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Background Duchenne muscular dystrophy (DMD) is an X‐linked recessive neuromuscular disorder characterised by progressive irreversible muscle weakness, primarily of the skeletal and the cardiac muscles. DMD is characterised by mutations in the dystrophin gene, resulting in the absence or sparse quantities of dystrophin protein. A precise and timely molecular detection of DMD mutations encourages interventions such as carrier genetic counselling and in undertaking therapeutic measures for the DMD patients. Results In this study, we developed a 2.1 Mb custom DMD gene panel that spans the entire DMD gene, including the exons and introns. The panel also includes the probes against 80 additional genes known to be mutated in other muscular dystrophies. This custom DMD gene panel was used to identify single nucleotide variants (SNVs) and large deletions with precise breakpoints in 77 samples that included 24 DMD patients and their matrilineage across four generations. We used this panel to evaluate the inheritance pattern of DMD mutations in maternal subjects representing 24 DMD patients. Conclusion Here we report our observations on the inheritance pattern of DMD gene mutations in matrilineage samples across four generations. Additionally, our data suggest that the DMD gene panel designed by us can be routinely used as a single genetic test to identify all DMD gene variants in DMD patients and the carrier mothers., In this study we have used an Next Generation Sequencing (NGS) panel covering the whole DMD gene to identify mutations in the 24 DMD patients and their matriliniage for up to four generations.

COVID-19 is a respiratory illness caused by a novel coronavirus called SARS-CoV-2. The viral spike (S) protein engages the human angiotensin-converting enzyme 2 (ACE2) receptor to invade host cells with ~10–15-fold higher affinity compared to SARS-CoV S-protein, making it highly infectious. Here, we assessed if ACE2 polymorphisms can alter host susceptibility to SARS-CoV-2 by affecting this interaction. We analyzed over 290,000 samples representing >400 population groups from public genomic datasets and identified multiple ACE2 protein-altering variants. Using reported structural data, we identified natural ACE2 variants that could potentially affect virus–host interaction and thereby alter host susceptibility. These include variants S19P, I21V, E23K, K26R, T27A, N64K, T92I, Q102P and H378R that were predicted to increase susceptibility, while variants K31R, N33I, H34R, E35K, E37K, D38V, Y50F, N51S, M62V, K68E, F72V, Y83H, G326E, G352V, D355N, Q388L and D509Y were predicted to be protective variants that show decreased binding to S-protein. Using biochemical assays, we confirmed that K31R and E37K had decreased affinity, and K26R and T92I variants showed increased affinity for S-protein when compared to wildtype ACE2. Consistent with this, soluble ACE2 K26R and T92I were more effective in blocking entry of S-protein pseudotyped virus suggesting that ACE2 variants can modulate susceptibility to SARS-CoV-2., Suryamohan, Diwanji, Stawiski et al. identify natural ACE2 variants that are predicted to alter virus–host interactions. They find that soluble ACE2 K26R and T92I variants are more effective in blocking the entry of SARS-CoV-2 S-protein pseudotyped virus, compared to wild-type ACE2. This study suggests that ACE2 variants may modulate the host susceptibility to SARS-CoV-2.

Sexual activities during sleep have been reported by some people, often along with the amnesia for the same. Such activities, when involuntary, may arise because of disorders of arousal or may be attributed to sleep related seizures. However, differentiation between the two etiological factors and, also from voluntary acts committed during sleep-period is important not only for the management of disorders but for medicolegal purpose! Subjective information as well gathered by the patients, bed-partners or victims as objective measures, namely polysomnography, long-term video EEG, and neuroimaging techniques may be helpful in achieving the same.

Plant pathogenic bacteria deliver effectors into plant cells to suppress immunity and promote pathogen survival (Buttner, 2016; Deslandes and Rivas, 2012); however, these effectors can be recognised by plant disease resistance (R) proteins to activate innate immunity (Jones and Dangl, 2006; Spoel and Dong, 2012). The bacterial acetyltransferase effectors HopZ5 and AvrBsT trigger immunity in Arabidopsis thaliana genotypes lacking SUPPRESSOR OF AVRBST-ELICITED RESISTANCE 1 (SOBER1) (Choi et al., 2018; Jayaraman et al., 2017),. Using an Arabidopsis accession, Tscha-1, that naturally lacks functional SOBER1 but is unable to recognise HopZ5, we demonstrate that RESISTANCE TO P. SYRINGAE PV MACULICOLA 1 (RPM1) and RPM1-INTERACTING PROTEIN 4 (RIN4) are indispensable for HopZ5- or AvrBsT-triggered immunity. Remarkably, T166 of RIN4, the phosphorylation of which is induced by AvrB and AvrRpm1, was directly acetylated by HopZ5 and AvrBsT. Furthermore, we demonstrate that acetylation of RIN4 T166 is required and sufficient for activation of HopZ5- or AvrBsT-triggered defence. Finally, we show that SOBER1 interferes with HopZ5- or AvrBsT-triggered immunity by deacetylating RIN4 T166. Our findings indicate that multiple pathogen effectors with distinct biochemical properties modify a single residue in a guardee protein and activate a plant NLR immune receptor. We have thus elucidated detailed molecular mechanisms underlying the activation and suppression of plant innate immunity triggered by bacterial acetyltransferases.

The world’s population depends heavily only on a limited number of crops for its basic nutrition, viz., carbohydrates, proteins, and fats. As of today, three unique and universal (almost pan-cultural) crops including wheat, rice, and maize are the main sources of carbohydrates for human dietary consumption. Besides these three staple crops, several neglected and underutilized crops (NUCs) are documented as rich sources of essential micro and macronutrients, however, these have neither been widely consumed nor exploited at a large scale for human consumption. One of the major bottlenecks in the large-scale utilization of these crops is the lack of scientific literature that limits our understanding of how these NUCs behave during various biotic and abiotic stressors. Development of various omics-based platforms including transcriptomics, proteomics, and metabolomics have facilitated the understanding of various model plants, such as Arabidopsis and rice, and the same can also be used in the future to decipher the NUCs responses to environmental fluctuations. In this chapter, we are presenting the technological advancements in the omics tools and downstream data analysis to understand the biology of these NUCs in greater detail. The information derived from these studies could be used in the future to exploit NUCs for their large-scale cultivation to address the issue of food security in the near future.

