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Objectives: Despite various challenges, orthopaedic sports surgeons are still providing the arthroscopic service in low-income and middle-income countries like Nepal; however, it is hardly being reported. The main purpose of this study was to compare the clinical outcomes and complications of patients undergoing arthroscopic anterior cruciate ligament reconstruction (ACLR) in the urban group and that of the rural group., Methods: We evaluated a total of 194 patients, including 98 patients in the urban group and 96 patients in the rural group, undergoing arthroscopic ACLR between August 2015 and February 2018, and had completed a minimum of 2-year follow-up. Subjective evaluations were performed using the Tegner-Lysolm score and International Knee Documentation Committee (IKDC) subjective knee evaluation form. Laxity assessments were performed using the Lachman test and the Pivot-shift test. Functional evaluation included the range of motion, single-leg hop test and overall IKDC score. Radiological assessment was performed according to the IKDC guidelines. SPSS was used for data analysis., Results: There was statistically significant differences in the subjective assessments between 2 groups. No statistically significant differences existed between 2 groups in terms of laxity and functional assessments. However, the proportion of laxity, in terms of Lachman test and Pivot-shift test, was higher in the young and active individuals and the proportion of abnormal and severely abnormal in all parameters of functional outcomes was higher in the older female in the rural group. Graft failure occurred in 19 (17.6%) knees in the urban group and 17 (16.8%) knees in the rural group. Graft failure in the urban group was higher in young and active male patients, whereas failure in the rural group was more in female patients. Similarly, overall infection occurred in 13 (6.2%) knees, including 5 (2.3%) deep infections and 8 (3.8%) superficial infections., Conclusion: We advised similar rehabilitation protocol for all the patients; however, the outcomes were significantly lower in patients living in rural areas as they are found to have poor compliance with the rehabilitation protocol. The overall graft failure rate was 17.2%; however, the reoperation rate was higher in the urban group than the rural group. The rate of deep infection was higher in the rural group as compared with the urban group., Level of Evidence: Level III, retrospective comparative study., Competing Interests: Competing interests: None declared., (© International Society of Arthroscopy, Knee Surgery and Orthopaedic Sports Medicine 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: Human identification systems based on STRs are widely used in human population genetics and forensic analysis. This study aimed to validate the cross-reactivity of three widely known human-specific STR identification systems i.e. GlobalFiler™ PCR Amplification Kit, Investigator 24plex QS Kit, and PowerPlex® Fusion 6C in chimpanzee., Results: The present study revealed the successful amplification of 18 loci using GlobalFiler™ PCR Amplification Kit, 18 loci using Investigator 24plex QS Kit, and 20 loci using PowerPlex® Fusion 6C system. The marker Amelogenin (AMEL) showed differential allele size between male and female revealing the gender identity of chimpanzees and thus validates their application concerning forensic examination, population estimation, and genetic analysis.

The successful treatment of Helicobacter pylori infections is becoming increasingly difficult due to the rise of resistance against current broad spectrum triple therapy regimens. In the search for narrow-spectrum agents against H. pylori , a high-throughput screen identified two structurally related thienopyrimidine compounds that selectively inhibited H. pylori over commensal members of the gut microbiota. To develop the structure-activity relationship (SAR) of the thienopyrimidines against H. pylori , this study employed four series of modifications in which systematic substitution to the thienopyrimidine core was explored and ultimately side-chain elements optimized from the two original hits were merged into lead compounds. During the development of this series, the mode of action studies identified H. pylori 's respiratory complex I subunit NuoD as the target for lead thienopyrimidines. As this enzyme complex is uniquely essential for ATP synthesis in H. pylori , a homology model of the H. pylori NuoB-NuoD binding interface was generated to help rationalize the SAR and guide further development of the series. From these studies, lead compounds emerged with increased potency against H. pylori , improved safety indices, and a good overall pharmacokinetic profile with the exception of high protein binding and poor solubility. Although lead compounds in the series demonstrated efficacy in an ex vivo infection model, the compounds had no efficacy in a mouse model of H. pylori infection. Additional optimization of pharmacological properties of the series to increase solubility and free-drug levels at the sequestered sites of H. pylori infection would potentially result in a gain of in vivo efficacy. The thienopyrimidine series developed in this study demonstrates that NuoB-NuoD of the respiratory complex I can be targeted for development of novel narrow spectrum agents against H. pylori and that thienopyrimines can serve as the basis for future advancement of these studies.

Background and Purpose: Perfusion imaging can risk stratify patients with symptomatic intracranial stenosis. We aim to determine the association between perfusion delay and length of hospital stay (LOS) in symptomatic middle cerebral artery (MCA) stenosis patients., Methods: This is a retrospective study of consecutive patients admitted to a comprehensive stroke center over 5 years with ischemic stroke or transient ischemic attack (TIA) within 7 days of symptom onset due to MCA stenosis (50-99%) and underwent perfusion imaging. Patients were divided into three groups: mismatch volume ≥ 15 cc based on T max > 6 second delay, T max 4-6 second delay, and <4 second delay. The outcome was LOS, both as a continuous variable and categorical (≥7 days [prolonged LOS] vs. <7 days). We used adjusted regression analyses to determine the association between perfusion categories and LOS., Results: One hundred and seventy eight of 194 patients met the inclusion criteria. After adjusting for age and NIHSS, T max >6 second mismatch was associated with prolonged LOS (OR 2.94 95% CI 1.06-8.18; P = .039), but T max 4-6 second was not (OR 1.45 95% CI .46-4.58, P = .528). We found similar associations when LOS was a continuous variable for T max > 6 second (β coefficient = 2.01, 95% CI .05-3.97, P = .044) and T max 4-6 second (β coefficient = 1.24, 95% CI -.85 to 3.34, P = .244)., Conclusion: In patients with symptomatic MCA stenosis, T max > 6 second perfusion delay is associated with prolonged LOS. Prospective studies are needed to validate our findings., (© 2021 American Society of Neuroimaging.)

Pangolins, despite banned through legislative measures, are threatened by heavy illegal poaching for the demand of meat and scales in the making of Traditional East Asian Medicines (TEAM), resulting in severe decline of the population sizes across the distribution range. Species assignment from the confiscated scales is pre-requisite to enforce the appropriate national and international law and legislations in the successful prosecution of the cases in the court of law. In the present study, we characterised the morphological features in voucher specimens of the Indian pangolin (Manis crassicaudata) and Chinese pangolin (Manis pentadactyla) and used the identified keys to establish the species identity from the confiscated scales. We investigated intra and inter genetic variations by sequencing 624 scales of pangolin for cytb gene and obtained unique haplotypes to Indian and Chinese pangolins by comparing sequences with all eight pangolin species. Scales from the voucher specimens, which varied in the size, shape and weight, were measured for morphological features to establish species signature of Indian and Chinese pangolins. The cumulative success of species assignment using morphological features from the confiscated scales was 98.33% and 100% from the large and caudal scales, respectively. The present study has generated reference signature of Indian and Chinese pangolins from the scales and facilitates the law enforcements for taking spot decision by ascertaining species identity from the seized scales., Competing Interests: Conflict of interest Authors declare that they have no conflict of interest., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Objectives: The primary aim of this study was to compare the clinical outcomes of patients undergoing arthroscopic Bankart repair and the open Latarjet procedure for recurrent dislocation of the shoulder. The secondary aims were to assess and compare the surgical cost, patient satisfaction, and complications, including recurrence and infection., Methods: We retrospectively compared the clinical outcomes of all consecutive patients undergoing either arthroscopic Bankart repair or the open Latarjet procedure from May 2015 to May 2018 with a minimum 2-year follow-up. Forty-one patients (32 men, 9 women) in the Bankart group and 40 patients (34 men, 6 women) in the Latarjet group were available for the final follow-up., Results: There were no statistically significant differences in the demographic parameters or clinical outcomes between the two groups. Functional satisfaction was higher with the Latarjet procedure. Bankart repair had a significantly higher operating cost than the Latarjet procedure. Three patients in the Bankart group and no patients in the Latarjet group developed recurrence., Conclusion: Both procedures provided satisfactory clinical outcomes. However, the Latarjet group had a higher rate of functional satisfaction and lower operating cost, and there was a trend toward higher recurrence in the arthroscopic Bankart group.

