An anatomic variant caudate lobe in a cadaver

The liver can present a number of congenital anomalies. Most common among them are the irregularities in shape and the number of lobules. Less common variations include presence of accessory lobes or accessory fissures. The accessory lobe may be attached to the liver through a mesentery or a bridge of hepatic tissue and they are usually asymptomatic. An accessory liver lobe though a very rare occurrence but when it exists it becomes clinically important because of its rarity. We are reporting one such case of accessory caudate lobe of liver found during routine dissection of embalmed cadaver of a 60 year old male. It was separated from the caudate lobe by a well-defined fissure. The quadrate lobe and fissure for ligamentum teres were totally absent. Ligamentum teres was found embedded in the substance of the liver on its inferior surface. The presence of additional lobes and fissures or the absence of normal lobes and fissures might lead to confusion during surgery or clinical misdiagnosis. Knowledge and awareness of these anomalies is useful to the clinician to rule out diseases, surgeons during segmental resection of liver and radiologist when interpreting liver radiologic findings

High division of sciatic nerve

Background: The Sciatic nerve is the largest and thickest nerve in the human body with a long course in the inferior extremity. It divides into tibial and common peroneal nerves which can occur at any level from the sacral plexus to the inferior part of the popliteal space. Sciatic nerve variations are relatively common. These variations may contribute to clinical conditions ex sciatica, coccygodynia and piriformis syndrome and have important clinical implications in anaesthesiology, neurology, sports medicine and surgery.Methods:10 cadavers were dissected with no previous history of trauma/surgery to study the anatomical variations of sciatic nerve.Results:In all except two cadavers, the nerve divided at the apex of the popliteal fossa. In two cadavers the sciatic nerve divided bilaterally in the upper part of thigh.Conclusion: The high division presented in this study can make popliteal nerve blocks partially ineffective. The high division of sciatic nerve must always be borne in mind as they have important clinical implications

Novel Heuristic Algorithm & its Application for Reliability Optimization

Heuristic algorithms are practical, easy to implement, and work fast to provide short-term, feasible solutions for any kind of problem within economical budgets as compared to other meta-heuristic algorithms. This paper presents a novel heuristic algorithm named the Dahiya-Garg Heuristic Algorithm (DG-Alg) to find the optimal solution for constrained reliability redundancy allocation optimization problems. The cornerstone of the novel DG-Alg is its novel selection factor, which is a mathematical formula that helps the heuristic algorithm search for optimal subsystems for reliability optimization. A novel formulated selection factor in DG-Alg has increased its effectiveness and efficiency. To analyze the performance of the proposed heuristic algorithm and the other three existing heuristic algorithms, they are applied to a problem taken from a pharmaceutical manufacturing plant named Yaris Pharmaceuticals. During the application of the heuristic algorithms, it was ensured that redundancy allocation was done within stipulated cost constraints. Further, a comparative analysis of the obtained results has been done to judge the performance of the proposed heuristic algorithm. It is deduced that the proposed heuristic algorithm gives optimized and computationally efficient results in comparison to the other existing heuristic algorithms

Development of a Fast SARS-CoV-2 IgG ELISA, Based on Receptor-Binding Domain, and Its Comparative Evaluation Using Temporally Segregated Samples From RT-PCR Positive Individuals

SARS-CoV-2 antibody detection assays are crucial for gathering seroepidemiological information and monitoring the sustainability of antibody response against the virus. The SARS-CoV-2 Spike protein's receptor-binding domain (RBD) is a very specific target for anti-SARS-CoV-2 antibodies detection. Moreover, many neutralizing antibodies are mapped to this domain, linking antibody response to RBD with neutralizing potential. Detection of IgG antibodies, rather than IgM or total antibodies, against RBD is likely to play a larger role in understanding antibody-mediated protection and vaccine response. Here we describe a rapid and stable RBD-based IgG ELISA test obtained through extensive optimization of the assay components and conditions. The test showed a specificity of 99.79% (95% CI: 98.82-99.99%) in a panel of pre-pandemic samples (n = 470) from different groups, i.e., pregnancy, fever, HCV, HBV, and autoantibodies positive. Test sensitivity was evaluated using sera from SARS-CoV-2 RT-PCR positive individuals (n = 312) and found to be 53.33% (95% CI: 37.87-68.34%), 80.47% (95% CI: 72.53-86.94%), and 88.24% (95% CI: 82.05-92.88%) in panel 1 (days 0-13), panel 2 (days 14-20) and panel 3 (days 21-27), respectively. Higher sensitivity was achieved in symptomatic individuals and reached 92.14% (95% CI: 86.38-96.01%) for panel 3. Our test, with a shorter runtime, showed higher sensitivity than parallelly tested commercial ELISAs for SARS-CoV-2-IgG, i.e., Euroimmun and Zydus, even when equivocal results in the commercial ELISAs were considered positive. None of the tests, which are using different antigens, could detect anti-SARS-CoV-2 IgGs in 10.5% RT-PCR positive individuals by the fourth week, suggesting the lack of IgG response

