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Background: Muscle relaxation in anesthesia serves two main purposes: Facilitating endotracheal intubation and achieving surgical relaxation. The period from the suppression of protective reflexes during induction to the completion of intubation is critical, with an increased risk of regurgitation. Ensuring a patent airway is fundamental to general anesthesia, commonly achieved through endotracheal intubation. Aims and Objectives: This study aims to evaluate the onset time, tracheal intubation conditions, duration of action, and maintenance of anesthesia using vecuronium and rocuronium, monitored by train-of-four (TOF). Materials and Methods: This double-blind, prospective, randomized study was conducted over 18 months on patients undergoing elective surgeries under general anesthesia at a tertiary hospital. Ethical committee approval and informed written consent from all participants were obtained. Patients were randomly assigned into two groups of 50 each. Results: Demographic parameters between both groups were statistically insignificant (P>0.05). The mean onset time, defined as the interval between the end of muscle relaxant administration and completion of intubation, was 99.6±12.03 s in Group A (rocuronium) and 231.0±13.21 s in Group B (vecuronium), a statistically significant difference (P

Abstract The physical interactome of a protein can be altered upon perturbation, modulating cell physiology and contributing to disease. Identifying interactome differences of normal and disease states of proteins could help understand disease mechanisms, but current methods do not pinpoint structure-specific PPIs and interaction interfaces proteome-wide. We used limited proteolysis–mass spectrometry (LiP–MS) to screen for structure-specific PPIs by probing for protease susceptibility changes of proteins in cellular extracts upon treatment with specific structural states of a protein. We first demonstrated that LiP–MS detects well-characterized PPIs, including antibody–target protein interactions and interactions with membrane proteins, and that it pinpoints interfaces, including epitopes. We then applied the approach to study conformation-specific interactors of the Parkinson’s disease hallmark protein alpha-synuclein (aSyn). We identified known interactors of aSyn monomer and amyloid fibrils and provide a resource of novel putative conformation-specific aSyn interactors for validation in further studies. We also used our approach on GDP- and GTP-bound forms of two Rab GTPases, showing detection of differential candidate interactors of conformationally similar proteins. This approach is applicable to screen for structure-specific interactomes of any protein, including posttranslationally modified and unmodified, or metabolite-bound and unbound protein states.

Introduction: Iodine deficiency disorders (IDD) have remained an unresolved public health problem in India. In this survey, we have estimated the prevalence of IDD among 6–12 years of school children in rural areas of north Karnataka, India and estimated the prevalence of low iodine content (

The current work reports the structure of the human organic cation transporter 3 (OCT3 / SLC22A3) and provides the structural basis of its inhibition by two specific inhibitors, decynium-22 and corticosterone.

Background: Muscle relaxation in anesthesia serves two main purposes: Facilitating endotracheal intubation and achieving surgical relaxation. The period from the suppression of protective reflexes during induction to the completion of intubation is critical, with an increased risk of regurgitation. Ensuring a patent airway is fundamental to general anesthesia, commonly achieved through endotracheal intubation. Aims and Objectives: This study aims to evaluate the onset time, tracheal intubation conditions, duration of action, and maintenance of anesthesia using vecuronium and rocuronium, monitored by train-of-four (TOF). Materials and Methods: This double-blind, prospective, randomized study was conducted over 18 months on patients undergoing elective surgeries under general anesthesia at a tertiary hospital. Ethical committee approval and informed written consent from all participants were obtained. Patients were randomly assigned into two groups of 50 each. Results: Demographic parameters between both groups were statistically insignificant (P>0.05). The mean onset time, defined as the interval between the end of muscle relaxant administration and completion of intubation, was 99.6±12.03 s in Group A (rocuronium) and 231.0±13.21 s in Group B (vecuronium), a statistically significant difference (P<0.001). Intubation conditions were excellent in 36 (72%) and good in 13 (26%) patients in Group A compared to excellent in 28 (56%) and good in 17 (34%) patients in Group B. Conclusion: Rocuronium provides earlier excellent and good intubating conditions compared to vecuronium, with similar cardiovascular stability during and after intubation. Rocuronium's rapid onset of action makes it more suitable for quick tracheal intubation in surgical patients under general anesthesia. [ABSTRACT FROM AUTHOR]

Adenylyl cyclases (ACs) generate the second messenger cAMP and play an important role in cellular signaling. Here, the authors use cryo-EM to trace the conformational changes resulting from binding to partial and full activators to one of these enzymes, AC9.