Objectives  Stringent quality control is an essential requisite of diagnostic laboratories to deliver consistent results. Measures used to assess the performance of a clinical chemistry laboratory are internal quality control and external quality assurance scheme (EQAS). However, the number of errors cannot be measured by the above but can be quantified by sigma metrics. The sigma scale varies from 0 to 6 with "6" being the ideal goal, which is calculated by using total allowable error (TEa), bias, and precision. However, there is no proper consensus for setting a TEa goal, and influence of this limiting factor during routine laboratory practice and sigma calculation has not been adequately determined. The study evaluates the impact of the choice of TEa value on sigma score derivation and also describes a detailed structured approach (followed by the study laboratory) to determine the potential causes of errors causing poor sigma score. Materials and Methods  The study was conducted at a clinical biochemistry laboratory of a central government tertiary care hospital. Internal and external quality control data were evaluated for a period of 5 months from October 2019 to February 2020. Three drugs (carbamazepine, phenytoin, and valproate) were evaluated on the sigma scale using two different TEa values to determine significant difference, if any. Statistical Analysis  Bias was calculated using the following formula: Bias% = (laboratory EQAS result - peer group mean) × 100 / peer group mean Peer group mean sigma metric was calculated using the standard equation: Sigma value = TEa - bias / coefficient of variation (CV)%. Results  Impressive sigma scores (> 3 sigma) for two out of three drugs were obtained with TEa value 25, while with TEa value 15, sigma score was distinctly dissimilar and warranted root cause analysis and corrective action plans to be implemented for both valproate and carbamazepine. Conclusions  The current study evidently recognizes that distinctly different sigma values can be obtained, depending on the TEa values selected, and using the same bias and precision values in the sigma equation. The laboratories should thereby choose appropriate TEa goals and make judicious use of sigma metric as a quality improvement tool., Competing Interests: Authorship CriteriaEthical ApprovalConflicts of Interest 1. Lokesh Kumar Sharma: conception and design, drafting the article, revising it critically for important intellectual content, and final approval of the version to be published. 2. Rashmi Rasi Datta: conception and design, acquisition of data, analysis and interpretation of data, and drafting the article. 3. Neera Sharma: revising it critically for important intellectual content and final approval of the version to be published. Not applicable. None declared., (The Indian Association of Laboratory Physicians. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Changes in mitochondrial DNA (mt-DNA) copy number in blood/tissue have been linked to increased risk of several cancers; however, studies on their association in breast cancer is still lacking. In this pilot study, we investigated mt-DNA copy number variation in peripheral blood and tissue samples from metastatic breast cancer patients and compared their differences. For the study, peripheral blood samples from non-cancer individuals (control) and breast cancer patients, along with resected tissues from adjacent and tumor sites from same breast cancer patients were collected. Total genomic DNA was isolated and changes in mt-DNA copy number were measured by relative quantification using SYBR green based quantitative real time PCR method. Our results indicated a significant reduction in mt-DNA copy number in blood samples of breast cancer patients compared to control. However, a significantly higher mt-DNA copy number was observed in tumor tissue when compared with paired non tumor tissue. There was no significant difference in mt-DNA copy number between blood and adjacent tumor tissue samples of the breast cancer patients. Overall, our study reports for the first time a comparison of mt-DNA copy number in blood and paired tissue together and suggested that mt-DNA copy number is differentially regulated in blood and tumor tissues in breast cancer., Competing Interests: None., (© 2021 The Authors. Published by Elsevier B.V.)

Large mammals that occur in low densities, particularly in the high-altitude areas, are globally threatened due to fragile climatic and ecological envelopes. Among bear species, the Himalayan brown bear (Ursus arctos isabellinus) has a distribution that is restricted to Himalayan highlands with relatively small and fragmented populations. To date, very little scientific information on the Himalayan brown bear, which is vital for the conservation of the species and the management of its habitats, especially in protected areas of the landscape, is available. The present study aims to understand the effectiveness of existing Himalayan Protected Areas in terms of representativeness for the conservation of Himalayan brown bear (HBB), an umbrella species in high-altitude habitats of the Himalayan region. We used the ensemble approach of the species distribution model and then assessed biological connectivity to predict the current and future distribution and movement of HBB in climate change scenarios for the year 2050. Approximately 33 protected areas (PAs) currently possess suitable habitats. Our model suggests a massive decline of approximately 73.38% and 72.87% under 4.5 and 8.5 representative concentration pathway (RCP) respectively in the year 2050 compared with the current distribution. The predicted change in suitability will result in loss of habitats from thirteen PAs; eight will become completely uninhabitable by the year 2050, followed by loss of connectivity in the majority of PAs. Habitat configuration analysis suggested a 40% decline in the number of suitable patches, a reduction in large habitat patches (up to 50%) and aggregation of suitable areas (9%) by 2050, indicating fragmentation. The predicted change in geographic isotherm will result in loss of habitats from thirteen PAs, eight of them will become completely inhabitable. Hence, these PAs may lose their effectiveness and representativeness in achieving the very objective of their existence or conservation goals. Therefore, we recommend adaptive spatial planning for protecting suitable habitats distributed outside the PA for climate change adaptation., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

The complete mitogenome of Himalayan black bear (Ursus thibetanus laniger) from Indian Himalayan region was assembled following the modified approach of mitochondrial baiting and mapping using the next-generation sequencing reads. The complete mitogenome was of 16,556 bp long, consisted of 37 genes that contained 13 protein-coding genes, 22 tRNAs, 2 rRNAs and 1 control region. The complete base composition was 31.33% A, 15.24% G, 25.45%C, and 27.98%T and gene arrangement was similar to the other sub-species of Asiatic black bear. The relative synonymous codon usage analysis revealed the maximum abundance of Isoleucine, Tyrosine, Leucine and Threonine. The assembled mitogenome of U. t. laniger exhibited 99% similarity with the mitogenomes of Himalayan black bear available from Nepal and Tibetan Plateau-Himalaya region. The findings of the present study has proven low depth sequencing data, adequate and highly efficient in rapid recovering the mitochondrial genome by overcoming the conventional strategies of obtaining long-range PCR and subsequently drawing phylogenetic inferences.

Pleistocene glaciations facilitated climatic oscillations that caused for enormous heterogeneity in landscapes, and consequently affected demography and distribution patterns of the mountain endemic species. In this context, we investigated demographic history and population genetic structure of red panda, distributed along the geographical proximity in the southern edge of the Qinghai-Tibetan Plateau. Bayesian based phylogeny demonstrated that red panda diverged about 0.30 million years ago (CI 0.23-0.39) into two phylogenetic (sub) species, that correspond to the middle-late Pleistocene transition. The observed intraspecific clades with respect to Himalayan and Chinese red panda indicated restricted gene flow resulting from the Pleistocene glaciations in the eastern and southern Tibetan Plateau. We found Himalayan red panda population at least in KL-India declined abruptly in last 5-10 thousand years after being under demographic equilibrium. We suggest revisiting the ongoing conservation activities through cross border collaboration by developing multi-nationals, and multi-lateral species-oriented conservation action plans to support the red panda populations in transboundary landscapes.

Background and Purpose: A survival advantage among individuals with higher body mass index (BMI) has been observed for diverse acute illnesses, including stroke, and termed the obesity paradox. However, prior ischemic stroke studies have generally tested only for linear rather than nonlinear relations between body mass and outcome, and few studies have investigated poststroke functional outcomes in addition to mortality., Methods: We analyzed consecutive patients with acute ischemic stroke enrolled in a 60-center acute treatment trial, the NIH FAST-MAG acute stroke trial. Outcomes at 3 months analyzed were (1) death; (2) disability or death (modified Rankin Scale score, 2-6); and (3) low stroke-related quality of life (Stroke Impact Scale

Objective: To describe the impact of COVID-19 on acute cerebrovascular disease care across 9 comprehensive stroke centers throughout Los Angeles County (LAC)., Methods: Volume of emergency stroke code activations, patient characteristics, stroke severity, reperfusion rates, treatment times, and outcomes from February 1 to April 30, 2020, were compared against the same time period in 2019. Demographic data were provided by each participating institution., Results: There was a 17.3% decrease in stroke code activations across LAC in 2020 compared to 2019 (1,786 vs. 2,159, respectively, χ2 goodness of fit test p < 0.0001) across 9 participating comprehensive stroke centers. Patients who did not receive any reperfusion therapy decreased by 16.6% in 2020 (1,527) compared to 2019 (1,832). Patients who received only intravenous thrombolytic (IVT) therapy decreased by 31.8% (107 vs. 157). Patients who received only mechanical thrombectomy (MT) increased by 3% (102 vs. 99). Patients who received both IVT and MT decreased by 31.8% (45 vs. 66). Recanalization treatment times in 2020 were comparable to 2019. CSCs serving a higher proportion of Latinx populations in the eastern parts of LAC experienced a higher incidence of MT in 2020 compared to 2019. Mild increase in stroke severity was seen in 2020 compared to 2019 (8.95 vs. 8.23, p = 0.046). A higher percentage of patients were discharged home in 2020 compared to 2019 (59.5 vs. 56.1%, p = 0.034), a lower percentage of patients were discharged to skilled nursing facility (16.1 vs. 20.7%, p = 0.0004), and a higher percentage of patients expired (8.6 vs. 6.3%, p = 0.008)., Conclusion: LAC saw a decrease in overall stroke code activations in 2020 compared to 2019. Reperfusion treatment times remained comparable to prepandemic metrics. There has been an increase in severe stroke incidence and higher volume of thrombectomy treatments in Latinx communities within LAC during the pandemic of 2020. More patients were discharged home, less patients discharged to skilled nursing facilities, and more patients expired in 2020, compared to the same time frame in 2019., (© 2021 S. Karger AG, Basel.)

