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Cardiovascular diseases (CVDs) are the leading cause of death globally and the prevention and control of these diseases tend to entail longer and larger social and economic commitments on the part of governments. This systematic review (SR) aims to understand the quantum, diversity, and quality of implementation research (IR) done in the field of CVDs in India with a view to maximizing the utility of the efforts made by the government. The evidence was collated on IR on CVDs in India conducted in the past 20 years (2001–2021) using a SR approach. The SR was drafted using Preferred Reporting Items for SRs and Meta-analyses guidelines. Academic databases (PubMed, Embase, and Science Direct) and nonacademic databases (Google Scholar and ProQuest) were chosen, along with repositories of gray literature. Retrieved articles were screened for titles and abstracts and assessed by two independent reviewers. The articles also underwent a concomitant risk of bias assessment utilizing checklists (STARI, STROBE, CONSORT, etc.,) and a narrative summary was drafted using SwiM guidelines. In the final analysis, 10 articles that fitted the inclusion criteria of IR for CVD in India were included, of which seven were directed at IR on hypertension, and three were related to coronary artery disease, myocardial infarction, and stroke. Acceptability, adoption, and feasibility were the only attributes of IR that were explored in these studies.

Abstract The Hypothalmic-Pituitary-Adrenal axis also known as the HPA axis is central to stress response. It also acts as the relay center between the body and the brain. We analysed hypothalamic proteome from mice subjected to chronic social defeat paradigm using iTRAQ based quantitative proteomics to identify changes associated with stress response. We identified greater than 2000 proteins after processing our samples analysed through Q-Exactive (Thermo) and Orbitrap Velos (Thermo) at 5% FDR. Analysis of data procured from the runs showed that the proteins whose levels were affected belonged primarily to mitochondrial and metabolic processes, translation, complement pathway among others. We also found increased levels of fibrinogen, myelin basic protein (MBP) and neurofilaments (NEFL, NEFM, NEFH) in the hypothalamus from socially defeated mice. Interestingly, research indicates that these proteins are upregulated in blood and CSF of subjects exposed to trauma and stress. Since hypothalamus secreted proteins can be found in blood and CSF, their utility as biomarkers in depression holds an impressive probability and should be validated in clinical samples.

Pregnancy is a complex process involving complex molecular interaction networks, such as between miRNA–protein, protein–protein, metabolite–metabolite, and protein–metabolite interactions. Advances in technology have led to the identification of many pregnancy-associated microRNA (miRNA), protein, and metabolite fingerprints in dairy cows. An array of miRNA, protein, and metabolite fingerprints produced during the early pregnancy of dairy cows were described. We have found the in silico interaction networks between miRNA–protein, protein–protein, metabolite–metabolite, and protein–metabolite. We have manually constructed miRNA–protein–metabolite interaction networks such as bta-miR-423-3p–IGFBP2–PGF2α interactomes. This interactome is obtained by manually combining the interaction network formed between bta-miR-423-3p–IGFBP2 and the interaction network between IGFBP2–PGF2α with IGFBP2 as a common interactor with bta-miR-423-3p and PGF2α with the provided sources of evidence. The interaction between bta-miR-423-3p and IGFBP2 has many sources of evidence including a high miRanda score of 169, minimum free energy (MFE) score of −25.14, binding probability (p) of 1, and energy of −25.5. The interaction between IGFBP2 and PGF2α occurs at high confidence scores (≥0.7 or 70%). Interestingly, PGF2α is also found to interact with different metabolites, such as PGF2α–PGD2, PGF2α–thromboxane B2, PGF2α–PGE2, and PGF2α–6-keto-PGF1α at high confidence scores (≥0.7 or 70%). Furthermore, the interactions between C3–PGE2, C3–PGD2, PGE2–PGD2, PGD2–thromboxane B2, PGE2–thromboxane B2, 6-keto-PGF1α–thromboxane B2, and PGE2–6-keto-PGF1α were also obtained at high confidence scores (≥0.7 or 70%). Therefore, we propose that miRNA–protein–metabolite interactomes involving miRNA, protein, and metabolite fingerprints of early pregnancy of dairy cows such as bta-miR-423-3p, IGFBP2, PGF2α, PGD2, C3, PGE2, 6-keto-PGF1 alpha, and thromboxane B2 may form the key regulatory networks and players of pregnancy regulation in dairy cows. This is the first study involving miRNA–protein–metabolite interactomes obtained in the early pregnancy stage of dairy cows.

Plain language summary The new WHO Labour Care Guide (LCG) is an innovative partograph that emphasises women-centred, evidence-based care during labour and childbirth. Together with clinicians working at four hospitals in India, we will develop and test a strategy to implement the LCG into routine care in labour wards of these hospitals. We will use a randomised trial design where this LCG strategy is introduced sequentially in each of the four hospitals, in a random order. We will collect data on all women giving birth and their newborns during this period and analyse whether the LCG strategy has any effects on the use of Caesarean section, women’s and newborn’s health outcomes, and women’s experiences during labour and childbirth. While the trial is being conducted, we will also collect qualitative and quantitative data from doctors, nurses and midwives working in these hospitals, to understand their perspectives and experiences of using the LCG in their day-to-day work. In addition, we will collect economic data to understand how much the LCG strategy costs, and how much money it might save if it is effective. Through this study, our international collaboration will generate critical evidence and innovative tools to support implementation of the LCG in other countries.

ABO incompatibility between O blood group mother and non–O blood group neonate is common. It rarely causes anemia and hyperbilirubinemia in neonate, requiring invasive management. Direct antiglobulin test may be positive in these cases with immunoglobulin (Ig)-G antibody specificity. There are few cases of hemolytic disease of newborn due to ABO incompatibility between mother and newborn with non ̶ O blood group mother. After obtaining consent from the patient, we reported a case of incompatibility in a B blood group mother and A blood group neonate, and it was managed with phototherapy.