Background Open fractures form one of the most common musculoskeletal injuries and are often complicated by infection. In this unprecedented situation, the additional infection rates, further add to the burden of the already compromised healthcare setup. The present study is done to see the effect of COVID-19 on management of open fractures. Methods A retrospective evaluation of patients with open fractures from March 25th, 2020 to July 21st, 2020 (group 1) and March 25th, 2019 to July 21st, 2019 (group 2) was performed. These patients were assessed for demographic details, diagnosis, type of surgery, delay from injury to admission, delay from admission to surgery, postoperative hospital stay, acute infection rates, readmission rates and associated injuries. Results A total of 52 patients with 59 open fractures in 2020 and 89 patients with 101 open fractures in 2019 met the inclusion criteria. The mean age was 34.76 years and 32.74 years in 2020 and 2019 respectively. Road side accidents were predominant in both the groups, comprising of 38 (73.07%) and 67 (75.28%) respectively(n.s.); adult patients were 42 (80.76%) and 79 (88.76%) respectively(n.s.); paediatric patients were 10 (19.23%) and 10 (11.23%) respectively(n.s.); tibia was the most common bone involved, comprising of 14 (23.72%) and 27 (26.73%) open fractures respectively(n.s.); external fixator was the most commonly used implant during COVID-19 time with 42 (71.18%) and 51 (50.49%) respectively(p = 0.005); the infection rate was 25.42% and 20.79% respectively(n.s.); the time for administration of first intravenous antibiotic dose was on 6.75 h and 4.04 h respectively(p

Background: Gloves are an integral component of standard precautions. Reprocessing and reuse of gloves are undertaken in hospitals in resource- limited settings to reduce the cost incurred in the procurement of single use disposable gloves. There is no standardized procedure to ascertain the integrity of gloves after reprocessing. The aim of the study was to calculate the cost of reprocessing gloves vis a vis use of disposable gloves. Methods: A prospective observational study was conducted in the CSSD. The cost incurred in all the steps of reprocessing of gloves in terms of manpower involved, consumables used and the cost of operating the equipment was determined. The overall cost was then divided by the number of total pairs of gloves reprocessed during the study period to arrive at the cost of reprocessing per pair of gloves.Results: Total cost incurred for running the machinery, manpower involved and consumables used was calculated to be Rs. 716,649. Number of pairs of gloves reprocessed was 42900. The total cost incurred in reprocessing one pair of glove in this setting was calculated to be Rs. 16.7 per glove, whereas the cost of sterile disposable surgical gloves was Rs. 11.50 during the study period. Conclusions: The results of the present study show that the reprocessing of gloves is not cheaper than using disposable gloves. The healthcare institutions should carefully look into the sterilisation techniques vis a vis the cost of using the disposable gloves.

LBA9025 Background: In CheckMate 227 part 1 (NCT02477826), 1L NIVO + IPI demonstrated long-term, durable survival benefit vs platinum-doublet chemo in patients (pts) with metastatic NSCLC regardless of tumor programmed death ligand 1 (PD-L1) expression level. Here we present the longest reported follow-up (5 y) of a phase 3 trial of 1L combination immunotherapy in metastatic NSCLC. Methods: Adults with previously untreated stage IV or recurrent NSCLC, no known EGFR/ ALK alterations , and an ECOG performance status ≤ 1 were enrolled and stratified by histology. Pts with tumor PD-L1 ≥ 1% were randomized 1:1:1 to NIVO (3 mg/kg Q2W) + IPI (1 mg/kg Q6W), NIVO (240 mg Q2W), or chemo. Pts with tumor PD-L1 < 1% were randomized 1:1:1 to NIVO + IPI, NIVO (360 mg Q3W) + chemo, or chemo. Pts were treated until progression, toxicity, or ≤ 2 y for immunotherapy. Assessments included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), and a novel efficacy endpoint, treatment-free interval. Treatment-free interval was measured in pts who discontinued study therapy (for any reason including treatment completion) and was defined as the time from last study dose to start of subsequent systemic therapy or death, whichever occurred first. Results: Minimum follow-up was 61.3 mo (database lock, Feb 15, 2022). In pts with tumor PD-L1 ≥ 1% (N = 1189), continued long-term OS benefit was seen with NIVO + IPI vs chemo (HR, 0.77 [95% CI, 0.66–0.91]); 5-y OS rates were 24% (NIVO + IPI), 17% (NIVO), and 14% (chemo). OS benefit also continued in pts with tumor PD-L1 < 1% (N = 550) for NIVO + IPI vs chemo (HR, 0.65 [95% CI, 0.52–0.81]); 5-y OS rates were 19% (NIVO + IPI), 10% (NIVO + chemo), and 7% (chemo). Clinical benefit with NIVO + IPI vs chemo was observed across additional efficacy endpoints in the overall population and in pts alive at 5 y (table). PFS, ORR, and DOR with NIVO and NIVO + chemo will be presented. Among pts alive at 5 y in the NIVO + IPI group, 66% (PD-L1 ≥ 1%) and 64% (PD-L1 < 1%) remained treatment-free ≥ 3 y after discontinuing study therapy; median (range) duration of NIVO ± IPI therapy was 17.7 (0-25.5) mo (PD-L1 ≥ 1%) and 9.5 (0-25.1) mo (PD-L1 < 1%). No new safety signals were observed. Conclusions: With a 5-y minimum follow-up, NIVO + IPI continues to provide long-term, durable clinical benefit vs chemo in previously untreated pts with metastatic NSCLC, regardless of PD-L1 expression. NIVO + IPI led to increased 5-y survivorship; the majority of these pts were treatment-free for ≥ 3 y post-treatment discontinuation. Clinical trial information: NCT02477826. [Table: see text]

e18036 Background: Oral cavity cancer is the second most common cancer in India; India bears the most burden of oral cancer in the world. The most effective way to study the effectiveness of treatments is in clinical trials, but the quality of life (QOL) and post-treatment effects of those treatments are seldom studied in real-world settings. Methods: All oral cancer survivors treated with curative intent at our institute from September 2019 to January 2021, who were disease-free for a minimum of six months following treatment, were included in this study. The QOL of these cancer survivors was compared with that of their caregivers using the WHOQOL BREF questionnaire. The complete survivorship profile was evaluated using a Constant shoulder score for shoulder dysfunction, clinical oral dryness score (CODS) for xerostomia, Sydney Swallow Questionnaire (SSQ) for swallowing dysfunction, Patterson scale for lymphedema, Comprehensive Score for financial Toxicity (COST)‐Functional Assessment of Chronic Illness Therapy (FACIT) questionnaire for financial toxicity, Depression, Anxiety and Stress Scale - 21 Items (DASS-21) for psychological wellbeing. Results: A total of seventy-nine survivors were included. The median age was 49 years. Though both survivors and caregivers had similar QOL scores in the physical and environmental domains, survivors had poor scores in the social (M = 58.7,SD = 21.9) and psychological domains (M = 60.4,SD = 15.6). The T stage (p = 0.06), surgery (p = 0.008), and trismus (p = 0.03) were significant factors affecting swallowing. Those patients who had undergone selective neck dissection had better shoulder scores compared to those who had modified radical neck dissection (p = 0.006). 75% of people had xerostomia and 10.9% had severe xerostomia. Internal lymphedema was seen in 30.4% of people. Depression and anxiety were recorded in 46 (58.2%) and 33 (41.8%) patients respectively. Employment status (p = 0.04) and treatment modality (p = 0.05) were significant factors affecting financial toxicity. Conclusions: Oral cancer survivors had a poor psychosocial QOL compared to their caregivers. Treatment-related functional sequelae had a significant negative impact on quality of life across all domains. Clinical trial information: CTRI/2020/07/026848.

