A Single Terminal [NiII-OH] Catalyst for Direct Julia-Type Olefination and α-Alkylation Involving Sulfones and Alcohols.

A terminal [NiII-OH] complex 1, supported by triflamide-functionalized NHC ligands, showed divergent reactivity for the reaction of sulfone with alcohol, contingent on base concentration, temperature, and time. Julia-type olefination of alcohols with sulfones was achieved using one equiv. of base, whereas lowering base loading to 0.5 equiv. afforded α-alkylated sulfones. Besides excellent substrate scope and selectivity, biologically active stilbene derivatives DMU-212, pinosylvin, resveratrol, and piceatannol were synthesized in high yield under Julia-type olefination conditions. An extensive array of controlled experiments and DFT calculations provide valuable insight on the reaction pathway.

Effect of an NHE3 inhibitor in combination with an NPT2b inhibitor on gastrointestinal phosphate absorption in Rodent models.

Many of the pathological consequences of chronic kidney disease can be attributed to an elevation in serum phosphate levels. Current therapies focused on decreasing intestinal phosphate absorption to treat hyperphosphatemia are inadequate. The most effective therapeutic strategy may be to target multiple absorptive pathways. In this study, the ability of a novel inhibitor of the intestinal sodium hydrogen exchanger 3 (NHE3), LY3304000, which inhibits paracellular, diffusional uptake of phosphate, to work in combination with an inhibitor of the active transporter, sodium dependent phosphate cotransporter 2b (NPT2b), LY3358966, was explored. LY3304000 modestly inhibited the acute uptake of phosphate into plasma of rats, while surprisingly, it doubled the rate of phosphate uptake in mice, an animal model dominated by NPT2b mediated acute phosphate uptake. In rats, LY3004000 and LY3358966 work in concert to inhibit acute phosphate uptake. On top of LY3358966, LY3304000 further decreased the acute uptake of phosphate into plasma. Studies measuring the recovery of radiolabeled phosphate in the intestine demonstrated LY3304000 and LY3358966 synergistically inhibited the absorption of phosphate in rats. We hypothesize the synergism is because the NHE3 inhibitor, LY3304000, has two opposing effects on intestinal phosphate absorption in rats, first it decreases diffusion mediated paracellular phosphate absorption, while second, it simultaneously increases phosphate absorption through the NPT2b pathway. NHE3 inhibition decreases proton export from enterocytes and raises the cell surface pH. In vitro, NPT2b mediated phosphate transport is increased at higher pHs. The increased NPT2b mediated transport induced by NHE3 inhibition is masked in rats which have relatively low levels of NPT2b mediated phosphate transport, by the more robust inhibition of diffusion mediated phosphate absorption. Thus, the inhibition of NPT2b mediated phosphate transport in rats in the presence of NHE3 inhibition has an effect that exceeds its effect in the absence of NHE3 inhibition, leading to the observed synergism on phosphate absorption between NPT2b and NHE3 inhibition.

Coronavirus infection and ABO blood grouping: Correlation or coincidence?

Background: Association between the ABO blood group and patient outcomes in COVID-19 patients is still unexplored. A known association may help to understand possible risks in advance to the management of such COVID-19 patients. The present study was designed to test such association if there is any, between the ABO blood group and the severity of COVID-19 patients. Methods: The present hospital-based observational study was conducted at a COVID-19 dedicated tertiary care hospital in North India over a period of six months during the first wave of the pandemic in the country. Five hundred consecutive patients, who tested positive for COVID-19 using RT-PCR on oropharyngeal/nasopharyngeal swabs, admitted to the hospital were included in the study. ABO and Rhesus (Rh) blood grouping was done on leftover hematology blood samples using gel column agglutination technology. Required clinical details of patients including age, gender, clinical symptoms, comorbidities, outcomes, etc., were obtained from the patient's case sheets. Results: The most common blood group was 'B' (42.8%) followed by 'O' (23.4%), and 'A' (22.4%) while the least common was 'AB' (11.4%). Rh positive was seen in 96.2% while 3.8% were negative. Baseline characteristics were comparable including length of hospital stay, duration of symptoms, and associated comorbid illnesses. The need for intensive care unit (ICU) admissions (P = 0.05) and intubations (P = 0.20) was similar across all four blood groups. Differences in the severity of COVID-19 disease and mortalities among the groups were non-significant. Conclusion: There was no observed association found between the ABO blood group and COVID-19 infection requiring hospitalization, ICU admission, intubation, and outcomes. However, there was a higher proportion of breathlessness and the presence of at least one comorbidity in blood group O as compared to others.

