Search

ABSTRACT Clinically validated human papillomavirus (HPV) assays are crucial in cervical cancer screening. In this study, we evaluated the Allplex HPV HR Detection assay (Seegene, SouthKorea) for its clinical accuracy and reproducibility according to the international criteria, using the RealTime High Risk HPV m2000 assay (Abbott, USA) as standard comparator. The Allplex HPV HR assay exhibits significant non-inferior sensitivity to detect cervical intraepithelial neoplasia grade (CIN) 2 or worse (CIN2+) with a ratio of 1.00 (95% CI: 0.97–1.03, P = 0.006), insignificant non-inferior sensitivity to detect CIN3+ with a ratio of 1.00 (95% CI: 0.88–1.13, P = 0.098), and non-inferior specificity to exclude CIN2+ with a ratio of 0.99 (95% CI: 0.99–1.00, P < 0.001) compared to the standard comparator. In addition, the assay shows an excellent reproducibility within the same laboratory [96.5% (95% CI: 94.6–97.9) with a kappa value of 0.91 (95% CI: 0.87–0.95)] and between laboratories [96.7% (95% CI: 94.8–98.0) with a kappa value of 0.91 (95% CI: 0.87–0.95)] for overall high-risk HPV positivity as well as for each individual HPV type. Pooling our study data with those of another independent study supports the consistency of our findings. We conclude that both the clinical accuracy to detect cervical precancer and the reproducibility of Allplex HPV HR Detection assay fulfill the international validation criteria of use in cervical cancer screening.IMPORTANCEThe clinical validation of human papillomavirus (HPV) assays in accordance with well-established international guidelines is crucial to ensure that only validated assays are used in the context of screening (Meijer et al., Int J Cancer, 2009). The guidelines, developed by an international consortium, require that a novel HPV assay has non-inferior accuracy against a standard comparator test for the detection of cervical intraepithelial neoplasia grade (CIN) 2 or worse (CIN2+). Additionally, a new HPV assay should meet specific criteria for both intra- and inter-laboratory reproducibility to ensure the assay consistently exhibits technical precision and robust performance. Pooling our study data with those of another independent study supports the consistency of our findings. In conclusion, both the clinical accuracy to detect cervical precancer and the reproducibility of Allplex HPV HR Detection assay fulfill the international validation criteria of use in cervical cancer screening.

Introduction: Region-specific data on individual factors associated with uptake of breast and cervical cancer screening or early testing in diverse Indian populations are limited. Aim: To assess the prevalence and individual determinants of uptake of breast and/or cervical cancer screening or testing among women aged 30–69 years in regionally representative populations of two large Indian cities: New Delhi and Chennai. Methods: We conducted an analysis of the cross-sectional data (2016–2017) nested within the Centre for Cardiometabolic Risk Reduction in South Asia cohort, established in 2010–2011 with 12,271 participants (5365 in New Delhi; 6906 in Chennai). Among 3310 women participants, we evaluated the associations of demographic, socioeconomic, lifestyle, medical, psychosocial, and reproductive factors with breast and/or cervical cancer screening or testing using multivariable logistic regression models with results expressed as adjusted odds ratios (OR) and 95% confidence intervals (CI). Results: At any point prior to 2016–2017, 193 women self-reported having undergone evaluations for breast and/or cervical cancer. The reasons for evaluation were ‘general examination’ or ‘physician’s advice’ (i.e., screening) or ‘being symptomatic’ (i.e., early testing). The overall prevalence was 5.8% for screening or testing and 2.5% for screening alone. Formal education (OR:1.88; 95% CI:1.12–3.15), high monthly household income (OR:2.27; 95% CI:1.59–3.25) and less ‘fear-of-judgement’ (OR:1.65; 95% CI:1.05–2.58) were positively associated with screening or testing uptake. When screening uptake was analysed separately, the results were generally similar. Conclusion: Our findings may have important implications for interventions at community-level (e.g., reducing ‘fear-of-judgement’, increasing awareness to screening programs and early symptoms) and health-system level (e.g., opportunistic screening).

ABSTRACTThe coronavirus disease 2019 (COVID-19) pandemic demonstrated the need for accurate diagnostic testing for the early detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although the pandemic has ended, accurate assays are still needed to monitor viral spread at national levels and beyond through population and wastewater surveillance. To enhance early detection, SARS-CoV-2 assays should have high diagnostic accuracy and should be validated to assure accurate results. Three distinct SARS-CoV-2 assays were evaluated with clinical samples using the VALCOR (VALidation of SARS-CORona Virus-2 assays) framework, with the TaqPath COVID-19 assay (ThermoFisher Scientific, USA) as a comparator. We evaluated clinical sensitivity, specificity, limit of detection (LOD), and overall concordance between comparator and three index Allplex SARS-CoV-2 assays (Seegene, South Korea): Allplex-SC2, Allplex-SC2Fast (Fast PCR), and Allplex-SC2FabR (SARS-CoV-2/FluA/FluB/respiratory syncytial virus). Analytical performance and LOD of index assays were assessed using a dilution series of three synthetic SARS-CoV-2 sequence reference materials (RMs). Ninety SARS-CoV-2 positives and 90 SARS-CoV-2 negatives were tested. All Allplex assays had 100.0% sensitivity (95%CI = 95.9%–100.0%). Allplex-SC2 and Allplex-SC2Fast assays had 97.8% specificity (95%CI = 92.3%–99.7%) and 98.9% overall concordance [κ = 0.978 (95%CI = 0.947–1.000)]. Allplex-SC2FabR assay showed 100.0% specificity (95%CI = 95.9%–100.0%) and 100.0% overall concordance [κ = 1.000 (95%CI = 1.000–1.000)]. LOD assessment of index assays revealed detection down to 2.61 × 102 copies/mL in clinical samples, while the analytical LOD was 9.00 × 102 copies/mL. In conclusion, the evaluation of the three Seegene Allplex SARS-CoV-2 assays showed high sensitivity and specificity and an overall good assay concordance with the comparator. The assays showed low analytical LOD using RM and even a slightly lower LOD in clinical samples. Non-overlapping target gene sequences between SARS-CoV-2 assays and RMs emphasize the need for aligning targeted sequences of diagnostic assays and RMs.IMPORTANCEThe coronavirus disease 2019 pandemic has a significant impact on global public health, economies, and societies. As shown through the first phases of the pandemic, accurate and timely diagnosis is crucial for disease control, prevention, and monitoring. Though the pandemic phase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has concluded, diagnostic assays remain in demand to monitor SARS-CoV-2 at the individual patient level, regionally, and nationally, as well as to remain an infectious disease preparedness instrument to monitor any new SARS-CoV-2 dissemination across borders using population and wastewater surveillance. The anticipation by WHO and central health care policy entities such as the Center for Disease Control, EMA, and multiple national health authorities is that SARS-CoV-2 will reside as an endemic respiratory disease for years to come. The key strategic consideration is hence shifting from combating a pandemic situation with a high number of patients to instead allowing precise diagnostics of suspected patients with the intention of correct management in a low-prevalence setting.