Objective To determine the rate at which commercially-insured patients fill prescriptions for naloxone after an opioid-related ED encounter as well as patient characteristics associated with obtaining naloxone. Methods This is a retrospective cohort study of adult patients discharged from the ED following treatment for an opioid-related condition from 2016 to 2018 using a commercial insurance claims database (Optum Clinformatics® Data Mart). The primary outcome was a pharmacy claim for naloxone in the 30 days following the ED encounter. A multivariable logistic regression model examined the association of patient characteristics with filled naloxone prescriptions, and predictive margins were used to report adjusted probabilities with 95% confidence intervals. Results 21,700 patients had opioid-related ED encounters during the study period, of which 1743 (8.0%) had encounters for heroin overdose, 8825 (40.7%) for overdose due to other opioids, 5400 (24.9%) for withdrawal, and 5732 (26.4%) for other opioid use disorder conditions. 230 patients (1.1%) filled a prescription for naloxone within 30 days. Patients with heroin overdose (2.6%; 95%CI 1.7 to 3.4), recent prescriptions for opioid analgesics (1.4%; 95%CI 1.1 to 1.7), recent prescriptions for buprenorphine (1.9%; 95%CI 1.0 to 2.9), and naloxone prescriptions in the prior year (3.3%; 95%CI 1.8 to 4.8) were more likely to obtain naloxone. The rate was significantly higher in 2018 [1.9% (95%CI 1.5 to 2.2)] as compared to 0.4% (95%CI 0.3 to 0.6) in 2016. Conclusions Few patients use insurance to obtain naloxone by prescription following opioid-related ED encounters. Clinical and policy interventions should expand distribution of this life-saving medication in the ED.

Fractures of the acetabulum in elderly patients were often caused by low energy trauma. Fractures involving anterior column are more common and often associated with impaction and comminution. Osteoporosis further complicates the management. Percutaneous fracture fixation has low morbidity but it is a technically demanding procedure. Open reduction and fracture fixation is done with or without simultaneous total hip replacement. Delayed total hip replacement is considered in posttraumatic arthritis patients. Patients with minimal displaced fractures, associated both-column fractures with secondary congruence of joint and patients who are medically unfit for surgery can be managed non-operatively. Whatever be the method of management, these elderly patients should be mobilised as early as possible.

Sleep disturbances are commonly reported in patients with chronic liver disease (CLD). Changes in quality of sleep in patients with CLD could be related to multiple factors viz., elevated levels of tryptophan, histamine, and increased turnover of dopamine in caudate-putamen and cingulate cortex. Also, iron metabolism disturbances are reported in patients with CLD. These changes may result in restless legs syndrome (RLS) that worsens sleep-quality. There have been reports suggesting an increased prevalence of RLS among patients with CLD. Literature was searched in PubMed, EMBASE, and Google Scholar. A total of twenty-two relevant articles were found. Out of these, nine studies have assessed the prevalence of RLS among patients with chronic liver disease or cirrhosis in the clinical population. Population prevalence reported from various studies was used to calculate odds ratio. Having included studies using various methods for diagnosis (clinical as well as questionnaires) pooled odds-ratio for the RLS was 8.62. It remains unaffected by study-method, gender, age, and geographical-area. However, studies using clinical diagnosis for RLS had lower odds compared to questionnaire based diagnosis. Studies varied with regards to diagnostic methods, age, gender, etiology, and severity of liver dysfunction. The severity and etiology of CLD and biochemical correlate of CLD were not found to be associated with RLS. Possible pathophysiological mechanisms are discussed for the occurrence of RLS in this population. In conclusion, the prevalence of RLS is higher among patients with CLD, however, the correlates are unknown.

Background Arterial hypertension is the most prevalent risk factor for cardiovascular disease in sub-Saharan Africa. Only a few and mostly small randomized trials have studied antihypertensive treatments in people of African descent living in sub-Saharan Africa. MethodsIn this open-label, three-arm, parallel randomized controlled trial conducted at two rural hospitals in Lesotho and Tanzania, we compare the efficacy and cost-effectiveness of three antihypertensive treatment strategies among participants aged ≥18 years. The study includes patients with untreated uncomplicated arterial hypertension diagnosed by a standardized office blood pressure ≥ 140/90mmHg. The trial encompasses a superiority comparison between a triple low-dose antihypertensive drug combination versus the current standard of care (monotherapy followed by dual treatment), as well as a non-inferiority comparison for a dual drug combination versus standard of care with optional dose titration after 4 and 8 weeks for participants not reaching the target blood pressure. The sample size is 1268 participants with parallel allocation and a randomization ratio of 2:1:2 for the dual, triple and control arms, respectively. The primary endpoint is the proportion of participants reaching a target blood pressure at 12 weeks of ≤130/80 mmHg and ≤140/90 mmHg among those aged

AIM: Infection after anterior cruciate ligament (ACL) reconstruction, though rare, is a potentially devastating complication and the evidence-based recommendation on the various topics in its management is limited. The purpose of this study was to develop recommendations for the prevention and management of infections in ACL reconstruction surgery by performing a structured expert consensus survey using Delphi methodology. MATERIALS AND METHODS: 22 topics of relevance in the prevention and management of infection following ACL reconstruction were chosen from an extensive literature review. 30 panelists were requested to respond to a three-round survey, with feedback, to develop a consensus statement on the topics. RESULTS: Consensus statements could be prepared in eleven out of twenty-two topics including: the graft is retained at the first arthroscopic debridement, the graft is removed when repeated debridement are needed, and revision ACL reconstruction is needed only if the patient develops instability. Concurrence could be obtained in the topics including: longer duration of antibiotics is needed in immunocompromised patients, soaking graft in antibiotic solution reduces infection risk, and knee swelling without warmth does not suggest infection. CONCLUSIONS: A proper skin preparation, a longer course of antibiotics in immunocompromised patients, and soaking the graft in antibiotics reduces the risk of infection. In case of infection, a healthy-looking graft must be retained at the first debridement and if the graft must be removed, revision ACL reconstruction is advised only if the patient develops instability. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s43465-021-00363-z.

