Comparison of efficacy of intercostal nerve block versus peritract infiltration with 0.25% bupivacaine in percutaneous nephrolithotomy: A prospective randomized clinical trial.

Introduction: Postoperative pain following percutaneous nephrolithotomy (PCNL) adds to the morbidity of patients requiring additional analgesia. Various modalities of pain control techniques, such as intercostal nerve block (ICNB) and peritract infiltration (PTI), are being studied for better pain management. This study compares the efficacy of ICNB with PTI for postoperative pain management. Methods: A double-blinded, prospective, randomized control study was conducted, in which 0.25% bupivacaine, either ICNB or PTI, was given at the puncture site at the end of PCNL. The primary outcome was a comparison of postoperative pain score measured with resting Visual analogue Scale (r-VAS) and dynamic VAS (D-VAS) recorded at 2 h, 4 h, 8 h, 10 h, 12 h, 24 h, and at discharge. Injection ketorolac was given as rescue analgesia. Secondary outcomes include time to first rescue analgesia and total analgesic requirement (TAR). Results: Sixty patients were randomized into two equal groups with 63.3% male and 36.6% female, with a mean age of 37.25 ± 13.09 years. In Group ICNB, 24 (40%) and 6 (10%) patients and in Group PTI, 21 (35%) and 9 (15%) patients underwent standard and mini PCNL, respectively, in each group. All cases were PCNL doen in prone position. The mean R-VAS and D-VAS scores at 2, 4, 8, 12, 24, and 48 h were similar in both groups. The mean TAR was 56.84 ± 0.33.00 mg and 55.54 ± 0.29.64 mg of injection ketorolac in Group ICNB and PTI, respectively (P < 0.894). The time to first rescue analgesic demand were 7.11 ± 4.898 h and 6.25 ± 3.354 h (P < 0.527). Both the groups were comparable in terms of length of hospital stay, stone clearance rate, and complication rate. Conclusion: The ICNB was as efficacious as PTI for postoperative pain control with 0.25% bupivacaine following PCNL.

Severe and rapidly changing hypophosphatemia in cannabinoid hyperemesis syndrome: a case report.

The increasing prevalence of cannabis worldwide requires awareness of a potential, less recognized, paradoxical entity, the cannabinoid hyperemesis syndrome (CHS). This includes cyclic episodes of nausea, vomiting, and compulsive hot water bathing for alleviation in individuals with chronic cannabis use. An 18-year-old male with daily and prolonged cannabis use has excessive nausea and vomiting, is diagnosed with CHS, and is further complicated by severe and rapidly fluctuating hypophosphatemia. He was successfully managed with intravenous (IV) antiemetic (metoclopramide) and IV normal saline in the emergency department. Hypophosphatemia was treated with IV phosphorous. Although hypophosphatemia in CHS is a rare encounter, the authors share their experience to promote broader recognition and insight into successful management.

Perception and Willingness Regarding Organ Transplantation/donation among Medical Students of Maharajgunj Medical Campus: A Cross-sectional Study.

BACKGROUND: Organ transplant is the procedure of replacing a failing or damaged organ with a functioning one. Positive attitude and awareness about donation are a must for donor organs to be available. This study explored the level of knowledge, perception and willingness regarding organ donation among medical students in Nepal. METHODS: A descriptive cross-sectional study was conducted with 180 medical students using a self-administered questionnaire. Descriptive statistics were used, and Pearson correlation was applied to examine the relationship between knowledge and perception of organ transplantation. Independent samples t-test and ANOVA was used to compare scores among year of study and gender. RESULTS: Results indicated that 86.1% of participants were aware of the need for organ donation, and 83.3% knew that both living and deceased individuals could be donors. While 93.9% believed in the need for effective laws, 72.8% perceived risks for donors. However, only 74.4% were willing to donate their organs, though 91.7% expressed willingness to promote organ donation among friends and family. Participants showed a positive perception towards organ donation. CONCLUSIONS: Despite a high level of awareness and knowledge regarding organ donation, participants exhibited a lower level of willingness to donate organs. Perceived risks for donors and a lack of robust laws and regulations presented significant barriers. Nevertheless, an inclination to promote organ donation was observed. This underlines the need for enhanced education and policy reform to increase organ donation rates.