The risk of developing pulmonary hypertension (PH) in people living with HIV is at least 300-fold higher than in the general population, and illicit drug use further potentiates the development of HIV-associated PH. The relevance of extracellular vesicles (EVs) containing both coding as well as non-coding RNAs in PH secondary to HIV infection and drug abuse is yet to be explored. We here compared the miRNA cargo of plasma-derived EVs from HIV-infected stimulant users with (HIV + Stimulants + PH) and without PH (HIV + Stimulants) using small RNA sequencing. The data were compared with 12 PH datasets available in the GEO database to identify potential candidate gene targets for differentially altered miRNAs using the following functional analysis tools: ingenuity pathway analysis (IPA), over-representation analysis (ORA), and gene set enrichment analysis (GSEA). MiRNAs involved in promoting cell proliferation and inhibition of intrinsic apoptotic signaling pathways were among the top upregulated miRNAs identified in EVs from the HIV + Stimulants + PH group compared to the HIV + Stimulants group. Alternatively, the downregulated miRNAs in the HIV + Stimulants + PH group suggested an association with the negative regulation of smooth muscle cell proliferation, IL-2 mediated signaling, and transmembrane receptor protein tyrosine kinase signaling pathways. The validation of significantly differentially expressed miRNAs in an independent set of HIV-infected (cocaine users and nondrug users) with and without PH confirmed the upregulation of miR-32-5p, 92-b-3p, and 301a-3p positively regulating cellular proliferation and downregulation of miR-5571, -4670 negatively regulating smooth muscle proliferation in EVs from HIV-PH patients. This increase in miR-301a-3p and decrease in miR-4670 were negatively correlated with the CD4 count and FEV1/FVC ratio, and positively correlated with viral load. Collectively, this data suggest the association of alterations in the miRNA cargo of circulating EVs with HIV-PH.

Spotted stem borer, Chilo partellus (Swinhoe) is one of the most destructive pests of sorghum and maize, and undergoes hibernation during harsh winters. Several aspects of diapause have been studied, however metabolic and biochemical processes underlying hibernation remain poorly understood in C. partellus. Present studies carried out during 2020–22 at ICAR-Indian Agricultural Research Institute, New Delhi deciphered the variations in nutritional biochemicals, digestive and stress enzymes, cryoprotectants in the hibernation and in non-hibernating larvae and pupae of C. partellus. These studies revealed that the total lipids and proteins were significantly greater during pre- hibernation and hibernation, and sugars were greater in non-hibernation larvae. Glycogen content was greater in pre- hibernation, and sorbitol, trehalose and glucitol contents consistently increased from pre-hibernation to hibernation stages in comparison to non-hibernation larvae of C. partellus. Total sugar and sorbitol contents decreased, while total protein, trehalose and glucitol increased, in post-hibernation than the non-hibernation pupae of C. partellus. Activities of ascorbic acid, lipid peroxidation, total antioxidant, catalase and superoxide dismutase were significantly greater during hibernation followed by pre-hibernation as compared to non-hibernation larvae, while the reverse was the case with protease activity. Ascorbic acid, lipid peroxidation, total antioxidant and catalase activities were greater in post-hibernation as compared to non-hibernation pupae of C. partellus. However, glutathione S-transferase activity was greater in the non-hibernation larvae and pupae than the hibernation larvae and post-hibernation pupae of C. partellus. These findings can be useful to design newer management strategies keeping in view the weak links like the state of nutritional metabolism and oxidative stress tolerance due to diapause in C. partellus.

Objective Antithrombin III (ATIII) deficiency may result from hereditary or acquired reduction in ATIII levels and is associated with an increase in venous thromboembolism (VTE) in the general population. VTE is a potentially preventable complication in the critically ill surgical patients. The objective of this study was to evaluate the relation between ATIII levels and VTE in surgical intensive care unit (SICU) patients.Methods All patients admitted to the SICU from January 2017 to April 2018 who had ATIII levels drawn were included in the study. An ATIII level below 80% of normal was considered low. The rate of VTE during the same admission was compared among patients with normal and low levels of ATIII. Prolonged length of stay (LOS >10 days) and mortality were also measured.Results Of the 227 patients included, 59.9% were male. The median age was 60 years. Overall, 66.9% of patients had low ATIII levels. Trauma patients had a higher rate of normal ATIII levels, whereas those weighing more than 100 kg had a higher rate of low ATIII levels. Patients with low ATIII levels had higher VTE rates compared with those with normal ATIII levels (28.9% vs. 16%, p=0.04). Patients with low ATIII levels also had prolonged LOS (76.3% vs. 60%, p=0.01) and increased mortality (21.7% vs. 6.7%, p

The present study was carried out to decipher the variation in plant phytochemicals, and their effect on developmental, reproduction and survival of Lipaphis erysimi (Kalt.) on diverse Brassica juncea cultivars. These studies revealed significant differences in total nymphal, reproductive and developmental periods, fecundity and offspring survival of L. erysimi on the test B. juncea cultivars. Development period was significantly longer on DRMR 150-35, PM 26, RLC 3 and PM 25, while fecundity and survival were lower on PM 27, RLC 3, NRCHB 101, RH 749, Pusa Tarak, RH 0406 and PM 30, except in a few cases. Total proteins, antioxidants, tannins, phenols and FRAP were significantly higher, and sugars lower in DRMR 150-35, RLC 3, PM 26 and NRCHB 101 as compared to other B. juncea cultivars. Total proteins, total tannins and antioxidants exhibited a significant and positive, while total sugars showed negative correlation, and explained 86.1% variability in total developmental period of L. erysimi. Total sugars revealed a significantly positive and FRAP negative correlation, explaining 35.5% variability in fecundity of L. erysimi. Furthermore, total proteins and total antioxidants also showed significant and negative correlation with offspring survival, and total phenols and antioxidants explained 28.9% variability in offspring survival of L. erysimi on the test B. juncea genotypes. Present study suggests that DRMR 150-35, RLC 3, NRCHB 101 and PM 26 have greater amounts of antinutritional plant defense compounds which adversely affect the developmental and reproductive biology of L. erysimi, and thus could be used in Brassica improvement programme for sustainable crop production.

Abstract Background The COVID-19 pandemic highlighted the importance of diagnostic testing against curbing the spread of SARS-CoV-2. The urgent need and scale for diagnostic tools resulted in manufacturers of SARS-CoV-2 assays receiving emergency authorization that lacked robust analytical or clinical evaluation. As it is highly likely that testing for SARS-CoV-2 will continue to play a central role in public health, the performance characteristics of assays should be evaluated to ensure reliable diagnostic outcomes are achieved. Methods VALCOR or “VALidation of SARS-CORona Virus-2 assays” is a study protocol designed to set up a framework for test validation of SARS-CoV-2 virus assays. Using clinical samples collated from VALCOR, the performance of Aptima SARS-CoV-2 assay was assessed against a standard comparator assay. Diagnostic test parameters such as sensitivity, specificity and overall per cent agreement were calculated for the clinical performance of Aptima SARS-CoV-2 assay. Results A total of 180 clinical samples were tested with an addition of 40 diluted clinical specimens to determine the limit of detection. When compared to the standard comparator assay Aptima had a sensitivity of 100.0% [95% CI 95.9–100.0] and specificity of 96.7% [95% CI 90.8–99.3]. The overall percent agreement was 98.3% with an excellent Cohen’s coefficient of κ = 0.967 [95% CI 0.929–1.000]. For the limit of detection, Aptima was able to detect all of the diluted clinical samples. Conclusion In conclusion. validation of Aptima SARS-CoV-2 assay using clinical samples collated through the VALCOR protocol showed excellent test performance. Additionally, Aptima demonstrated high analytical sensitivity by detecting all diluted clinical samples corresponding to a low limit of detection.