Waitlist and Transplant Outcomes in Organ Donation After Circulatory Death: Trends in the United States.

OBJECTIVES: To summarize waitlist and transplant outcomes in kidney, liver, lung, and heart transplantation using organ donation after circulatory death (DCD). BACKGROUND: DCD has expanded the donor pool for solid organ transplantation, most recently for heart transplantation. METHODS: The United Network for Organ Sharing registry was used to identify adult transplant candidates and recipients in the most recent allocation policy eras for kidney, liver, lung, and heart transplantation. Transplant candidates and recipients were grouped by acceptance criteria for DCD versus brain-dead donors [donation after brain death (DBD)] only and DCD versus DBD transplant, respectively. Propensity matching and competing-risks regression was used to model waitlist outcomes. Survival was modeled using propensity matching and Kaplan-Meier and Cox regression analysis. RESULTS: DCD transplant volumes have increased significantly across all organs. Liver candidates listed for DCD organs were more likely to undergo transplantation compared with propensity-matched candidates listed for DBD only, and heart and liver transplant candidates listed for DCD were less likely to experience death or clinical deterioration requiring waitlist inactivation. Propensity-matched DCD recipients demonstrated an increased mortality risk up to 5 years after liver and kidney transplantation and up to 3 years after lung transplantation compared with DBD. There was no difference in 1-year mortality between DCD and DBD heart transplantation. CONCLUSIONS: DCD continues to expand access to transplantation and improves waitlist outcomes for liver and heart transplant candidates. Despite an increased risk for mortality with DCD kidney, liver, and lung transplantation, survival with DCD transplant remains acceptable.

Hydroarylation of alkynes via dual ortho-C-H functionalization of diaryl amines on a dicopper(I,I) platform.

A pyridine and morpholine-functionalized dicopper(I,I)-NHC complex (1) features both terminal and bridging coordination modes of NHC within the same molecule, and catalyzes dual ortho-C-H functionalization of diaryl amines for the hydroarylation of alkynes. A bimetallic construct in catalyst 1 allows sequential activation of ortho-C-H bonds of two aryl units to furnish a wide variety of 9,10-dihydroacridine derivatives without the explicit use of a directing group.

Multilevel Intervention to Improve Racial Equity in Access to Kidney Transplant.

BACKGROUND: African Americans (AAs) have reduced access to kidney transplant (KTX). Our center undertook a multilevel quality improvement endeavor to address KTX access barriers, focused on vulnerable populations. This program included dialysis center patient/staff education, embedding telehealth services across South Carolina, partnering with community providers to facilitate testing/procedures, and increased use of high-risk donors. STUDY DESIGN: This was a time series analysis from 2017 to 2021 using autoregression to assess trends in equitable access to KTX for AAs. Equity was measured using a modified version of the Kidney Transplant Equity Index (KTEI), defined as the proportion of AAs in South Carolina with end-stage kidney disease (ESKD) vs the proportion of AAs initiating evaluation, completing evaluation, waitlisting, and undergoing KTX. A KTEI of 1.00 is considered complete equity; a KTEI of <1.00 is indicative of disparity. RESULTS: From January 2017 to September 2021, 11,487 ESKD patients (64.7% AA) were referred, 6,748 initiated an evaluation (62.8% AA), 4,109 completed evaluation (59.7% AA), 2,762 were waitlisted (60.0% AA), and 1,229 underwent KTX (55.3% AA). The KTEI for KTX demonstrated significant improvements in equity. The KTEI for initiated evaluations was 0.89 in 2017, improving to 1.00 in 2021 (p = 0.0045). Completed evaluation KTEI improved from 0.85 to 0.95 (p = 0.0230), while waitlist addition KTEI improved from 0.83 to 0.96 (p = 0.0072). The KTEI for KTX also improved from 0.76 to 0.91, which did not reach statistical significance (p = 0.0657). CONCLUSIONS: A multilevel intervention focused on improving access to vulnerable populations was significantly associated with reduced disparities for AAs.

