Foxp3 depends on Ikaros for control of regulatory T cell gene expression and function.

Ikaros is a transcriptional factor required for conventional T cell development, differentiation, and anergy. While the related factors Helios and Eos have defined roles in regulatory T cells (Treg), a role for Ikaros has not been established. To determine the function of Ikaros in the Treg lineage, we generated mice with Treg-specific deletion of the Ikaros gene (Ikzf1). We find that Ikaros cooperates with Foxp3 to establish a major portion of the Treg epigenome and transcriptome. Ikaros-deficient Treg exhibit Th1-like gene expression with abnormal production of IL-2, IFNg, TNFa, and factors involved in Wnt and Notch signaling. While Ikzf1-Treg-cko mice do not develop spontaneous autoimmunity, Ikaros-deficient Treg are unable to control conventional T cell-mediated immune pathology in response to TCR and inflammatory stimuli in models of IBD and organ transplantation. These studies establish Ikaros as a core factor required in Treg for tolerance and the control of inflammatory immune responses.

Characterization of human extreme heat exposure using an outdoor thermal manikin.

Extreme heat is a current and growing global health concern. Current heat exposure models include meteorological and human factors that dictate heat stress, comfort, and risk of illness. However, radiation models simplify the human body to a cylinder, while convection ones provide conflicting predictions. To address these issues, we introduce a new method to characterize human exposure to extreme heat with unprecedented detail. We measure heat loads on 35 body surface zones using an outdoor thermal manikin ("ANDI") alongside an ultrasonic anemometer array and integral radiation measurements (IRM). We show that regardless of body orientation, IRM and ANDI agree even under high solar conditions. Further, body parts can be treated as cylinders, even in highly turbulent flow. This geometry-rooted insight yields a whole-body convection correlation that resolves prior conflicts and is valid for diverse indoor and outdoor wind flows. Results will inform decision-making around heat protection, adaptation, and mitigation.

Multi-objective and multi constrained task scheduling framework for computational grids.

Grid computing emerged as a powerful computing domain for running large-scale parallel applications. Scheduling computationally intensive parallel applications such as scientific, commercial etc., computational grids is a NP-complete problem. Many researchers have proposed several task scheduling algorithms on grids based on formulating and solving it as an optimization problem with different objective functions such as makespan, cost, energy etc. Further to address the requirements/demands/needs of the users (lesser cost, lower latency etc.) and grid service providers (high utilization and high profitability), a task scheduler needs to be designed based on solving a multi-objective optimization problem due to several trade-offs among the objective functions. In this direction, we propose an efficient multi-objective task scheduling framework to schedule computationally intensive tasks on heterogeneous grid networks. This framework minimizes turnaround time, communication, and execution costs while maximizing grid utilization. We evaluated the performance of our proposed algorithm through experiments conducted on standard, random, and scientific task graphs using the GridSim simulator.

Performance evaluation and chemical oxygen demand removal of tannery wastewater through the aerobic-anaerobic route.

With characterized for complex and maximum substance (suspended solids, broke up oil, a mixture of inorganic and chromium sulfides), tannery wastewater was subjected to a treatment process on removal of chemical oxygen demand (COD) via upstream anaerobic sludge blanket reactor where we found reduced departure efficiencies and that process limits were affected by the assortments in regular stacking rates, closeness of chromium, and sulfides. Hence, a combination of the aerobic-anaerobic hybrid reactor was set up for sequential treatment to determine possible COD reduction. This study investigated the biological degradation of tannery wastewater in a laboratory-scale sequential up-flow aerobic-anaerobic reactor. The aerobic zone at the top was packed with spherical ball-shaped polyhedral polypropylene, and the anaerobic zone at the bottom was packed medium with granular media. The aeration flow rate varied by 2 L/min, 4 L/min, and 6 L/min in the aerobic zone, and the reactor maintained an organic loading rate (OLR) of 5 kg COD/m3/d. Parameters like COD and gas yield assess the performance of the reactor. The maximum COD of 86% is removed in the anaerobic zone with an aeration rate of 6 L/min, and the 1800-mL methane gas yield is measured by the 29th day.