Brain maturity and many clinical treatments such as therapeutic hypothermia (TH) can significantly influence the morphology of neonatal EEG seizures after hypoxia–ischemia (HI), and so there is a need for generalized automatic seizure identification. This study validates efficacy of advanced deep-learning pattern classifiers based on a convolutional neural network (CNN) for seizure detection after HI in fetal sheep and determines the effects of maturation and brain cooling on their accuracy. The cohorts included HI–normothermia term (n = 7), HI–hypothermia term (n = 14), sham–normothermia term (n = 5), and HI–normothermia preterm (n = 14) groups, with a total of >17,300 h of recordings. Algorithms were trained and tested using leave-one-out cross-validation and k-fold cross-validation approaches. The accuracy of the term-trained seizure detectors was consistently excellent for HI–normothermia preterm data (accuracy = 99.5%, area under curve (AUC) = 99.2%). Conversely, when the HI–normothermia preterm data were used in training, the performance on HI–normothermia term and HI–hypothermia term data fell (accuracy = 98.6%, AUC = 96.5% and accuracy = 96.9%, AUC = 89.6%, respectively). Findings suggest that HI–normothermia preterm seizures do not contain all the spectral features seen at term. Nevertheless, an average 5-fold cross-validated accuracy of 99.7% (AUC = 99.4%) was achieved from all seizure detectors. This significant advancement highlights the reliability of the proposed deep-learning algorithms in identifying clinically translatable post-HI stereotypic seizures in 256Hz recordings, regardless of maturity and with minimal impact from hypothermia.

Abstract Recent advances in high-throughput experiments and systems biology approaches have resulted in hundreds of publications identifying “immune signatures”. Unfortunately, these are often described within text, figures, or tables in a format not amenable to computational processing, thus severely hampering our ability to fully exploit this information. Here we present a data model to represent immune signatures, along with the Human Immunology Project Consortium (HIPC) Dashboard ( www.hipc-dashboard.org ), a web-enabled application to facilitate signature access and querying. The data model captures the biological response components (e.g., genes, proteins, cell types or metabolites) and metadata describing the context under which the signature was identified using standardized terms from established resources (e.g., HGNC, Protein Ontology, Cell Ontology). We have manually curated a collection of >600 immune signatures from >60 published studies profiling human vaccination responses for the current release. The system will aid in building a broader understanding of the human immune response to stimuli by enabling researchers to easily access and interrogate published immune signatures.

Abstract Heart failure (HF) is a complex disease associated with multisystem organ failure, recurrent hospital admissions, and increased mortality. Acute decompensated heart failure (ADHF) increases central venous pressure (CVP) with resultant hepatic congestion, and this relationship has prognostic significance. The gold standard method of measuring CVP, right heart catheterization, is invasive and costly, prompting further investigation into more accurate non‐invasive assessments in HF patients, including liver elastography. Liver elastography relies on imaging techniques to assess liver stiffness measurements (LSM), with high values equating to increased stiffness. While this was developed to assess fibrosis in liver disease, LSM also reflect increased CVP and hepatic congestion. Multiple studies involving ADHF patients, find that increased LSM are independently predictive of increased cardiac events, all‐cause mortality, and worse post‐operative outcome after both acute HF exacerbation and left ventricular assist device (LVAD) placement. In this review, we discuss the role of LSM as a surrogate for CVP and their applications in determining prognosis in both the ADHF and LVAD populations.

Neurofibromatosis 2 is an inheritable disorder characterized by bilateral vestibular nerve schwannomas. The usual presentation of such patients is hearing loss and difficulties with balancing. However, we report a case of a 20-year-old female presenting with a long-standing 3rd nerve palsy without any hearing disturbances. Although it is a rare presentation, neuroimaging must be performed in all cases of nerve palsies to rule out any CNS manifestations. Management in such conditions should be multidisciplinary especially under the leadership of a neurologist as the cardinal complications are central.

BackgroundSepsis is a dysfunctional host response to infection. The syndrome leads to millions of deaths annually (19.7% of all deaths in 2017) and is the cause of most deaths from severe Covid infections. High throughput sequencing or ‘omics’ experiments in molecular and clinical sepsis research have been widely utilized to identify new diagnostics and therapies. Transcriptomics, quantifying gene expression, has dominated these studies, due to the efficiency of measuring gene expression in tissues and the technical accuracy of technologies like RNA-Seq.ObjectiveMost of these studies seek to uncover novel mechanistic insights into sepsis pathogenesis and diagnostic gene signatures by identifying genes differentially expressed between two or more relevant conditions. However, little effort has been made, to date, to aggregate this knowledge from such studies. In this study we sought to build a compendium of previously described gene sets that combines knowledge gained from sepsis-associated studies. This would enable the identification of genes most associated with sepsis pathogenesis, and the description of the molecular pathways commonly associated with sepsis.MethodsPubMed was searched for studies using transcriptomics to characterize acute infection/sepsis and severe sepsis (i.e., sepsis combined with organ failure). Several studies were identified that used transcriptomics to identify differentially expressed (DE) genes, predictive/prognostic signatures, and underlying molecular responses and pathways. The molecules included in each gene set were collected, in addition to the relevant study metadata (e.g., patient groups used for comparison, sample collection time point, tissue type, etc.).ResultsAfter performing extensive literature curation of 74 sepsis-related publications involving transcriptomics, 103 unique gene sets (comprising 20,899 unique genes) from thousands of patients were collated together with associated metadata. Frequently described genes included in gene sets as well as the molecular mechanisms they were involved in were identified. These mechanisms included neutrophil degranulation, generation of second messenger molecules, IL-4 and -13 signaling, and IL-10 signaling among many others. The database, which we named SeptiSearch, is made available in a web application created using the Shiny framework in R, (available at https://septisearch.ca).ConclusionsSeptiSearch provides members of the sepsis community the bioinformatic tools needed to leverage and explore the gene sets contained in the database. This will allow the gene sets to be further scrutinized and analyzed for their enrichment in user-submitted gene expression data and used for validation of in-house gene sets/signatures.