Effect of Yoga on Quality of Life in Patients with Pulmonary Tuberculosis: A Randomized Control Trial.

Introduction: Yoga is emerging as one of the holistic approaches to respiratory diseases. The scope of yoga is expanding in communicable diseases with physical, mental, and societal benefits. Aim and Objective: The present study aims to evaluate the effect of integrated yoga as an adjuvant therapy to the National Tuberculosis Elimination Programme (NTEP) on assessing health-related Quality of Life (QoL) in patients with pulmonary tuberculosis (PTB). Setting and Design: A randomized controlled trail study was conducted in a tertiary care teaching hospital. Methodology: The study screened 826 PTB patients; 72 patients were found suitable and agreed to participate. The PTB patients were randomly assigned to either a yoga group (n = 36) or a control group (n = 36) using the sequentially numbered opaque sealed envelope technique. The control group received standard-of-care treatment as per NTEP, and the yoga group practiced 45 min of integrated yoga for 8 weeks along with standard of care. The World Health Organization Quality of Life (WHOQOL-BREF) questionnaire was used to collect the data at baseline and after 8 weeks of intervention. Results: The results of within-group comparisons in both the groups showed that there was a significant improvement in physical (P < 0.01), psychological (P < 0.01), and social (P < 0.01), with P ≤ 0.05 being considered statistically significant except environmental domain. Between groups, analysis shows that in the preintervention, there was no difference between the yoga and control group as P > 0.05. After the yoga intervention, there was an enhancement in QoL scores with three domains except the environmental domain (P = 0.28). Conclusion: The study evidence supports the use of yoga as a complementary therapy for the NTEP in patients with PTB may improve their QoL.

Apolipoprotein L1 Opinions of African American Living Kidney Donors, Kidney Transplant Patients, and Nonpatients.

INTRODUCTION: The discovery of apolipoprotein L1 (ApoL1) has raised important ethical and clinical questions about genetic testing in the context of living and deceased kidney donation. Largely missing from this discussion are the perspectives of those African Americans (AA) most likely to be impacted by ApoL1 testing. METHODS: We surveyed 331 AA potential and former living kidney donors (LKDs), kidney transplant candidates and recipients, and nonpatients at three United States transplant programs about their ApoL1 testing attitudes. RESULTS: Overall, 72% felt that transplant programs should offer ApoL1 testing to AA potential LKDs. If a potential LKD has the high-risk genotype, 79% felt that the LKD should be allowed to make their own donation decision or participate in shared decision-making with transplant doctors. More than half of the potential LKDs (58%) would undergo ApoL1 testing and 81% of former LKDs would take the test now if offered. Most transplant candidates expressed a low likelihood of accepting a kidney from a LKD (79%) or a deceased donor (67%) with the high-risk genotype. CONCLUSIONS: There is strong support among LKDs and transplant patients for ApoL1 testing when evaluating potential kidney donors of African ancestry. Inclusion of AA stakeholders in developing guidelines and educational programs for ApoL1 testing is critical.

Early Assessment of National Kidney Allocation Policy Change.