In 2015, Australia updated premigration screening for tuberculosis (TB) disease in children 2–10 years of age to include testing for infection with Mycobacterium tuberculosis and enable detection of latent TB infection (LTBI). We analyzed TB screening results in children

Abstract Background There is controversy regarding the impact of delayed graft function (DGF) on kidney transplant outcomes. We hypothesize that the duration of DGF, rather than DGF itself, is associated with long-term kidney graft function. Methods We analyzed all deceased donor kidney transplants (DDKT) done at our center between 2008 to 2020. We determined factors associated with DGF duration. DGF duration was assessed at three 14-day intervals: 28 DGF days. We studied the impact of DGF duration on survival and graft function and resource utilization, including hospital length of stay and readmissions. Results 1714 DDKT recipients were included, 59.4% (n = 1018) had DGF. The median DGF duration was 10 days IQR (6,15). The majority of recipients (95%) had resolution of DGF within 28 days. Donor factors associated with DGF days were longer cold ischemia time, donor on inotropes, older age, donation after circulatory death, higher terminal creatinine, and hypertension. Recipient factors associated with increased DGF duration included male sex, length on dialysis before transplant, and higher body mass index. There were no differences in acute rejection events or interstitial fibrosis progression by 4 months when comparing DGF days. The median length of stay was 3 days. However, readmissions increased with increasing DGF duration. Death-censored graft survival was not associated with the length of DGF except when DGF lasted > 28 days. Conclusions Inferior graft survival was observed only in recipients of DDKT with DGF lasting beyond 28 days. DGF lasting

Abstract Background The present study aimed to translate the Satisfaction with Amplification in Daily Life (SADL) questionnaire into Hindi. The translated questionnaire was administered to 80 Hindi-speaking individuals with hearing impairment. Results A good reliability was found in the questions using the Cronbach alpha test. The Pearson r correlation revealed a significant positive correlation between the degree of hearing loss and the global satisfaction scores. It suggests that there is a direct proportion of degree of hearing loss and global scores as the user has severe hearing loss the communication difficulty is also great in magnitude. Conclusion From the findings of the current study, it can be inferred that the Hindi translation of the SADL questionnaire can be used in clinical settings to measure the hearing aid/s outcome after fitting.

Background: COVID-19 pandemic led to increased self-medication of antimicrobials, vitamins, and immune boosters among the common people and consuming without prescription can lead to adverse consequences including antimicrobial resistance. Methods: A cross-sectional study was conducted on community pharmacies in Jodhpur, India. They were inquired regarding the prescription and increased sales (75% increase in vitamin C sales. Conclusion: There was an increase in the demand for COVID-19 medications without prescription. This study was unable to detect a significant increase in sales of antimicrobials, which is encouraging.

Mahaveer Singh,1 Abhishek Sharma,2 Kalpana Sankhala,3 Hemant Bareth,4 Supriya Suman4 1Department of Endocrinology, National Institute of Medical Sciences and Research Hospital, Nims University Rajasthan, Jaipur, India; 2Department of General Medicine, National Institute of Medical Sciences and Research Hospital, Nims University Rajasthan, Jaipur, India; 3Department of Pathology, National Institute of Medical Sciences and Research Hospital, Nims University Rajasthan, Jaipur, India; 4Department of Pharmacy Practice, Nims Institute of Pharmacy, Nims University Rajasthan, Jaipur, IndiaCorrespondence: Mahaveer SinghDepartment of Endocrinology, National Institute of Medical Sciences and Research Hospital, Nims University, Rajasthan, Jaipur, 303121, IndiaTel +918949836075Email drms.mamcmed@gmail.comAbstract: Disseminated histoplasmosis is a systemic disease caused by the dimorphic fungus Histoplasma capsulatum. Here, we are presenting a case of shock who was diagnosed to have primary adrenal insufficiency. This 68-year-old man had bilateral adrenal mass and later presented with chronic fever and ulcerated anal mass in the oncology clinic. The oncologist made a provisional diagnosis of anal carcinoma with adrenal metastasis. He was suspected of having an adrenal crisis and was admitted to the intensive care unit. He also had granulomatous hepatitis and acute kidney injury. The working diagnosis was changed to systemic inflammatory/infective pathology. The biopsy of the anal tissue done to look for the aetiology showed Histoplasma. He was started on oral itraconazole therapy. He improved symptomatically (resolution of fever, improvement in pain) when assessed after seven days. His anal ulcer healed after 21 days of itraconazole therapy.Keywords: adrenal metastasis, anal carcinoma, Histoplasma, ulcerated anal mass

Abstract Background Visual impairment is an important cause of disability in children. There is a lack of information on rehabilitation needs and low vision support services for children with visual impairment in Nepal. This is a pilot study designed to translate, culturally adapt and pre-test the Dutch version of the Participation and Activity Inventory for Children and Youth (PAI-CY) with visual impairment aged 7–17 years to develop a Nepali version. Questionnaires (PAI-CY versions for 7–12 and 13–17 years) were translated using standardized methods and were culturally adapted by a panel of experts. They were pretested to evaluate comprehensibility and relevance among six children with visual impairment and blindness. Finally, participants completed a questionnaire evaluation form. Results The translation and cultural adaptation process resulted in the adaptation of nine items to make them suitable for Nepali culture. Most children had comprehensibility problems with some specific items because of vocabulary, sentence structure and the composition of items. Most of the children were satisfied with the questionnaires. Conclusion The study resulted in the development of a Nepali version of the PAI-CY. We worked with a small group of content experts and a small but representative sample of children which allowed us to use rigorous translation procedures to address language and cultural differences. A population based study has been planned to investigate the psychometric properties of these questionnaires.