Seizures are common in preterm newborns and are associated with poor neurodevelopmental outcomes. Current anticonvulsants have poor efficacy, and many have been associated with upregulation of apoptosis in the developing brain. Apigenin, a natural bioactive flavonoid, is a potent inhibitor of hyaluronidase and reduces seizures in adult animal models. However, its impact on perinatal seizures is unclear. In the present study, we examined the effect of apigenin and S3, a synthetic, selective hyaluronidase inhibitor, on seizures after cerebral ischemia in preterm fetal sheep at 0.7 gestation (98–99 days, term ~147 days). Fetuses received sham ischemia (n = 9) or ischemia induced by bilateral carotid occlusion for 25 min. Immediately after ischemia, fetuses received either a continuous infusion of vehicle (0.036% dimethyl sulfoxide, n = 8) or apigenin (50 µM, n = 6). In a pilot study, we also tested infusion of S3 (2 µM, n = 3). Fetuses were monitored continuously for 72 h after ischemia. Infusion of apigenin or S3 were both associated with reduced numbers of animals with seizures, total seizure time, and mean seizure burden. S3 was also associated with a reduction in the total number of seizures over the 72 h recovery period. In animals that developed seizures, apigenin was associated with earlier cessation of seizures. However, apigenin or S3 treatment did not alter recovery of electroencephalographic power or spectral edge frequency. These data support that targeting brain hyaluronidase activity with apigenin or S3 may be an effective strategy to reduce perinatal seizures following ischemia. Further studies are required to determine their effects on neurohistological outcomes.

Objectives In resource-constrained settings, cancer epidemiology research typically relies on self-reported diagnoses. To test a more systematic alternative approach, we assessed the feasibility of linking a cohort with a cancer registry.Setting Data linkage was performed between a population-based cohort in Chennai, India, with a local population-based cancer registry.Participants Data set of Centre for Cardiometabolic Risk Reduction in South-Asia (CARRS) cohort participants (N=11 772) from Chennai was linked with the cancer registry data set for the period 1982–2015 (N=140 986).Methods and outcome measures Match*Pro, a probabilistic record linkage software, was used for computerised linkages followed by manual review of high scoring records. The variables used for linkage included participant name, gender, age, address, Postal Index Number and father’s and spouse’s name. Registry records between 2010 and 2015 and between 1982 and 2015, respectively, represented incident and all (both incident and prevalent) cases. The extent of agreement between self-reports and registry-based ascertainment was expressed as the proportion of cases found in both data sets among cases identified independently in each source.Results There were 52 self-reported cancer cases among 11 772 cohort participants, but 5 cases were misreported. Of the remaining 47 eligible self-reported cases (incident and prevalent), 37 (79%) were confirmed by registry linkage. Among 29 self-reported incident cancers, 25 (86%) were found in the registry. Registry linkage also identified 24 previously not reported cancers; 12 of those were incident cases. The likelihood of linkage was higher in more recent years (2014–2015).Conclusions Although linkage variables in this study had limited discriminatory power in the absence of a unique identifier, an appreciable proportion of self-reported cases were confirmed in the registry via linkages. More importantly, the linkages also identified many previously unreported cases. These findings offer new insights that can inform future cancer surveillance and research in low-income and middle-income countries.

Cerebral small vessel disease (SVD) is a major cause of cognitive impairment in older people. As secondary endpoints in a phase-2 randomised clinical trial, we tested the effects of single administration of a widely-used PDE5 inhibitor, tadalafil, on cognitive performance in older people with SVD. In a double-blinded, placebo-controlled, cross-over trial, participants received tadalafil (20 mg) and placebo on two visits ≥ 7 days apart (randomised to order of treatment). The Montreal Cognitive Assessment (MOCA) was administered at baseline, alongside a measure to estimate optimal intellectual ability (Test of Premorbid Function). Then, before and after treatment, a battery of neuropsychological tests was administered, assessing aspects of attention, information processing speed, working memory and executive function. Sixty-five participants were recruited and 55 completed the protocol (N = 55, age: 66.8 (8.6) years, range 52–87; 15/40 female/male). Median MOCA score was 26 (IQR: 23, 27], range 15–30). No significant treatment effects were seen in any of the neuropsychological tests. There was a trend towards improved performance on Digit Span Forward (treatment effect 0.37, C.I. 0.01, 0.72; P = 0.0521). We did not identify significant treatment effects of single-administration tadalafil on neuropsychological performance in older people with SVD. The trend observed on Digit Span Forward may help to inform future studies. Clinical trial registration: http://www.clinicaltrials.gov. Unique identifier: NCT00123456, https://eudract.ema.europa.eu. Unique identifier: 2015–001,235–20NCT00123456.

The Coronavirus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) and its sublineages pose a new challenge to healthcare systems worldwide due to its ability to efficiently spread in immunized populations and its resistance to currently available therapies. COVID-19, although targeting primarily the respiratory system, is also now well established that later affects every organ in the body. Most importantly, despite the available therapy and vaccine-elicited protection, the long-term consequences of viral infection in breakthrough and asymptomatic individuals are areas of concern. In the past two years, investigators accumulated evidence on how the virus triggers our immune system and the molecular signals involved in the cross-talk between immune cells and structural cells in the pulmonary vasculature to drive pathological lung complications such as endothelial dysfunction and thrombosis. In the review, we emphasize recent updates on the pathophysiological inflammatory and immune responses associated with SARS-CoV-2 infection and their potential long-term consequences that may consequently lead to the development of pulmonary vascular diseases.

Abstract Maize is an important industrial crop where yield and quality enhancement both assume greater importance. Clean production technologies like conservation agriculture and integrated nutrient management hold the key to enhance productivity and quality besides improving soil health and environment. Hence, maize productivity and quality were assessed under a maize–wheat cropping system (MWCS) using four crop-establishment and tillage management practices [FBCT–FBCT (Flat bed–conventional tillage both in maize and wheat); RBCT–RBZT (Raised bed–CT in maize and raised bed–zero tillage in wheat); FBZT–FBZT (FBZT both in maize and wheat); PRBZT–PRBZT (Permanent raised bed–ZT both in maize and wheat], and five P-fertilization practices [P100 (100% soil applied-P); P50 + 2FSP (50% soil applied-P + 2 foliar-sprays of P through 2% DAP both in maize and wheat); P50 + PSB + AM-fungi; P50 + PSB + AMF + 2FSP; and P0 (100% NK with no-P)] in split-plot design replicated-thrice. Double zero-tilled PRBZT–PRBZT system significantly enhanced the maize grain, starch, protein and oil yield by 13.1–19% over conventional FBCT–FBCT. P50 + PSB + AMF + 2FSP, integrating soil applied-P, microbial-inoculants and foliar-P, had significantly higher grain, starch, protein and oil yield by 12.5–17.2% over P100 besides saving 34.7% fertilizer-P both in maize and on cropping-system basis. P50 + PSB + AMF + 2FSP again had significantly higher starch, lysine and tryptophan content by 4.6–10.4% over P100 due to sustained and synchronized P-bioavailability. Higher amylose content (24.1%) was observed in grains under P50 + PSB + AMF + 2FSP, a beneficial trait due to its lower glycemic-index highly required for diabetic patients, where current COVID-19 pandemic further necessitated the use of such dietary ingredients. Double zero-tilled PRBZT–PRBZT reported greater MUFA (oleic acid, 37.1%), MUFA: PUFA ratio and P/S index with 6.9% higher P/S index in corn-oil (an oil quality parameter highly required for heart-health) over RBCT-RBCT. MUFA, MUFA: PUFA ratio and P/S index were also higher under P50 + PSB + AMF + 2FSP; avowing the obvious role of foliar-P and microbial-inoculants in influencing maize fatty acid composition. Overall, double zero-tilled PRBZT–PRBZT with crop residue retention at 6 t/ha per year along with P50 + PSB + AMF + 2FSP while saving 34.7% fertilizer-P in MWCS, may prove beneficial in enhancing maize productivity and quality so as to reinforce the food and nutritional security besides boosting food, corn-oil and starch industry in south-Asia and collateral arid agro-ecologies across the globe.