BACKGROUND: The new kidney allocation changes with elimination of donor service areas (DSAs) and Organ Procurement and Transplantation Network regions were initiated to improve equity in organ allocation. The aim of this evaluation was to determine the operational, financial, and recipient-related effect of the new allocation system on a large rural transplantation program. STUDY DESIGN: A retrospective, cross-sectional analysis of organ offers, allograft outcomes, and attributed costs in a comparative time cohort, before (December 16, 2020 to March 14, 2021) and after (March 15, 2021 to June 13, 2021) the allocation change was performed. Outcomes were limited to adult, solitary, deceased donor kidney transplantations. RESULTS: We received 198,881 organ offers from 3,886 organ donors at our transplantation center from December 16, 2020 to June 31, 2021: 87,643 (1,792 organ donors) before the change and 111,238 (2094 organ donors) after the change, for a difference of +23,595 more offers (+302 organ donors). This resulted in 6.5 more organs transplanted vs a predicted loss of 4.9 per month. Local organ offers dropped from 70% to 23%. There was a statistically significantly increase in donor terminal serum creatinine (1.2 ± 0.86 mg/dL vs 2.2 ± 2.3 mg/dL, p < 0.001), kidney donor profile index (KDPI) (39 ± 20 vs 48 ± 22, p = 0.017), cold ischemia time (16 ± 7 hours vs 21 ± 6 hours, p < 0.001), and delayed graft function rates (23% vs 40%, p = 0.020). CONCLUSION: The new kidney allocation policy has led to an increase in KDPI of donors with longer cold ischemia time, leading to higher delayed graft function rates. This has resulted in increasing logistical and financial burdens on the system. Implementing large-scale changes in allocation based predominantly on predictive modeling needs to be intensely reassessed during a longer follow up.

Surgical Outcomes Improvement and Health Inequity in a Regional Quality Collaborative.

BACKGROUND: Surgical quality improvement initiatives may impact sociodemographic groups differentially. The objective of this analysis was to assess the trajectory of surgical morbidity by race and age over time within a Regional Collaborative Quality Initiative. STUDY DESIGN: Adults undergoing eligible general surgery procedures in South Carolina Surgical Quality Collaborative hospitals were analyzed for the presence of at least 1 of 22 morbidities between August 2015 and February 2020. Surgery-level multivariable logistic regression assessed the racial differences in morbidity over time, stratified by age group (18 to 64 years, 65 years and older), and adjusting for potential patient- and surgical-level confounders. RESULTS: A total of 30,761 general surgery cases were analyzed, of which 28.4% were performed in Black patients. Mean morbidity rates were higher for Black patients than non-Black patients (8.5% vs 6.0%, p < 0.0001). After controlling for race and other confounders, a significant decrease in monthly mean morbidity through time was observed in each age group (odds ratio [95% CI]: age 18 to 64 years, 0.986 [0.981 to 0.990]; age 65 years and older, 0.991 [0.986 to 0.995]). Comparing morbidity rates from the first 4 months of the collaborative to the last 4 months reveals older Black patients had an absolute decrease in morbidity of 6.2% compared with 3.6% for older non-Black patients. Younger Black patients had an absolute decrease in morbidity of 4.7% compared with a 3.0% decrease for younger non-Black patients. CONCLUSIONS: Black patients had higher morbidity rates than non-Black patients even when controlling for confounders. The reasons for these disparities are not apparent. Morbidity improved over time in all patients with older Black patients seeing a larger absolute decrease in morbidity.

Reasons for Suicide Attempts in South India during the COVID-19 Pandemic.

Objective: By increasing the risk of isolation, fear, stigma, abuse, and economic fallout, COVID-19 has led to an increase in the risk of psychiatric disorders, chronic trauma, and stress. These factors eventually increase suicidality and suicidal behavior. This study intends to evaluate the reasons for suicide attempts due to the COVID-19 pandemic in the south Indian population.Design: Cross-sectional studySetting: The study was conducted in R. L. Jalappa Hospital and Research Centre, Kolar.Participants: This study was conducted on 91 patients admitted to the general medicine department for a suicide attempt because of the COVID 19 pandemic.Methods: A single examiner conducted a structured interview with a pretested questionnaire with each participant. Participants were asked to indicate the primary reason or motivation for their suicide attempt. Patients answered a set of questions regarding personal and family concerns (marginalization, fear and uncertainty, domestic abuse, loneliness, grief over loss of loved one) and work-related concerns (economic fallout, high-risk environment, shortage of personnel and personal protective equipment [PPE]). We employed mean and standard deviation to descriptively analyze quantitative variables. Categorical variables were expressed in terms of frequency and proportion. For non-normally-distributed quantitative parameters, medians and interquartile range (IQR) were compared across study groups using the Kruskal-Wallis test (> 2 groups). Data was analyzed using coGuide software, V.1.03.Results: The mean age of participants was 29.47±11.06 years, the majority (43.63%) of which were aged between 21 to 40 years of age. The majority (72.53%) of participants reported personal and family concerns as reasons/motivation for suicide, whereas only 17.58% reported work-related concerns. There was a statistically significant difference across reason or motivation for suicide with age (in years) and gender (P value < 0.001).Conclusion: The study concluded that more than half of the patients indicated personal and family concerns as the major reason for suicide attempts during the pandemic. It is vital to emphasize the mental health well-being of the population and take proactive steps to minimize its detrimental effects during the COVID-19 pandemic.

