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The enzyme methyl-coenzyme M reductase (MCR) plays an important role in mediating global levels of methane by catalyzing a reversible reaction that leads to the production or consumption of this potent greenhouse gas in methanogenic and methanotrophic archaea. In methanogenic archaea, the alpha subunit of MCR (McrA) typically contains four to six posttranslationally modified amino acids near the active site. Recent studies have identified enzymes performing two of these modifications (thioglycine and 5-[S]-methylarginine), yet little is known about the formation and function of the remaining posttranslationally modified residues. Here, we provide in vivo evidence that a dedicated S-adenosylmethionine-dependent methyltransferase encoded by a gene we designated methylcysteine modification (mcmA) is responsible for formation of S-methylcysteine in Methanosarcina acetivorans McrA. Phenotypic analysis of mutants incapable of cysteine methylation suggests that the S-methylcysteine residue might play a role in adaption to mesophilic conditions. To examine the interactions between the S-methylcysteine residue and the previously characterized thioglycine, 5-(S)-methylarginine modifications, we generated M. acetivorans mutants lacking the three known modification genes in all possible combinations. Phenotypic analyses revealed complex, physiologically relevant interactions between the modified residues, which alter the thermal stability of MCR in a combinatorial fashion that is not readily predictable from the phenotypes of single mutants. High-resolution crystal structures of inactive MCR lacking the modified amino acids were indistinguishable from the fully modified enzyme, suggesting that interactions between the posttranslationally modified residues do not exert a major influence on the static structure of the enzyme but rather serve to fine-tune the activity and efficiency of MCR.

Objectives Methods Results Conclusion Our study aimed to evaluate the effect of superior hypogastric nerve plexus (SHNP) block in postoperative pain management in the first 24 h after minimally invasive gynecological (MIG) surgeries.We conducted a double‐blinded, randomized controlled trial in the Department of Obstetrics and Gynecology at a tertiary care centre from May 1, 2023 to September 30, 2023 in women undergoing major MIG surgeries. At the completion of the surgery, women were randomized to the intervention group who received SHNP block with ropivacaine 10 mL (0.75%) before port removal, whereas no intervention was taken in the control group. The extubation time was noted, and the pain score was assessed after 1, 2, 6, 12, and 24 h of extubation in the postoperative period using the visual analog scale (VAS). Statistical analysis was done, with a significance level of 0.05, to test the differences between the two groups.A total of 64 patients were randomly allocated to intervention and control groups. The median pain score was lower at 1 and 2 h post‐extubation and comparable between the two groups at 6, 12, and 24 h. The surrogate markers that is need for additional analgesia and duration of stay did not differ significantly in the two groups, with P‐values of 0.08 and 0.943, respectively.Although the SHNP group experienced considerably lower immediate postoperative pain levels in the initial hours following extubation, the impact of this benefit remains uncertain in the longer postoperative period. The effectiveness of this modality for pain control needs further study, particularly at later postoperative hours. [ABSTRACT FROM AUTHOR]

Background: Spinal anesthesia is the most popular regional anesthesia technique for lower limb and lower abdominal surgery. Bupivacaine 0.5% heavy is commonly used for intrathecal use. New long-acting local anesthetic agents such as ropivacaine have claimed benefits of reduced cardiac toxicity on overdose and more specific effects on sensory rather than motor nerve fibers. The use of intrathecal hyperbaric ropivacaine is not much studied. With this background, we studied intrathecal ropivacaine hyperbaric 0.75% against intrathecal bupivacaine hyperbaric 0.5% for lower abdominal and lower limb surgery. Aims and Objectives: To note the effectiveness of intrathecal ropivacaine and bupivacaine on characteristics of subarachnoid block such as sensory block, motor block, hemodynamic parameters, and complications if any. Materials and Methods: We randomized patients undergoing lower abdominal surgeries and lower limb orthopedic surgeries under spinal anesthesia into two groups so as to receive intrathecal either ropivacaine 0.75% hyperbaric (3 mL) or bupivacaine 0.5% hyperbaric (3mL) and noted study parameters. Results: Time of sensory block onset (P=0.0005), peak sensory level (P=0.0029), and onset of L1 bromage-3 motor block (P=1.27E--08) was significantly delayed in the ropivacaine group as compared to bupivacaine group. However, maximum sensory level achieved (T6), time required for two-segment sensory regressions (P=0.1162), and time of onset of pain (P=0.1162) were comparable in both groups. Conclusion: Intrathecal ropivacaine 0.75% hyperbaric produced slow onset sensory and motor block than 0.5% hyperbaric bupivacaine with comparable cephalic spread and duration of sensory block. [ABSTRACT FROM AUTHOR]