Glioblastoma is highly recurrent and aggressive tumor with poor prognosis where existence of glioma stem cell (GSCs) population is well established. The GSCs display stem cell properties such as self-renewable, proliferation and therapeutic resistance which contribute to its role in tumor progression, metastasis and recurrence. Cancer stem cells (CSCs) can also be induced from non-stem cancer cells in response to radio/chemotherapy that further contribute to cancer relapse post therapy. Role of autophagy has been implicated in the existence of CSCs in different cancers; however, its role in GSCs is still unclear. Moreover, since autophagy is induced in response to various chemotherapeutic agents, it becomes imperative to understand the role of autophagy in therapy-induced pool of CSCs. Here, we investigated the role of autophagy in the maintenance of GSCs and temozolomide (TMZ)-induced therapeutic response. Glioblastoma cell lines (U87MG, LN229) were cultured as monolayer as well as GSC enriched tumorspheres and sub-spheroid population. Our results demonstrated that the tumorspheres maintained higher level of autophagy than the monolayer cells and inhibition of autophagy significantly reduced the percentage of GSCs and their self-renewal capacity. Further, TMZ at clinically relevant concentration resulted in an induction of survival autophagy in glioblastoma cells. We also observed that TMZ treatment significantly increased the expression of GSC markers, suggesting an increased pool of GSCs. Importantly, inhibition of autophagy prevented this TMZ-induced increased GSC population, suggesting a critical role for autophagy in therapy-induced generation of GSC pool. Overall, our findings revealed; i) higher levels of autophagy in GSCs; ii) TMZ induces protective autophagy and up-regulates pool of GSCs; and iii) inhibition of autophagy prevents TMZ-induced GSCs pool suggesting its role regulating GSC population in response to chemotherapy. Our study signifies a positive contribution of autophagy in survival of GSCs which implicates the use of autophagy inhibitors in a combinational approach to target TMZ-induced GSCs for developing effective therapeutic strategies. Further efforts are required to study the role of autophagy in therapy- induced GSC pool in other cancer types for its broad therapeutic implication., Competing Interests: None, (Copyright © Journal of Stem Cells and Regenerative Medicine.)

Three-dimensional in vitro spheroids are a reliable model to study tumor biology and drug toxicity. However, inconsistencies exist in terms of seeding cell density that governs spheroid size and shape, influencing the experimental outcome. We investigated the effect of varying cell densities using glioblastoma cells on tumorsphere formation and their responsiveness to drug treatment. Our results demonstrated that in comparison with spheroids formed with lower cell density, spheroids formed with higher cell density were not only larger in size but also had a larger necrotic core surrounded by a higher number of quiescent cells and were irresponsive to drug treatment. Our study highlights the importance of predetermination of cell density to obtain desired/appropriate spheroid size to produce consistent and reliable data on drug toxicity studies in tumor cells.

The novel coronavirus 2019 (COVID-19) global pandemic has drastically affected the world economy, raised public anxiety, and placed a substantial psychological burden on the governments and healthcare professionals by affecting over 4.7 million people worldwide. As a preventive measure to minimise the risk of community transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in India, a nationwide lockdown was imposed initially for 21 days to limit the movement of 1.3 billion people. These restrictions continue in most areas, with a conditional relaxation occurring in a few Indian states. In an attempt to assess the emerging mutants of SARS-CoV-2 and determine their spread in India, we analysed 112 complete genomes of SARS-CoV-2 in a time-lapse manner. We found 72 distinct SARS-CoV-2 haplotypes, defined by 143 polymorphic sites and high haplotype diversity, suggesting that this virus possesses a high evolutionary potential. We also demonstrated that early introduction of SARS-CoV-2 into India was from China, Italy and Iran and observed signs of community spread of the virus following its rapid demographic expansion since its first outbreak in the country. Additionally, we identified 18 mutations in the SARS-CoV-2 spike glycoprotein and a few selected mutations showed to increase stability, binding affinity, and molecular flexibility in the overall tertiary structure of the protein that may facilitate interaction between the receptor binding domain (RBD) of spike protein and the human angiotensin-converting enzyme 2 (ACE2) receptor. The study provides a pragmatic view of haplotype-dependent spread of SARS-CoV-2 in India which could be important in tailoring the pharmacologic treatments to be more effective for those infected with the most common haplotypes. The findings based on the time-lapse sentinel surveillance of SARS-CoV-2 will aid in the development of a real-time practical framework to tackle the ongoing, fast-evolving epidemic challenges in the country., Competing Interests: Dr. Mukesh Thakur is a PLOS ONE Academic Editor. However, this does not alter the authors' adherence to all the PLOS ONE policies including sharing data, materials and peer review process.

COVID-19 pandemic has resulted in 16,114,449 cases with 646,641 deaths from the 217 countries, or territories as on July 27th 2020. Due to multifaceted issues and challenges in the implementation of the safety and preventive measures, inconsistent coordination between societies-governments and most importantly lack of specific vaccine to SARS-CoV-2, the spread of the virus that initially emerged at Wuhan is still uprising after taking a heavy toll on human life. In the present study, we mapped immunogenic epitopes present on the four structural proteins of SARS-CoV-2 and we designed a multi-epitope peptide based vaccine that, demonstrated a high immunogenic response with a vast application on world's human population. On codon optimization and in-silico cloning, we found that candidate vaccine showed high expression in E. coli and immune simulation resulted in inducing a high level of both B-cell and T-cell mediated immunity. The results predicted that exposure of vaccine by administrating three injections significantly subsidized the antigen growth in the system. The proposed candidate vaccine found promising by yielding desired results and hence, should be validated by practical experimentations for its functioning and efficacy to neutralize SARS-CoV-2.

Background and Aims: The impact of altered cholesterol metabolism on post-prandial lipids in Indians with hypothyroidism is not known. This study evaluated the impact of overt primary hypothyroidism (OPH) and subclinical hypothyroidism (ScH) on post-prandial lipids after a standardised, carbohydrate-rich, mixed meal., Methods: Endocrinology outpatients were screened for possible inclusion into the study. Patients >18 years of age with hypothyroidism who were not taking levothyroxine and who did not present with any comorbidities underwent biochemical evaluation following a carbohydrate-rich, mixed meal. Assessments included total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), triglycerides, lipoprotein-A (Lp-A), apolipoprotein-A1 (apo-A1), apolipoprotein-B (apo-B), insulin and fasting glucose. Assessments were carried out 1 hour, 2 hours and 4 hours after the meal. Patients were compared against healthy matched controls recruited from healthcare professionals in the hospital (asymptomatic and apparently healthy nursing staff, reception staff and ward staff)., Results: Data from 194 patients (161 with ScH and 33 with OPH) and 40 euthyroid controls were analysed. Anthropometry, body mass index, glycaemia and insulin resistance were comparable among patients with OPH and ScH, and controls. LDL-C and Lp-A were significantly higher in those with OPH, compared with ScH and controls, at baseline, 1 hour, 2 hours and 4 hours after mixed meal consumption (all p<0.05). There was progressive and similar decline in post-prandial TC, LDL-C and Lp-A in all three groups. Triglycerides were similar among the OPH, ScH and control groups, both in fasting and post-prandial state, with a progressive and similar increase in post-prandial triglycerides in all three groups., Conclusion: This study demonstrated that severity of hypothyroidism had no impact on post-prandial TC, LDL-C and Lp-A. In addition, hypothyroidism had no impact on post-prandial triglycerides. Therefore, we conclude that lipid profile can be reliably estimated in a non-fasting state in individuals with ScH and OPH., Competing Interests: Disclosures: Lokesh Kumar Sharma, Neera Sharma, Bindu Kulshreshtha, Rahul Bansal, Anshita Aggarwal and Deep Dutta have no financial or non-financial relationships or activities to declare in relation to this article. Deep Dutta is is a member of the journal’s Editorial Board., (© Touch Medical Media 2020.)