Nitrous oxide splurge in a tertiary health care center and its environmental impact: No more laughing stock

Background@#Nitrous oxide has been an integral part of surgical anesthesia for many years in the developed world and is still used in developing countries such as India. The other main concerns in low-resource countries are the lack of an advanced anesthesia gas-scavenging system and modular surgical theatres. As a greenhouse gas that has been present in the atmosphere for more than 100 years and damages the ozone layer, nitrous oxide is three times worse than sevoflurane. Here, we conducted an observational study to quantify the annual nitrous oxide consumption and its environmental impact in terms of carbon dioxide equivalence in one of busiest tertiary health care and research centers in Northern India. @*Methods@#Data related to nitrous oxide expenditure’ from the operation theatre and manifold complex of our tertiary care hospital and research center from 2018 to 2021 were collected monthly and analyzed. The outcomes were extracted from our observational study, which was approved by our institutional ethics board (INT/IEC/2017/1372 Dated 25.11.2017) and registered prospectively under the Central Registry (CTRI/2018/07/014745 Dated 05.07.2018). @*Results@#The annual nitrous oxide consumption in our tertiary care hospital was 22,081.00, 22,904.00, 17,456.00, and 18,392.00 m 3 (cubic meters) in 2018, 2019, 2020, and 2021, respectively. This indicates that the environmental impact of nitrous oxide (in terms of CO2 equivalents) from our hospital in 2018, 2019, 2020, and 2021 was 13,016.64, 13,287.82, 10,289.94, and 10,841.24 tons, respectively. @*Conclusion@#This huge amount of nitrous oxide splurge is no longer a matter of laughter, and serious efforts should be made at every central and peripheral health center level to reduce it.

Lactobacillus pentosus Modulates Immune Response by Inducing IL-10 Producing Tr1 Cells

Several gut commensals have been shown to modulate host immune response. Recently, many food derived microbes have also been reported to affect the immune system. However, a mechanism to identify immunostimulatory and immunoregulatory microbes is needed. Here, we successfully established an in vitro screening system and identified an immunoregulatory bacterium, Lactobacillus pentosus KF340 (LP340), present in various fermented foods. LP340 induced a regulatory phenotype in mice Ag presenting cells which, in turn, induced IL-10 and IFN-γ producing Type 1 regulatory T cells (Tr1 cells) from naïve CD4⁺ T cells. Naïve CD4⁺ T cells co-cultured with LP340 treated dendritic cells highly expressed cytokine receptor IL-27R and were CD49b and lymphocyte-activation gene 3 double positive. Oral administration of LP340 in mice with atopic dermatitis reduced cellular infiltration in affected ear lobes and serum IgE levels, thus, ameliorating the disease symptoms. This suggests a systemic immunoregulatory effect of LP340. These findings demonstrate that LP340, a bacterium derived from food, prevents systemic inflammation through the induction of IL-10 producing Tr1 cells.

Intravesical Migration of an Intrauterine Contraceptive Device with Secondary Calculus Formation / 가정의학회지

Intrauterine contraceptive devices (IUCDs) are a common form of reversible contraception owing to fewer systemic side effects and low cost, especially in a developing country like India. However, IUCDs are not without complications. Migration of a device into adjacent organs is the most morbid of all the documented complications. A patient who presents with a history that suggests loss or disappearance of an IUCD thread associated with urinary symptoms should raise suspicions that a device may have migrated into the bladder. Physicians should also be aware of possible secondary vesical calculus formation. Further radiological investigations and appropriate management are warranted. We present a case report describing the migration of an IUCD into the bladder with secondary calculus formation.

SARS-CoV-2 inactivation by human defensin HNP1 and retrocyclin RC-101

Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 is an enveloped virus responsible for the COVID-19 respiratory disease pandemic. While induction of adaptive antiviral immunity via vaccination holds promise for combatting the pandemic, the emergence of new potentially more transmissible and vaccine-resistant variants of SARS-CoV-2 is an ever-present threat. Thus, it remains essential to better understand innate immune mechanisms that are active against the virus. One component of the innate immune system with broad anti-pathogen, including antiviral, activity is a group of cationic immune peptides termed defensins. The defensins ability to neutralize enveloped and non-enveloped viruses and to inactivate numerous bacterial toxins correlate with their ability to promote the unfolding of thermodynamically pliable proteins. Accordingly, we found that human neutrophil a-defensin HNP1 and retrocyclin RC-101 destabilize SARS-CoV-2 Spike protein and interfere with Spike-mediated membrane fusion and SARS-CoV-2 infection in cell culture. We show that HNP1 binds to Spike with submicromolar affinity. Although binding of HNP1 to serum albumin is more than 20-fold weaker, serum reduces the anti-SARS-CoV-2 activity of HNP1. At high concentrations of HNP1, its ability to inactivate the virus was preserved even in the presence of serum. These results suggest that specific a- and 8-defensins may be valuable tools in developing SARS-CoV-2 infection prevention strategies.

An Adaptive, Interacting, Cluster-Based Model Accurately Predicts the Transmission Dynamics of COVID-19

The SARS-CoV-2 driven disease, COVID-19, is presently a pandemic with increasing human and monetary costs. COVID-19 has put an unexpected and inordinate degree of pressure on healthcare systems of strong and fragile countries alike. In order to launch both containment and mitigation measures, each country requires accurate estimates of COVID-19 incidence as such preparedness allows agencies to plan efficient resource allocation and design control strategies. Here, we have developed a new adaptive, interacting, and cluster-based mathematical model to predict the granular trajectory COVID-19. We have analyzed incidence data from three currently afflicted countries of Italy, the United States of America, and India, and show that our approach predicts state-wise COVID-19 spread for each country with high accuracy. We show that R0 as the basic reproduction number exhibits significant spatial and temporal variation in these countries. However, by including a new function for temporal variation of R0 in an adaptive fashion, the predictive model provides highly reliable estimates of asymptomatic and undetected COVID-19 patients, both of which are key players in COVID-19 transmission. Our dynamic modeling approach can be applied widely and will provide a new fillip to infectious disease management strategies worldwide.