Objectives: To evaluate the root and canal morphology of primary maxillary and mandibular molars in an Indian population using cone-beam computed tomography (CBCT). Methods: A retrospective cross-sectional study was performed, where CBCT scans of children less than 10 years of age taken for valid diagnostic purposes previously were considered and images were analyzed. The number of roots, root canals, and variations in morphology were recorded. Left–right symmetry was also noted. Results: A total of 433 deciduous maxillary and mandibular primary molars were studied. It was observed that two separate roots with three separate canals were common in primary mandibular first molars, whereas two separate roots with two canals in each root were common in mandibular second primary molars. In primary maxillary molars, three separate roots with one canal each were the most common. Maxillary first molars (17.21%) and 17.35% second molars had fused distobuccal and palatal roots. It was observed that primary maxillary molars showed more left–right symmetry (86.7% in first molars and 82.7% in second molars) compared to primary mandibular molars (54.05% in first molars and 68% in second molars). Conclusions: It was concluded that in both primary maxillary first and second molars, three separate roots, a mesiobuccal root, a distobuccal root, and a palatal root with one canal in each root, were the most common. Two separate roots with three separate canals were the most common in primary mandibular first molars, whereas two separate roots with two canals each in both roots were more common in mandibular second primary molars.

Genetic variation within plants and herbivores influence the biological attributes and insect-plant interactions. We studied biological performance of different agro-ecological Chilo partellus (Swinhoe) populations on diverse maize genotypes during 2016-17 at ICAR-Indian Agricultural Research Institute, New Delhi. There was significant variation in larval period, larval survival, pupal period, pupal weight, and adult emergence of C. partellus populations on the test maize genotypes. Larval period of Hisar, and pupal periods of Hisar and Parbhani populations were significantly longer than other C. partellus populations across test maize genotypes. Pupal weight across maize genotypes was significantly higher in Delhi as compared to other populations. Larval survival and adult emergence were significantly higher in Delhi and Hisar, while lower in Raichur and Parbhani populations than other C. partellus populations across maize genotypes. Longer developmental periods, lower survival and adult emergence of C. partellus across populations on CPM 2 and CPM 8 indicate stable resistance in these maize genotypes against this pest. Higher survival in Hisar and Delhi populations across maize genotypes indicate their higher aggressiveness than other C. partellus populations. The differential resistance reaction, development and survival of different stem borer populations on diverse maize genotypes indicate the existence of different biotypes/ecotypes of C. partellus in India.

Hybrids have been successfully used to improve crop productivity, including Brassicas. Nucleo-cytoplasmic interactions have been reported to influence the expression of resistance to insect pests in several crops. We studied the effects of Cytoplasmic Male Sterility (CMS) in Brassica juncea carrying alien cytoplasms and their respective maintainer (B) lines on the antibiosis mechanism of resistance, involving development, survival, reproduction potential and population build-up of mustard aphid, Lipaphis erysimi, and the levels of defense phyto-chemicals. Present findings revealed that the numbers of aphids/plant, aphid multiplication rate and aphid resistance index were lower on ber CMS under natural, mori CMS under artificial infestation conditions, and juncea under both the test conditions indicating nucleo-cytoplasmic interactions for aphid reaction. Across cytoplasms, nymphal, reproductive and total developmental periods were significantly longer on SEJ 8, NPJ 161, LES 39, and NPJ 93, while the reproductive potential and survival were lower on PM 30, Pusa Tarak and SEJ 8 as compared to other nuclear backgrounds. Across nuclear backgrounds, nymphal, reproductive and total developmental periods were significantly longer on ber CMS, while reproductive potential and survival were lower on ber and mori CMS as compared to other cytoplasms. Total glucosinolates were significantly greater and myrosinase lower in Pusa Agrani, SEJ 8, LES 39, PM 30, NPJ 112, and Pusa Tarak as compared to the other nuclear backgrounds. Furthermore, total glucosinolates were significantly greater and myrosinase lower in ber CMS and juncea as compared to other cytoplasms. The studies suggest that CMS as well as cytoplasmic and nuclear gene interactions regulate the expression of defense compounds such as glucosinolates and determine the expression of resistance/susceptibility to L. erysimi. These findings shall help in identification of suitable L. erysimi tolerant nucleo-cytoplasmic combinations for their deployment in B. juncea hybrid breeding program.

Fetal growth restriction (FGR) is a major cause of stillbirth, prematurity and impaired neurodevelopment. Its etiology is multifactorial, but many cases are related to impaired placental development and dysfunction, with reduced nutrient and oxygen supply. The fetus has a remarkable ability to respond to hypoxic challenges and mounts protective adaptations to match growth to reduced nutrient availability. However, with progressive placental dysfunction, chronic hypoxia may progress to a level where fetus can no longer adapt, or there may be superimposed acute hypoxic events. Improving detection and effective monitoring of progression is critical for the management of complicated pregnancies to balance the risk of worsening fetal oxygen deprivation in utero, against the consequences of iatrogenic preterm birth. Current surveillance modalities include frequent fetal Doppler ultrasound, and fetal heart rate monitoring. However, nearly half of FGR cases are not detected in utero, and conventional surveillance does not prevent a high proportion of stillbirths. We review diagnostic challenges and limitations in current screening and monitoring practices and discuss potential ways to better identify FGR, and, critically, to identify the “tipping point” when a chronically hypoxic fetus is at risk of progressive acidosis and stillbirth.

Perinatal hypoxia-ischemia (HI) is still a significant contributor to mortality and adverse neurodevelopmental outcomes in term and preterm infants. HI brain injury evolves over hours to days, and involves complex interactions between the endogenous protective and pathological processes. Understanding the timing of evolution of injury is vital to guide treatment. Post-HI recovery is associated with a typical neurophysiological profile, with stereotypic changes in cerebral perfusion and oxygenation. After the initial recovery, there is a delayed, prolonged reduction in cerebral perfusion related to metabolic suppression, followed by secondary deterioration with hyperperfusion and increased cerebral oxygenation, associated with altered neurovascular coupling and impaired cerebral autoregulation. These changes in cerebral perfusion are associated with the stages of evolution of injury and injury severity. Further, iatrogenic factors can also affect cerebral oxygenation during the early period of deranged metabolism, and improving clinical management may improve neuroprotection. We will review recent evidence that changes in cerebral oxygenation and metabolism after HI may be useful biomarkers of prognosis.