Cell surface ectodomain integrity of a subset of functional HIV-1 envelopes is dependent on a conserved hydrophilic domain containing region in their C-terminal tail

Abstract Background HIV-1 Env gp160 is cleaved to form gp120 and gp41 and the functional HIV-1 Env is a trimer of non-covalently associated heterodimeric subunits, gp120 and gp41. The cleaved, native, trimeric form of Envs expose only broadly neutralizing antibody (bNAb) epitopes while occluding epitopes targeted by non-neutralizing antibodies (non-NAbs). We and others have previously observed that efficient cleavage of Envs into their constituent subunits co-relates with specific binding to bNAbs and poor binding to non-neutralizing antibodies (non-NAbs). Such Envs have been identified from clades A, B and C which make up a majority of globally circulating HIV-1 strains. Frequently, the C-terminal tail (CT) of Envs is deleted to enhance expression and stabilize soluble Env-based vaccine immunogens. Deletion of CT of efficiently cleaved Indian clade C Env 4-2.J41 results in recognition by both NAbs and non-NAbs. It is to be noted that uncleaved Envs bind to both NAbs and non-NAbs. So we investigated whether altered antigenicity upon CT deletion of efficiently cleaved Envs is due to inefficient cleavage or conformational change as the mechanism by which the CT regulates the ectodomain (ET) integrity is not well understood. Results We studied the effect of CT deletion in four membrane bound efficiently cleaved Envs, A5 (clade A), 4-2.J41 (clade C), JRFL and JRCSF (clade B). Deletion of CT of the Envs, JRCSF and 4-2.J41, but not JRFL and A5 alter their ET antigenicity/conformation without affecting the cleavage efficiency. We carried out a series of deletion mutation in order to determine the region of the CT required for restoring native-like antigenicity/conformation of the ET of 4-2.J41 and JRCSF. Extending the CT up to aa753 in 4-2.J41 and aa759 in JRCSF, which includes a conserved hydrophilic domain (CHD), restores native-like conformation of these Envs on the plasma membrane. However, CT-deletion in 4-2.J41 and JRCSF at the pseudovirus level has either no or only modest effect on neutralization potency. Conclusion Here, we report that the CHD in the CT of Env plays an important role in regulating the ET integrity of a subset of efficiently cleaved, functional Envs on the cell surface

MOESM2 of Cell surface ectodomain integrity of a subset of functional HIV-1 envelopes is dependent on a conserved hydrophilic domain containing region in their C-terminal tail

Additional file 2: Fig. S1. Domains and endocytosis signals in JRFL, JRCSF, 4-2.J41 and A5. (a) Sequence comparisons of the C-terminal tails of 4-2.J41 (clade A), JRFL and JRCSF (clade B), A5 (clade A) and HxB2 showing that the endocytosis signals (highlighted in yellow) are largely conserved. Amino acid changes are marked in red. CHD (KE): Conserved Hydrophilic Region (Kennedy Epitope); LLP1, LLP2, LLP3 (Lentivirus Lytic Peptides 1,2,3). (b) Bright field image of A5 and A5ΔCT transfected whole cells

Proinflammatory Innate Cytokines and Distinct Metabolomic Signatures Shape the T Cell Response in Active COVID-19

The underlying factors contributing to the evolution of SARS-CoV-2-specific T cell responses during COVID-19 infection remain unidentified. To address this, we characterized innate and adaptive immune responses with metabolomic profiling longitudinally at three different time points (0–3, 7–9, and 14–16 days post-COVID-19 positivity) from young, mildly symptomatic, active COVID-19 patients infected during the first wave in mid-2020. We observed that anti-RBD IgG and viral neutralization are significantly reduced against the delta variant, compared to the ancestral strain. In contrast, compared to the ancestral strain, T cell responses remain preserved against the delta and omicron variants. We determined innate immune responses during the early stage of active infection, in response to TLR 3/7/8-mediated activation in PBMCs and serum metabolomic profiling. Correlation analysis indicated PBMCs-derived proinflammatory cytokines, IL-18, IL-1β, and IL-23, and the abundance of plasma metabolites involved in arginine biosynthesis were predictive of a robust SARS-CoV-2-specific Th1 response at a later stage (two weeks after PCR positivity). These observations may contribute to designing effective vaccines and adjuvants that promote innate immune responses and metabolites to induce a long-lasting anti-SARS-CoV-2-specific T cell response

MOESM4 of Cell surface ectodomain integrity of a subset of functional HIV-1 envelopes is dependent on a conserved hydrophilic domain containing region in their C-terminal tail

Additional file 4: Fig. S3. Infectivity and neutralization assays of JRCSF and JRCSFΔCT pseudoviruses. (a) Infectivity of JRCSF Env wild type and JRCSFΔCT mutant pseudoviruses using TZM-bl reporter based cell assay. (b) IC50 values of JRCSF wild type and JRCSFΔCT mutant pseudoviruses with the cleavage non-specific bNAb VRC01, glycan-dependent and conformational bNAb PG9, PGT121, trimer-selective and cleavage-specific bNAbs PGT151 and PGT145, MPER-directed bNAbs 10E8 and non-NAbs F105 and 17b