rac1 binding partner p67(phox) from phagosomes containing Mtb or Ndk-coated latex beads. Exclusion of p67(phox) was associated with a defect of both NOX2 assembly and production of reactive oxygen species (ROS) in response to wild type Mtb. In contrast, Mtb Ndk-AS, which lost the capacity to disrupt Rac1-p67(phox) interaction, induced a strong ROS production. Given the established link between NOX2 activation and apoptosis, the proportion of Annexin V positive cells and levels of intracellular active caspase 3 were significantly higher in cells infected with Mtb Ndk-AS compared to wild type Mtb. Thus, knock down of Ndk converted Mtb into a pro-apoptotic mutant strain that has a phenotype of increased susceptibility to intracellular killing and reduced virulence in vivo. Taken together, our in vitro and in vivo data revealed that Ndk contributes significantly to Mtb virulence via attenuation of NADPH oxidase-mediated host innate immunity.

Among chromatin remodeling factors, the ISWI family displays a nucleosome-enhanced ATPase activity coupled to DNA translocation. While these enzymes are known to bind to DNA, their activity has not been fully characterized. Here we use TEM imaging and single molecule manipulation to investigate the interaction between DNA and yeast Isw1a. We show that Isw1a displays a highly cooperative ATP-independent binding to and bridging between DNA segments. Under appropriate tension, rare single nucleation events can sometimes be observed and loop DNA with a regular step. These nucleation events are often followed by binding of successive complexes bridging between nearby DNA segments in a zipper-like fashion, as confirmed by TEM observations. On nucleosomal substrates, we show that the specific ATP-dependent remodeling activity occurs in the context of cooperative Isw1a complexes bridging extranucleosomal DNA. Our results are interpreted in the context of the recently published partial structure of Isw1a and support its acting as a "protein ruler" (with possibly more than one tick).

Candida albicans, a human fungal pathogen, undergoes morphogenetic changes that are associated with virulence. We report here that GAL102 in C. albicans encodes a homolog of dTDP-glucose 4,6-dehydratase, an enzyme that affects cell wall properties as well as virulence of many pathogenic bacteria. We found that GAL102 deletion leads to greater sensitivity to antifungal drugs and cell wall destabilizing agents like Calcofluor white and Congo red. The mutant also formed biofilms consisting mainly of hyphal cells that show less turgor. The NMR analysis of cell wall mannans of gal102 deletion strain revealed that a major constituent of mannan is missing and the phosphomannan component known to affect virulence is greatly reduced. We also observed that there was a substantial reduction in the expression of genes involved in biofilm formation but increase in the expression of genes encoding glycosylphosphatidylinositol-anchored proteins in the mutant. These, along with altered mannosylation of cell wall proteins together might be responsible for multiple phenotypes displayed by the mutant. Finally, the mutant was unable to grow in the presence of resident peritoneal macrophages and elicited a weak pro-inflammatory cytokine response in vitro. Similarly, this mutant elicited a poor serum pro-inflammatory cytokine response as judged by IFNγ and TNFα levels and showed reduced virulence in a mouse model of systemic candidiasis. Importantly, an Ala substitution for a conserved Lys residue in the active site motif YXXXK, that abrogates the enzyme activity also showed reduced virulence and increased filamentation similar to the gal102 deletion strain. Since inactivating the enzyme encoded by GAL102 makes the cells sensitive to antifungal drugs and reduces its virulence, it can serve as a potential drug target in combination therapies for C. albicans and related pathogens.

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BCG has been administered globally for more than 75 years, yet tuberculosis (TB) continues to kill more than 2 million people annually. Further, BCG protects childhood TB but is quite inefficient in adults. This indicates that BCG fails to induce long-term protection. Hence there is a need to explore alternative vaccination strategies that can stimulate enduring T cell memory response. Dendritic cell based vaccination has attained extensive popularity following their success in various malignancies. In our previous study, we have established a novel and unique vaccination strategy against Mycobacterium tuberculosis (M. tb) and Salmonella typhimurium by utilizing infected macrophages (IM). In short-term experiments (30 days), substantial degree of protection was observed. However, remarkable difference was not observed in long-term studies (240 days) due to failure of the vaccine to generate long-lasting memory T cells. Hence, in the present study we employed T cell memory augmenting cytokines IL-1+IL-6+TNF-α and IL-7+IL-15 for the induction of the enhancement of long-term protection by the vaccine. We co-administered the M. tb infected macrophages vaccine with IL-1+IL-6+TNF-α (IM-1.6.α) and IL-7+IL-15 (IM-7.15). The mice were then rested for a reasonably large period (240 days) to study the bona fide T cell memory response before exposing them to aerosolized M. tb. IM-1.6.α but not IM-7.15 significantly improved memory T cell response against M. tb, as evidenced by recall responses of memory T cells, expansion of both central as well as effector memory CD4 and CD8 T cell pools, elicitation of mainly Th1 memory response, reduction in the mycobacterial load and alleviated lung pathology. Importantly, the protection induced by IM-1.6.α was significantly better than BCG. Thus, this study demonstrates that not only antigen-pulsed DCs can be successfully employed as vaccines against cancer and infectious diseases but also macrophages infected with M. tb can be utilized with great efficacy especially in protection against TB.