The concept of physical literacy is continuing to gain traction internationally. This increasing interest has also given rise to concerns about the use, interpretation and meaning of the term “literacy” within the context of physical literacy. This paper explores the development of the terms literate, illiterate, literacy, and illiteracy identifying their historical origin and contemporary meaning. This provides the backdrop to explore the use of the term literacy within the context of physical literacy. In the final part of this introductory section the recent popularity of the literacies movement is explored. Our discussion identifies key intersections and areas of tension associated with the use, interpretation and meaning of literacy in the context of physical literacy. We adopt Whitehead's philosophy of physical literacy and discussion is informed further by Derrida's notion of differance, and Barad's challenge to singular representations of concepts. Once harnessing these concepts, we reach a juncture of an in-between space; entry points of nonidentity (sameness) and points where multiple effects of difference are created. Key discussion topics include: discourse, language and interpretations of literacy; in/tangibility of literacy; capturing literacy; literacy as a process or a product; connotations of the terms literate and illiterate; neoliberalism and literacy and finally literacy as learning. We believe that when understood as the productive and meaningful interaction with/in/through the world, literacy is still the appropriate term within the context of physical literacy. Our discussion leads us to conclude that as embodied individuals, physical literacy is often the literacy through which other literacies have to pass. Through physical activity individuals can not only nurture their own physical literacy but also contribute toward a global or holistic literacy that helps us navigate, connect and make sense of ourselves, others and the world around us. However, the paper acknowledges that this meaning is not always grasped with the historical understanding of literacy as well as it's translations into other languages presenting challenges in articulating the intended use, meaning and connotations of the contemporary understanding of physical literacy.

Abstract Because of variation in incidence and severity of damage by Chilo partellus (Swinhoe) in different geographical regions, it is difficult to identify stable sources of resistance against this pest. Therefore, the present studies were undertaken on biological attributes (damage in resistant and susceptible genotypes, survival and development) and biochemical profiles (amino acids and lipophilic compound) of C. partellus populations from eight geographical regions to understand it’s population structure in India. There was a significant variation in biological attributes and biochemical profiles of C. partellus populations from different geographical regions. Based on virulence and biological attributes, similarity index placed the C. partellus populations in five groups. Likewise, lipophilic and amino acid profiling also placed the C. partellus populations in five groups. However, the different clusters based on biological and biochemical attributes did not include populations from the same regions. Similarity index based on virulence, biological attributes, and amino acids and lipophilic profiles placed the C. partellus populations in six groups. The C. partellus populations from Hisar, Hyderabad, Parbhani and Coimbatore were distinct from each other, indicating that there are four biotypes of C. partellus in India. The results suggested that sorghum and maize genotypes need to be tested against these four populations to identify stable sources of resistance. However, there is a need for further studies to establish the restriction in gene flow through molecular approaches across geographical regions to establish the distinctiveness of different biotypes of C. partellus in India.

Introduction: Selective nonoperative management of neck injuries from penetrating mechanism has become an acceptable management strategy. We herein characterize current management strategies of cervical pharyngoesophageal injuries implemented by trauma surgeons in the United States. Methods: The National Trauma Data Bank datasets 2007–2011 were queried for penetrating pharyngeal and/or cervical esophageal injuries. Subjects surviving 24 hours or more were analyzed based on whether a surgical exploration was pursued and by gunshot versus stabbing mechanism. Results: In all, 1,256 patients were identified, representing 6% of all penetrating neck injuries during the study period. The majority (84%) were male, with a median age of 27 years. Injury severity was high (median score of 14). Compared to stabbing victims, gunshot patients were more likely to have associated cervical spine (24% vs. 1%, p

Abstract Background Non-communicable diseases contribute to 62% of total deaths in India; of concern are the preventable premature deaths, which account for a staggering 48% of mortality. The objective of this study was to establish a consensus research agenda for non-communicable disease prevention and control that has the potential to impact polices, programmes and healthcare delivery in India. Methods To develop a non-communicable disease research agenda, we engaged our community collaborative board and scientific advisory group in a three-step process using two web-based surveys and one in-person meeting. First, the Delphi methodology was used to generate topics. Second, these ideas were deliberated upon during the in-person meeting, leading to the prioritisation of 23 research questions, which were subjected to Strength, Weakness, Opportunities and Threat analysis by the stakeholders using the Snow Card methodology with the scientific advisory group and community collaborative board. This step resulted in the identification of 15 low effort, high impact priority research questions for various health outcomes across research disciplines based on discussion with the larger group to reach consensus. Finally, the second web-based survey resulted in the identification of 15 key priority research questions by all stakeholders as being the most important using a linear mixed effect regression model. Results The final set of 15 priority research questions focused on interventions at the individual, community, systems and policy levels. Research questions focused on identifying interventions that strengthen healthcare systems and healthcare delivery, including models of care and improved access to non-communicable disease screening, diagnosis and treatment, determining the impact of government policies, assessing the effectiveness of prevention programmes (e.g. tobacco, environmental improvements), and testing research tools and resources to monitor non-communicable diseases at the population level. Conclusion To produce the evidence base for selecting and implementing non-communicable disease programmes and policies in India, investments are needed. These investments should be guided by a national research agenda for the prevention and control of non-communicable diseases in India. Our findings could form the backbone of a national research agenda for non-communicable diseases in India that could be refined and then adopted by government agencies, the private sector, non-governmental and community-based organisations.

In the present study, host selection behaviour and biological performance of Sesamia inferens on different maize (Zea mays L.) genotypes was investigated in 2018–19, and constitutive and insect damage-induced levels of various photosynthetic pigments were determined. There were significant differences in larval period, larval survival, larval weight, pupal period, pupal weight, adult emergence, and fecundity of S. inferens on the test maize genotypes. The S. inferens that fed on maize genotypes, viz. CPM 2, CPM 4, CPM 8, CPM 15 and CML 345 showed significant increase in developmental period, decrease in larval weight, and reduced larval survival, adult emergence and fecundity as compared to other test genotypes. The S. inferens larval recovery and preference were significantly lower, while the larvae took longer time to establish in the whorls of CPM 2, CPM 15 and CML 345 as compared to other test maize genotypes. The chlorophyll A, chlorophyll B and total chlorophyll content varied significantly in the seedlings of different maize genotypes, under healthy and S. inferens damaged conditions (except, chlorophyll B), while the genotype × treatment interactions were non-significant. The differences for total carotenoids were non-significant. The S. inferens infestation reduced these photosynthetic pigments in the seedlings of all test maize genotypes, except Basi Local, with lowest reduction in CPM 2. The study suggests that the maize genotypes, viz. CPM 2, CPM 4, CPM 8, CPM 15 and CML 345 have greater detrimental effects on the development, survival and fecundity of S. inferens, and can be used in maize improvement program.

Continuous and intermittent intraoperative nerve monitoring (IONM) has become an important asset for endocrine surgeons over the past few decades. The ability to determine neurophysiologic integrity of the recurrent laryngeal nerve (RLN) and external branch of the superior laryngeal nerve (EBSLN) on top of identification and meticulous dissection of the nerve in the surgical field, has allowed for advances in technology and improved outcomes when it comes to prevention of vocal fold immobility. This article aims to compare in review continuous and intermittent nerve monitoring (CIONM, IIONM), as well as review the current paradigms of their use. This article will also discuss the future of intraoperative nerve monitoring technologies in scarless thyroid surgery and percutaneous approaches to thyroid pathology in form of radiofrequency ablation (RFA).