Wildlife management in rapid changing landscapes requires critical planning through cross cutting networks, and understanding of landscape features, often affected by the anthropogenic activities. The present study demonstrates fine-scale spatial patterns of genetic variation and contemporary gene flow of red panda (Ailurus fulgens) populations with respect to landscape connectivity in Kangchenjunga Landscape (KL), India. The study found about 1,309.54 km 2 area suitable for red panda in KL-India, of which 62.21% area fell under the Protected Area network. We identified 24 unique individuals from 234 feces collected at nine microsatellite loci. The spatially explicit and non-explicit Bayesian clustering algorithms evident to exhibit population structuring and supported red panda populations to exist in meta-population frame work. In concurrence to the habitat suitability and landscape connectivity models, gene flow results supported a contemporary asymmetric movement of red panda by connecting KL-India in a crescent arc. We demonstrate the structural-operational connectivity of corridors in KL-India that facilitated red panda movement in the past. We also seek for cooperation in Nepal, Bhutan and China to aid in preparing for a comprehensive monitoring plan for the long-term conservation and management of red panda in trans-boundary landscapes.

YPEL3 that induces cellular senescence in both normal and tumour cells of humans may show altered expression under the influence of incidental mutations. In this study, we proposed the first structure of Native YPEL3 protein and its five possible deleterious mutants-V40M, C61Y, G98R, G108S, and A131T and predicted their deleterious effects to alter stability, flexibility and conformational changes in the protein. The MD simulation (RMSD, RMSF, Rg, h-bond and SASA) analysis revealed that the variants V40M, G98R and G108S increased the flexibility in protein, and variant V40M imparted more compactness to the protein.. In general, variants attributed changes in the native conformation and structure of the YPEL3 protein which might affect the native function of cellular senescence. The study provides opportunities for health professionals and practitioners in formulating précised medicines to effectively cure various cancers. We propose in-vitro or in-vivo studies should consider these reported nsSNPs while examining any malfunction in the YPEL3 protein.

Genetic diversity indices and forensic parameters at 20 autosomal short tandem repeat (STR) loci were evaluated in 233 unrelated individuals of Himachal Pradesh, India. In total, 255 alleles were observed with an average of 11.25 ± 0.88 alleles per locus. None of the loci deviated from Hardy Weinberg Equilibrium. The most polymorphic and discriminative locus was Penta E. The combined power of exclusion and the combined power of discrimination were found to be 0.99 and 1. Additionally, the genetic relationship of the Himachal Pradesh population with the populations of the neighboring state was also investigated. All the STR loci were found polymorphic, and the select panel of STRs was found suitable for population genetic studies and forensic analysis.

Demand for pangolin scales in East Asia has increased dramatically in the past two decades, raising concern to the pangolin survival and bringing them to the brink of local extinction. Enumerating the number of individuals from the seized pangolin scales primarily goes undocumented, mostly due to the unavailability of the appropriate methods. In this study, we developed a Pangolin Indexing System, a multi-locus STR panel of eight dinucleotide microsatellites that showed promising results in individualization and assignment of scales into Chinese and Indian pangolins. The combined power of exclusion was 0.83 and 0.99 for Chinese and Indian pangolin. The select panel of eight polymorphic STRs exhibited the cumulative probability of identity 3.7 × 10 -9 for Indian pangolin and 3.6 × 10 -7 for Chinese pangolin and identified 51 unique genotypes from the 74 scales selected from the four pangolin seizures. The study demonstrated the first report of cross-species validation of STRs developed from Malayan pangolin to Indian pangolin and showed the potential application of Pangolin Indexing System in screening of large seizures through DNA profiling from the scales of Indian and Chinese pangolin.

Aims: No meta-analysis is available which has summarized and holistically analyzed the efficacy and safety of evogliptin. We undertook this meta-analysis to address this gap in knowledge., Methods: Electronic databases were searched for RCTs involving diabetes patients receiving evogliptin in intervention arm and placebo/active comparator in control arm. Primary outcome was to evaluate changes in HbA1c. Secondary outcomes were to evaluate alterations in fasting glucose, postprandial glucose, lipids, insulin resistance, patients achieving glycemic targets of HbA1c <7% and <6.5%, and adverse events., Results: From initially screened 57 articles, data from six RCTs involving 887 patients was analyzed [three having sitagliptin/linagliptin as active comparator; three having placebo in control group]. Evogliptin was noninferior to sitagliptin/linagliptin regarding HbA1c reduction at 12 weeks [mean difference (MD) -0.06%; 95%CI: -0.23-0.11%; P = 0.48] and 24 weeks (MD 0.04%; 95%CI: -0.11-0.19%; P = 0.60) follow-up. Evogliptin was superior to placebo regarding HbA1c reduction at 12-weeks (MD -0.57%; 95%CI: -0.62- -0.52%; P < 0.001) and 24 weeks (MD -0.28%; 95%CI: -0.47 - -0.09%; P = 0.004). Evogliptin was noninferior to sitagliptin/linagliptin regarding patients achieving HbA1c <7% and <6.5% at 12 weeks and 24 weeks follow-up. Total adverse events [Risk ratio (RR) 0.98; 95% CI: 0.72-1.32; P = 0.89] and severe adverse events (RR 0.65; 95% CI: 0.25-1.67; P = 0.37) were not significantly different among groups. Patients receiving evogliptin did not have increased symptomatic (RR 0.46; 95% CI: 0.10-2.16; P = 0.32) and asymptomatic (RR 1.09; 95% CI: 0.61-1.97; P = 0.77) hypoglycaemia., Conclusion: Evogliptin is well tolerated and has good glycemic efficacy over 6 months use for T2DM management., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Indian Journal of Endocrinology and Metabolism.)

Abdominal tuberculosis (ATB) continues to pose a major diagnostic challenge for clinicians due to its nonspecific clinical presentation, variable anatomical location and lack of sensitive diagnostic tools. In spite of the development of several assays till date; no single test has proved to be adequate for ATB diagnosis. In this study, we for the first time report the detection of circulating cell-free Mycobacterium tuberculosis (M. tuberculosis) DNA (cfMTB-DNA) in ascitic fluid (AF) samples and its utility in ATB diagnosis. Sixty-five AF samples were included in the study and processed for liquid culture, cytological, biochemical and molecular assays. A composite reference standard (CRS) was formulated to categorize the patients into 'Definite ATB' (M. tuberculosis culture positive, n = 2), 'Probable ATB' (n = 16), 'Possible ATB' (n = 13) and 'Non-TB' category (n = 34). Two molecular assays were performed, namely, the novel cfMTB-DNA qPCR assay targeting M. tuberculosis devR gene and Xpert MTB/RIF assay (Xpert), and their diagnostic accuracy was assessed using CRS as reference standard. Clinical features such as fever, loss of weight, abdominal distension and positive Mantoux were found to be strongly associated with ATB disease (p<0.05). cfMTB-DNA qPCR had a sensitivity of 66.7% (95% CI:40.9,86.7) with 97.1% specificity (95% CI:84.7,99.9) in 'Definite ATB' and 'Probable ATB' group collectively. The sensitivity increased to 70.9% (95% CI:51.9,85.8) in the combined 'Definite', 'Probable' and 'Possible' ATB group with similar specificity. The cfMTB-DNA qPCR assay performed significantly better than the Xpert assay which demonstrated a poor sensitivity of ≤16.7% with 100% (95% CI:89.7,100) specificity (p<0.001). We conclude that cfMTB-DNA qPCR assay is an accurate molecular test that can provide direct evidence of M. tuberculosis etiology and has promise to pave the way for improving ATB diagnosis., Competing Interests: The authors have declared that no competing interests exist.

Background: Adult acne has been classified into two major subtypes: "persistent acne" and "late onset acne". A surrogate marker of hyperandrogenism (HA) in adult female acne is the presence of clinical signs of HA and biochemical hyperandrogenemia. We compared the clinical and hormonal profiles of the two acne subtypes and evaluated the likely source of androgen excess - ovarian or adrenal., Methods: Female acne patients 25 years of age and older were evaluated for clinical HA. Hormonal assessment included total testosterone (TT), sex hormone binding globulin (SHBG), free androgen index (FAI), anti-Mullerian hormone (AMH), 17-hydroxyprogesterone (17-OHP), dehydroepiandrosterone sulfate (DHEAS), follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), and prolactin. DHEAS and 17-OHP represented adrenal androgens and AMH indicated ovarian reserve., Results: Of 120 cases, clinical HA was seen in 71.67% while biochemical hyperandrogenemia was detected in only 18.33% of patients. Though late onset was more common in adult acne patients (56.6%), the persistent acne subgroup (43.33%) had a younger age at onset, a past history of adolescent acne (51.92%), truncal predilection (44.23%), polycystic ovary syndrome (PCOS) (44.23%), significant presence of irregular menses (40.38%) and hirsutism (57.69%), and increased TT (13.46%), 17-OHP (76.92%), AMH (44.23%), and increased LH/FSH (15.38%) ratio. PCOS was seen more in the persistent acne patients with clinical HA and increased 17-OHP levels., Conclusion: Persistent acne patients had marked clinical HA, PCOS, and hormonal abnormalities necessitating an endocrinological evaluation. As a corollary, this subgroup would benefit from antiandrogen therapy., (© 2020 The International Society of Dermatology.)