Balvir S Tomar,1 Mahaveer Singh,2 Deepak Nathiya,3 Abhishek Sharma,4 Eshan Sharma,4 Hemant Bareth,3 Supriya Suman,3 Darshan Purshotambhai Ruparelia,4 Jaykumar Bharatbhai Patel,4 Vikrant Kantilal Gajera4 On Behalf of the NIMS COVID 19 Investigator Group1Institute of Gastroenterology, Hepatology & Transplant, Nims University Rajasthan, Jaipur, India; 2Department of Endocrinology, National Institute of Medical Sciences and Research Hospital, Nims University Rajasthan, Jaipur, 303121, India; 3Department of Pharmacy Practice, Institute of Pharmacy, Nims University Rajasthan, Jaipur, India; 4Department of General Medicine, National Institute of Medical Sciences and Research Hospital, Nims University Rajasthan, Jaipur, IndiaCorrespondence: Mahaveer SinghDepartment of Endocrinology, National Institute of Medical Sciences and Research Hospital, Nims University Rajasthan, Jaipur, 303121, IndiaTel +91 8949836075Email drms.mamcmed@gmail.comDeepak NathiyaDepartment of Pharmacy Practice, Institute of Pharmacy, Nims University Rajasthan, Jaipur, 303121, IndiaTel +91 9929600137Email dnathiya@nimsuniversity.orgPurpose: To assess the prevalence of post-COVID symptoms in patients with recovered COVID-19 (nasopharyngeal RT PCR negative) who were discharged from an acute COVID care facility at a tertiary care teaching hospital in North India.Methods: This study was an observational study with retrospective data collection, conducted in the COVID follow-up clinic, a combined clinic of medicine and endocrinology. Patients discharged from the acute COVID care facility were recruited after 14 days of discharge if they fulfilled inclusion and exclusion criteria. The retrospective data was collected from the hospital records/EMR and analysed by the SPSSv23.Results: Fifty patients, who fulfilled the inclusion and exclusion criteria, were included in the study. The Mean age of patients was 53.4± 13.8 years (range 28– 77). Seventy six percent were male, and 38% had type 2 diabetes. Fever (94%), cough (78%) and breathlessness (68%), were the most common symptoms at presentation to acute care facility. Oxygen saturation at presentation had a negative correlation with D-Dimer, age, and C reactive protein. When patients were evaluated clinically, after 14 days (range 15 to 50 days) of the discharge, 82% of patients had at least one persistent symptom. Fatigue (74%) was the most common symptoms in follow-up followed by breathlessness (44%), and muscle weakness (36%). Two patients had persistent fever, even after negative RT PCR status.Conclusion: Patients discharged from the acute COVID care facility had a high prevalence of post-COVID symptoms even after 14 days.Keywords: COVID-19, diabetes, SARS-CoV-2, oxygen saturation, post-COVID

The SARS-CoV-2 virus needs multiple copies for its multiplication using an enzyme RNA-dependent RNA polymerase (RdRp). Remdesivir inhibits viral RdRp, controls the multiplication of the virus, and protects patients. However, treatment of COVID-19 with remdesivir involves adverse effects. Many ongoing clinical trials are exploring the potential of the combination of remdesivir with repurposed drugs by targeting multiple targets of virus and host human simultaneously. Better results were obtained with the remdesivir–baricitinib combination treatment for COVID-19 compared to the treatment with remdesivir alone. Notably, recovery from COVID-19 was found to be 8 days less via the remdesivir–baricitinib combination treatment as compared to remdesivir treatment alone. Furthermore, the mortality rate via the remdesivir–baricitinib combination treatment was lower compared to the remdesivir-only treatment. Remdesivir targets the SARS-CoV-2 enzyme while baricitinib targets the host human enzyme. Simultaneously, remdesivir and baricitinib as a combination inhibit their target viral RdRp and human Janus kinase, respectively. Ongoing trials for the combination of drugs will suggest in the future whether they may reduce the recovery time, reduce the mortality rate, and improve patient clinical status for noninvasive ventilation. In the future, simultaneously targeting virus replication enzymes and host human kinases may be the strategy for SARS-CoV-2 therapeutics.

Abstract Background Data on the cost-effectiveness of lifestyle-based diabetes prevention programs are mostly from high-income countries, which cannot be extrapolated to low- and middle-income countries. We performed a trial-based cost-effectiveness analysis of a lifestyle intervention targeted at preventing diabetes in India. Methods The Kerala Diabetes Prevention Program was a cluster-randomized controlled trial of 1007 individuals conducted in 60 polling areas (electoral divisions) in Kerala state. Participants (30–60 years) were those with a high diabetes risk score and without diabetes on an oral glucose tolerance test. The intervention group received a 12-month peer-support lifestyle intervention involving 15 group sessions delivered in community settings by trained lay peer leaders. There were also linked community activities to sustain behavior change. The control group received a booklet on lifestyle change. Costs were estimated from the health system and societal perspectives, with 2018 as the reference year. Effectiveness was measured in terms of the number of diabetes cases prevented and quality-adjusted life years (QALYs). Three times India’s gross domestic product per capita (US$6108) was used as the cost-effectiveness threshold. The analyses were conducted with a 2-year time horizon. Costs and effects were discounted at 3% per annum. One-way and multi-way sensitivity analyses were performed. Results Baseline characteristics were similar in the two study groups. Over 2 years, the intervention resulted in an incremental health system cost of US$2.0 (intervention group: US$303.6; control group: US$301.6), incremental societal cost of US$6.2 (intervention group: US$367.8; control group: US$361.5), absolute risk reduction of 2.1%, and incremental QALYs of 0.04 per person. From a health system perspective, the cost per diabetes case prevented was US$95.2, and the cost per QALY gained was US$50.0. From a societal perspective, the corresponding figures were US$295.1 and US$155.0. For the number of diabetes cases prevented, the probability for the intervention to be cost-effective was 84.0% and 83.1% from the health system and societal perspectives, respectively. The corresponding figures for QALY gained were 99.1% and 97.8%. The results were robust to discounting and sensitivity analyses. Conclusions A community-based peer-support lifestyle intervention was cost-effective in individuals at high risk of developing diabetes in India over 2 years. Trial registration The trial was registered with Australia and New Zealand Clinical Trials Registry ( ACTRN12611000262909 ). Registered 10 March 2011.