SummaryMulti-sectoral collaborative approaches with strong community engagement are essential for addressing health disparities. A valid tool for assessing organizational research and capacity for community health research stakeholders could help strengthen organizational capacity for engagement in such collaborations. This study was conducted to validate an innovative tool for assessing research activity and capacity of a spectrum of stakeholder organizations to provide support for strengthening community health research capacity in Bhutan. In-person interviews with academics (n = 10), clinicians (n = 10), government staff (n = 10), consultants (n = 2) and management of health-related civil society organizations (CSOs; n = 12 interviews/organizations, 13 individuals) were recorded and transcribed. Questions covered individual and organizational research activity and capacity, research networks and an international version of the Community Research Assessment Tool (CREAT-I). Almost all participants (84%) had participated in community health research projects. Social network analysis showed a large, interconnected cluster with a few key individuals linking across sectors. CREAT-I responses identified the highest capacity in organizational support for research among academic participants, while clinical and CSO participants reported highest capacity in practical research experiences and government participants reported highest capacity in research specific experiences. The CREAT-I tool showed strong internal reliability (Cronbach’s α = 0.91) and validity. Limited money, time and skilled staff were identified as barriers to research. The CREAT-I assesses community health research capacity of organizations, and such a tool could be useful in identifying research capacity needs, monitoring impact of research capacity-building activities and contributing to a greater capacity for multi-sectoral collaborative approaches to community health research in international settings.

Because of the rise in global temperature, heat stress has become a major concern for crop production. Heat stress deteriorates plant productivity and alters phenological and physiological responses that aid in precise monitoring and sensing of mild-to-severe transient heat stress. Plants have evolved several sophisticated mechanisms including hormone-signaling pathways to sense heat stimuli and acquire heat stress tolerance. In response to heat stress, ethylene, a gaseous hormone, is produced which is indispensable for plant growth and development and tolerance to various abiotic stresses including heat stress. The manipulation of ethylene in developing heat stress tolerance targeting ethylene biosynthesis and signaling pathways has brought promising out comes. Conversely increased ethylene biosynthesis and signaling seem to exhibit inhibitory effects in plant growth responses from primitive to maturity stages. This review mainly focuses on the recent studies of ethylene involvement in plant responses to heat stress and its functional regulation, and molecular mechanism underlying the plant responses in the mitigation of heat-induced damages. Furthermore, this review also describes the crosstalk between ethylene and other signaling molecules under heat stress and approaches to improve heat stress tolerance in plants.

Highlights • Parkinson's disease symptoms worsened during home confinement. • Difficulty in availing formal neurology consultations and/or medicines. • Quality of life in Parkinson's disease patients declined during home confinement. • Use of telemedicine may benefit patients.

The PRKAG2 syndrome is a rare autosomal dominant phenocopy of sarcomeric hypertrophic cardiomyopathy (HCM), characterized by ventricular pre-excitation, progressive conduction system disease and left ventricular hypertrophy. This study describes the phenotype, genotype and clinical outcomes of a South-Asian PRKAG2 cardiomyopathy cohort over a 7-year period. Clinical, electrocardiographic, echocardiographic, and cardiac MRI data from 22 individuals with PRKAG2 variants (68% men; mean age 39.5 ± 18.1 years), identified at our HCM centre were studied prospectively. At initial evaluation, all of the patients were in NYHA functional class I or II. The maximum left ventricular wall thickness was 22.9 ± 8.7 mm and left ventricular ejection fraction was 53.4 ± 6.6%. Left ventricular hypertrophy was present in 19 individuals (86%) at baseline. 17 patients had an WPW pattern (77%). After a mean follow-up period of 7 years, 2 patients had undergone accessory pathway ablation, 8 patients (36%) underwent permanent pacemaker implantation (atrio-ventricular blocks—5; sinus node disease—2), 3 patients developed atrial fibrillation, 11 patients (50%) developed progressive worsening in NYHA functional class, and 6 patients (27%) experienced sudden cardiac death or equivalent. PRKAG2 cardiomyopathy must be considered in patients with HCM and progressive conduction system disease.

Though smoking remains one of the established risk factors of esophageal squamous cell carcinoma, there is limited data on molecular alterations associated with cigarette smoke exposure in esophageal cells. To investigate molecular alterations associated with chronic exposure to cigarette smoke, non-neoplastic human esophageal epithelial cells were treated with cigarette smoke condensate (CSC) for up to 8 months. Chronic treatment with CSC increased cell proliferation and invasive ability of non-neoplastic esophageal cells. Whole exome sequence analysis of CSC treated cells revealed several mutations and copy number variations. This included loss of high mobility group nucleosomal binding domain 2 (HMGN2) and a missense variant in mediator complex subunit 1 (MED1). Both these genes play an important role in DNA repair. Global proteomic and phosphoproteomic profiling of CSC treated cells lead to the identification of 38 differentially expressed and 171 differentially phosphorylated proteins. Bioinformatics analysis of differentially expressed proteins and phosphoproteins revealed that most of these proteins are associated with DNA damage response pathway. Proteomics data revealed decreased expression of HMGN2 and hypophosphorylation of MED1. Exogenous expression of HMGN2 and MED1 lead to decreased proliferative and invasive ability of smoke exposed cells. Immunohistochemical labeling of HMGN2 in primary ESCC tumor tissue sections (from smokers) showed no detectable expression while strong to moderate staining of HMGN2 was observed in normal esophageal tissues. Our data suggests that cigarette smoke perturbs expression of proteins associated with DNA damage response pathways which might play a vital role in development of ESCC.

Background Tumor mutational burden (TMB) is a key biomarker for immune checkpoint inhibitor across several cancer types. While TMB as calculated from whole exome sequencing of the tumor tissue is still the gold standard, enabling TMB in clinical labs requires targeted sequencing panels for faster turnaround time and low input requirements. Herein, we assess two commercially available, targeted sequencing (research-use-only) TMB assays for the possibility of offering in the Medgenome labs. Methods Two assays, Oncomine Tumor Mutation Load Assay (or Oncomine) by Thermo Fisher Scientific and QIAseq Tumor Mutational Burden Panel (or QIAseq) by Qiagen, were studied. One negative control (NA12878), five positive control (A549, lung; T47D, breast; SKMEL2, skin; HCT-15, large intestine; HCT116, large intestine) cell lines, and 18 FFPE (13 colon, 1 lung, 1 testicular, and 1 oral cancer; 2 healthy) samples were ran on both assays. Sample QC was performed through measuring DNA fragmentation on TapeStation and concentration on Qubit. Failure rates on FFPE samples were investigated. TMB values by both assays were compared on all samples, as well as with expected TMB on cell line samples. Expected TMB on the negative control was considered zero; expected TMB for positive cell lines was calculated by restricting somatic mutations (from cBioPortal.com) to each panel, normalizing by panel size, and averaging. TMB values of 3 samples with known MSI were evaluated and signature patterns of relatively high TMB samples were studied. Results On cell line samples, high correlation (r2 = 0.9994) was observed between TMB values by both assays. TMB values were consistently zero on negative control by both assays. Both assays estimated lower than expected TMB on positive control samples. 6/18 FFPE samples failed on both assays, with Oncomine’s error mode was high deamination (i.e., number of C:G>T:A mutations at low allelic frequency) and QIAseq’s was low confidence (i.e., 50 by both assays, but 14 by QIAseq and 33 by Oncomine on one MSI FFPE sample. Four out of five FFPE samples with > 25 TMB by both assays displayed MSI signature patterns from COSMIC or incorporated a pathogenic mutation in MLH1 gene. Conclusions Preliminary analyses showed comparative accuracy and failure rates on FFPE samples. Future analyses will aim at comparison with WES based TMB on reference cell line and FFPE material.