Objective: To compare the cardioprotective efficacy of equimolar doses (50 mM/kg, p.o.) of phloretin and genistein against doxorubicin-induced cardiotoxicity in rats. Methods: Cardiotoxicity was induced in rats by intraperitoneal injection of 6 mg/kg doxorubicin on alternative days till the cumulative dose reached 30 mg/kg. This study included four treatment groups of rats (n=6): the control group (0.5% carboxymethyl cellulose solution-treated), the doxorubicin- treated group (0.5% carboxymethyl cellulose solution along with doxorubicin), the genistein-treated group (50 mM/kg/day; p.o. along with doxorubicin) and phloretin-treated group (50 mM/kg/day; p.o. along with doxorubicin). On the 10th day of dosing, rats were anesthetized for recording ECG, mean arterial pressure, and left ventricular function. Oxidative stress, nitric oxide levels, and inflammatory cytokines were estimated in the cardiac tissue. Cardiac function parameters (creatine kinase MB, lactate dehydrogenase, aspartate aminotransferase, and alanine transaminase) were estimated in the serum samples. Results: Phloretin treatment inhibited doxorubicin-induced oxidative stress and also reduced nitric oxide levels in cardiac tissues of rats. Phloretin administration attenuated doxorubicin- induced alterations in hemodynamic parameters (heart rate, mean arterial blood pressure, and left ventricular function) and suppressed the expression of pro-inflammatory cytokines. The cardiac injury markers like creatine kinase MB, lactate dehydrogenase, aspartate aminotransferase, and alanine transaminase were reduced by both genistein and phloretin. All these effects of phloretin were more prominent than genistein. Conclusions: Phloretin offers cardioprotection that is comparable to genistein, a clinically validated cardioprotectant against doxorubicin-induced cardiotoxicity. Further studies are needed to confirm and establish the therapeutic utility of phloretin as a chemopreventive adjuvant to doxorubicin chemotherapy.

Perianal presentations of rectal adenocarcinoma are uncommon. Perianal/ischiorectal conditions which harbour malignancy can occur due to infiltration by rectosigmoid growths, invasion of or implantation in previous fistula tracts, or de-novo. Rarely, an ischiorectal abscess or fistula alone can be the sole presenting symptom of locally advanced rectosigmoid adenocarcinoma. Such an abscess may be inadequately treated and will then fail to heal. We report a patient whose sole symptom was an ischiorectal abscess which had failed to heal. On examination, we diagnosed a rectal growth. Biopsies from the lesion and abscess/fistula tracts showed rectal adenocarcinoma. Computerized tomography confirmed the diagnosis of locally advanced rectal adenocarcinoma with ischiorectal fossa infiltration. A high index of suspicion, thorough examination while draining such abscess, and biopsy of such abscesses or tracts will help in averting mishaps, appropriate diagnosis of cause and prompt planning.

Mycobacterium tuberculosis adenylyl cyclase (AC) Rv1625c/Cya is an evolutionary ancestor of the mammalian membrane ACs and a model system for studies of their structure and function. Although the vital role of ACs in cellular signalling is well established, the function of their transmembrane (TM) regions remains unknown. Here, we describe the cryo-EM structure of Cya bound to a stabilizing nanobody at 3.6 Å resolution. The TM helices 1–5 form a structurally conserved domain that facilitates the assembly of the helical and catalytic domains. The TM region contains discrete pockets accessible from the extracellular and cytosolic side of the membrane. Neutralization of the negatively charged extracellular pocket Ex1 destabilizes the cytosolic helical domain and reduces the catalytic activity of the enzyme. The TM domain acts as a functional component of Cya, guiding the assembly of the catalytic domain and providing the means for direct regulation of catalytic activity in response to extracellular ligands.