Lymph node metastasis is common in differentiated thyroid cancer especially papillary thyroid cancer. Presence of lymph node metastasis does not have an impact on survival in younger patients. Therapeutic central and lateral neck dissection in the presence of clinically or radiologically evident lymph nodes has resulted in good overall survival. However, disease persistence in the lymph node/early recurrences may be seen in patients owing to lymph nodes that may be missed during the initial neck dissection. These observed locations are retropharyngeal and parapharyngeal nodal location, retro carotid location, sublingual, axillary, and intraparotid locations, supraclavicular and superficial to the sternothyroid muscle. We aim to highlight these locations with the goal to minimize persistence or early recurrence of disease at these locations.

Abstract The lung is the organ with the highest vascular density in the human body. It is therefore perceivable that the endothelium of the lung contributes significantly to the circulation of extracellular vesicles (EVs), which include exosomes, microvesicles, and apoptotic bodies. In addition to the endothelium, EVs may arise from alveolar macrophages, fibroblasts and epithelial cells. Because EVs harbor cargo molecules, such as miRNA, mRNA, and proteins, these intercellular communicators provide important insight into the health and disease condition of donor cells and may serve as useful biomarkers of lung disease processes. This comprehensive review focuses on what is currently known about the role of EVs as markers and mediators of lung pathologies including COPD, pulmonary hypertension, asthma, lung cancer and ALI/ARDS. We also explore the role EVs can potentially serve as therapeutics for these lung diseases when released from healthy progenitor cells, such as mesenchymal stem cells.

Abstract Background Exposure to inflammation during pregnancy can predispose to brain injury in premature infants. In the present study, we investigated the effects of prolonged exposure to inflammation on the cerebrovasculature of preterm fetal sheep. Methods Chronically instrumented fetal sheep at 103–104 days of gestation (full term is ~ 147 days) received continuous low-dose lipopolysaccharide (LPS) infusions (100 ng/kg over 24 h, followed by 250 ng/kg/24 h for 96 h plus boluses of 1 μg LPS at 48, 72, and 96 h) or the same volume of normal saline (0.9%, w/v). Ten days after the start of LPS exposure at 113–114 days of gestation, the sheep were killed, and the fetal brain perfused with formalin in situ. Vessel density, pericyte and astrocyte coverage of the blood vessels, and astrogliosis in the cerebral cortex and white matter were determined using immunohistochemistry. Results LPS exposure reduced (P < 0.05) microvascular vessel density and pericyte vascular coverage in the cerebral cortex and white matter of preterm fetal sheep, and increased the activation of perivascular astrocytes, but decreased astrocytic vessel coverage in the white matter. Conclusions Prolonged exposure to LPS in preterm fetal sheep resulted in decreased vessel density and neurovascular remodeling, suggesting that chronic inflammation adversely affects the neurovascular unit and, therefore, could contribute to long-term impairment of brain development.

Abstract Background Increased circulating levels of tumor necrosis factor (TNF) are associated with greater risk of impaired neurodevelopment after preterm birth. In this study, we tested the hypothesis that systemic TNF inhibition, using the soluble TNF receptor Etanercept, would attenuate neuroinflammation in preterm fetal sheep exposed to lipopolysaccharide (LPS). Methods Chronically instrumented preterm fetal sheep at 0.7 of gestation were randomly assigned to receive saline (control; n = 7), LPS infusion (100 ng/kg i.v. over 24 h then 250 ng/kg/24 h for 96 h plus 1 μg LPS boluses at 48, 72, and 96 h, to induce inflammation; n = 8) or LPS plus two i.v. infusions of Etanercept (2 doses, 5 mg/kg infused over 30 min, 48 h apart) started immediately before LPS-exposure (n = 8). Sheep were killed 10 days after starting infusions, for histology. Results LPS boluses were associated with increased circulating TNF, interleukin (IL)-6 and IL-10, electroencephalogram (EEG) suppression, hypotension, tachycardia, and increased carotid artery perfusion (P

As coronavirus disease 2019 (COVID-19) spreads, we are encountering multiple different symptoms and related complications. Although the vast majority of literature is focused on its pulmonary manifestations, recent reports have mentioned neurologic manifestations but typically those related to the central nervous system and diagnosed utilizing magnetic resonance imaging. We present two cases of COVID-19–associated peripheral polyneuropathy diagnosed utilizing musculoskeletal ultrasound (US), which to our knowledge is the first such case report. US is an instrumental portable modality that can be used for COVID-19 patients in isolation. As this virus continues to spread, understanding and recognizing these COVID-19 related complications and their sonographic findings are crucial.

Purpose: To compare and study the clinical outcome of tarsorrhaphy and amniotic membrane transplant in the healing of persistent corneal epithelial defects in terms of clinical improvement and symptomatic relief. Methods: This was an interventional, prospective study in which a total of 60 patients with persistent epithelial defects (PED's), randomly divided into two groups of 30 patients each who underwent tarsorrhaphy (Group A) or amniotic membrane transplantation (Group B) with a 4-week-follow-up period, were included. The main parameters studied were the size of an epithelial defect, total healing time, pain score, and complications. Results: The study included 60 eyes of 60 patients with PED. The healing time was 9.83 ± 6.51 days in Group A (median = 9.50 days, IQR = 1–7 days) vs. 18.33 ± 13.46 days (median = 19.50 days, IQR = 1–21 days) in Group B. A total of ten eyes (16.7%) did not heal at the end of 4 weeks. Conclusion: There was a significant reduction in the area of epithelial defect at the end of the 1 week and 2 week follow up postoperatively, in both the treatment forms. The mean healing time in patients of Group A was less as compared to that of the patients in Group B.

Background: International rotations with hands-on experience are commonly cited as a potential supplement to the current experience of surgical trainees in trauma; however, quantification of this experience remains unclear. Methods: A link to an online survey was distributed by electronic mail to physicians who rotated for any period of time at the Trauma Unit of the Groote-Shuur Hospital of the University of Cape Town from January 1, 2006, to December 2016. Results: Of 160 participants, 75 (47%) completed the survey. A high proportion (45%) had performed less than 25 trauma-related surgical procedures during their previous training. Most (56%) performed ≥10 trauma laparotomies and sternotomies/thoracotomies during their rotation, whereas 43% performed ≥5 vascular procedures. The level of perceived confidence in managing trauma patients increased significantly from a median of 3/10 to 7/10 (P < .05). Conclusion: Rotations at large-volume trauma centers abroad offer the opportunity for a hands-on operative experience and may enhance the confidence of surgical trainees. Further standardization of these opportunities may result in a larger-scale participation of graduate residents and fellows.

