Introduction: Coronavirus Disease 2019 (COVID-19) pandemic has affected healthcare systems worldwide. Healthcare Workers (HCWs) form one of the most at-risk population groups for acquiring infection. ...Trend analysis of anti Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) antibody titres in vaccination naïve HCWs will give an insight into the role of natural protective immunity against re-infection. Aim: To understand the dynamics of anti SARS-CoV-2 antibody response and its protective role against re-infection in a cohort of HCWs. Materials and Methods: This observational longitudinal cohort study was conducted in a tertiary care hospital in Gurugram, North India from June to December 2020. The study was approved by the Institutional Ethics Committee. Serum specimens from 230 HCWs were tested for anti-spike protein Immunogloublin G (IgG) antibodies by chemiluminescence immunoassay. The HCWs with positive antibody status and previous Polymerase Chain Reaction (PCR) confirmed infection (n=47) were followed-up over 180 days for serial antibody titres at four visits, each at a gap of 30-45 days. Participants were classified into asymptomatic (n=18), mild (n=17) and moderate (n=12) disease categories based on severity of previous COVID19 illness. SPSS version 22.0 was used for statistical analysis. Intergroup comparison of means was done using Kruskal-Wallis test and chi-square test. p<0.05 was considered statistically significant. Results: Positivity rate for anti SARS-CoV-2 IgG antibodies was 25.7%. Seroconversion rate was 90.74% in HCWs with history of previous Real Time-Polymerase Chain Reaction (RTPCR) confirmed COVID-19 infection. Incidence of infection in seronegative group (n=171) was 12.96 per 10,000 person days while in seropositive group, it was 1.29 per 10,000 person days. Risk ratio for infection (baseline seronegative vs baseline seropositive) was determined to be 8.12 95% Confidence Interval (CI) 1.068-61.755. Incidence of PCR confirmed SARSCoV-2 re-infection was inversely associated with antibody titres (p=0.018). Antibody response trend showed a peak in mean titres in the 46-90 days period followed by steep decline till 135 days and a gradual waning till 180 days. Conclusion: Significant postinfection immunity is offered by even low to moderate amounts of antibodies and this occurs regardless of whether a seropositive HCW had previous asymptomatic or symptomatic infection. These findings have significant implications in establishing the protective role of anti-spike protein antibodies against subsequent infection.
The authors present a case of a 49-year-old woman who underwent coronary artery bypass grafting after suffering from an acute coronary syndrome and later developed phlegmasia cerulea dolens with ...heparin-induced thrombocytopenia (HIT) and HIT thrombosis (HITT).
species are basidiomycetous yeast-like organisms found ubiquitous in nature. They are increasingly been recognized as opportunistic pathogens capable of causing life-threatening invasive diseases ...(trichosporonosis), especially in immuno-suppressed patients and rarely in immuno-competent patients too. Earlier multiple members of the genus
were clubbed together as
but after the advent of molecular techniques, more than 50 different subspecies and around 16 different strains causing human diseases are reported. It is known to cause a wide range of diseases, from superficial to probable and proven invasive diseases to summer hypersensitivity. The ability of
strains to form biofilms on implanted devices, glucuronoxylomannan in their cell walls, and production of proteases and lipases lead to the virulence of this genus. This ubiquitous fungus exhibits intrinsic resistance to echinocandins, variable minimum inhibitory concentrations (MIC) for amphotericin B, and moderate susceptibility to fluconazole and Itraconazole, which are the commonly used anti-fungal agents for any invasive fungal infections which lead to the re-emergence of this notorious yet neglected pathogen and hence the reports of breakthrough infections among patients receiving these antifungals. This review is to understand the epidemiological, clinical details, and antifungal susceptibility pattern of various
infections and it highlights the importance of early detection and treatment for this emerging yeast and also will add to the ongoing surveillance for the anti-fungal susceptibility pattern for this fungus.