National trends and outcomes of heart-kidney transplantation using hepatitis C positive donors.

BACKGROUND: This study evaluated the outcomes of combined heart-kidney transplantation in the United States using hepatitis C positive (HCV+) donors. METHODS: Adults undergoing combined heart-kidney transplantation from 2015 to 2020 were identified in the United Network for Organ Sharing registry. Patients were stratified by donor HCV status. Kaplan-Meier curves with multivariable Cox regression models were used for risk-adjustment in a propensity-matched cohort. RESULTS: A total of 950 patients underwent heart-kidney transplantation of which 7.8% (n = 75) used HCV+ donors; 68% (n = 51) were viremic and 32% (n = 24) were non-viremic donors. Unadjusted 1-year recipient survival was similar between HCV+ versus HCV- donors (84% vs 88%, respectively; P = .33). Risk-adjusted analysis in the propensity-matched cohort showed HCV+ donor use did not confer increased risk of 1-year mortality (hazard ratio .63, 95% CI .17-2.32; P = .49). Sub-group analysis showed viremic and non-viremic HCV+ donors had similar 1-year survival as well (84% vs 84%; P = .95). CONCLUSIONS: Compared with recipients of HCV- donor dual heart-kidney transplants, recipients of HCV+ organs had comparable 1-year survival and clinical outcomes after combined transplantation. Although future studies should evaluate other outcomes related to HCV+ donor use, this practice appears safe and should be expanded further in the heart-kidney transplant population.

The Perioperative Patient Experience During COVID-19.

BACKGROUND: Access to elective surgical procedures has been impacted by the COVID-19 pandemic. METHODS: We sought to understand the patient experience by developing and distributing an anonymous online survey to those who underwent non-emergency surgery at a large academic tertiary medical center between March and October 2020. RESULTS: The survey was completed by 184 patients; the majority were white (84%), female (74.6%), and ranged from 18 to 88 years old. Patients were likely unaware of case delay as only 23.6% reported a delay, 82% of which agreed with that decision. Conversely, 44% felt that the delay negatively impacted their quality of life. Overall, 82.7% of patients indicated high satisfaction with their care. African American patients more often indicated a "neutral" vs "satisfactory" hospital experience (P < .05) and considered postponing their surgery (P < .01). Interestingly, younger patients (<60) were more likely than older (≥60) patients to note anxiety associated with having surgery during the pandemic (P < .01), feeling unprepared for discharge (P < .02), not being allowed visitors (P < .02), and learning about the spread of COVID-19 from health care providers (P < .02). DISCUSSION: These results suggest that patients are resilient and accepting of changes to health care delivery during the current pandemic; however, certain patient populations may have higher levels of anxiety which could be addressed by their care provider. These findings can help inform and guide ongoing and future health care delivery adaptations in response to care disruptions.

The impact of race on metabolic, graft, and patient outcomes after pancreas transplantation.

BACKGROUND: Racial disparities following pancreas transplantation (PTX) are poorly defined. METHODS: This was a large-scale, single-center, longitudinal cohort study including adult PTX recipients. Patients were grouped by race to allow for comparisons. RESULTS: 287 PTX recipients were included; 125 (43.5%) were African American (AA). At baseline, AAs had a significantly higher proportion of T2DM (19.4% vs. 5.7%, p = 0.001), were younger, and more likely to be female. AAs experienced significantly higher rates of pancreatic leaks and post-operative bleeding. PTX rejection was comparable, however, kidney rejection tended to be higher among AA SPKs. Long-term mean HgbA1C levels were significantly higher among AAs (6.9% vs. 6.3%, p = 0.039). Patient and graft survival was comparable between groups, but early patient survival tended to be lower in AAs. CONCLUSIONS: This study demonstrated significant perioperative health disparities among AA PTX recipients, including poorer glycemic control and more early deaths, despite similar long-term patient and graft survival.