Many approaches to identify therapeutically relevant neoantigens couple tumor sequencing with bioinformatic algorithms and inferred rules of tumor epitope immunogenicity. However, there are no reference data to compare these approaches, and the parameters governing tumor epitope immunogenicity remain unclear. Here, we assembled a global consortium wherein each participant predicted immunogenic epitopes from shared tumor sequencing data. 608 epitopes were subsequently assessed for T cell binding in patient-matched samples. By integrating peptide features associated with presentation and recognition, we developed a model of tumor epitope immunogenicity that filtered out 98% of non-immunogenic peptides with a precision above 0.70. Pipelines prioritizing model features had superior performance, and pipeline alterations leveraging them improved prediction performance. These findings were validated in an independent cohort of 310 epitopes prioritized from tumor sequencing data and assessed for T cell binding. This data resource enables identification of parameters underlying effective anti-tumor immunity and is available to the research community.

Backgroud Complete peroneal nerve dysfunction associated with congenital clubfoot is uncommonly reported. Our retrospective study highlights the recognition of clinical presentation and mid-term outcomes of treatment in these patients. Methods Eight out of 658 patients undergoing treatment for clubfoot were identified with unilateral complete peroneal nerve dysfunction associated with congenital clubfoot. Three patients presented primarily to our center; 5 were treated elsewhere initially. All patients were treated with Ponseti casts, Achilles tenotomy, and subsequent foot abduction bracing. Diagnosis of complete peroneal nerve dysfunction was confirmed using nerve conduction velocity studies in all patients. After full-time bracing, an insole polythene molded ankle foot orthosis was given. Three patients underwent tibialis posterior transfer to improve foot dorsiflexor power. Results The mean age at presentation was 1.3 years (range, 1 week–5 years). All patients had prominence of lateral 3 metatarsal heads and dimpling of intermetatarsal spaces. At a mean follow-up of 5.1 years, mean shortening of 1.2 cm in tibia (range, 1–2.5 cm) and mean calf wasting of 4.4 cm were observed. There was no relapse of any clubfoot deformity till the final follow-up. Conclusions Prominence of lateral metatarsal heads and dimpling of intermetatarsal spaces should raise early suspicion of peroneal nerve dysfunction. Standard Ponseti protocol is useful in treatment of these patients. Tibialis posterior transfer to dorsum partially restores the ankle dorsiflexion.

Population-scale genetic studies can identify drug targets and allow disease risk to be predicted with resulting benefit for management of individual health risks and system-wide allocation of health care delivery resources. Although population-scale projects are underway in many parts of the world, genetic variation between population groups means that additional projects are warranted. South Asia has a population whose genetics is the least characterized of any of the world’s major populations. Here we describe GenomeAsia studies that characterize population structure in South Asia and that create tools for economical and accurate genotyping at population-scale. Prior work on population structure characterized isolated population groups, the relevance of which to large-scale studies of disease genetics is unclear. For our studies we used whole genome sequence information from 4,807 individuals recruited in the health care delivery systems of Pakistan, India and Bangladesh to ensure relevance to population-scale studies of disease genetics. We combined this with WGS data from 927 individuals from isolated South Asian population groups, and developed a custom SNP array (called SARGAM) that is optimized for future human genetic studies in South Asia. We find evidence for high rates of reproductive isolation, endogamy and consanguinity that vary across the subcontinent and that lead to levels of homozygosity that approach 100 times that seen in outbred populations. We describe founder effects that increase the power to associate functional variants with disease processes and that make South Asia a uniquely powerful place for population-scale genetic studies.

Sleep-related movement disorders include disorders that manifest as simple and mostly stereotyped movements occurring at sleep–wake interface or during sleep. Restless legs syndrome (RLS), the most common sleep-related movement disorder. RLS is a treatable condition that psychiatrists must be familiar with due to its common comorbidity with a broad range of psychiatric disorders. In addition, commonly used psychotropic medications are known to induce or worsen RLS symptoms in predisposed individuals, and these symptoms may be mistaken for akathisia or sleep-initiation insomnia and lead to mismanagement. This chapter discusses, among other RLS-related topics, the diagnosis, epidemiology, predisposing factors, genetic factors, and the role of iron metabolism.

Background Posterior Cruciate Ligament (PCL) injuries seldom occur in isolation and majority occurs in conjugation with other ligament injuries. Posterior Cruciate Ligament (PCL) reconstruction continues to be taken into consideration as a complicated surgical procedure, with heterogeneity in literature regarding clinical and functional outcomes in isolated PCL and combined ACL and PCL injuries. Methods The retrospective evaluation of patients with isolated PCL reconstruction (group 1) and combined Anterior Cruciate Ligament (ACL) and PCL reconstruction (group 2) was performed. A total of 66 patients with either isolated PCL or combined ACL and PCL reconstruction surgeries that met the inclusion criteria, were included in the study. These patients were assessed for functional outcome scores including Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) score, Lysholm score, International Knee Documentation Committee (IKDC) and Tegner activity score at a minimum follow-up of 5 years. Results The mean follow-up of patients was 82.09 ± 12.43 months in group 1 and 79.36 ± 11.24 months in group 2, with a total of 29 patients in group 1 and 21 patients in group 2. Both the groups were found to be comparable in terms of age, gender, duration of injury and pre-injury Tegner activity level. Post-surgical functional outcome scores (WOMAC score, Lysholm score and Tegner score) were found to be comparable between 2 groups at a mean follow-up of 5 years. Further, 22 patients in group 1 and 16 patients in group 2 had normal or near normal objective IKDC outcome scores at a mean follow-up of 5 years. Conclusions No differences were observed in functional outcome scores (WOMAC score, Lysholm score, Tegner score and IKDC score) between isolated reconstructed PCL and combined ACL and PCL reconstructed patients.

Drought has been highly prevalent around the world especially in Sub-Saharan Africa and South-East Asian countries. Consistent climatic instabilities and unpredictable rainfall patterns are further worsening the situation. Rice is a C3 staple cereal and an important food crop for the majority of the world's population and drought stress is one of the major growth retarding threats for rice that slashes down grain quality and yield. Drought deteriorates rice productivity and induces various acclimation responses that aids in stress mitigation. However, the complexity of traits associated with drought tolerance has made the understanding of drought stress-induced responses in rice a challenging process. An integrative understanding based on physiological adaptations, omics, transgenic and molecular breeding approaches successively backed up to developing drought stress-tolerant rice. The review represents a step forward to develop drought-resilient rice plants by exploiting the knowledge that collaborates with omics-based developments with integrative efforts to ensure the compilation of all the possible strategies undertaken to develop drought stress-tolerant rice.

