Dark Matter spikes around Sgr A* in γ\gamma-rays

We use H.E.S.S. $\gamma$-ray observations of Sgr A* to derive novel limits on the Dark Matter (DM) annihilation cross-section. We quantify their dependence on uncertainties i) in the DM halo profile, which we vary from peaked to cored, and ii) in the shape of the DM spike around Sgr A*, dynamically heated by the nuclear star cluster. For peaked halo profiles and depending on the heating of the spike, our limits are the strongest existing ones for DM masses above a few TeV. Our study contributes to assessing the influence of the advancements in our knowledge of the Milky Way on determining the properties of DM particles.Comment: Published in JCAP, added discussion on energy resolution impact for DM annihilation into photons channe

A charge reversal differentiates (p)ppGpp synthesis by monofunctional and bifunctional Rel proteins

A major regulatory mechanism evolved by microorganisms to combat stress is the regulation mediated by (p)ppGpp (the stringent response molecule), synthesized and hydrolyzed by Rel proteins. These are divided into bifunctional and monofunctional proteins based on the presence or absence of the hydrolysis activity. Although these proteins require Mg2+ for (p)ppGpp synthesis, high Mg2+ was shown to inhibit this reaction in bifunctional Rel proteins from Mycobacterium tuberculosis and Streptococcus equisimilis. This is not a characteristic feature in enzymes that use a dual metal ion mechanism, such as DNA polymerases that are known to carry out a similar pyrophosphate transfer reaction. Comparison of polymerase Polβ and RelSeq structures that share a common fold led to the proposal that the latter would follow a single metal ion mechanism. Surprisingly, in contrast to bifunctional Rel, we did not find inhibition of guanosine 5′-triphosphate, 3′-diphosphate (pppGpp) synthesis at higher Mg2+ in the monofunctional RelA from Escherichia coli. We show that a charge reversal in a conserved motif in the synthesis domains explains this contrast; an RXKD motif in the bifunctional proteins is reversed to an EXDD motif. The differential response of these proteins to Mg2+ could also be noticed in fluorescent nucleotide binding and circular dichroism experiments. In mutants where the motifs were reversed, the differential effect could also be reversed. We infer that although a catalytic Mg2+ is common to both bifunctional and monofunctional proteins, the latter would utilize an additional metal binding site formed by EXDD. This work, for the first time, brings out differences in (p)ppGpp synthesis by the two classes of Rel proteins

Effect of a behaviour-change intervention on handwashing with soap in India (SuperAmma): a cluster-randomised trial.

BACKGROUND: Diarrhoea and respiratory infections are the two biggest causes of child death globally. Handwashing with soap could substantially reduce diarrhoea and respiratory infections, but prevalence of adequate handwashing is low. We tested whether a scalable village-level intervention based on emotional drivers of behaviour, rather than knowledge, could improve handwashing behaviour in rural India. METHODS: The study was done in Chittoor district in southern Andhra Pradesh, India, between May 24, 2011, and Sept 10, 2012. Eligible villages had a population of 700-2000 people, a state-run primary school for children aged 8-13 years, and a preschool for children younger than 5 years. 14 villages (clusters) were selected, stratified by population size (1200), and randomly assigned in a 1:1 ratio to intervention or control (no intervention). Clusters were enrolled by the study manager. Random allocation was done by the study statistician using a random number generator. The intervention included community and school-based events incorporating an animated film, skits, and public pledging ceremonies. Outcomes were measured by direct observation in 20-25 households per village at baseline and at three follow-up visits (6 weeks, 6 months, and 12 months after the intervention). Observers had no connection with the intervention and observers and participant households were told that the study was about domestic water use to reduce the risk of bias. No other masking was possible. The primary outcome was the proportion of handwashing with soap at key events (after defecation, after cleaning a child's bottom, before food preparation, and before eating) at all follow-up visits. The control villages received a shortened version of the intervention before the final follow-up round. Outcome data are presented as village-level means. FINDINGS: Handwashing with soap at key events was rare at baseline in both the intervention and control groups (1% [SD 1] vs 2% [1]). At 6 weeks' follow-up, handwashing with soap at key events was more common in the intervention group than in the control group (19% [SD 21] vs 4% [2]; difference 15%, p=0·005). At the 6-month follow-up visit, the proportion handwashing with soap was 37% (SD 7) in the intervention group versus 6% (3) in the control group (difference 31%; p=0·02). At the 12-month follow-up visit, after the control villages had received the shortened intervention, the proportion handwashing with soap was 29% (SD 9) in the intervention group and 29% (13) in the control group. INTERPRETATION: This study shows that substantial increases in handwashing with soap can be achieved using a scalable intervention based on emotional drivers. FUNDING: Wellcome Trust, SHARE