Background Unlike adults, primary membranous nephropathy (PMN) comprises only 1-2% of childhood nephrotic syndrome. The clinical behaviour of PMN in children is not explicit and we report upon clinical presentation and outcome. Methods This prospective study includes children and adolescents (< 20 years) with biopsy-proven PMN without secondary causes. Anti-PLA2R assessment: before and after completing therapy. Outcome: percentage of patients achieving remission. Results Study cohort included 48 (M:F ratio 1.1:1) patients and median age 17 (IQR 15-18) years, with 35 (72.9%) PLA2R related. Median interval from symptom onset to presentation was 5 months, where median proteinuria, serum albumin and creatinine were 4.9 g/day, 2.1 g/dL and 0.63 mg/dL, respectively. Forty-seven patients received immunosuppressive therapy, with various agents used as first-line therapy: cyclical CYC/GC (53.1%), CNI/GC (21.3%), rituximab (14.9%), prednisolone alone (4.3%), azathioprine (4.3%) and mycophenolate mofetil (2.1%). Median follow-up was 29 (14, 59) months. At 6 months, 11 (24.4%) and 17 (37.7%) had complete remission (CR) or partial remission (PR), while at last follow-up (median 29 months), 20 (45.4%) and 14 (31.8%) had CR and PR respectively. No significant differences in outcome were observed with different agents. A total of 60% patients treated with rituximab as first line/for relapsing disease, and all cases with resistant disease receiving rituximab had CR or PR at last follow-up. PLA2R antibody presence was associated with clinical outcome. Conclusions Three-quarters of PMN in children and adolescents is PLA2R related and two-thirds respond to immunosuppressive therapy. Rituximab is a promising agent to manage PMN in children. Anti-PLA2R is associated with clinical outcomes., Author(s): Raja Ramachandran [sup.1] , Saurabh Nayak [sup.1] , Vinod Kumar [sup.2] , Ashwani Kumar [sup.3] , Neha Agrawal [sup.1] , Ritika Bansal [sup.1] , Karalanglin Tiewsoh [sup.4] , Ritambhra [...]

This article, published in the Indian Journal of Medical & Paediatric Oncology, explores the mechanism of resistance to the drug imatinib in patients with chronic myeloid leukemia (CML) blast crisis. The study focuses on the role of β1-integrin, a protein that is found at reduced levels in imatinib-resistant cells. The researchers found that knocking down β1-integrin in imatinib-sensitive cells led to the activation of signaling pathways associated with resistance. Additionally, the study revealed that amplification of the PLAG1 gene in resistant cells contributed to reduced levels of β1-integrin. Overall, the research provides insights into the Bcr-Abl-independent mechanism of resistance in CML blast crisis. [Extracted from the article]

Introduction: The relevance of plasma cells in the allograft liver is of utmost importance and objective assessment of these infiltrates and correlation with other ancillary findings needs to be evaluated. Materials and Methods: Three hundred and sixty‑eight graft liver biopsies received in the department from 2012 to 2022 and 115 allograft liver biopsies with histopathological diagnosis of rejection were selected. Based on plasma cells percentage in the portal tracts, the biopsies were divided into three groups: Group 1 showing not more than an occasional plasma cell, Group 2 showing <10% plasma cells, and Group 3 showing >10% plasma cells. Rejection activity index (RAI), portal/lobular inflammation, interface activity, subendothelial inflammation (portal and central vein), duct damage/loss, presence of cholestasis, apoptosis, perivenulitis, necrosis, rosette along with serial liver function tests (LFTs), and patient status at 1 year of follow‑up were recorded and compared between the groups. Results: Plasma cell infiltrates were observed in 52.6% of the specimens, with the mean percentage of plasma cells in the infiltrates being 4.9. Increased plasma cell infiltrates were associated with higher RAI scores, marked duct damage, marked portal and central vein endotheliitis, marked portal inflammation, and presence of interface activity. Higher levels of transaminitis were recorded at the time of biopsy, but no significant association was observed in the fall of serial LFTs over a 2‑week period with the presence of plasma cells. Conclusion: Identifying plasma cell infiltrates in liver allografts can serve as a clue toward increased severity of rejection in liver allograft biopsies. Further studies with emphasis on correlation with the clinical outcome and response to treatment are needed to validate its utility as an objective tool. [ABSTRACT FROM AUTHOR]

Byline: Arjun. Prakashey, Hita. Mehta, Neha. Agrawal, Dharm. Sondagar Sir, Molluscum contagiosum (MC) is a common benign cutaneous viral infection caused by a poxvirus and is transmitted by skin-to-skin contact [...]

Occupational noise-induced hearing loss prominently occurs due to unavoidable sound frequencies mainly in the range of 3000 to 6000 Hz. This frequency region thus holds great importance for acoustic insulation. Polymeric foams with open cellular frameworks are mostly employed for sound absorption in these frequency regions. To enhance their sound-absorbing ability, nanofillers are integrated with the polymeric matrix. However, the majority of the incorporation methods result in a single-phased porous structure, which limits their potential. Herein, an altered method of modification of multiwall carbon nanotubes (MWCNTs) is explored for the preparation of modified polyurethane foam via a simple one-pot immersion-hydrothermal-evaporation method. A unique self-assembled nanolayered structure with nanopores was fabricated through optimized experimental conditions resembling a double three-dimensional form. This gave rise to an additional resonating-type structure within the porous-type matrix. Thus, a hybrid-type sound-absorbing material with distinctive structure was fabricated which could help achieve focused sound absorption ability at the desired frequency. The sound pressure level evaluated at a frequency of 4000 Hz was found to improve through incorporation of 0.5 wt % modified CNTs. The mean percentage enhancement in sound isolation for treated foam in comparison to untreated foam is 15 to 20% at 4000 Hz. The development of distinctive structures within the polymeric framework opens up a plethora of horizons that could be employed at the industrial level as well, and such structures could be engaged for achieving other eccentric properties, which would further enhance their applicability. [ABSTRACT FROM AUTHOR]