The Bengal monitor lizard or Common Indian monitor lizard (Varanus bengalensis Daudin, 1802) is classified as Least Concern under the IUCN and listed under the Schedule-I of the Indian Wildlife Protection Act 1972. Further, the trade of the species is prohibited as the species is listed in Appendix I of CITES. It is widely distributed over Western Asia, the Indian Subcontinent, and Southeast Asia (Koch et al. 2013). It is reported to occupy both terrestrial as well as freshwater habitats from desert areas to floodplains, scrubland to forests, in different types of terrains at elevations below 1500m (Auffenberg 1994; Papenfuss et al. 2010). Body size of individuals varies from 61 to 175 cm from the tip of the snout to the end of the tail (Auffenberg 1994; Losos and Greene, 1998). Adults are generally grey or greenish-grey in color, with a ventral pattern of grey to black crossbars from the chin to the tail. Adult individuals are less contrasting and have a less distinct pattern than younger individuals. The species shows a sexual dimorphism, with males being heavier (around 7.18 to 10 kg) than females which are about 40% smaller in size (Papenfuss et al. 2010).

The Indian rhino (Rhinoceros unicornis) is susceptible to habitat change and fragmentation due to illegal logging, rapid urbanization and non-forest use and therefore were confined in to isolated areas throughout its distribution. The present study was conducted in Gorumara landscape which is composed of two protected areas (PAs) viz., Gorumara National Park (GNP) and Chapramari Wildlife Sanctuary. Both PAs were separated by a territorial forest range (Bridge Area), which is between both the PAs and under high anthropogenic disturbance. The study was designed to understand the impacts of landcover change on habitat suitability of R. unicornis in a multi-temporal scenario from 1998 to 2018 using ensemble approach and also to simulate the future habitat suitability for 2028. Our result suggests a significant increase in woodland cover inside the PAs, whereas the grassland cover has increased outside the PA in territorial range. We found a strong positive association of R. unicornis with grasslands. The Comparison of the future suitability model of 2028 with that of 2018 indicates a substantial increase in rhino suitable area by 13% in the territorial forest. Hence, bringing the territorial forest into the PA network, will be a crucial step to increase the fodder availability and better connectivity for the long term survival of the species.

Context: High perinatal mortality in India may be caused by inaccurate dating of pregnancy resulting from suboptimal uptake of antenatal care and ultrasound services during pregnancy., Aim: To determine the discrepancy in the last menstrual period (LMP) assigned expected date of delivery (EDD) and ultrasound assigned EDD in pregnant women in a rural district of central India., Methods: Data from an ongoing cross-sectional screening program providing fetal radiology imaging in Guna district of Madhya Pradesh from 2012-2019 was analyzed for recall of LMP and discordance between LMP and ultrasound assigned EDD. The discrepancy was present when EDD assigned by ultrasound differed by 3 or more days at gestational ages less than 8 +6 weeks, 5-7 days at gestational ages 8 +6 weeks till 14 weeks, and 7-10 days at gestational ages 14-20 weeks., Results: The program screened 14,701 pregnant women of which 4,683 (31.86%, 95% CI: 31.11, 32.61) could not recall LMP. EDD assigned by LMP and ultrasound matched in 7,035 (70.22%, 95% CI: 69.32, 71.12) of the remaining 10,018 pregnant women. EDD was overestimated by LMP for 26.06% (95% CI: 25.21, 26.93) women; these foetuses were at risk of being misclassified as a term fetus. In 2018, the project had no maternal deaths, infant mortality rate of 24.7, low birth weight rate of 9.69%, and 100% antenatal coverage., Conclusion: Accurate dating of pregnancy and systematic follow-up integrating radiology imaging and obstetrics care for appropriate risk-based management of pregnant women can significantly improve perinatal statistics of India., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Indian Journal of Radiology and Imaging.)

The Gorumara National Park (GNP) is an important conservation area located in the northern region of West Bengal State, India, as it provides habitat for three megaherbivores: Indian One-horned rhinoceros (Rhinoceros unicornis), Asian elephants (Elephas maximus) and Gaurs (Bos gaurus). It harbours one of the last population of the one-horned rhino. In the present study, landscape change and configuration were investigated by comparing three Landsat images, from 1998, 2008 and 2018. The images were classified into six different landcover classes following standard methodology. The present study also involves evaluation of landscape and anthropogenic predictors influence on the megaherbivores of GNP, followed by future landcover simulation for the year 2028. The result shows a significant decrease in the grassland cover from 18.87 km2 to 8.27 km2 from 1998 to 2018, whereas the woodland cover has increased from 50.14 km2 to 62.09 km2 between 1998 and 2018. The landscape configuration indices such as Number of Patches (NP), Patch Density (PD), Interspersion and Juxtaposition (IJI), Aggregation Index (AI) and Mean Shape Index (SHAPE AM) indicated that the landscapes has lost complexity in the spatial placement of patches of different Land Use and Land Cover (LULC) classes. Also, the landscape over the three decades has become uniform in terms of diversity of patches, because of earlier plantation activities by the forest managers. Result also indicated that grassland, along with its class metrics are the top predictors contributing 43.6% in explaining the spatial distribution of megaherbivores in GNP. Results from the simulated landcover of 2028 suggest a possible decline in overall grassland by 6.23% and a subsequent upsurge in woodland by 6.09% from 2018. The present result will be useful in guiding the forest management in developing habitat improvement strategies for the long- term viability of megaherbivore populations of rhino, gaur and elephant in the GNP., Competing Interests: The authors have declared that no competing interests exist.

Illegal trade of fishes is common and has been in practice since ages for the support of livelihood and as dietary supplements. However, several species are protected in the Wildlife (Protection) Act, 1972 of India and their trade is restricted under CITES. In this article, we report trade of Sharpnose guitarfish ( Glaucostegus granulatus) for the ethnomedicinal remedy, identified using DNA barcoding in the Keylong district of Lahaul and Spiti, Himachal Pradesh. This study provides the first DNA barcode of Sharpnose guitarfish. In order to handle wildlife offense cases we emphasize that a large reference database for other fishes in trade is needed., Competing Interests: The authors report no conflict of interest. All authors have read and agree with the content of the paper. Authors are responsible for the content and writing of this article. Figure 1.Glaucostegus granulatus skin (a) and bone (b). Maximum Likelihood tree based on 12S rRNA (c) and cyt b (d) sequence showing the relationship between the collected specimen (in box) and other suspected close relative species., (© 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Competing Interests: None

Background: Telestroke is an efficient, cost-effective way to standardize care and improve access to immediate neurologic expertise for rural hospitals and other underserved areas. Hands-free wearable technology potentially allows for faster evaluations that fit easily within prehospital workflows and could improve prehospital triage of stroke patients to appropriate receiving stroke centers. The goal of this study is to assess the feasibility and inter-rater reliability of wearable eyeglass video technology in assessing stroke-related neurologic deficits in patients with suspected acute stroke., Methods: Consecutive patients with suspected stroke were evaluated concurrently by an on-site neurologist using wearable eyeglass video technology and a remotely located neurologist viewing the patient through an online platform. Inter-rater reliability in assigning National Institutes of Health Stroke Scale (NIHSS) scores was evaluated using inter-rater correlation coefficient (ICC) and weighted kappa scores., Results: Among 17 enrolled patients, mean age was 58 (SD ± 20) and 29% were female. There was a high degree of correlation in total NIHSS score (ICC .99 and weighted kappa .88) and across all NIHSS subitems (ICC .81-1 and weighted kappa .68-1) between the examiner evaluating remotely via wearable eyeglass video technology with access to the patient and the in-person examiner. The maximum difference between the 2 NIHSS scores was 3., Conclusions: The use of wearable eyeglass video technology in telestroke is feasible and reliable. Use of this technology in the prehospital setting has the potential to improve early assessment of patients with acute stroke symptoms and to facilitate transfer to appropriate stroke centers in the regional systems of care., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Context: India has a high perinatal mortality rate. The Indian Radiological and Imaging Association (IRIA) is supplementing efforts to address perinatal mortality in India through the Samrakshan program., Aims: To describe various elements of the Samrakshan program that aims to reduce perinatal mortality in India., Methods: Samrakshan focuses on two priority areas, preeclampsia (PE) and fetal growth restriction (FGR). Samrakshan aims at technical skill upgradation, specifically focused on improved interpretative ability, prognostic and therapeutic efficacy using Doppler studies, a free online learning platform and offline continuous medical educations (CMEs), building an evidence base from the program to develop policy and guidelines, and improving synergy with the RAKSHA program of IRIA and other fetal care stakeholders., Results: Two courses on Doppler studies focused on first trimester and third trimester, supplemented by case discussions and journal articles, have started on the online platform with 230 registrants. The first statewide CME was held at Indore. Samrakshan screening identified 10 (17.24%, 95% CI: 8.59, 29.43) women at high risk for preterm PE and 29 (50.00%, 95% CI 36.58, 63.42) women at high risk for FGR in the first trimester. Ten fetuses (7.63%, 95% CI: 3.72, 13.59) including 9 with stage 1 FGR were identified in the third-trimester screening., Conclusions: Samrakshan is a flagship program of IRIA that aims to reduce perinatal mortality in India through a synergistic, holistic approach that complements and supplements existing efforts in India., Competing Interests: There are no conflicts of interest., (Copyright: © 2019 Indian Journal of Radiology and Imaging.)