A clinico-pathological study of pigmented cutaneous lesions: a one-year prospective study in a tertiary care hospital

Background: Pigmented lesions are group of lesions which have melanocytic proliferation with very common clinical presentation. Diagnosing these pigmented lesions and differentiating cutaneous melanocytic lesions from non-melanocytic lesions poses a great challenge for the pathologist.Methods: A Prospective study was conducted for one year from June 2016 to June 2017 sent to the Department of Pathology, Andhra Medical College, Visakhapatnam, a tertiary care centre in southern India consisting of 44 pigmented lesions. Specimens were formalin fixed and the tissue was adequately processed for histopathological examination. The sections were stained routinely with hematoxylin and eosin stain and examined under light microscopy.Results: Out of 44 cases, 24 cases were cutaneous melanocytic lesions which include benign naevi 22 (50%) and 2 (4.6%) malignant melanoma cases. The other 20 cases were cutaneous non melanocytic lesions which include 5 (11.4%) pigmented seborrheic keratosis, 6 (13.7%) pigmented basal cell carcinoma, 1 (2.3%) pigmented actinic keratosis and 8 (18%) cases of naevus sebaceous. Most common effected age group was <21 years (31.81%), male: female ratio is 1:2 and most common site involved was face 29 cases (65.9%). Most common pigmented lesions were benign melanocytic nevi 22 (50%) followed by naevus sebaceous 8 (18%) cases. 32 (72.71%) cases were consistent with both clinico-histopathological correlation.Conclusions: Benign melanocytic nevi are most common lesions obtained, seborric keratosis and pigmented basal cell carcinoma were most common mimickers of melanocytic lesions, hence a careful histopathological diagnosis is important

CLINICAL PROFILE, PRESCRIPTION PATTERNS, AND ADVERSE DRUG REACTIONS IN PATIENTS WITH VITILIGO: A PROSPECTIVE STUDY

Objectives: The objectives of the study were to assess clinical profile (age of onset, age of presentation, gender, site of involvement, severity (stage), type of vitiligo, triggering factors, and associated diseases), prescription patterns (monotherapy, combination therapy, oral, topical, and therapeutic categories of drugs prescribed) and to monitor and report adverse drug reactions (based on World Health Organization [WHO] causality assessment scale) in vitiligo patients. Methods: A hospital-based prospective observational study was carried out by evaluating and assessing the clinical profile and prescription patterns of 85 patients who attended dermatology venereology and leprosy (DVL) outpatient department at Sri Padmavathi Medical College for Women, SVIMS, Tirupati, over a period of 6 months from June 2019 to December 2019. Results: In our study, forty four (51.77%) patients were female, vitiligo vulgaris is the most common morphological type observed in twenty seven (31.76%) patients. 31–50 years was the predominant age group. The mean age of onset and presentation was 38.35 (standard deviation of 18.37) and 43.27 (standard deviation of 17.96) years, respectively. Forty-one (48.23%) patients were having Stage 1 vitiligo. Fifty (58.85%) patients were having vitiligo at more than 1 site. Twelve (14.11%) patients were having a positive family history of vitiligo. Thirty-seven (43.53%) patients had triggering factors. Associated diseases were found in thirty (35%) patients. Combination therapy was given to sixty one (71.77%) patients. Topical medications were given to fifty two (61.18%) patients. During the study, we did not have a single patient complaining of any adverse drug reaction. Conclusion: Longer the time after appearance of vitiligo, lesser the number of patients attending follow-up. If vitiligo is diagnosed at the earliest stage, more are the chances for complete repigmentation. Patients with a poor economic background are less bothered about their skin condition and are not using medications properly

Perception and buying behaviour of consumers towards FPOs food products in Tamil Nadu

The present study was carried out to map the perception of consumers and to identify the factors influencing the consumer buying behaviour towards the food products of FPOs in Tamil Nadu. The results concluded that majority of the respondents purchased jaggery and sugar, cold pressed oil, snacks and millets category from the retail shops of FPOs. The quality and nutrient content were major product traits influencing consumers for purchasing the FPO food products. Most of the consumers felt that the quality and price of the food products were high in FPOs retail stores compared with other retail stores. So, FPOs should target high income people with high purchasing power who appreciate quality. Local people were purchasing the FPOs food products anytime. FPOs can devise effective marketing strategies to attract new customers from local and non-local customers. Most of the people have no awareness about FPOs retail outlets. Therefore, FPOs should pay attention in promoting their products and increasing the retail outlets for attracting the consumers and increasing the sales

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570