Objectives: To analyse COVID-19 antibody response, duration of protection, half-life kinetics and its association with disease severity in health care workers (HCW's). Methodology: Prospective cohort ...study conducted in 230 HCW's of a 1250-bedded tertiary care hospital in India. Baseline IgG antibodies estimated and followed up for RT-PCR positive infection. Seropositive HCWs were followed up with serial titres every 45 days until 6 months. Statistical analysis: SPSS ver. 22.0 used employing chi-square test for association of seropositivity with PCR outcome. Assuming log-normal distribution of antibody-titres, half-life estimated using linear regression model. Adjusted risk ratio was computed for incidence rate in baseline seronegative versus seropositive cases. Results: Seroconversion rate was 93.8% in seropositive HCWs at 30 days post infection. Incidence rate of infection was 12.96 (in seronegatives) and 1.29 (in seropositives) per 10,000 person days. Adjusted risk ratio was 8.12 (95% Cl 1.068 61.755, p<0.001). Incidence of future infection was inversely associated with baseline seropositivity (p=0.018) with spike in infectivity seen during Aug-Sep 2020 and again in Nov. 2020. A peak in mean titres seen at 46-90 day follow-up followed by steep decline till 135 days and gradual waning till 180 days. Median half-life was 125 days (62-155 days). 95.7% seropositive cases sustained seropositivity till the end of study and only 2 asymptomatic ones demonstrated complete seroreversion. Conclusion: Dynamics of humoral immune response revealed an 8-times higher risk of infection in seronegative HCW's. Anti SARS CoV2 IgG antibodies persist for at least 6 months post-infection, offering significant protective immunity against reinfection. Keywords: SARS CoV2 antibodies, healthcare workers, COVID-19
Objectives : To analyse the seroconversion rate of COVID-19 antibody and its association with risk of future infection in frontline COVID warriors. Methodology: Longitudinal cohort study conducted in ...218 frontline COVID warriors. Baseline anti-spike IgG antibodies estimated and followed up for RT-PCR positive infection. Seropositive subjects were followed up with serial titres at 4 visits upto 6 months. Statistical analysis: SPSS ver. 22.0 used employing chi-square test for association of seropositivity with RT-PCR outcome. Antibody kinetics was calculated using a mathematical linear regression model. Incidence rate was calculated per 10000 person years at risk and relative risk was calculated. Results: IgG positivity was seen in 93.8% subjects who had COVID infection in past 30 days. Significantly higher incidence of infection was observed in seronegative subjects who were at 10 times higher risk of infection than seropositive cases (p<0.001). A sharp rise in infectivity was seen in August 2020 which declined after 2 months. Antibody titres peaked during 1.5-3 months followed by steep decline till 4th-5th month and gradual decline till 6 months. Only 2 asymptomatic cases turned seronegative by the end of study. Conclusion: Analysis of natural antibody response postulated a persistence of antibodies till 6 months post RT PCR confirmed infection. The seronegative subjects were 10 times more prone to COVID infection due to lack of innate immunity. Keywords : COVID IgG antibody, frontline COVID warriors, COVID-19 high risk group, immunity
Stable adherens junctions (AJs) are required for formation of restrictive endothelial barrier. Vascular endothelial cadherin from contiguous endothelial cells forms AJs, which are stabilized ...intracellularly by binding of p120-catenin and cortical actin. Mechanisms inducing cortical actin formation and enabling its linkage with p120-catenin remain enigmatic. We altered the function of neural Wiskott-Aldrich syndrome protein (N-WASP), which induces actin polymerization through actin-related protein 2/3 complex (Arp2/3), to address the role of N-WASP in regulating AJ stability and thereby endothelial permeability. We show that depletion of N-WASP in endothelial cells impaired AJ adhesion and favored the organization of actin from cortical actin to stress fibers, resulting thereby in formation of leaky endothelial barrier. Exposure of the N-WASP-depleted endothelial cell monolayer to the permeability-increasing mediator, thrombin, exaggerated AJ disruption and stress fiber formation, leading to an irreversible increase in endothelial permeability. We show that N-WASP binds p120-catenin through its verprolin cofilin acid (VCA) domain, induces cortical actin formation through Arp2, and links p120-catenin with cortical actin. The interaction of N-WASP with p120-catenin, actin, and Arp2 requires phosphorylation of N-WASP at the Tyr-256 residue by focal adhesion kinase. Expression of the VCA domain of N-WASP or phosphomimicking (Y256D)-N-WASP mutant in endothelial cells stabilizes AJs and facilitates barrier recovery after thrombin stimulation. Our study demonstrates that N-WASP, by mediating p120-catenin interaction with actin-polymerizing machinery, maintains AJs and mitigates disruption of endothelial barrier function by edemagenic agents, therefore representing a novel target for preventing leaky endothelial barrier syndrome.
