A comparison of intrathecal dexmedetomidine and clonidine as adjuvants to hyperbaric bupivacaine for gynecological surgery

Background: Various adjuvants are being used with local anesthetics for prolongation of intraoperative and post-operative analgesia. Dexmedetomidine, a highly selective alpha2 adrenergic agonist, is a new neuraxial adjuvant gaining popularity. The purpose of this study was to compare the onset, duration of sensory and motor block, hemodynamic effects, post-operative analgesia, and adverse effects of dexmedetomidine and clonidine with hyperbaric 0.5% bupivacaine for spinal anesthesia.Methods: 60 patients belonging to ASA Grade 1 and 2 undergoing elective gynecological surgery under spinal anesthesia were studied in this prospective. The patients were allocated in two groups (30 patients each). Group bupivacaine + clonidine (BC) received 17.5 mg of bupivacaine supplemented 45 mcg clonidine and Group bupivacaine + dexmedetomidine (BD) received 17.5 mg bupivacaine supplemented 5 mcg dexmedetomidine. The onset time of sensory and motor level, time to reach peak sensory and motor level, the regression time of sensory and motor level, hemodynamic changes, and side effects were recorded.Results: Patients in Group BD had significantly longer sensory and motor block time than patients in Group BC. The onset time to reach dermatome T4 and modified Bromage3 motor block were not significantly different between two groups. Dexmedetomidine group showed significantly less and delayed requirement of rescue analgesic.Conclusion: Intrathecal dexmedetomidine is associated with prolonged motor and sensory block, hemodynamic stability and reduced demand of rescue analgesic in 24 hrs as compared to clonidine

DEVELOPMENT AND VALIDATION OF NEW RP-HPLC METHOD FOR THE ESTIMATION OF LINEZOLID IN LINEZOLID GEL

Objective: Development and validation of new RP-HPLC method for the estimation of linezolid in linezolid gel.Methods: Linezolid was chromatographed on a reverse phase symmetry C18 column (150 x 4.6 mm x 3.5 µm) in a mobile phase consisting of potassium dihydrogen phosphate buffer (pH 4.6 adjusted with 10% orthophosphoric acid) and methanol in the ratio of 55:45. The mobile phase was pumped at a flow rate of 1.2 ml/min with detection at 250 nm.Results: The retention time for Linezolid was found about 2.94 min. The detector response was linear in the concentration of 20 µg/ml to 160µg/ml with correlation coefficient of 0.9997. The percentage recovery of Linezolid at target concentration was found to be 97.8%. The limit of detection and limit of quantification was found to be 10 μg/ml and 5 μg/ml respectively. All other validation parameter were within acceptance criteria.Conclusion: The proposed method was found to be simple, fast, accurate, precise and reproducible and could be used for routine quality control analysis of Linezolid in Linezolid gel.Â

Utility of pathologist panels for achieving consensus in NASH histologic scoring in clinical trials: Data from a phase 3 study

Copyright \ua9 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.Background: Liver histopathologic assessment is the accepted surrogate endpoint in NASH trials; however, the scoring of NASH Clinical Research Network (CRN) histologic parameters is limited by intraobserver and interobserver variability. We designed a consensus panel approach to minimize variability when using this scoring system. We assessed agreement between readers, estimated linear weighted kappas between 2 panels, compared them with published pairwise kappa estimates, and addressed how agreement or disagreement might impact the precision and validity of the surrogate efficacy endpoint in NASH trials. Methods: Two panels, each comprising 3 liver fellowship-trained pathologists who underwent NASH histology training, independently evaluated scanned whole slide images, scoring fibrosis, inflammation, hepatocyte ballooning, and steatosis from baseline and month 18 biopsies for 100 patients from the precirrhotic NASH study REGENERATE. The consensus score for each parameter was defined as agreement by ≥2 pathologists. If consensus was not reached, all 3 pathologists read the slide jointly to achieve a consensus score. Results: Between the 2 panels, the consensus was 97%-99% for steatosis, 91%-93% for fibrosis, 88%-92% for hepatocyte ballooning, and 84%-91% for inflammation. Linear weighted kappa scores between panels were similar to published NASH CRN values. Conclusions: A panel of 3 trained pathologists independently scoring 4 NASH CRN histology parameters produced high consensus rates. Interpanel kappa values were comparable to NASH CRN metrics, supporting the accuracy and reproducibility of this method. The high concordance for fibrosis scoring was reassuring, as fibrosis is predictive of liver-specific outcomes and all-cause mortality

Student assistantship programme: an evaluation of impact on readiness to transit from medical student to junior doctor.