The SARS-CoV-2 infection triggers host kinases and is responsible for heavy phosphorylation in the host and also in the virus. Notably, phosphorylations in virus were achieved using the host enzyme for its better survival and further mutations. We have attempted to study and understand the changes that happened in phosphorylation during and post SARS-CoV-2 infection. There were about 70 phosphorylation sites detected in SARS-CoV-2 viral proteins including N, M, S, 3a, and 9b. Furthermore, more than 15,000 host phosphorylation sites were observed in SARS-CoV-2-infected cells. SARS-CoV-2 affects several kinases including CMGC, CK2, CDK, PKC, PIKFYVE, and EIF2AK2. Furthermore, SARS-CoV-2 regulates various signaling pathways including MAPK, GFR signaling, TGF-β, autophagy, and AKT. These elevated kinases and signaling pathways can be potential therapeutic targets for anti-COVID-19 drug discovery. Specific inhibitors of these kinases and interconnected signaling proteins have great potential to cure COVID-19 patients and slow down the ongoing COVID-19 pandemic.

Cerebral oximetry is touted as a magic wand to detect cerebral hypoperfusion. Inability to completely exclude extracranial oxygen however is a limitation. Variation in scalp vascularity can magnify the limitations of relatively short emitter–detector distances. The combination of brain ischemia and cutaneous hyperemia, as is the situation during anaphylaxis and anaphylactoid reactions, can be associated with a paradoxical increase in cerebral oximetry values. This could compromise the quality and accuracy of care delivered. We report the association of red man syndrome with exaggerated cerebral oximetry values.

BACKGROUND: Rapid turnaround time of blood culture reports should be the main motive for a clinical microbiologist for optimal patient care. Categorical agreement (CA) between direct disk diffusion (dDD) and reference disk diffusion (rDD) may vary between laboratories. AIMS AND OBJECTIVES: This study was designed to determine the CA and understand various types of errors associated with antibiotic organism combination, so that caution can be derived while interpreting and reporting dDD results in the earliest meaningful time frame. MATERIALS AND METHODS: In the present study, dDD results were compared to the rDD results from the positive blood culture bottles. CA and various types of errors were evaluated. RESULTS: A total of 965 pathogens and 7106 organism antibiotic combinations were evaluated in this study. Overall, there was a CA of 96% which was extremely satisfactory. The categorical disagreement was found only in 4% of organism antibiotic combinations; majority of which were major error (ME, 2.1%) followed by very ME (1%) and minor error (0.9%). The errors were marginally high for Enterobacteriaceae testing against β lactam- β lactamase inhibitor combinations, for Pseudomonas species; against aminoglycosides and ciprofloxacin and Staphylococcus species against cefoxitin, one should be vigilant while reporting dDD result of these antibiotic organism combinations. CONCLUSION: dDD is of paramount importance for early institution of targeted therapy and is considered as one of the key stewardship intervention. Our study gives an insight that every laboratory must perform dDD for positively flagged blood culture specimens; the result of which should be confirmed later by performing rDD. One should be vigilant while reporting dDD result of BL BLI for Enterobacteriaceae; aminoglycosides and CF for Pseudomonas species; cefoxitin for Staphylococcus species and HLG for Enterococcus species. Supplementary tests such as MRSA latex should be included when necessary.

Background: Basal cell carcinoma (BCC) has not been studied in the population of the Sub-Himalayan region in the North India, as it has been done in the rest of India. This study was performed to analyze the clinicopathological spectrum of BCC in this population. Materials and Methods: The present study is a hospital-based open-cohort observational study which was carried out in the Departments of Pathology and Dermatology at a tertiary care center of Himachal Pradesh, India, from January 2012 to December 2017. All the patients with the histopathological diagnosis of BCC were included in this study. Results: Of the 46 cases of BCC analyzed during the 6-year study period, 30 (65.3%) cases were female and 16 (34.7%) cases were male. The mean age was 65.7 ± 12.9 years and 31.4% (14/46) were in the 61–70 years age group. Majority of the lesions were located in the head-and-neck area and the nose was the most common site. The most common histological type was the solid variant. Conclusion: This study highlights that BCC is not rare in Indians and is more common in females in this region. This study also reveals the frequency of clinicopathological patterns of BCC in this region.

Background: Few low-incidence countries are on track to achieve the ambitious target of reaching TB pre-elimination by 2035. Australia is a high-income country with a low burden of TB, which is particularly concentrated in migrant populations. As part of Australia's migration program, permanent, provisional and humanitarian visa applicants are screened for TB, along with some applicants for temporary visas.Methods: We calculated the prevalence of all forms of active TB and bacteriologically-confirmed TB among onshore and offshore applicants for visas to Australia from July 2014 to June 2017, and investigated associated risk factors using logistic regression.Findings: Visa applicants were predominantly young adults from various Asian countries. Among 2,381,217 applicants, 1263 cases of active TB were diagnosed, including 852 cases of bacteriologically-confirmed TB. Overall TB prevalence was 53.0 per 100,000, corresponding to one TB diagnosis for every 1887 applicants screened. TB rates increased with age and were higher among humanitarian applicants and those previously treated for TB, although most cases occurred in applicants without these risk factors. TB prevalence by country of origin was similar to WHO estimates for some countries, but considerably lower for others. For several highly represented countries of origin, rates appear to have fallen relative to earlier comparable studies.Interpretation: Prevalence of TB among visa applicants to Australia and the consequent risk to the Australian community appear to be declining and remain low. In this context, support for TB control programs overseas and preventive interventions are likely to have the greatest impact on domestic TB burden.