Methicillin-resistant Staphylococcus aureus (MRSA) strains that are resistant to all forms of penicillin have become an increasingly common and urgent problem threatening human health. They are responsible for a wide variety of infectious diseases ranging from minor skin abscesses to life-threatening severe infections. The vra operon that is conserved among S. aureus strains encodes a three-component signal transduction system ( vraTSR ) that is responsible for sensing and responding to cell wall stress. We developed a novel and multifaceted assay to identify compounds that potentiate the activity of oxacillin, essentially restoring efficacy of oxacillin against MRSA, and performed high-throughput screening (HTS) to identify oxacillin potentiators. HTS of 13,840 small-molecule compounds from an antimicrobial-focused Life Chemicals library, using the MRSA cell-based assay, identified three different inhibitor scaffolds. Checkerboard assays for synergy with oxacillin, reverse transcriptase PCR (RT-PCR) assays against vraR expression, and direct confirmation of interaction with VraS by surface plasmon resonance (SPR) further verified them to be viable hit compounds. A subsequent structure-activity relationship (SAR) study of the best scaffold with diverse analogs was utilized to improve potency and provides a strong foundation for further development., (Copyright © 2019 American Society for Microbiology.)

Different Biogeographic provinces and environmental factors are known to influence the dispersibility of long-ranging carnivores over the landscape. However, lack of empirical data on long-ranging carnivores may lead to erroneous decisions in formulating management plans. The Indian Grey wolf (Canis lupus pallipes) is known to be distributed in the vast areas of the Indian subcontinent. However, the actual population estimates are available only for Gujarat, Karnataka, Rajasthan and Bihar. Whereas, its distribution, population and habitat ecology is poorly known from the eastern region. Hence, this article aimed to evaluate the habitat suitability along with landscape connectivity for the species over the two major biogeographic provinces of India, i.e., Lower Gangetic Plains (7b) and Chhota Nagpur Plateau (6b). The present model with significantly higher Area under the curve (AUC) value of 0.981, indicates its accuracy in predicting the suitable habitats and identifying biological corridors by using environmental, topological and anthropogenic variables. Precipitation of the driest quarter and the precipitation of seasonality were the two best performing variables in our model, capable of explaining about 26% and 22.4% variation in the data respectively. Out of the total area i.e. 4,16,665 Km2, about 18,237 Km2 (4.37%) was found to be highly suitable area and about 3,16,803 Km2 (76.03%) areas as least suitable. The corridor analysis indicated that the habitat connectivity was highest in the border line area of the two biotic provinces located in the south-eastern zone via districts of Purba Singhbhum and Paschim Singhbhum of Jharkhand state and Bankura and West Midnapore districts of West Bengal state. Among the Protected Areas (PAs), natural corridors exist connecting the Simlipal National Park (NP)-Satkosia Wildlife Santuray (WLS), Dalma ranges of Chotta Nagpur plateau along with Badrama WLS, Khulasuni WLS and Debrigarh WLS. Differential management through landscape level planning may be helpful in securing the future of the species in the landscape., Competing Interests: The authors have declared that no competing interests exist.

Leber's hereditary optic neuropathy (LHON) is a classical mitochondrial disease caused by mutations in the mitochondrial DNA encoding complex I subunits. Oxidative stress associated with complex I defect has been implicated in developing LHON phenotype such as retinal ganglion cell (RGC) death and loss of vision. However, the mechanism of LHON pathogenesis is still not very clear and thus no effective therapies are available to date. Using cybrid models for LHON, we show that autophagy is significantly compromised in cells carrying LHON-specific mtDNA mutations, which results in reduced clearance of dysfunctional mitochondria contributing to cell death. We further show that pharmacological activation of autophagy selectively clears the damaged mitochondria and thus repairs mitochondrial defects and improves overall cell survival in LHON cell models. Our results suggest that compromised autophagy is the missing link from oxidative stress to LHON pathogenesis. Activation of mitophagy ameliorates mitochondrial defects and exerts a protective role by improving cell survival in cells carrying LHON mutations that could be utilized as a potential therapeutic target for LHON treatment.

Background and Purpose: Endovascular therapy (ET) has become the standard of care for selected patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO). However, many LVO or medium vessel occlusion (MVO) patients are ineligible for ET, including some who harbor salvageable tissues. To develop complementary therapies for these patients, it is important to delineate their prevalence, clinical features, and outcomes., Methods: In a prospectively maintained database, we reviewed consecutive AIS patients between December 2015 and September 2016. Based on the first multimodal computed tomography or magnetic resonance imaging, patients were categorized as having substantial penumbra if perfusion lesion volume (Tmax >6 seconds) exceeded ischemic core volume (relative cerebral blood flow <30% on CT perfusion or apparent diffusion coefficient <620 on diffusion weighted image) by ≥20%., Results: Among 174 consecutive AIS patients presenting within 24 hours of last known well time, 29 (17%) had LVO or MVO and substantial penumbra, but were deemed ET ineligible. Among these patients, mean age was 81 (±13), 45% were female, and median National Institute of Health Stroke Scale score was 11 (interquartile range [IQR]: 5-19). The most common reasons for not pursuing ET were: distal occlusion (28%), mild neurologic deficit (16%), and temporally advanced core injury (16%). Ischemic core volume was 20 mL (±31), penumbral volume was 54 mL (±63), and mismatch ratio median was 5.6 (IQR: 2-infinite). Severe disability or death at discharge (modified Rankin scale: 4-6) occurred in 72% of the patients., Conclusion: Even in the modern stent retriever era, 1 in 6 AIS patients presents with substantial penumbra judged not appropriate for ET. This population may benefit from the development of alternative therapies, including collateral enhancement, neuroprotection, and thrombectomy devices deployable in distal arteries., (© 2018 by the American Society of Neuroimaging.)

Pantothenate kinase (PANK) is a metabolic enzyme that regulates cellular coenzyme A (CoA) levels. There are three human PANK genes, and inactivating mutations in PANK2 lead to pantothenate kinase associated neurodegeneration (PKAN). Here we performed a library screen followed by chemical optimization to produce PZ-2891, an allosteric PANK activator that crosses the blood brain barrier. PZ-2891 occupies the pantothenate pocket and engages the dimer interface to form a PANK•ATP•Mg 2+ •PZ-2891 complex. The binding of PZ-2891 to one protomer locks the opposite protomer in a catalytically active conformation that is refractory to acetyl-CoA inhibition. Oral administration of PZ-2891 increases CoA levels in mouse liver and brain. A knockout mouse model of brain CoA deficiency exhibited weight loss, severe locomotor impairment and early death. Knockout mice on PZ-2891 therapy gain weight, and have improved locomotor activity and life span establishing pantazines as novel therapeutics for the treatment of PKAN.

Background: Pushing and pulling in workplaces are common actions. Repetitive forceful exertions in long-duration works lead to increased risk of musculoskeletal disorders and injuries., Aim: To investigate the upper extremity strength in generic push-pull modes while using hand tools and forecasting the limits of the workers while frequent or continuous operation., Settings and Design: The study was conducted among men workers in Ahmedabad city, India, and the design was cross-sectional study., Materials and Methods: In all, 100 men were recruited (Group 1: 18-39 years and Group 2: 40-60 years). Upper extremity muscular strength (isometric mode) testing of the preferred hand during push-pull type of manual hand-tool operations was carried out for 60 s. Forecasting of strength to generate predictions for future events (120 s) based on known past events (measured 60 s) was carried out using Holt-Winters time-series model., Statistical Analysis: Descriptive statistics was used for analysis. For prediction model evaluation, WEKA 3.8.2 was used., Results: Anthropometric parameters of both groups were similar, having no effect on generated strength. Largely, pull strength was recorded to be higher than push strength, wherein Group 2 men generated slightly higher strength. Seated strength was also higher than standing exertion. Forecasting reveals steady strength values for Group 1 men, whereas steep decline among Group 2 men with increasing duration of trial., Conclusion: The strength data generated would aid in work schedule design. Strength forecasting model would assist in developing engineering guidelines in the design of tools at workplace., Competing Interests: There are no conflicts of interest.