Prospective quantitative study: Doppler ultrasound in the evaluation of chronic renal allograft disease and correlation with histopathological finding.

Background and Objectives: Renal allograft biopsy is the gold standard for diagnosing chronic allograft nephropathy, but noninvasive methods are needed to avoid unnecessary biopsies. Doppler ultrasonography, particularly the resistive index (RI), correlates with renal allograft dysfunction. This study aims to assess the relationship between renal sonographic parameters and biochemical parameters in diagnosing graft interstitial fibrosis. Methods: The study evaluated 60 renal allograft recipients for sonographic renal morphological features and Doppler indices. The estimated glomerular filtration rate (eGFR) was calculated, and cortical fibrosis after the biopsy was determined using the Banff score. Continuous variables like mean and SD were calculated, and categorical variables were reported using frequencies and proportions. Associations were examined using independent sample t-tests, χ 2tests, and multivariate regression analysis. Results: The mean eGFR was 75.23±25.45 ml/min/1.73 m2. A significant correlation of eGFR with RI (r=0.341, P=0.008) was seen. A significant difference in mean RI (F=10.167; df=2,57; P<0.001) was seen among the histological grades of fibrosis. Among the histological grades of fibrosis, significant differences in RI among mild and moderate (S.E. 0.033, P=0.043), mild and severe (S.E. 0.026, P=0.001) as well as moderate and severe (S.E. 0.036, P=0.029) was seen. Conclusion: Doppler was able to noninvasively predict allograft fibrosis and could be used as a complementary imaging tool during the follow-up of renal allograft patients. Future research is needed to improve evidence, diagnostic criteria, guidelines, and long-term impact.

Association of Baseline Frailty with Patient-Reported Outcomes in Systemic Lupus Erythematosus at 1 Year.

The relationship of baseline frailty with subsequent patient-reported outcomes in systemic lupus erythematosus (SLE) remains unclear. We assessed these associations in a pilot prospective cohort study. Frailty based on the FRAIL scale and the Fried phenotype and patient-reported outcomes, namely Patient Reported Outcomes Measurement Information System computerized adaptive tests and Valued Life Activities disability, were measured at baseline and 1 year among women aged 18-70 years with SLE enrolled at a single center. Differences in Patient Reported Outcomes Measurement Information System computerized adaptive tests between frail and non-frail participants were evaluated using Wilcoxon rank sum tests, and the association of baseline frailty with self-report disability at 1 year was estimated using linear regression. Of 51 participants, 24% (FRAIL scale) and 16% (Fried phenotype) met criteria for frailty at baseline despite median age of 55.0 and 56.0 years, respectively. Women with (versus without) baseline frailty using either measure had worse 1-year Patient Reported Outcomes Measurement Information System computerized adaptive test scores across multiple domains and greater self-report disability. Baseline frailty was significantly associated with self-report disability at 1 year (FRAIL scale: parameter estimate 0.55, 95% confidence interval (CI) 0.21-0.89, p<0.01; Fried phenotype: parameter estimate 0.61, 95% CI 0.22-1.00, p<0.01), including only slight attenuation after adjustment for SLE cumulative organ damage (FRAIL scale: parameter estimate 0.45, 95% CI 0.09-0.81, p=0.02; Fried phenotype: parameter estimate 0.49, 95% CI 0.09-0.90, p=0.02). These preliminary findings support frailty as an independent risk factor for clinically relevant patient-reported outcomes, including disability onset, among women with SLE.

Thoracoscopic repair of congenital diaphragmatic hernia in neonates: Tips and tricks learned from an institutional experience.