Introduction: Sexual health issues are highly prevalent but are underdiagnosed and underrecognized in day-to-day clinical practice. The lack of awareness of the specific health care needs of the patients with sexual dysfunctions and resource limitations might be certain reasons why many hospitals are not been equipped with the sexual health care units. There is paucity of specialized psychosexual health care services across the country. Trained interdisciplinary team with prepared environment in sexual medicine is the need of the hour. We started this psychosexual medicine unit with an emphasis on sexual wellness to deliver comprehensive sexual health care which will be a primary care linkage to patients presenting with symptoms of sexual disorders, so also treatment emergent sexual dysfunction in psychiatry and other medical and surgical branches. Aim: To portray the methods, opportunities, and challenges that we experienced in establishing a specialty psychosexual medicine facility as a different unit in a private university-based medical college and hospital in Mysuru, India. Methods: This triweekly psychosexual medicine unit is situated in the Outpatient Division of Psychiatry and is staffed with a multidisciplinary group of health care professionals. Structured survey tools and proforma are utilized to assess all patients. Case conclusions are made according to International Classification of Diseases, Tenth Revision, symptomatic/clinical explanations and diagnostic recommendations, and furthermore Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) when required. Patient care included interventions in the form of psychotherapy and pharmacotherapy. Results: It is possible to set up a functional psychosexual medicine facility as a different unit with a trained interdisciplinary group of professionals. Patient-centered approach is vital in our care plan and management. Postgraduate students and internees posted in psychiatry division have been undertaking rotations respectively as per their duty rota. There is also a robust academic program that includes once-weekly seminars pertaining to topics of psychosexual health and monthly journal club gatherings interchanging with seminars on sexual health and well-being appraisal devices. Conclusion: By investing on improving infrastructure and available human resources, the specialty psychosexual medicine unit was established. The psychosexual medicine unit not only gave chances for a more comprehensive assessment of individuals with sexual disorders but also improved training and education for residents with focused interdisciplinary research in the field of sexual medicine. It portrays a versatile model that can be replicated in settings of similar type.

Abstract The investigation of post-translational modifications (PTMs) plays an important role for the study of type 2 diabetes. The importance of PTMs has been realized with the advancement of analytical techniques. The challenging detection and analysis of post-translational modifications is eased by different enrichment methods and by high throughput mass spectrometry based proteomics studies. This technology along with different quantitation methods provide accurate knowledge about the changes happening in disease conditions as well as in normal conditions. In this review, we have discussed PTMs such as phosphorylation, N-glycosylation, O-GlcNAcylation, acetylation and advanced glycation end products in type 2 diabetes which have been characterized by high throughput mass spectrometry based proteomics analysis.

Abstract Background While several efficacy trials have demonstrated diabetes risk reduction through targeting key lifestyle behaviours, there is a significant evidence gap in relation to the successful implementation of such interventions in low- and middle-income countries (LMICs). This paper evaluates the implementation of a cluster randomised controlled trial of a group-based lifestyle intervention among individuals at high-risk of developing type 2 diabetes mellitus (T2DM) in the state of Kerala, India. Our aim is to uncover provider-, participant- and community-level factors salient to successful implementation and transferable to other LMICs. Methods The 12-month intervention program consisted of (1) a group-based peer-support program consisting of 15 sessions over a period of 12 months for high-risk individuals, (2) peer leader (PL) training and ongoing support for intervention delivery, (3) diabetes education resource materials and (4) strategies to stimulate broader community engagement. The evaluation was informed by the RE-AIM and PIPE frameworks. Results Provider-level factors: Twenty-nine (29/30, 97%) intervention groups organised all 15 sessions. A 2-day PL training was attended by 51(85%) of 60 PLs. The PL handbook was found to be ‘very useful’ by 78% of PLs. Participant-level factors: Of 1327 eligible individuals, 1007(76%) participants were enrolled. On average, participants attended eight sessions. Sixty-eight percent rated their interest in group sessions as ‘very interested’, and 55% found the group sessions ‘very useful’ in making lifestyle changes. Inconvenient time (43%) and location (21%) were found to be important barriers for participants who did not attend any sessions. Community-level factors: Community-based activities reached to 41% of the participants for walking groups, 40% for kitchen garden training, and 31% for yoga training. PLs were readily available for support outside the sessions, as 75% of participants reported extracurricular contacts with their PLs. The commitment from the local partner institute and political leaders facilitated the high uptake of the program. Conclusion A comprehensive evaluation of program implementation from the provider-, participant- and community-level perspectives demonstrates that the K-DPP program was feasible and acceptable in changing lifestyle behaviours in high-risk individuals. The findings from this evaluation will guide the future delivery of structured lifestyle modification diabetes programs in LMICs. Trial registration Trial registration: Australia and New Zealand Clinical Trials Registry ACTRN12611000262909. Registered 10 March 2011.

Objectives: We assessed the effect of an active case finding (ACF) project on tuberculosis (TB) case notification and the yields from a household and neigbourhood intervention (screening contacts of historical index TB patients diagnosed >24 months ago) and a community intervention (screening attendants of health education sessions/mobile clinics). Design: Cross-sectional analysis of project records, township TB registers and annual TB reports. Results: In the household and neigbourhood intervention, of 56,709 people screened, 1,076 were presumptive TB and 74 patients were treated for active TB with a screening yield of 0.1% and a yield from presumptive cases of 6.9%. In the community intervention, of 162,881 people screened, 4,497 were presumptive TB and 984 were treated for active TB with a screening yield of 0.6% and yield from presumptive cases of 21.9%. Of active TB cases, 94% were new, 89% were pulmonary, 44% were bacteriologically-confirmed and 5% had HIV. Case notification rates per 100,000 in project townships increased from 142 during baseline (2011-2013) to 148 during intervention (2014-2016) periods. Conclusions: The yield from household and neigbourhood intervention was lower than community intervention. This finding highlights reconsidering the strategy of screening of contacts from historical index cases. Strategies to reach high-risk groups should be explored for future ACF interventions to increase yield of TB. Keywords: Tuberculosis, Community-based active case finding, TB screening, Myanmar

Abstract Background This study aims to explore the prevalence and causes of low vision and blindness focused on retinal disease in a population above 60 years in Nepal. Methods Two thousand one hundred subjects were enrolled in a population-based cross-sectional study. History, presenting and best corrected visual acuity after subjective refraction, anterior and posterior segment examinations was obtained in detail. Results Among the total subjects, 1860 (88.57%) had complete information. Age varies from 60 to 95 (mean age: 69.64 ± 7.31) years. Low vision and blindness in both eyes at presentation was found in 984 (52.90%, 95% confidence interval (CI): 50.60–55.19) and 36 (1.94%, 95% CI: 1.35–2.66) subjects respectively. After best correction, bilateral low vision and blindness was found in 426 (22.92%, 95% CI: 21.01–24.88), and 30 (1.61%, 95% CI: 0.10–2.30) subjects respectively. As compared to 60–69 years old, risk of visual impairment was four times higher (95% CI:3.26–5.58) in the 70–79 year olds and 14 times higher (95% CI: 9.72–19.73) in the age group 80 years and above. Major causes of bilateral low vision were cataract (68.07%), followed by retinal disorders (28.64%), and for blindness; retinal disorders (46.66%), followed by cataract (43.33%). Illiteracy was significantly associated with visual impairment. Conclusion Among the elderly population, prevalence of visual impairment was high. Refractive error, cataract and retinal disorders were the major cause of low vision. Screening the population at the age 60 years and above, focused on cataract and posterior segment diseases, providing glasses and timely referral can help reduce visual impairment.