Background: Mechanisms linking cortical actin with adherens junctions (AJs) required for forming restrictive endothelial barrier remain unclear.
Results: We show that neural Wiskott-Aldrich syndrome protein (N-WASP) binds AJ constituent, p120-catenin, forms cortical actin, and links AJs with actin.
Conclusion: N-WASP stabilizes AJs and thereby maintains endothelial barrier function.
Significance: N-WASP represents a novel target for preventing leaky endothelial barrier syndrome.
Increased vascular permeability is a hallmark of sepsis and acute respiratory distress syndrome. Angiopoietin (Ang2) induces vascular leak, and excess Ang2 generation is associated with patient ...mortality from these diseases. However, mechanisms dampening Ang2 generation during injury remain unclear. Interestingly, microRNA (miR)-150 levels were decreased in septic patients. miR regulate signaling networks by silencing mRNAs containing complementary sequences. Thus, we hypothesized that miR-150 suppresses Ang2 generation and thereby resolves vascular injury.
Wild-type or miR-150(-/-) mice or endothelial cells were exposed to lipopolysaccharide or sepsis, and Ang2 levels, adherens junction reannealing, endothelial barrier function, and mortality were determined. Although Ang2 transiently increased during lipopolysaccharide-induced injury in wild-type endothelial cells and lungs, miR-150 expression was elevated only during recovery from injury. Deletion of miR-150 caused a persistent increase in Ang2 levels and impaired adherens junctions reannealing after injury, resulting thereby in an irreversible increase in vascular permeability. Also, miR-150(-/-) mice died rapidly after sepsis. Rescuing miR-150 expression in endothelial cells prevented Ang2 generation, thereby restoring vascular barrier function in miR-150(-/-) mice. miR-150 terminated Ang2 generation by targeting the transcription factor, early growth response 2. Thus, early growth response 2 or Ang2 depletion in miR-150(-/-) endothelial cells restored junctional reannealing and reinstated barrier function. Importantly, upregulating miR-150 expression by injecting a chemically synthesized miR-150 mimic into wild-type mice vasculature decreased early growth response 2 and Ang2 levels and hence mortality from sepsis.
miR-150 is a novel suppressor of Ang2 generation with a key role in resolving vascular injury and reducing mortality resulting from sepsis.