Background: Although ejections from motor vehicles are considered a marker of a significant mechanism and a predictor of severe injuries and mortality, scant recent data exist to validate these outcomes. This study investigates whether ejections increase the mortality risk following a motor vehicle crash using data that reflect the introduction of new vehicles to the streets of a large city in the United States. Methods: The Trauma and Emergency Medicine Information System of Los Angeles County was queried for patients ≥16 years old admitted following a motor vehicle crash between 2002 and 2012. Ejected patients were compared to nonejected. Primary outcome was mortality. A logistic regression model was used to identify predictors of mortality and severe trauma. Results: A total of 9,742 (6.8%) met inclusion criteria. Of these, 449 (4.6%) were ejected; 368 (82.0%) were passengers and 81 (18.0%) were drivers. The rate of ejection decreased linearly (6.1% in 2002 to 3.4% in 2012). Compared to nonejected patients, ejected patients were more likely to require intensive care unit admission (43.7% vs 22.1%, P 25) (24.2% vs 7.3%, P 25) with adjusted odds ratio of 2.48 (P

Present studies were carried out on development and survival of Lipaphis erysimi (Kaltenbach) on diverse Brassica juncea (L.) Czern. & Coss. genotypes, and decipher the role of certain biochemical compounds in plant defense against mustard aphid. There were significant differences among test B. juncea genotypes for total nymphal duration, reproductive period, total developmental period, fecundity and survival of L. erysimi. The development period was significantly longer on PDZM 31, NRCHB 101, RP 7-3-2-2-1, TS 18-5124, RP 11-2-1-3-1, YSG, RLC 3, NPJ 50, IC 355399, MSTWR 17-1, EC 61-9-2-2-2, GP 454 and Kranti, while fecundity and survival were significantly lower on RLC 3, Kranti, IC 355399, Rohini, GP 454, NPJ 50 and TS 18-5124 as compared to other B. juncea genotypes. The biochemical constituents like, total antioxidants, tannins, phenols and FRAP were also significantly higher in RLC 3, Kranti, IC 355399, Rohini, GP 454, NPJ 50 and TS 18-5124 as compared to other B. juncea genotypes, except in a few cases. The total antioxidants and total tannins had significant and negative association, and explained 78.5% and 91.3% variability for fecundity and survival of L. erysimi, indicating their detrimental effects on progeny production and survival of mustard aphid on B. juncea. Present studies suggest that the B. juncea genotypes RLC 3, IC 355399, Rohini, GP 454, NPJ 50, TS 18-5124 and Kranti have higher amounts of test defense biochemicals and impart adverse effects on the reproductive period, fecundity and survival of L. erysimi.

Background We sought to compare enoxaparin dosing for venous thromboembolism (VTE) prophylaxis in trauma patients with and without traumatic brain injury (TBI) to better understand the time and dose required to reach target anti-Xa levels. Our hypothesis was that patients with TBI have significant delays in the initiation of adequate pharmacological prophylaxis and require a higher enoxaparin dose than currently recommended.Methods The medical records of trauma patients who received enoxaparin dosing based on anti-Xa trough levels between August 2014 and October 2016 were reviewed. Patients were included if their anti-Xa trough level reached the target range (0.1 IU/mL to 0.2 IU/mL).Results A total of 163 patients had anti-Xa levels within the target range of which 41 (25.2%) had TBI. Patients with TBI had longer delays before initiating enoxaparin (7.5 days vs. 1.5 days after admission, p

Abstract Coronavirus disease‐2019 (COVID‐19), caused by the novel severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2), has lead to a global pandemic with a rising toll in infections and deaths. Better understanding of its pathogenesis will greatly improve the outcomes and treatment of affected patients. Here we compared the inflammatory and cardiovascular disease‐related protein cargo of circulating large and small extracellular vesicles (EVs) from 84 hospitalized patients infected with SARS‐CoV‐2 with different stages of disease severity. Our findings reveal significant enrichment of proinflammatory, procoagulation, immunoregulatory and tissue‐remodelling protein signatures in EVs, which remarkably distinguished symptomatic COVID‐19 patients from uninfected controls with matched comorbidities and delineated those with moderate disease from those who were critically ill. Specifically, EN‐RAGE, followed by TF and IL‐18R1, showed the strongest correlation with disease severity and length of hospitalization. Importantly, EVs from COVID‐19 patients induced apoptosis of pulmonary microvascular endothelial cells in the order of disease severity. In conclusion, our findings support a role for EVs in the pathogenesis of COVID‐19 disease and underpin the development of EV‐based approaches to predicting disease severity, determining need for patient hospitalization and identifying new therapeutic targets.

Hypoxic-ischemic encephalopathy is brain injury resulting from the loss of oxygen and blood supply around the time of birth. It is associated with a high risk of death or disability. The only approved treatment is therapeutic hypothermia. Therapeutic hypothermia has consistently been shown to significantly reduce the risk of death and disability in infants with hypoxic-ischemic encephalopathy. However, approximately 29% of infants treated with therapeutic hypothermia still develop disability. Recent preclinical and clinical studies have shown that there is still persistent neuroinflammation even after treating with therapeutic hypothermia, which may contribute to the deficits seen in infants despite treatment. This suggests that potentially targeting this persistent neuroinflammation would have an additive benefit in addition to therapeutic hypothermia. A potential additive treatment is Exendin-4, which is a glucagon-like peptide 1 receptor agonist. Preclinical data from various in vitro and in vivo disease models have shown that Exendin-4 has anti-inflammatory, mitochondrial protective, anti-apoptotic, anti-oxidative and neurotrophic effects. Although preclinical studies of the effect of Exendin-4 in perinatal hypoxic-ischemic brain injury are limited, a seminal study in neonatal mice showed that Exendin-4 had promising neuroprotective effects. Further studies on Exendin-4 neuroprotection for perinatal hypoxic-ischemic brain injury, including in large animal translational models are warranted to better understand its safety, window of opportunity and effectiveness as an adjunct with therapeutic hypothermia.

Background: Hypoxic–ischemic encephalopathy (HIE) around the time of birth results from loss of oxygen (hypoxia) and blood supply (ischemia). Exogenous infusion of multi-potential cells, including human amnion epithelial cells (hAECs), can reduce hypoxic–ischemic (HI) brain injury. However, there are few data on treatment of severe HI in large animal paradigms at term. The aim of the current study was to determine whether infusion of hAECs early after injury may reduce brain damage after ischemia in near-term fetal sheep. Methods: Chronically instrumented fetal sheep (0.85 gestation) received 30 min of global cerebral ischemia followed by intravenous infusion of hAECs from 2 h after the end of ischemia (ischemia-hAEC, n = 6) or saline (ischemia-vehicle, n = 7). Sham control animals received sham ischemia with vehicle infusion (sham control, n = 8). Results: Ischemia was associated with significant suppression of EEG power and spectral edge frequency until the end of the experiment and a secondary rise in cortical impedance from 24 to 72 h, which were not attenuated by hAEC administration. Ischemia was associated with loss of neurons in the cortex, thalamus, striatum and hippocampus, loss of white matter oligodendrocytes and increased microglial numbers in the white matter, which were not affected by hAEC infusion. Conclusions: A single intravenous administration of hAECs did not reduce electrographic or histological brain damage after 30 min of global cerebral ischemia in near-term fetal sheep.

Objectives To demonstrate that an in‐office superior laryngeal nerve (SLN) block with lidocaine and steroids is an effective alternative to neuromodulators for patients with neurogenic cough. Study Design Retrospective study. Methods A retrospective review of 10 patients who underwent in office nerve block to the laryngeal nerve (SLN) for neurogenic cough. Demographic data and pre‐ and postcough survey index are the measure outcomes. Follow‐up was 3–6 months. Results We find that all patients in this study that underwent an SLN block showed significant improvement in cough severity index (CSI). The average number of blocks was 2.3. The mean follow‐up time from the first SLN block is 3.4 months. The mean CSI improvement 16.30. 95% confidence interval, 11.44–21.16; P