Abstract Background PD is a progressive neurodegenerative disorder commonly treated by levodopa. The findings from genetic studies on adverse effects (ADRs) and levodopa efficacy are mostly inconclusive. Here, we aim to identify predictive genetic biomarkers for levodopa response (LR) and determine common molecular link with disease susceptibility. A systematic review for LR was conducted for ADR, and drug efficacy, independently. All included articles were assessed for methodological quality on 14 parameters. GWAS of PD were also reviewed. Protein-protein interaction (PPI) analysis using STRING and functional enrichment using WebGestalt was performed to explore the common link between LR and PD. Results From 37 candidate studies on levodopa toxicity, 18 genes were found associated, of which, CAn STR 13, 14 (DRD2) was most significantly associated with dyskinesia, followed by rs1801133 (MTHFR) with hyper-homocysteinemia, and rs474559 (HOMER1) with hallucination. Similarly, 8 studies on efficacy resulted in 4 genes in which rs28363170, rs3836790 (SLC6A3) and rs4680 (COMT), were significant. To establish the molecular connection between LR with PD, we identified 35 genes significantly associated with PD. With 19 proteins associated with LR and 35 with PD, two independent PPI networks were constructed. Among the 67 nodes (263 edges) in LR, and 62 nodes (190 edges) in PD pathophysiology, UBC, SNCA, FYN, SRC, CAMK2A, and SLC6A3 were identified as common potential candidates. Conclusion Our study revealed the genetically significant polymorphism concerning the ADRs and levodopa efficacy. The six common genes may be used as predictive markers for therapy optimization and as putative drug target candidates.

Abstract Background This study aims to explore the prevalence, pattern and risk factors of retinal vein occlusion (RVO) in an elderly population of Nepal. Method One thousand eight hundred sixty subjects of age 60 years and above were enrolled in a population-based, cross-sectional study. Detailed history, visual acuity, anterior segment and posterior segment examinations were done. Blood pressure, non-fasting blood sugar, body mass index and abdominal girth were measured. Retinal vein occlusions were further divided into branch retinal (BRVO), hemi-retinal and central retinal vein occlusion (CRVO). Result Age ranged from 60 to 95 years with a mean of 69.64 ± 7.31 years. Overall population prevalence for RVO was 2.95% (95% Confidence interval (CI): 2.23–3.83), BRVO 2.74% (95% CI: 2.05–3.58) and CRVO 0.21% (95% CI: 0.06–0.55). BRVO was seen in 51 subjects (92.73%) and CRVO in 4 (7.27%). Among the total RVO, unilateral and bilateral involvement was 85.45% and 14.55%, respectively. Among the subjects with BRVO and CRVO, 37.25% and 50% had low vision, respectively. The risk of RVO increased with ageing and was more among males. There was an increased risk of RVO among those with hypertension, and with diabetes and hypertension. There was also an increased risk of RVO among subjects with hypermetropia, those with pseudophakia and those who were smokers and consumed alcohol. Conclusion Retinal vein occlusion is a common retinal vascular disorder in the elderly population of Nepal. The main risk factors for RVO were increasing age and hypertension.

Background: Pleural fluid cytology is a quick and accurate method to diagnose malignant pleural effusions. The optimal volume of fluid for cytological analysis has not yet been identified, and clinical recommendation based on some published clinical experiences has been to send large volumes of fluid for cytological analysis. A quality improvement initiative at our institution was conducted to determine the volume of fluid sufficient for a diagnosis of malignant pleural effusion. Materials and Methods: The study was approved by the Institutional Review Board. All pleural fluid specimens that were divided into three volumes (25 mL, 50 mL, and 150 mL) and sent for cytological examination were reviewed. Results: A total of 74 samples from 60 individual patients were evaluable. Thirty-six patients (60%) had a previous diagnosis of malignancy. Of the 74 specimens, 26 (35.1%) were positive for malignancy. The detection rate for malignant pleural effusion by cytology for 25 mL, 50 mL, and 150 mL were 88.5%, 96.2%, and 100.0%, respectively (P = 0.16). Two specimens that were negative in the 25 mL samples turned out to be positive in the 50 mL and 150 mL samples. One specimen was negative in the 25 mL and 50 mL samples but positive in the 150 mL sample. Conclusions: Our study did not show any statistically significant difference in the detection of malignant effusion in the 25 mL, 50 mL, and 150 mL group.

Aim: The study was undertaken: 1) To assess salivary glucose (SaG) levels in diabetic and nondiabetic subjects and to determine if saliva could be used as a noninvasive tool to diagnose and monitor Type II diabetes mellitus. 2) Correlation of SaG levels with serum glucose (SeG) levels in nondiabetic and diabetic patients. 3) To correlate the oral manifestations of diabetes mellitus with serum and SaG levels. Material and Methods: Both fasting and postprandial serum and SaG levels were analyzed from 70 Type II diabetic and 70 nondiabetic subjects. The detailed examination of oral cavity in relation to periodontal and dental status and subjective oral complaints were recorded. The obtained values were subjected to statistical analysis. Results: The mean fasting salivary glucose (FSaG) was 5.469 + 2.347 mg/dL and 7.634 + 4.468 mg/dL in nondiabetic and diabetics, respectively (P = 0.000) and postprandial salivary glucose (PSaG) was 6.434 + 2.111 mg/dL and 8.736 + 4.962 mg/dL in nondiabetic and diabetics, respectively (P = 0.000). The positive correlation was found between SeG levels and SaG in diabetics (P = 0.000). Strong positive correlation was observed between SeG and SaG with oral manifestations in Type II diabetic patients (P < 0.05). Conclusion: Saliva can be a useful tool in regular monitoring of “already diagnosed Type II diabetics” (by their SeG levels) rather than diagnosing subjects with “unknown status of diabetes mellitus.” Strong positive correlation exists between SeG level and SaG level with oral manifestations in Type II diabetic patients.