Distribution of HCV genotypes and HCV RNA viral load in hepatitis infected patients of Kolar region, Karnataka, India.

Decisions and disease progression prediction, understanding the distribution of the hepatitis C virus (HCV) genotype and its association with viral load is significant for treatment. Therefore, it is of interest to document the distribution pattern of HCV genotypes and their association with viral load among HCV infected patients in Kolar, Karnataka. Seventy-four HCV-positive patients and not on antiviral therapy were enrolled from R.L. Jalappa hospital in Kolar, Karnataka. Blood samples were taken and demographics were recorded. HCV RNA was isolated after plasma was separated. qPCR was performed to measure the viral load, and RT-PCR was performed to determine the genotype. Genotype 3 was the prevalent (n=11, 40.7%) followed by genotype 4 (n=8, 29.6%), 2 (n=6, 22.2%), 1 (n= 13.7%), and mix (n=1, 13.7%). The median viral load of genotype 3 was a 2,87,835 IU/mL (IQR 10, 780-3, 71, 66) , genotype 2 was 81,030 IU/mL (IQR 66,495-95,565), genotype 4 was 43, 410 IU/mL (IQR 38, 355-48, 465) belongs to viral load less than 8,00,000 IU/mL. The median viral load genotype 3 was a 1, 05, 19, 500 IU/mL (IQR 49, 37, 250-2, 36, 71, 500), genotype 2 was 2,55,99,000 IU/mL (IQR 2,00,10,000-32,725,500), genotype 4 was 1,67,40,000 IU/mL (IQR 1,45,50,000-17,493,000) belonging to viral load more than 8,00,000 IU/mL category. A correlation between genotype and viral load was observed (p =1.5x10-12), of which genotype 3 showed a high viral load. Thus, HCV genotypes 1 2, 3, 4, and mixed genotype was observed in the patients studied. HCV genotype was associated with viral load in patient plasma. This data finds use in the treatment and prevention of hepatitis C in Kolar, Karnataka.

Acceptability of a Mobile-Health Living Kidney Donor Advocacy Program for Black Wait-Listed Patients.

Marked racial disparities exist in rates of living donor kidney transplantation (LDKT). The Living Organ Video Educated Donors (LOVED) program is a distance-based, mobile health program designed to help Black kidney transplant wait-list patients advocate for a living donor. This study reported on the acceptability outcomes to aid in future refinements. Participants were randomized to LOVED (n = 24, mean age = 50.9 SD (9.2) years), male = 50%) and usual care groups (n = 24 (mean age 47.9 SD (10.0), male 50%). Four LOVED groups completed an eight-week intervention that consisted of six online video education modules and eight group video chat sessions led by a Black navigator. Qualitative analysis from post-study focus groups resulted in six themes: (1) video chat sessions provided essential support and encouragement, (2) videos motivated and made participants more knowledgeable, (3) connectivity with tablets was acceptable in most areas, (4) material was culturally sensitive, (5) participation was overall a positive experience and (6) participants were more willing to ask for a kidney now. The video chat sessions were pertinent in participant satisfaction, though technology concerns limited program implementation. Results showed that the LOVED program was acceptable to engage minorities in health behavior changes for living donor advocacy but barriers exist that require future refinement.

A distance-based living donor kidney education program for Black wait-list candidates: A feasibility randomized trial.