Background: Congenital diaphragmatic hernia (CDH) is an anomaly with significant morbidity in neonates. It has been traditionally managed by an open approach with a recent trend toward a minimally invasive approach. Aim: This is a retrospective study of our institutional experience with neonatal thoracoscopic management of CDH, with the impact of few technical nuances. Patients and Methods: The data was collected on neonatal thoracoscopic CDH repair between January 2015 and December 2018, in terms of the demographics, intra-operative parameters, post-operative status, recurrence, and mortality. While analyzing data, we found few technical modifications adopted by the surgeon such as trimming the margin of the defect, use of prosthetic mesh overlay reinforcement for repairs under tension, and to prefer extra-corporeal knotting along with higher placement of trocar, temporary increase in CO2, maximal use of muscle relaxant, extra-corporeal corner hitch stitch at some point, and continuation for further cases. An internal comparison was made to analyze the technical modifications influencing the outcomes, by dividing them into two groups, those with (group A) and without modifications (group B). The data was analyzed using SPSS software (IBM, Version 23). A P value of <0.05 was considered statistically significant. Results: Out of 45 newborns 64.4% were males with an average birth weight of 2.6 kg. Baseline variables were comparable between the groups. The operating time significantly reduced after a higher-level camera port was used (P-value: 0.0001). The mean follow-up was 30.8 months. There were totally seven recurrences (6 in group A and 1 in group B), all within 12 months. Seven parents gave the overall post-treatment feedback as "unsatisfied". The operating time, recurrence rate, and parental satisfaction feedback were significantly less in group B (P-value: 0.001). Conclusion: We recommend trimming the margin of the defect, use of prosthetic mesh overlay reinforcement for repairs under tension, and to prefer extra-corporeal knotting along with higher placement of trocar, temporary increase in CO2, maximal use of muscle relaxant, extra-corporeal corner hitch stitch to reduce the operating time, and recurrence after thoracoscopic CDH repair.

Nocardia in an Immunocompetent Host Masquerading As Lung Cancer: A Case Report.

Nocardiosis is generally regarded as an opportunistic infection that can present as a cutaneous, pulmonary, or disseminated disease based on host immunity status. Pulmonary nocardiosis is typically seen in immunocompromised patients; however, it can rarely be present in immunocompetent patients. We present a rare case of an immunocompetent patient who was thought to have a lung malignancy but was found to have pulmonary nocardiosis upon further investigation.

Implicating effector genes at COVID-19 GWAS loci using promoter-focused Capture-C in disease-relevant immune cell types.

BACKGROUND: SARS-CoV-2 infection results in a broad spectrum of COVID-19 disease, from mild or no symptoms to hospitalization and death. COVID-19 disease severity has been associated with some pre-existing conditions and the magnitude of the adaptive immune response to SARS-CoV-2, and a recent genome-wide association study (GWAS) of the risk of critical illness revealed a significant genetic component. To gain insight into how human genetic variation attenuates or exacerbates disease following SARS-CoV-2 infection, we implicated putatively functional COVID risk variants in the cis-regulatory landscapes of human immune cell types with established roles in disease severity and used high-resolution chromatin conformation capture to map these disease-associated elements to their effector genes. RESULTS: This functional genomic approach implicates 16 genes involved in viral replication, the interferon response, and inflammation. Several of these genes (PAXBP1, IFNAR2, OAS1, OAS3, TNFAIP8L1, GART) were differentially expressed in immune cells from patients with severe versus moderate COVID-19 disease, and we demonstrate a previously unappreciated role for GART in T cell-dependent antibody-producing B cell differentiation in a human tonsillar organoid model. CONCLUSIONS: This study offers immunogenetic insight into the basis of COVID-19 disease severity and implicates new targets for therapeutics that limit SARS-CoV-2 infection and its resultant life-threatening inflammation.

Evaluation of dissimilar intestinal bacteria incorporated feeds on growth of ornamental fish Swordtail Xiphophorus helleri.