The emergence and spread of multidrug-resistant tuberculosis (MDR-TB) poses a major threat to the global targets for TB control. In recent years, an evolving science and evidence base for MDR-TB has led to much needed changes in international guidelines promoting the use of newer TB drugs and regimens for MDR-TB, however, there remains a significant implementation gap. Due to the complexity of treating MDR-TB, management of cases is often supported by an expert multidisciplinary team, or clinical expert group. This service is often centralized, and may be delivered through a telemedicine platform. We have implemented a Web-based “store-and-forward” telemedicine service to optimize MDR-TB patient care in Daru, a remote and resource limited setting in Papua New Guinea (PNG). From April 2016 to February 2019, 237 cases were discussed using the service. This encompassed diagnostic (presumptive) and treatment cases, and more recently, support to the scale up of preventative therapy for latent TB infection. There were 75 cases in which the use of Bedaquiline was discussed or mentioned, with a high frequency of discussions occurring in the initial period (26 cases in the first 12 months), which has appeared to decrease as clinicians gained familiarity with use of the drug (15 cases in the last 12 months). This service has supported high quality clinical care and fostered collaboration between clinicians and technical experts in a shared learning environment.

Introduction: Myanmar is one of the countries in the Asia-Pacific region hit hardest by the HIV epidemic that is concentrated among urban areas and key populations. In 2014, the National AIDS Programme (NAP) launched a new model of decentralized service delivery with the establishment ART satellite sites with care delivered by HIV peer workers.Methods: ART satellite sites are implemented by non-government organizations to service high burden HIV areas and populations that suffer stigma or find access to public sector services difficult. They provide continuity of HIV care from outreach testing, counseling, linkage to care, and retention in care. Anti-retroviral (ART) initiation occurs at health facilities by specialist physicians. We conducted a retrospective cohort study of people living with HIV (PLHIV) who were initiated on ART from 2015 to 2016 at five ART satellite sites in Yangon, Myanmar to assess outcomes and time from enrolment to ART initiation.Results: Of 1,339 PLHIV on ART treatment in 2015–16, 1,157 (89%) were retained, and 5% were lost from care and 5% reported dead, at the end of March 2018. Attrition rates (death and lost-to-follow-up) were found to be significantly associated with a CD4 count ≤ 50 cells/mm3 and having baseline weight ≤ 50 kg. Median time taken from enrolment to ART initiation was 1.9 months (interquartile range: 1.4–2.5).Conclusion: We report high rates of retention in care of PLHIV in a new model of ART satellite sties in Yangon, Myanmar after 3 years of follow-up. The delays identified in time taken from enrolment to ART initiation need to be explored further and addressed. This initial study supports continuation of plans to scale-up ART satellite sites in Myanmar. To optimize outcomes for patients and the program and accelerate progress to reduce HIV transmission and end the HIV epidemic, operational research needs to be embedded within the response.

Measurements of fasting glucose (FG) or glycated hemoglobin A1c (HbA1c) are two clinically approved approaches commonly used to determine glycemia, both of which are influenced by genetic factors. Obtaining accurate measurements of FG or HbA1c is not without its challenges, though. Measuring glycated serum protein (GSP) offers an alternative approach for assessing glycemia. The aim of this study was to estimate the heritability of GSP and GSP expressed as a percentage of total serum albumin (%GA) using a variance component approach and localize genomic regions (QTLs) that harbor genes likely to influence GSP and %GA trait variation in a large extended multigenerational pedigree from Jiri, Nepal (n=1,800). We also performed quantitative bivariate analyses to assess the relationship between GSP or %GA and several cardiometabolic traits. Additive genetic effects significantly influence variation in GSP and %GA levels (p values: 1.15×10−5 and 3.39×10−5, respectively). We localized a significant (LOD score=3.18) and novel GSP QTL on chromosome 11q, which has been previously linked to type 2 diabetes. Two common (MAF>0.4) SNPs within the chromosome 11 QTL were associated with GSP (adjusted pvalue

Ellis-van Creveld (EVC) syndrome, a form of skeletal and chondroectodermal dysplasia, is an autosomal recessive disorder characterized by a tetrad of disproportionate dwarfism, postaxial polydactyly, ectodermal dysplasia, and heart defects. In the present article, we hereby present a case of a 13-year-old girl of Indian ethnicity with EVC syndrome with a remarkable number of classical oral and dental features, with unusual findings such as taurodontism and talons cusp. Such dental findings were reported in few cases only. Despite the fact that oral manifestations play an important role in the diagnosis of EVC, only a few detailed reports have been published in the dental literature.

SETTING:Myanmar National AIDS Program has had significant scale-up of services and changes in CD4 eligibility criterion for ART initiation from 2013 to 2016. This study assessed early death within 6 months and attrition (death and loss to follow-up, LTFU) after ART initiation and their associated factors. DESIGN:A retrospective cohort study on people living with HIV (PLHIV >15 year of age) enrolled at three specialist hospitals in Yangon from 1st June 2013 to 30th June 2016. Cox regression was used to calculate hazard ratios (HRs) of early death and attrition. RESULTS:Of 11,727 adults enrolled, 11,186 (95%) were initiated on ART, providing 15,964 person-years of follow-up. At baseline, median age was 36 years [IQR: 30-43], 58% were men and median CD4 count was 151 cells/mm3 (IQR: 54-310). There were 733(6%) early deaths, 961(9%) total deaths and 1371 (12%) LTFU during the study period. Independent risk factors for early death were older age (41-50 and ≥51 years) [aHR 1.38, 1.07-1.78 and 1.68, 1.21-2.34], male (1.84, 1.44-2.35), low weight (2.06, 1.64-2.59), bedridden, (3.81, 2.57-5.66) and CD4 count ≤ 50 cells/mm3 (6.83, 2.52-18.57). In addition to above factors, high attrition was associated with an abacavir-based regimen. CONCLUSION:Although there was a low rate of early deaths, patients were being diagnosed late and there was a high attrition rate from specialist hospitals. Concerted effort is required to increase early diagnosis and ART initiation, and strengthen community systems for HIV care to achieve ambitious goal of ending AIDS epidemic by 2030.