Introduction: KOA is progressively disabling in nature, and developing effective treatment strategies is crucial to impede disease progression. Recent research has explored the role of core muscle ...exercises in mitigating KOA progression. This study evaluates the effectiveness of integrating core strengthening exercises into standard KOA rehabilitation. The study aims to assess the efficacy of incorporating core strengthening exercises and a routine rehabilitation program for knee osteoarthritis (KOA) over 4 weeks and evaluate its impact on physical function tests, knee muscle strength, and core endurance. Methods: Fifteen participants meeting specific KOA criteria completed a four-week intervention combining conventional rehabilitation and core exercises. Selection criteria included orthopedic diagnosis, incorporating medical history, radiographic imaging, and clinical indicators of KOA. A pre-post analysis was done, wherein a portable dynamometer was used to assess for knee muscle strength and physical function tests (stair climb, 30-second sit-to-stand, 40-meter fast-paced walking, and timed up-and-go), and core endurance was evaluated. Statistical analysis using JAMOVI was done, with a significance level of P < 0.05. Result: Knee muscle strength in the affected knee’s flexors and unaffected knee’s extensors and 30-second sit-to-stand showed no significant difference. In contrast, the timed up-and-go test, stair climb test, 40-second fast-paced walking test, and endurance test showed statistically significant differences. Conclusion: After a four-week supervised exercise program, participants exhibited enhanced core endurance and physical function, showcasing the positive effects of exercise in these domains. However, knee muscle strength did not significantly differ, resulting in the need for longer follow-up studies. The study implies that integrating core exercises into routine KOA rehabilitation can enhance physical function and endurance, emphasizing the need for their inclusion in long-term treatment plans for KOA patients.
Cornelia de Lange syndrome (CdLS) is a multisystem disorder with distinctive facial appearance, intellectual disability and growth failure as prominent features. Most individuals with typical CdLS ...have de novo heterozygous loss-of-function mutations in NIPBL with mosaic individuals representing a significant proportion. Mutations in other cohesin components, SMC1A, SMC3, HDAC8 and RAD21 cause less typical CdLS.
We screened 163 affected individuals for coding region mutations in the known genes, 90 for genomic rearrangements, 19 for deep intronic variants in NIPBL and 5 had whole-exome sequencing.
Pathogenic mutations including mosaic changes were identified in: NIPBL 46 3 (28.2%); SMC1A 5 1 (3.1%); SMC3 5 1 (3.1%); HDAC8 6 0 (3.6%) and RAD21 1 0 (0.6%). One individual had a de novo 1.3 Mb deletion of 1p36.3. Another had a 520 kb duplication of 12q13.13 encompassing ESPL1, encoding separase, an enzyme that cleaves the cohesin ring. Three de novo mutations were identified in ANKRD11 demonstrating a phenotypic overlap with KBG syndrome. To estimate the number of undetected mosaic cases we used recursive partitioning to identify discriminating features in the NIPBL-positive subgroup. Filtering of the mutation-negative group on these features classified at least 18% as 'NIPBL-like'. A computer composition of the average face of this NIPBL-like subgroup was also more typical in appearance than that of all others in the mutation-negative group supporting the existence of undetected mosaic cases.
Future diagnostic testing in 'mutation-negative' CdLS thus merits deeper sequencing of multiple DNA samples derived from different tissues.
To address international food security concerns and sustain a growing global population, global agricultural output needs to increase by 70% by the year 2050. Current agricultural techniques to ...increase crop yields, specifically the application of chemicals, have resulted in a wide range of negative impacts on the environment and human health. The maintenance of good quality soil organic matter, a key concern in tropical countries such as India, requires a steady input of organic residues to maintain soil fertility. A tree with many uses, Leucaena leucocephala, has attracted much attention over the past decades. As per our literature review, no research has been conducted examining Leucaena leucocephala leaves for their fungal decomposition and their use as green manure. A study of the fungal colonization of Leucaena leucocephala leaves at various stages of decomposition was conducted to get an insight into which fungi play a critical role in the decomposition process. In total, fifty-two different species of fungi were isolated. There was an increase in the percentage of fungus occurrences as the leaves senesced and then finally decomposed. Almost all decomposition stages were characterized by a higher percentage occurrence of Deuteromycetes (75.47%) and by a lower rate of Ascomycetes (9.43%). A gradual increase of basidiomycetes such as unidentified sclerotia and Rhizoctonia solani was seen as the leaves senesced and finally decomposed. In the moist chamber, Didymium nigripes was the only Myxomycete isolated from completely decomposed leaves. In the present study, on average, there were more fungi in wet seasons than in the dry seasons.
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