Characterization of neutralizing versus binding antibodies and memory B cells in COVID-19 recovered individuals from India

India is one of the countries most affected by the recent COVID-19 pandemic. Characterization of humoral responses to SARS-CoV-2 infection, including immunoglobulin isotype usage, neutralizing activity and memory B cell generation, is necessary to provide critical insights on the formation of immune memory in Indian subjects. In this study, we evaluated SARS-CoV-2 receptor-binding domain (RBD)-specific IgG, IgM, and IgA antibody responses, neutralization of live virus, and RBD-specific memory B cell responses in pre-pandemic healthy versus convalescent COVID-19 individuals from India. We observed substantial heterogeneity in the formation of humoral and B cell memory post COVID-19 recovery. While a vast majority (38/42, 90.47%) of COVID-19 recovered individuals developed SARS-CoV-2 RBD-specific IgG responses, only half of them had appreciable neutralizing antibody titers. RBD-specific IgG titers correlated with these neutralizing antibody titers as well as with RBD-specific memory B cell frequencies. In contrast, IgG titers measured against SARS-CoV-2 whole virus preparation, which includes responses to additional viral proteins besides RBD, did not show robust correlation. Our results suggest that assessing RBD-specific IgG titers can serve as a surrogate assay to determine the neutralizing antibody response. These observations have timely implications for identifying potential plasma therapy donors based on RBD-specific IgG in resource-limited settings where routine performance of neutralization assays remains a challenge. ImportanceOur study provides an understanding of SARS-CoV-2-specific neutralizing antibodies, binding antibodies and memory B cells in COVID-19 convalescent subjects from India. Our study highlights that PCR-confirmed convalescent COVID-19 individuals develop SARS-CoV-2 RBD-specific IgG antibodies, which correlate strongly with their neutralizing antibody titers. RBD-specific IgG titers, thus, can serve as a valuable surrogate measurement for neutralizing antibody responses. These finding have timely significance for selection of appropriate individuals as donors for plasma intervention strategies, as well as determining vaccine efficacy.

Structural insights for neutralization of BA.1 and BA.2 Omicron variants by a broadly neutralizing SARS-CoV-2 antibody

The SARS-CoV-2 BA.1 and BA.2 (Omicron) variants contain more than 30 mutations within the spike protein and evade therapeutic monoclonal antibodies (mAbs). Here, we report a receptor-binding domain (RBD) targeting human antibody (002-S21F2) that effectively neutralizes live viral isolates of SARS-CoV-2 variants of concern (VOCs) including Alpha, Beta, Gamma, Delta, and Omicron (BA.1 and BA.2) with IC50 ranging from 0.02 - 0.05 g/ml. This near germline antibody 002-S21F2 has unique genetic features that are distinct from any reported SARS-CoV-2 mAbs. Structural studies of the full-length IgG in complex with spike trimers (Omicron and WA.1) reveal that 002-S21F2 recognizes an epitope on the outer face of RBD (class-3 surface), outside the ACE2 binding motif and its unique molecular features enable it to overcome mutations found in the Omicron variants. The discovery and comprehensive structural analysis of 002-S21F2 provide valuable insight for broad and potent neutralization of SARS-CoV-2 Omicron variants BA.1 and BA.2.

Molecular basis of SARS-CoV-2 Omicron variant evasion from shared neutralizing antibody response

A detailed understanding of the molecular features of the neutralizing epitopes developed by viral escape mutants is important for predicting and developing vaccines or therapeutic antibodies against continuously emerging SARS-CoV-2 variants. Here, we report three human monoclonal antibodies (mAbs) generated from COVID-19 recovered individuals during first wave of pandemic in India. These mAbs had publicly shared near germline gene usage and potently neutralized Alpha and Delta, but poorly neutralized Beta and completely failed to neutralize Omicron BA.1 SARS-CoV-2 variants. Structural analysis of these three mAbs in complex with trimeric spike protein showed that all three mAbs are involved in bivalent spike binding with two mAbs targeting class-1 and one targeting class-4 Receptor Binding Domain (RBD) epitope. Comparison of immunogenetic makeup, structure, and function of these three mAbs with our recently reported class-3 RBD binding mAb that potently neutralized all SARS-CoV-2 variants revealed precise antibody footprint, specific molecular interactions associated with the most potent multi-variant binding / neutralization efficacy. This knowledge has timely significance for understanding how a combination of certain mutations affect the binding or neutralization of an antibody and thus have implications for predicting structural features of emerging SARS-CoV-2 escape variants and to develop vaccines or therapeutic antibodies against these.