Background: No data is available evaluating the difference in serum versus plasma sample assay of commonly tested parameters in the emergency department, where the sample processing time can be significantly reduced if plasma is used for analysis instead of conventionally used serum. Hence, this study aimed to evaluate the differences in serum versus plasma sample estimation of commonly evaluated biochemical parameters using dry chemistry technology., Materials and Methods: Paired blood samples were collected from a single venipuncture of 405 patients admitted to the emergency department. Dry chemistry autoanalyzer (Vitros-350, Ortho Clinical Diagnostics) was used to process all the samples., Results: Data from 401 patients were analyzed. Percentage differences between serum versus plasma samples for all analytes ranged from 0.0% to 57.44% and were <±4% for a majority of parameters, except uric acid (-6.25%), albumin (+11.90%), chloride (-5.05%), phosphorus (-6.06%), creatine phosphokinase (CPK) total (-57.44%), amylase (-37.53%), lipase (-42.74%), lactate dehydrogenase (LDH) (-8.53%), and C-reactive protein (-7.44%). For albumin, CPK total, amylase, and lipase, the difference between serum and plasma samples was more than the accepted upper range recommended by College of American Pathologists., Conclusion: Glucose, urea, creatinine, bilirubin, total protein, serum glutamate-pyruvate transaminase, total cholesterol, high-density lipoprotein cholesterol, triglycerides, sodium, and CPK-mb can be reliably assayed from either serum or plasma samples in emergency/routine practice. CPK total, amylase, and lipase should always be assayed from serum and not plasma due to significant variations. Uric acid, chloride, phosphorous, and LDH only in emergency situations should be assayed from plasma. For routine assays, serum should be preferred., Competing Interests: There are no conflicts of interest.

Background and Purpose: The impact of blood-brain barrier (BBB) disruption can be detected by intraparenchymal hyperdense lesion on the computed tomography (CT) scan after endovascular stroke therapy. The purpose of this study was to determine whether early BBB disruption predicts intracranial hemorrhage and poor outcome in patients with acute ischemic stroke treated with mechanical thrombectomy., Methods: We analyzed patients with anterior circulation stroke treated with mechanical thrombectomy and identified BBB disruption on the noncontrast CT images immediately after endovascular treatment. Follow-up CT or magnetic resonance imaging scan was performed at 24 hours to assess intracranial hemorrhage. We dichotomized patients into those with moderate BBB disruption versus those with minor BBB disruption and no BBB disruption. We evaluated the association of moderate BBB disruption after mechanical thrombectomy with intracranial hemorrhage and clinical outcomes., Results: Moderate BBB disruption after mechanical thrombectomy was found in 56 of 210 patients (26.7%). Moderate BBB disruption was independently associated with higher rates of hemorrhagic transformation (OR 25.33; 95% CI 9.93-64.65; P < .001), parenchymal hematoma (OR 20.57; 95% CI 5.64-74.99; P < .001), and poor outcome at discharge (OR 2.35; 95% CI 1.09-5.07; P = .03). The association of BBB disruption with intracranial hemorrhage remained in patients with successful reperfusion after mechanical thrombectomy. The location of BBB disruption was not associated with intracranial hemorrhage and poor outcome., Conclusions: Moderate BBB disruption is common after mechanical thrombectomy in a quarter of patients with acute ischemic stroke and increases the risk of intracranial hemorrhage and poor outcome., (Copyright © 2018 by the American Society of Neuroimaging.)

Background & Objectives: Data on bone mineral density (BMD) and sarcopenia are scant from young females with HIV. This study was conducted to determine occurrence, predictors and impact of body composition alterations on osteoporosis in pre-menopausal women with HIV., Methods: A total of 214 females with serologically documented HIV infection were screened, of whom 103 pre-menopausal women, 25-45 yr age, clinically stable, having at least one year follow up data, underwent hormonal and dual-energy X-ray absorptiometry analysis for BMD and body composition. Seventy five matched controls were also evaluated., Results: Females with HIV had significantly lower BMD and., Z: -score at lumbar spine (LS), total femur, neck of femur (NOF), and radius ultra-distal (UD) compared to controls. Osteoporosis at least at one site was observed in 34.95 per cent patients, compared to eight per cent in controls (P<0.001). Most common site of osteoporosis in females with HIV was radius UD (24.27%), followed by radius 33 per cent (17.48%), radius total (15.53%) and greater trochanter, NOF and LS (6.80% each). HIV patients had significantly lower bone mineral content, lean mass (LM), fat per cent, android (A) fat, gynoid (G) fat, and A/G ratio. LM and fat mass (FM) were -15.65 and -11.54 per cent lower in HIV patients, respectively. Osteoporosis patients had significantly higher use of antiretroviral therapy and lower LM, FM and fat per cent. On logistic regression, LM followed by A/G ratio and BMI were the best predictors of osteoporosis. Sarcopenia was observed in 17.5 per cent patients., Interpretation & Conclusions: Our results showed that osteoporosis and sarcopenia were significant problems in young women with HIV. HIV was associated with greater LM loss, which was critical for bone health. Sarcopenia may predict low BMD in HIV., Competing Interests: None

The purpose of this study was to develop and evaluate a scoring system for assessing reperfusion status based on arterial spin labeled (ASL) perfusion MRI in acute ischemic stroke (AIS) patients receiving thrombolysis and/or endovascular treatment. Pseudo-continuous ASL with background suppressed 3D GRASE was acquired along with DWI in 90 patients within 24 h post-treatment. An automatic reperfusion scoring system (auto-RPS) was devised based on the Alberta Stroke Program Early CT Score (ASPECTS) template, and compared with manual RPS and DWI-ASPECTS. TICI (thrombolysis in cerebral infarction) scores were graded in 48 patients who received endovascular treatment. Favorable outcomes were defined by a modified Rankin Scale score of 0-2 at three months. Auto-RPS was positively correlated with DWI-ASPECTS (ρ = 0.6, P < 0.001) and was on average 1 point lower than DWI-ASPECTS ( P < 0.001). The area under the receiver operating characteristic curve for discriminating poor functional outcome (n = 90) was 0.75 (95% CI, 0.64-0.86) for manual RPS, 0.85 (95% CI, 0.76-0.94) for auto-RPS, and 0.81 (95% CI, 0.71-0.90) for DWI-ASPECTS. Multiple logistic regression analysis in the TICI-graded patients (n = 48) showed that auto-RPS is highly associated with functional outcome (OR = 25.2, 95% CI 4.02-496, P < 0.01). Post treatment auto-RPS within 24 h provides a useful tool to predict functional outcome in AIS patients.

Background and Purpose: Prehospital scales have been developed to identify patients with acute cerebral ischemia (ACI) because of large vessel occlusion (LVO) for direct routing to Comprehensive Stroke Centers (CSCs), but few have been validated in the prehospital setting, and their impact on routing of patients with intracranial hemorrhage has not been delineated. The purpose of this study was to validate the Los Angeles Motor Scale (LAMS) for LVO and CSC-appropriate (LVO ACI and intracranial hemorrhage patients) recognition and compare the LAMS to other scales., Methods: The performance of the LAMS, administered prehospital by paramedics to consecutive ambulance trial patients, was assessed in identifying (1) LVOs among all patients with ACI and (2) CSC-appropriate patients among all suspected strokes. Additionally, the LAMS administered postarrival was compared concurrently with 6 other scales proposed for paramedic use and the full National Institutes of Health Stroke Scale., Results: Among 94 patients, age was 70 (±13) and 49% female. Final diagnoses were ACI in 76% (because of LVO in 48% and non-LVO in 28%), intracranial hemorrhage in 19%, and neurovascular mimic in 5%. The LAMS administered by paramedics in the field performed moderately well in identifying LVO among patients with ACI (C statistic, 0.79; accuracy, 0.72) and CSC-appropriate among all suspected stroke transports (C statistic, 0.80; accuracy, 0.72). When concurrently performed in the emergency department postarrival, the LAMS showed comparable or better accuracy versus the 7 comparator scales, for LVO among ACI (accuracies LAMS, 0.70; other scales, 0.62-0.68) and CSC-appropriate (accuracies LAMS, 0.73; other scales, 0.56-0.73)., Conclusions: The LAMS performed in the field by paramedics identifies LVO and CSC-appropriate patients with good accuracy. The LAMS performs comparably or better than more extended prehospital scales and the full National Institutes of Health Stroke Scale., (© 2018 American Heart Association, Inc.)