Microfluidic based sensors are one of the emerging alternatives for bringing solutions studies on paper platforms. Microfluidic paper assisted platform was developed over here through a simple, easy, cost effective and instrument free process. The self‐same method of waxing through crayoning, was estimated thoroughly on different paper platforms. Varied parameter including type of crayoning, way of patterning, color effect, wicking rate and channel optimization was performed on paper milieus. Optimized time of baking for obtaining controlled penetration ranges from 2 min to 8 min depending on the type of paper used. Wax crayoning was preferred over oil pasteling for making hydrophobic barriers uniformly, solid as well fully penetrated within paper inner layers. Fabrication through this easy cost‐effective route allows a formation of hydrophilic reaction or sensing zone of 0.25 cm2 with sufficient reactive area. Further sensing of dopamine on paper platform was carried using paper chip adsorbed with fluorescent modified graphene quantum dots as sensing material. The patterned paper showed advantage as only few microliter (5 μl to 10 μl) range of sample volume was required for testing. Fluorescence quenching with increase of concentration was witnessed where around 25–75 μM dopamine concentration was positively tested through naked eye; which for the first time was demonstrated here via robust wax crayoning method for developing paper based biosensor. [ABSTRACT FROM AUTHOR]

Introduction: Open fractures of the distal femur are a uncommon and intricate type of injury that typically occur in individuals who have sustained multiple traumas. These types of fractures are often accompanied by bone loss, contamination, damaged soft tissue, and a patient's overall poor health condition. The purpose of this study is to examine the outcomes of patients who were treated for open distal femur fractures using a staged protocol, which involves initial external fixation with debridement, followed by definitive fixation using an anatomical locking plate and bone grafting at a later stage. Method: The study included a group of 20 patients of open distal femurfractures who were operated with temporary external fixator and later on converted to definitive fixation with condylar locking plate with bone grafting. These patients were operated with our staged protocol and clinical outcome was evaluated using the functional evaluation scoring system by Sander's et al and Knee Society Scoring. Out of these 20 patients, 1 was lost to follow up at 3 months and 2 others were lost to follow up at 6 months. These 3 were excluded from our study. Results: Fracture union was seen in all 17 patients. The average time to union was 22.65+3.3 weeks. Two patients were complicated with infection and delayed union. Ilizarov application was doneto achieve union and gain length once the infection subsided. Conclusion- Staged protocol of temporary external fixator followed by definitive fixation with condylar locking plate and bone grafting is a safe and reliable method for the management of open distal femur fractures. [ABSTRACT FROM AUTHOR]

Simple Summary: The treatment for advanced and metastatic esophagogastric malignancies has historically required time-intensive multi-agent chemotherapy regimens, where patients spend time away from home to engage in therapy administrations and supportive care. With the addition of immunotherapies to the standard of care, the authors completed this study to estimate the time spent in health care across various systemic treatment regimens. The authors estimated the time toxicity, or the days spent in health care facilities, due to cancer diagnosis and treatment with immunotherapy- and chemotherapy-based treatment regimens for esophagogastric cancers. (1) Background: The purpose of this study was to evaluate the time toxicity, or time spent in health care, of immunotherapy- versus chemotherapy-based regimens for metastatic esophageal and gastric cancers. (2) Methods: A literature search was conducted, and 18 phase III clinical trials of immune checkpoint inhibitors were selected for analysis. Health care days were calculated based on the number of days associated with receiving therapy and the adverse events reported in the clinical trials. Both the number of health care days and the median overall survival were compared among chemotherapy-only, immunotherapy-only, and chemo-immunotherapy regimens across this cohort of drug registration trials. (3) Results: The estimated median number of health care days was 37 (range of 7–52) days, or 1.2 (range of 0.2–1.7) months, compared to a median survival of 10.2 months across these 18 studies. For the chemotherapy-only regimens, the median number of health care days was 39 (range of 21–51) days, and for chemo-immunotherapy, it was 39 (range of 30–52) days. The immunotherapy-only regimens had fewer days, a median of 28 (range of 24–41), p < 0.05, compared to the other two arms. (4) Conclusions: The chemo-immunotherapy regimens did not add time toxicity compared to chemotherapy alone. The immunotherapy-only regimens had lower time toxicity compared to chemotherapy alone. In the setting of decreased time toxicity and improved overall survival, further development of immunotherapy-based regimens could improve outcomes in advanced esophageal and gastric cancers. [ABSTRACT FROM AUTHOR]