BACKGROUND: Hip fractures are considered as a major cause of mortality worldwide. Even after being the second most populous country in world and facing huge burden of hip fractures, there is scarcity of data from India. For the first time in Indian context, we analysed the predictors of mortality after hip fracture surgery in patients with age 50 years and above. MATERIALS AND METHODS: In this prospective cohort study, patients with age ≥ 50 years and having hip fractures presented to our institute from January 2018 through October 2018 were enrolled after meeting including and excluding criteria. Patients were followed-up for minimum 1 year after surgery. Association between 1-year mortality and different affecting variables were analysed. Significant variables were further analysed using logistic regression to find independent predictors. RESULTS: Out of 87 patients followed-up for 1 year, 25 patients died within 1 year of surgery. Age > 75 years, road traffic accident as mode of injury, delay in surgery > 48 h, > 2 co-morbidities, haemoglobin level ≤ 10 at the time of admission and osteoporosis are significantly associated with high mortality. When these significant variables were further analysed using logistic regression, age > 75 years and > 2 co-morbidities were only factors associated independently with high mortality. CONCLUSION: In patients with age 50 years and above, following hip fracture surgery, age > 75 years and > 2 co-morbidities are the predictors of 1-year mortality when adjusted for other variable. A better designed multi-centric study can be more helpful in understanding the things in Indian context.

Background Sleep services are assigned a non-essential status during COVID-19. The American Academy of Sleep Medicine strongly urges sleep clinicians to continue postponing non-urgent care until a later date, if such a recommendation is made by state officials due to local conditions. At the same time, one cannot ignore the fact that sleep is important for people’s health and wellbeing. Therefore, to protect the health of the population, it is essential to find ways and means to continue the practice of sleep medicine even during the COVID-19 pandemic. Method Social environment and work ethics in sleep clinics and sleep laboratories in Asia, Africa, and Latin America are different from those in the US. Under these circumstances, the Indian Society for Sleep Research (ISSR) created a task force to develop guidelines for the practice of sleep medicine, not only for the Indian environment but also for other countries that are affected by the COVID-19 pandemic. The task force examined documents regarding practice of sleep medicine and associated specialities during COVID-19 by various professional organizations and governmental authorities. The recommendations were examined for their applicability. Wherever gaps were identified, consensus was reached keeping in view the available evidences. Outcome and Recommendations The emphasis of the guidelines is on avoiding doctor to patient contact during the pandemic. Teleconsultation and other modes of audio-visuals can be used as modes for medical practice during the COVID-19 pandemic. However, in addition to the patient, the presence of a family member, or a reliable informant is recommended. Patients of most sleep disorders can be provided tele-aftercare service. ISSR guidelines also give a list of medications allowed to be prescribed during the first and the follow-up teleconsultation. Hospitals and clinics are slowly opening in India and many other countries. As sleep services resume operations, there is a need to find innovative ways to reduce contact with COVID-19 patients, follow personal protection guidelines, as well as social distancing. This article does discuss strategies for the safe conduct of Level 1 sleep studies. Home sleep testing, which had greater acceptance during the last few years, should be given more attention during the COVID-19 period. Once the decision to reopen the sleep laboratory and resume operations is made, the safety of the patients and office staff should become the major priority. The ISSR recommendation is to postpone and reschedule in-laboratory positive pressure therapy, but it mentions the considerations to be followed in emergency situations. At the same time, high clinical risk patients may be diagnosed on the basis of clinical findings, and without performing polysomnography or home sleep testing. However, at some point, there is a need to reinitiate the in-lab testing. In addition, daily assessment of the COVID-19 situation in the community, along with a review of the situation with local public health and the state health department is advised.

Esophageal squamous cell carcinoma (ESCC) is the most common histological subtype of esophageal cancer in India. Cigarette smoking and chewing tobacco are known risk factors associated with ESCC. However, genomic alterations associated with ESCC in India are not well-characterized. In this study, we carried out exome sequencing to characterize the mutational landscape of ESCC tumors from subjects with a varied history of tobacco usage. Whole exome sequence analysis of ESCC from an Indian cohort revealed several genes that were mutated or had copy number changes. ESCC from tobacco chewers had a higher frequency of C:G > A:T transversions and 2-fold enrichment for mutation signature 4 compared to smokers and non-users of tobacco. Genes, such as TP53, CSMD3, SYNE1, PIK3CA, and NOTCH1 were found to be frequently mutated in Indian cohort. Mutually exclusive mutation patterns were observed in PIK3CA–NOTCH1, DNAH5–ZFHX4, MUC16–FAT1, and ZFHX4–NOTCH1 gene pairs. Recurrent amplifications were observed in 3q22-3q29, 11q13.3-q13.4, 7q22.1-q31.1, and 8q24 regions. Approximately 53% of tumors had genomic alterations in PIK3CA making this pathway a promising candidate for targeted therapy. In conclusion, we observe enrichment of mutation signature 4 in ESCC tumors from patients with a history of tobacco chewing. This is likely due to direct exposure of esophagus to tobacco carcinogens when it is chewed and swallowed. Genomic alterations were frequently observed in PIK3CA-AKT pathway members independent of the history of tobacco usage. PIK3CA pathway can be potentially targeted in ESCC which currently has no effective targeted therapeutic options.

Objective Ilio-inguinal approach has been considered standard anterior approach for acetabulum fracture fixation. Different modifications of this approach have been described. This study analysed the patients treated using a Combined Anterior Pelvic (CAP) approach - minimal AIP (anterior intra-pelvic) with modified ilio-femoral along with ’anterior superior iliac spine’ osteotomy. This combined approach provides wide exposure of pelvis to direct visualise the entire anterior column from sacroiliac joint to pubic symphysis, medial side of quadrilateral plate and entire iliac wing with minimal retraction of soft tissues required. Methods Data of patients treated from July 2014 to June 2018 for acetabulum fracture using CAP approach was retrieved from hospital record system. Inclusion criteria were - acetabulum fractures treated surgically using CAP approach. Exclusion criteria were – age less than 18 years, associated pelvis ring injury and incomplete peri-operative radiological record (pre-operative/post-operative antero-posterior, 45° obturator and 45° iliac oblique radiographs and pre-operative computed tomographic (CT) scans. 62 patients who met inclusion exclusion criteria were called in out-patient-department for final functional evaluation using Matta modified Merle d’aubigne score. Results Out of 62 patients 47 patients who turned up for final functional evaluation were included in study. 19 patients had excellent, 15 had good, 2 had fair and 11 had poor results. Age less than 40 years, anterior column fracture pattern, Pre-operative fracture displacement >20 mm, fracture comminution and post-operative fracture reduction within 3 mm were the predictors of the functional outcome. When analysed using logistic regression model, post-operative fracture reduction was found to be the only significant predictor of functional outcome. Conclusion CAP approach is useful anterior approach to acetabulum. Fracture reduction is the independent predictor of functional outcome. Comparison of this approach with other anterior approaches to acetabulum can be area of further research.