Addressing racial disparities in living donor kidney transplants (LDKT) among Black patients warrants innovative programs to improve living donation rates. The Living Organ Video Educated Donors (LOVED) program is a 2-arm, culturally-tailored, distance-based, randomized controlled feasibility trial. The group-based, 8-week program used peer-navigator led video chat sessions and web-app video education for Black kidney waitlisted patients from United States southeastern state. Primary feasibility results for LOVED (n = 24) and usual care (n = 24) arms included LOVED program tolerability (i.e., 95.8% retention), program fidelity (i.e., 78.9% video education adherence and 72.1% video chat adherence). LDKT attitudinal and knowledge results favored the LOVED group where a statistically significant effect was reported over 6-months for willingness to approach strangers (estimate ± SE: -1.0 ± .55, F(1, 45.3) = 7.5, P = .009) and self-efficacy to advocate for a LDKT -.81 ± .31, F(1, 45.9) = 15.2, P < .001. Estimates were improved but not statistically significant for willingness to approach family and friends, LDKT knowledge and concerns for living donors (all P's > .088). Secondary measures at 6 months showed an increase in calls for LOVED compared to usual care (P = .008) though no differences were found for transplant center evaluations or LDKTs. Findings imply that LOVED increased screening calls and attitudes to approach potential donors but feasibility outcomes found program materials require modification to increase adherence.

Comparative analysis of antibodies to SARS-CoV-2 between asymptomatic and convalescent patients.

The SARS-CoV-2 viral pandemic has induced a global health crisis, which requires more in-depth investigation into immunological responses to develop effective treatments and vaccines. To understand protective immunity against COVID-19, we screened over 60,000 asymptomatic individuals in the Southeastern United States for IgG antibody positivity against the viral Spike protein, and approximately 3% were positive. Of these 3%, individuals with the highest anti-S or anti-RBD IgG level showed a strong correlation with inhibition of ACE2 binding and cross-reactivity against non-SARS-CoV-2 coronavirus S-proteins. We also analyzed samples from 94 SARS-CoV-2 patients and compared them with those of asymptomatic individuals. SARS-CoV-2 symptomatic patients had decreased antibody responses, ACE2 binding inhibition, and antibody cross-reactivity. Our study shows that healthy individuals can mount robust immune responses against SARS-CoV-2 without symptoms. Furthermore, IgG antibody responses against S and RBD may correlate with high inhibition of ACE2 binding in individuals tested for SARS-CoV-2 infection or post vaccination.

U.S. FDA Approved Drugs from 2015-June 2020: A Perspective.

In the present work, we report compilation and analysis of 245 drugs, including small and macromolecules approved by the U.S. FDA from 2015 until June 2020. Nearly 29% of the drugs were approved for the treatment of various types of cancers. Other major therapeutic areas of focus were infectious diseases (14%); neurological conditions (12%); and genetic, metabolic, and cardiovascular disorders (7-8% each). Itemization of the approved drugs according to the year of approval, sponsor, target, chemical class, major drug-metabolizing enzyme(s), route of administration/elimination, and drug-drug interaction liability (perpetrator or/and victim) is presented and discussed. An effort has been made to analyze the pharmacophores to identify the structural (e.g., aromatic, heterocycle, and aliphatic), elemental (e.g., boron, sulfur, fluorine, phosphorus, and deuterium), and functional group (e.g., nitro drugs) diversity among the approved drugs. Further, descriptor-based chemical space analysis of FDA approved drugs and several strategies utilized for optimizing metabolism leading to their discoveries have been emphasized. Finally, an analysis of drug-likeness for the approved drugs is presented.

Insulin resistance and decreased spexin in Indian Patients with Type 2 Diabetes Mellitus.

Spexin is novel biomarker, which plays a potential role in glucose and lipid metabolisms. However, there was paucity of serum spexin levels in obesity and diabetes mellitus subjects. Hence the current study was aimed to find the relationship between the serum spexin levels in type 2 Diabetes mellitus (type 2 DM) with extrapolation of cardiovascular disease (CVD) risk. A cross-sectional study included 330 participants, subdivided as control (n=110), type 2 DM (n=110) and type 2 DM with CVD groups (n=110). HbA1c, insulin, lipid profile, spexin & leptin including blood pressure and body mass index were analyzed from all the participants. The serum spexin levels (ng/ml) were significantly decreased in type 2 DM (mean ± sd: 0.65 ± 0.03) and type 2 DM with CVD (0.48 ± 0.02) groups compared to the control (0.79 ± 0.03) group (p<0.001). The decreased spexin levels were observed in type 2 DM, and further more decreased in type 2 DM with CVD patients compared to controls indicating that spexin levels could be served as an early prediction of obesity-induced T2DM with CVD risk.