Background & Objectives: : Adrenal insufficiency (AI) is rarely diagnosed in patients with HIV infection, in spite of autopsy studies showing very high rates of adrenal involvement. This study was aimed to determine the presence, patterns and predictors of AI in patients with HIV infection., Methods: : Consecutive HIV patients, 18-70 yr age, without any severe co-morbid state, having at least one-year follow up at the antiretroviral therapy clinic, underwent clinical assessment and hormone assays., Results: : From initially screened 527 patients, 359 patients having good immune function were analyzed. Basal morning cortisol <6 μg/dl (<165 nmol/l; Group 1), 6-11 μg/dl (165-300 nmol/l; Group 2), 11-18 μg/dl (300-500 nmol/l; Group 3) and ≥18 μg/dl (500 nmol/l; Group 4) were observed in 13, 71, 199 and 76 patients, respectively. Adrenocorticotropic hormone (ACTH) stimulation test revealed 87 patients (24.23%) to have AI. AI in groups 1-4 was 100, 56.34, 17.09 and 0 per cent, respectively. AI patients were more likely to be females (P< 0.05), having longer disease duration (P< 0.05), immune reconstitution inflammatory syndrome, hyperkalaemia (P< 0.01), lower fasting glucose (P< 0.01), dehydroepiandrosterone sulphate (DHEAS) and vitamin D. Regression analysis revealed morning cortisol and DHEAS to be best predictors of AI (P=0.004 and 0.028, respectively)., Interpretation & Conclusions: : AI is a significant problem in HIV-infected individuals, observed in nearly a quarter of patients. Diagnosis warrants high index of suspicion and low threshold for screening, especially in those having low DHEAS and hyperkalaemia. Morning cortisol is a reasonable screening test, with ACTH stimulation warranted to confirm diagnosis, especially in patients with morning cortisol <11 μg/dl (300 nmol/l)., Competing Interests: None

Prevalence of hyperprolactinemia in children with subclinical hypothyroidism (ScH) is not known. This study aimed to determine the occurrence and predictors of hyperprolactinemia in euthyroid children and in children with ScH and overt primary hypothyroidism (OPH). Serum prolactin levels were estimated in consecutive children <18 years of age undergoing thyroid function evaluation and diagnosed to have normal thyroid function, ScH, or OPH. Children with pituitary adenomas, secondary hypothyroidism, multiple pituitary hormone deficiency, comorbid states, and drug-induced hyperprolactinemia were excluded. From the initially screened 791 children, hormonal data from 602 children who fulfilled all criteria were analyzed. Seventy-one (11.79%) of these had ScH, and 33 (5.48%) had OPH. Occurrence of hyperprolactinemia was highest in the OPH group (51.51%), followed by ScH (30.98%) and euthyroid children (4.41%) (p<0.001). Median (25 th -75 th percentiles) levels for prolactin in euthyroid, ScH, and OPH children were 13.3 (9.4-17.95), 19.15 (15.97-30.12), and 28.86 (17.05-51.9) ng/mL, respectively (p<0.001). In children, prolactin levels were comparable in males and females. An age-related increase in serum prolactin was noted in euthyroid children, which was statistically significant in post-pubertal (16-18 years) children. Area under the curve for thyroid stimulating hormone (TSH) in predicting hyperprolactinemia in children was 0.758 (95% confidence interval: 0.673-0.829; p<0.001). TSH ≥4.00 mIU/L had a sensitivity of 69.4% and specificity of 77.6% in detecting hyperprolactinemia. Hyperprolactinemia is common in children with ScH and OPH. TSH ≥4.00 mIU/L has a good sensitivity and specificity in predicting hyperprolactinemia in children. More studies are needed to establish if hyperprolactinemia should be an indication for treating ScH in children.

Background: The 15q24-25 loci contain genes (CHRNA5 and CHRNA3) encoding nicotinic acetylcholine receptor subunits. We here determined for the first time the association of genetic variants rs16969968 and rs3743074 in CHRNA5 and CHRNA3, respectively, on nicotine dependence and lung cancer risk in a North Indian population by a case-control approach. Methods: Venous blood samples were obtained from 324 participants (108 lung cancer patients and 216 healthy individuals). DNA was extracted and PCR amplified with primers flanking the SNPs rs16969968 and rs3743074. Amplicons were subjected to sequencing and logistic regression was used to analyze association between variables. Results: The risk variant SNP rs16969968 in both heterozygous and homozygous forms appeared to exert a significant effect on nicotine dependence [GA (OR=2.77) and AA (OR=2.53)]. As expected, smoking was strongly associated with lung cancer (OR= 2.62). Risk allele rs16969968 in CHRNA5 also showed a significant association with increased lung cancer risk in our cohort, alone (OR= 4.99) and with smoking as a co-variable (OR= 4.28). Comparison of our analysis with other populations suggested that individuals with rs16969968 risk allele in the Indian population are more susceptible to lung cancer. Conclusion: Overall, the results strongly indicated that, in our cohort North Indian population, the genetic variant rs16969968, but not rs3743074, is significantly associated with both nicotine dependence and increased risk of lung cancer. While the results are significant, there is further need to increase the sample size and improve precision of our risk prediction., (Creative Commons Attribution License)

Background & Objectives: Data on hypogonadism among human immunodeficiency virus (HIV)-infected Indians are not available. This study was aimed to evaluate the occurrence, pattern and predictors of hypogonadism in HIV-infected Indians., Methods: Consecutive stable HIV-infected patients, 18-70 yr age, without any severe comorbid state, having at least one year follow up data at the antiretroviral therapy clinic, underwent clinical assessment and hormone assays., Results: From initially screened 527 patients, 359 patients (225 males; 134 females), having disease duration of 61.44±39.42 months, 88.58 per cent on highly active antiretroviral therapy (HAART), 40.67 per cent having tuberculosis history and 89.69 per cent with vitamin D insufficiency were analyzed. Testosterone <300 ng/dl was documented in 39.11 per cent males. Primary, hypogonadotropic hypogonadism (HypoH) and compensated hypogonadism were observed in 7.56, 31.56 and 12.44 per cent males, respectively. Males with hypogonadism were significantly older (P=0.009), and had higher opportunistic infections (P<0.001) with longer disease duration (P=0.05). Menstrual abnormalities were observed in 40.3 per cent females, who were significantly older (P<0.001), had lower CD4 count (P=0.038) and higher tuberculosis history (P=0.005). Nearly 46.3, 16.2 and 13 per cent women with menstrual abnormalities were in peri-/post-menopausal state, premature ovarian insufficiency (POI) and HypoH, respectively. Age, CD4 count at diagnosis and 25(OH)D were best predictors of male hypogonadism. Age and CD4 count increment in first 6-12 months following HAART were the best predictors of POI., Interpretation & Conclusions: Hypogonadism was observed to be a significant problem in HIV-infected men and women in India, affecting 39 and 29 per cent patients, respectively. HypoH was the most common form in males whereas ovarian failure being the most common cause in females.

In Maine, potato yield is consistent, 38 t·ha -1 , for last 10 years except 2016 (44 t·ha -1 ) which confirms that increasing the yield and quality of potatoes with current fertilization practices is difficult; hence, new or improvised agronomic methods are needed to meet with producers and industry requirements. Normalized difference vegetative index (NDVI) sensors have shown promise in regulating N as an in season application; however, using late N may stretch out the maturation stage. The purpose of the research was to test Trimble GreenSeeker ® (TGS) and Holland Scientific Crop Circle™ ACS-430 (HCCACS-430) wavebands to predict potato yield, before the second hilling (6-8 leaf stage). Ammonium sulfate, S containing N fertilizer, is not advised to be applied on acidic soils but accounts for 60-70% fertilizer in Maine's acidic soils; therefore, sensors are used on sulfur deficient site to produce sensor-bound S application guidelines before recommending non-S-bearing N sources. Two study sites investigated for this research include an S deficient site and a regular spot with two kinds of soils. Six N treatments, with both calcium ammonium nitrate and ammonium nitrate, under a randomized complete block design with four replications, were applied at planting. NDVI readings from both sensors were obtained at V8 leaf stages (8 leaf per plant) before the second hilling. Both sensors predict N and S deficiencies with a strong interaction with an average coefficient of correlation ( r ²) ~45. However, HCCACS-430 was observed to be more virtuous than TGS. The correlation between NDVI (from both sensors) and the potato yield improved using proprietor-proxy leaf area index (PPLAI) from HCCACS-430, e.g., r ² value of TGS at Easton site improve from 48 to 60. Weather data affected marketable potato yield (MPY) significantly from south to north in Maine, especially precipitation variations that could be employed in the N recommendations at planting and in season application. This case study addresses a substantial need to revise potato N recommendations at planting and develop possible in season N recommendation using ground based active optical (GBAO) sensors.