Four dissimilar bacterial colonies were isolated from the intestine of ornamental fish Swordtail Xiphophorus helleri through serial dilution. The isolated colonies were identified as Enterobacter sp., Bacillus sp., Streptococcus sp. and Pseudomonas sp. using biochemical tests. Enzyme productivity and antibacterial activity of intestinal bacteria of Swordtail were carried out against pathogens such as Enterococcus faecalis, Shigella flexneri, Streptococcus pyogenes and Klebshilla pneumoniae along with commercial antibiotic Tetracycline. Based on biochemical tests, enzyme productivity and antibacterial activity mass multiplication of Enterobacter sp., Bacillus sp. and Streptococcus sp. were done in nutrient broth. Four different feeds such as feed I (Control) (without bacteria), Feed II (1ml Bacillus sp.), Feed III (1 ml of each of Bacillus sp. and Streptococcus sp.) and Feed IV (1 ml each of Bacillus sp., Streptococcus sp. and Enterobacter sp.) were prepared. A total of 60 fishes were used for the study. Feed utilization parameters of the Swordtail were estimated after 21 days. Based on the antibacterial test, the Bacillus sp. and Enterobacter sp. have higher inhibition. Most of the feed utilization parameters were higher in feed IV. From the results, it was concluded that the combination of three dissimilar bacteria in the feed enhanced the growth of the Swordtail.

Association between overcrowded households, multigenerational households, and COVID-19: a cohort study.

OBJECTIVES: The role of overcrowded and multigenerational households as a risk factor for COVID-19 remains unmeasured. The objective of this study is to examine and quantify the association between overcrowded and multigenerational households and COVID-19 in New York City (NYC). STUDY DESIGN: Cohort study. METHODS: We conducted a Bayesian ecological time series analysis at the ZIP Code Tabulation Area (ZCTA) level in NYC to assess whether ZCTAs with higher proportions of overcrowded (defined as the proportion of the estimated number of housing units with more than one occupant per room) and multigenerational households (defined as the estimated percentage of residences occupied by a grandparent and a grandchild less than 18 years of age) were independently associated with higher suspected COVID-19 case rates (from NYC Department of Health Syndromic Surveillance data for March 1 to 30, 2020). Our main measure was an adjusted incidence rate ratio (IRR) of suspected COVID-19 cases per 10,000 population. Our final model controlled for ZCTA-level sociodemographic factors (median income, poverty status, White race, essential workers), the prevalence of clinical conditions related to COVID-19 severity (obesity, hypertension, coronary heart disease, diabetes, asthma, smoking status, and chronic obstructive pulmonary disease), and spatial clustering. RESULTS: 39,923 suspected COVID-19 cases were presented to emergency departments across 173 ZCTAs in NYC. Adjusted COVID-19 case rates increased by 67% (IRR 1.67, 95% CI = 1.12, 2.52) in ZCTAs in quartile four (versus one) for percent overcrowdedness and increased by 77% (IRR 1.77, 95% CI = 1.11, 2.79) in quartile four (versus one) for percent living in multigenerational housing. Interaction between both exposures was not significant (ßinteraction = 0.99, 95% CI: 0.99-1.00). CONCLUSIONS: Overcrowdedness and multigenerational housing are independent risk factors for suspected COVID-19. In the early phase of the surge in COVID cases, social distancing measures that increase house-bound populations may inadvertently but temporarily increase SARS-CoV-2 transmission risk and COVID-19 disease in these populations.

Epidemiological and clinical profile, management and outcomes of young patients (≤40 years) with acute coronary syndrome: A single tertiary care center study.