Pregnancy is associated with a number of physiologic changes in the body including hormonal, anatomical, and mechanical. These changes alter many physiologic functions including sleep. The literature suggests that a number of women develop changes in duration, pattern, and quality of sleep during pregnancy. In addition, these changes also pave the way for expression of sleep disorders (e.g., insomnia, obstructive sleep apnea, and restless legs syndrome). Change in sleep and appearance of sleep disorders not only influence pregnant women, but also have negative influences on the fetus and outcomes of pregnancy. However, optimal management of these disorders may reverse adverse consequences. In this chapter, risk factors, clinical presentation, and management of insomnia, obstructive sleep apnea, and restless legs syndrome during pregnancy are discussed in view of the available literature.

With impact of COVID-19 gradually increasing in many countries of the world with each passing day, there is a need to relook into the conservative management for some common sports related injuries. Awareness of all kinds of sports injuries, their symptoms, and preventive measures including education on rehydration, nutrition, monitoring team members, behavioural skills and techniques will further help in preventing the potential sporting injuries. Further, telemedicine and online portals including eSanjeevani outpatient department services should be encouraged.

Background: The COVID-19 pandemic has created an unprecedented challenge for medical professionals throughout the world to tackle the rapidly changing scenario. The objective of this survey was to analyze the change in neurosurgical practice in India following the COVID-19 outbreak and assess its impact on practising neurosurgeons. Materials and Methods: Between May 7th and 23rd, 2020, a validated questionnaire was circulated amongst practising neurosurgeons across the country by social media and e-mails, regarding changes in the patterns of patients seen, adaptations made in their practice, effect on surgeries performed, financial burden, and impact on their personal lives. The responses were kept anonymous and were analyzed for correlations between the changes observed and independent factors such as hospital affiliations, teaching professions, and neurosurgical experience. Results: Our survey showed a drastic fall in the number of neurosurgical patients seen in the outpatient department (OPD) as well as the number of surgeries performed. A drop of 76.25% was seen in OPD patients (P = 0.000) and that of 70.59% in surgeries performed (P = 0.000). There was no uniformity among the neurosurgeons in the number of COVID-19 tests being done before elective/emergency surgery and in the use of protective gear while examining patients. Private practitioners were more affected financially as compared to those in the government sector. The pandemic has affected the research work of 53.23% of all respondents, with those in the teaching profession (70.96%) more affected than those in the non-teaching profession (24.67%). Conclusions: Evidence-based policies, screening COVID-19 tests with better sensitivity, and better-quality personal protective equipment kits in adequate numbers are required to protect our medical professionals from COVID-19. Mental health issues among neurosurgeons may also be an issue, this being a high risk speciality and should be closely watched for.

Soaking of soybean seeds is a prerequisite for the production of soy foods, and it has been shown that the extent of water absorbed during different imbibition conditions directly affects the quality of the subsequent soybean seed products by yet unknown mechanisms. In order to elucidate the molecular changes in soybean seeds during different soaking temperatures, we performed an integrated proteomics and metabolomics analysis of seeds soaked at 4, 25, and 55 °C. Proteomics analysis revealed that various enzymes related to carbohydrate and protein hydrolysis were activated in soybean seeds during water soaking at 55 °C. Interestingly, results obtained from this integrated proteomics and metabolomics study showed changes in various metabolites, including isoflavones, amino acids, and sugars, that were positively correlated with proteome changes occurring upon soaking at 55 °C. Furthermore, soaking of soybean seeds at 55 °C resulted in degradation of indigestible anti-nutrients such as raffinose oligosaccharides. Taken together, our results suggest that the seed soaking at a high temperature (55 °C) increases the nutritional value of soybean seeds by decreasing the contents of some of the common anti-nutrients.

Despite the significant technical advancements in mass spectrometry-based proteomics and bioinformatics resources, dynamic resolution of soybean seed proteome is still limited because of the high abundance of seed storage proteins (SSPs). These SSPs occupy a large proportion of the total seed protein and hinder the identification of low-abundance proteins. Here, we report a TMT-based quantitative proteome analysis of matured and filling stages seeds of high-protein (Saedanbaek) and low-protein (Daewon) soybean cultivars by application of a two-way pre-fractionation both at the levels of proteins (by PS) and peptides (by basic pH reverse phase chromatography). Interestingly, this approach led to the identification of more than 5900 proteins which is the highest number of proteins reported to date from soybean seeds. Comparative protein profiles of Saedanbaek and Daewon led to the identification of 2200 and 924 differential proteins in mature and filling stages seeds, respectively. Functional annotation of the differential proteins revealed enrichment of proteins related to major metabolism including amino acid, major carbohydrate, and lipid metabolism. In parallel, analysis of free amino acids and fatty acids in the filling stages showed higher contents of all the amino acids in the Saedanbaek while the fatty acids contents were found to be higher in the Daewon. Taken together, these results provide new insights into proteome changes during filling stages in soybean seeds. Moreover, results reported here also provide a framework for systemic and large-scale dissection of seed proteome for the seeds rich in SSPs by two-way pre-fractionation combined with TMT-based quantitative proteome analysis.

Salinity stress is one of the major threats to agricultural productivity across the globe. Research in the past three decades, therefore, has focused on analyzing the effects of salinity stress on the plants. Evidence gathered over the years supports the role of ethylene as a key regulator of salinity stress tolerance in plants. This gaseous plant hormone regulates many vital cellular processes starting from seed germination to photosynthesis for maintaining the plants’ growth and yield under salinity stress. Ethylene modulates salinity stress responses largely via maintaining the homeostasis of Na+/K+, nutrients, and reactive oxygen species (ROS) by inducing antioxidant defense in addition to elevating the assimilation of nitrates and sulfates. Moreover, a cross-talk of ethylene signaling with other phytohormones has also been observed, which collectively regulate the salinity stress responses in plants. The present review provides a comprehensive update on the prospects of ethylene signaling and its cross-talk with other phytohormones to regulate salinity stress tolerance in plants.

Subcellular proteome analysis is one of the most effective ways to reduce the complexity of total proteome. With the advancement in protein extraction methodologies, it is now possible to fractionate and isolate the proteins from subcellular compartments without significant contamination from the cytoplasm and other organelles. Of the different subcellular proteomes, plasma membrane remained largely uncharacterized because of the difficulties in isolation of contamination free plasma membrane proteins. Moreover, proteome analysis in the past two decades majorly relied on the two-dimensional gel electrophoresis which showed limited protein loading ability and poor separation of highly hydrophobic plasma membrane proteins. Development of shotgun proteomics methods has facilitated the identification and quantification of hydrophobic proteins isolated from plasma membrane or other cellular membranes. Here, we present a simplified procedure for the isolation of plasma membrane proteins by a two-phase partitioning method and their identification by shotgun proteomics approach using rice as a model plant.