Background: Leptin, a 16 kDa peptide hormone synthesized and secreted specifically from white adipose cells protects neurons against amyloid β-induced toxicity, by increasing Apolipoprotein E (APO E)-dependent uptake of β amyloid into the cells, thereby, protect individuals from developing Alzheimer′s disease (AD). The APO E ε4 allele is a known genetic risk factor for AD by accelerating onset. It is estimated that the lifetime risk of developing AD increases to 29% for carriers with one ε4 allele and 9% for those with no ε4 allele. Objectives: To determine the levels of serum leptin, cholesterol, low density lipoprotein (LDL-C), and high density lipoprotein (HDL-C) in the diagnosed cases of AD and the association of them with cognitive decline and Apolipoprotein E (APO E) genotypes in AD. Materials and Methods: Serum levels of serum leptin, cholesterol, LDL-C, and HDL-C along with APO E polymorphism were studied in 39 subjects with probable AD and 42 cognitive normal individuals. Results: AD group showed significantly lower levels of leptin (P = 0.00) as compared to control group. However, there was no significant difference in cholesterol, triglycerides, LDL-C, and HDL-C levels in AD and control groups. The frequency of ε4 allele in AD (38.5%) was found to be significantly higher than in control (10.3%). ε3 allele was more frequent than ε4 allele in AD and control group.

Background: Standard methods of CD4 counts and plasma viral load estimation require specialized equipment, highly trained personnel and are extremely expensive. This remains a major challenge for the initiation of anti-retroviral therapy for patients in resource-limited settings. Objective: To assess the clinical utility of the total lymphocyte count (TLC) to serve as a surrogate marker for predicting a CD4 counts

We present a rare case of acute promyelocytic leukemia (APL) presenting as pulmonary thromboembolism being misdiagnosed as community.acquired pneumonia. Thrombotic phenomenon in APL are poorly understood and grossly underreported. In our case, following no response to standard antibiotic treatment, the patient was further investigated and detected to have an acute pulmonary thromboembolism following right lower limb deep vein thrombosis (DVT). Though, complete blood picture revealed only mild hyperleukocytosis, bone marrow biopsy and aspiration revealed 60% blasts and a positive t (15,17)(q22,12) and PML retinoic acid receptor alpha (RARA) fusion protein on molecular cytogenetics. He was diagnosed as APL and received treatment with all.transretinoic acid (ATRA) and arsenic trioxide (ATO) and therapeutic anticoagulation

Currently, only 62% of incident tuberculosis (TB) cases are reported to the national programme in Pakistan. Several innovative interventions are being recommended to detect the remaining 'missed' TB cases. One such intervention involved expanding contact investigation to the community using the Xpert MTB/RIF test.This was a before and after intervention study involving retrospective record review. Passive case finding and household contact investigation was routinely done in the pre-intervention period July 2011-June 2013. Four districts with a high concentration of slums were selected as intervention areas; Lahore, Rawalpindi, Faisalabad and Islamabad. Here, in the intervention period, July 2013-June 2015, contact investigation beyond household was conducted: all people staying within a radius of 50 metres (using Geographical Information System) from the household of smear positive TB patients were screened for tuberculosis. Those with presumptive TB were investigated using smear microscopy and the Xpert MTB/RIF test was performed on smear negative patients. All the diagnosed TB patients were linked to TB treatment and care.A total of 783043 contacts were screened for tuberculosis: 23741(3.0%) presumptive TB patients were identified of whom, 4710 (19.8%) all forms and 4084(17.2%) bacteriologically confirmed TB patients were detected. The contribution of Xpert MTB/RIF to bacteriologically confirmed TB patients was 7.6%. The yield among investigated presumptive child TB patients was 5.1%. The overall yield of all forms TB patients among investigated was 22.3% among household and 19.1% in close community. The intervention contributed an increase of case detection of bacteriologically confirmed tuberculosis by 6.8% and all forms TB patients by 7.9%.Community contact investigation beyond household not only detected additional TB patients but also increased TB case detection. However, further long term assessments and cost-effectiveness studies are required before national scale-up.

Thyroid tuberculosis is a rare disease even in countries where tuberculosis is endemic. Clinically tuberculosis is not often suspected in cases of thyroid nodule or swelling. We report a case of 11 years female child who presented with a thyroid swelling. Fine-needle aspiration cytology revealed caseating epithelioid granulomas and acid fast bacilli. Patient improved with antitubercular drugs. Tuberculosis may be considered as differential diagnosis of thyroid swelling.

In Ayurveda, Withania somnifera is commonly known as Ashwagandha, its roots are specifically used in medicinal and clinical applications. It possesses numerous therapeutic actions which include anti-inflammatory, sedative, hypnotic and narcotic. Extracts from this plant have been reported for its anticancer properties. In this study we evaluated for the first time, the cytotoxic effect of Withania root extract on human malignant melanoma A375 cells. The crude extract of Withania was tested for cytotoxicity against A375 cells by MTT assay. Cell morphology of treated A375 cells was visualized through phase contrast as well as fluorescence microscopy. Agarose gel electrophoresis was used to check DNA fragmentation of the crude extract treated cells. Crude extract of Withania root has the potency to reduce viable cell count in dose as well as time dependent manner. Morphological change of the A375 cells was also observed in treated groups in comparison to untreated or vehicle treated control. Apoptotic body and nuclear blebbing were observed in DAPI stained treated cells under fluorescence microscope. A ladder of fragmented DNA was noticed in treated cells. Thus it might be said that the crude water extract of Withania somnifera has potent cytotoxic effect on human malignant melanoma A375 cells.