OBJECTIVE: To study the epidemiological and clinical profile, angiographic patterns, reasons for the delay in presentation, management, and outcomes of the acute coronary syndrome (ACS) in young patients (≤40yrs) presenting to a tertiary care hospital in North India. METHODS: We included a total of 182 patients aged ≤40 years and presenting with ACS to the cardiology critical care unit of our department from January 2018 to July 2019. RESULTS: The mean age of the study population was 35.5 ± 4.7years. 96.2% were males. Risk factors prevalent were smoking (56%), hypertension (29.7%), family history of premature coronary artery disease (18.2%), and diabetes (15.9%). The median time to first medical contact and revascularization was 300 (10-43200) minutes and 2880 (75-68400) minutes, respectively. ST-elevation ACS (STE-ACS) accounted for 82% and Non-ST-elevation ACS (NSTE-ACS) accounted for 18% of cases. Thrombolysis was done in 51.7% of the cases. Coronary angiography was done in 91.7% and percutaneous coronary intervention (PCI) in 52.2% (95/182) of the total cases. Coronary artery bypass surgery (CABG) was done in 2 patients (1.1%). Among those who underwent coronary angiography, single-vessel disease (SVD) was seen in 53% of the cases. There were no deaths in hospital, and only one patient died during the 30 days follow up. CONCLUSIONS: STE-ACS was the most common presentation of ACS in the young population. Smoking was the most common risk factor. The majority of the patients had single-vessel disease, and there was a significant delay in first medical contact and revascularization.

Photonic Crystal Fiber-Based Reconfigurable Biosensor Using Phase Change Material.

A reconfigurable biosensor with different spectral sensitivities could provide new opportunities to increase the label-free selectivity and sensitivity for biomolecules. Here, we propose and numerically demonstrate a phase change chalcogenide material (Ge2 Sb2 Te5)-based photonic crystal fiber (PCF) sensor for tunable and enhanced refractive index sensing at near infrared (NIR) wavelengths. In order to achieve this, we integrate a thin hybrid sensing layer of Au/Ge2 Sb2 Te5 with D-shaped PCF. By switching the structural phase of Ge2 Sb2 Te5 from amorphous to crystalline, we realize tunable and enhanced refractive index sensing with a large figure of merit (FOM) for the sensing range from 1.35 to 1.40, which covers most known analytes such as proteins, cancer cells, glucose and viruses or DNA/RNA. The obtained average bulk refractive index sensitivity is 17,600 nm/RIU and 8,000 nm/RIU for crystalline and amorphous phase, respectively. The observed large tunable differential response of the proposed sensor offers a promising opportunity to design an assay for the selective detection of higher and lower molecular weight biomolecules through future artificial intelligence-based sensing.

Production, characterization and in-vitro applications of single-domain antibody against thyroglobulin selected from novel T7 phage display library.

Single- domain antibodies (SdAbs) have been deployed in various biomedical applications in the recent past. However, there are no reports of their use in the immunoradiometric assays (IRMA) for thyroglobulin (Tg). Tg is the precursor molecule for the biosynthesis of thyroid hormones: thyroxine and triiodothyronine, which are essential for the regulation of normal metabolism in all vertebrates. Patients with differentiated thyroid cancer (DTC) require periodic monitoring of their serum thyroglobulin levels, as it serves as a prognostic marker for DTC. Here, we report a methodology to produce SdAbs against human-Tg, by a hybrid immunization/directed-evolution approach by displaying the SdAb gene-repertoire derived from a hyperimmune camel in the T7 phage display system. We have demonstrated the immunoreactivity of anti-Tg-SdAb (KT75) in immunoassays for thyroglobulin and measured its affinity by surface plasmon resonance (KD ~ 18 picomolar). Additionally, we have shown the quantitative-binding property of SdAb for the first time in IRMA for thyroglobulin. The serum Tg values obtained from SdAb-Tg-IRMA and in-house assay using murine anti-Tg-monoclonal antibody as tracer significantly correlated, r = 0.81, p < 0.05. Our results highlight the scope of using the T7 phage display system as an alternative for the conventional M13-phage to construct single-domain antibody display libraries.