Vitamin D deficiency is a worldwide pandemic problem. With vitamin D having some role in exercise-induced inflammation, skeletal muscle mass and endurance, we studied its effect on functional outcome of athletes' post-Anterior Cruciate Ligament (ACL) reconstruction.A total of 153 patients who underwent primary ACL reconstruction were enrolled in the study. All patients were screened for vitamin D levels preoperatively. Patients were divided into 3 groups on basis of vitamin D levels; Group 1 patients had 20 ng/ml, group 2 patients 20-30 ng/ml and group 3 30 ng/ml. All patients were followed up for a minimum of 2 years.A total of 153 patients were enrolled in study. The average age of the patients was 24.12 ± 2.12 years in group 1, 25.24 ± 3.20 years in group 2 and 24.74 ± 2.86 in group 3. The mean follow-up of patients was 2.8 ± 1.2 years. At 2 years, the mean Lysholm score was 96.12, 96.49 and 97.0, respectively (p = 0.75); mean WOMAC score was 3.33, 3.38 and 3.20, respectively (p = 0.91); mean difference between the pre-injury and post-surgery Tegner level of sports activity at 2 years follow-up was 0.78, 0.78 and 0.85, respectively (P = 0.51) and graft failure rate was 5.88%, 1.96% and 1.96%, respectively (p = 0.43).Vitamin D has no effect on functional outcome and graft rupture rates in patients' post-primary ACL reconstruction.Prospective Cohort Study (Level III).

A sinus of Valsalva aneurysm (SOVA) is usually a silent entity until one of its complications arises, such as heart failure. SOVA itself is uncommon, but it is more frequently associated with a supracristal ventricular septal defect (SVSD). We present a 67-year-old man with a history of an asymptomatic SVSD who presented to the emergency department with signs and symptoms of heart failure. He was subsequently found to have a ruptured SOVA and underwent urgent surgical repair.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of coronavirus disease (COVID-19) that has resulted in a global pandemic. It is a highly contagious positive strand RNA virus and its clinical presentation includes severe to critical respiratory disease that appears to be fatal in ∼3-5% of the cases. The viral spike (S) coat protein engages the human angiotensin-converting enzyme2 (ACE2) cell surface protein to invade the host cell. The SARS-CoV-2 S-protein has acquired mutations that increase its affinity to human ACE2 by ∼10-15-fold compared to SARS-CoV S-protein, making it highly infectious. In this study, we assessed if ACE2 polymorphisms might alter host susceptibility to SARS-CoV-2 by affecting the ACE2 S-protein interaction. Our comprehensive analysis of several large genomic datasets that included over 290,000 samples representing >400 population groups identified multiple ACE2 protein-altering variants, some of which mapped to the S-protein-interacting ACE2 surface. Using recently reported structural data and a recent S-protein-interacting synthetic mutant map of ACE2, we have identified natural ACE2 variants that are predicted to alter the virus-host interaction and thereby potentially alter host susceptibility. In particular, human ACE2 variants S19P, I21V, E23K, K26R, T27A, N64K, T92I, Q102P and H378R are predicted to increase susceptibility. The T92I variant, part of a consensus NxS/T N-glycosylation motif, confirmed the role of N90 glycosylation in immunity from non-human CoVs. Other ACE2 variants K31R, N33I, H34R, E35K, E37K, D38V, Y50F, N51S, M62V, K68E, F72V, Y83H, G326E, G352V, D355N, Q388L and D509Y are putative protective variants predicted to show decreased binding to SARS-CoV-2 S-protein. Overall, ACE2 variants are rare, consistent with the lack of selection pressure given the recent history of SARS-CoV epidemics, however, are likely to play an important role in altering susceptibility to CoVs.

In orthopedic and trauma surgical operations, drilling of bone is one of the commonly used procedures performed in hospitals and is a clinical practice for fixing the fractured parts of human bones. Force, torque and temperature play a significant role during the bone drilling and decide the stability of the medical implants. Therefore, it is necessary to minimize force, torque and temperature while drilling to avoid the thermal necrosis and osteosynthesis. This study focused on studying the influence of various types of bone drilling parameters (rotational speed, feed rate, drill diameter and ultrasonic amplitude), tools (solid tool, hollow tool and conventional twist drill bit) and techniques (conventional surgical drilling, rotary ultrasonic bone drilling and rotary bone drilling) on force, torque, temperature and microcracks produced in the drilled surface of the bone. The experimental investigations were conducted on porcine bone samples to perform the comparative study. Results revealed that increasing the diameter of drill tool and feed rate results in the increase in force, torque and temperature, while low rotational speed (500 r/min) generated a low temperature, high cutting force and torque for all types of drilling processes and tools evaluated in this study. Experimental results also revealed that rotary ultrasonic bone drilling with hollow tool generated the lowest cutting force, torque, temperature (

Tomato spotted wilt virus (TSWV), transmitted by small insects known as thrips, is one of the major threats to tomato productivity across the globe. In addition to tomato, this virus infects more than 1000 other plants belonging to 85 families and is a cause of serious concern. Very little, however, is known about the molecular mechanism of TSWV induced signaling in plants. Here, we used a tandem mass tags (TMT)-based quantitative proteome approach to investigate the protein profiles of tomato leaves of two cultivars (cv 2621 and 2689; susceptible and resistant to TSWV infection, respectively) following TSWV inoculation. This approach resulted in the identification of 5112 proteins of which 1022 showed significant changes in response to TSWV. While the proteome of resistant cultivar majorly remains unaltered, the proteome of susceptible cultivar showed distinct differences following TSWV inoculation. TSWV modulated proteins in tomato included those with functions previously implicated in plant defense including secondary metabolism, reactive oxygen species (ROS) detoxification, mitogen-activated protein (MAP) kinase signaling, calcium signaling and jasmonate biosynthesis, among others. Taken together, results reported here provide new insights into the TSWV induced signaling in tomato leaves and may be useful in the future to manage this deadly disease of plants.

We present the case of an 83-year-old woman, with known asthma, admitted with increasing dyspnoea, wheeze and a productive cough. In addition to maintenance inhaled therapy, the patient was also on long-term mirtazapine and furosemide. Following acute treatment with nebulised salbutamol she became increasingly dyspnoeic and developed a metabolic acidosis with a significantly raised blood lactate level. After cessation of ß2-adrenergic medication, the patient's clinical condition improved with resolution of her lactic acidosis; salbutamol induced lactic acidosis was diagnosed. This clinical scenario is common but not well described. Here we discuss the mechanisms, investigation and management of raised serum lactate and lactic acidosis in the context of acute asthma and the possible interactions of polypharmacy and comorbidities in the acute medical setting.