BACKGROUND: Studies report that medical graduates are not prepared for practice as expected, and interventions have been developed to prepare them for practice. One such intervention is the assistantship, which provides hands-on opportunities to hone clinical skills and undertake responsibilities under supervision. The Lee Kong Chian School of Medicine (LKCMed) is Singapore's newest medical school, and students undergo a Student Assistantship Programme (SAP) to prepare for practice as junior doctors (PGY1). This study evaluated the SAP from the students' and clinical supervisors' perspectives. METHODS: Students completed online questionnaires to assess readiness for practice before and after SAP, and a subsample were interviewed about their experiences of SAP and its impact on their preparedness for PGY1. In addition, after our graduates had begun work as PGY1 doctors, their clinical supervisors completed an online questionnaire and were interviewed about the perceived benefits of SAP and the attributes of our graduates as junior doctors. RESULTS: Fifty (96%) students completed the pre-SAP questionnaire and 46 (92%) completed the post-SAP questionnaire. Levels of preparedness increased post-SAP (mean scores range pre-SAP: 2.38 to 4.32 vs post-SAP: 3.08 to 4.48); so did opportunities to undertake PGY1 duties (pre-SAP: 56% vs post-SAP: 96%), and hands-on experience in medical emergencies (pre-SAP: 76% vs post-SAP: 89%).Experience of acute care situations increased except "paracetamol overdose". Readiness to be first respondents in ten acute situations improved (statistically significant for asthma, chronic obstructive pulmonary disease exacerbation, gastrointestinal bleed, sepsis, and adverse drug reactions). Three themes emerged from twenty-five student interviews: learning about the work environment, opportunities to learn in a safe environment, and enhancing SAP for future students. Thirty-three supervisors completed the questionnaire, and 70% rated SAP positively in preparing students for PGY1. Eight supervisors interviewed shared positively about the content, timing, and duration of SAP; and suggested future SAPs help students to develop coping and reflective skills. CONCLUSIONS: The SAP improved students' preparedness and experience across clinical areas, and students felt the SAP helped bridge undergraduate curriculum and work, provided opportunities to hone their skills and learn from junior doctors. Most clinical supervisors rated the SAP effective in preparing students for PGY1. This is the first formal evaluation of an assistantship in Singapore, and the findings are encouraging from the perspective of students and PGY1 supervisors

Role of social comparison in preparedness for practice as a junior doctor in Singapore: a longitudinal qualitative study

ObjectivesTo date, most research on medical graduates’ preparedness for practice has conceptualised preparedness as something possessed by the individual. However, new doctors work within social settings with other people and, given this, we argue that preparedness has a social and comparative dimension. The aim of this paper is to explore medical students’/graduates’ self-assessments of their preparedness for practice using the lens of social comparison theory.SettingWe invited medical students from one of Singapore’s three medical schools who were in their final-year Student Assistantship Programme to participate in semi-structured interviews, and follow-up interviews 6 months later when they were working as junior doctors. Data was collected from two cohorts, in 2018 and 2019. Initial analysis of interview transcripts was inductive and thematic. Social comparison theory was used for subsequent theory-driven analysis.Participants31 participants took part, of whom 21 also engaged in follow-up interviews.ResultsWe identified three uses of social comparison: as coping strategy to manage uncertainties in transitions where there was no formal, objective testing of their performance; as a means to confirm their self-perceived preparedness (upwards or downwards, eg, being better or worse prepared than comparator others); and as the basis for decision-making (eg, changing career choices).ConclusionsSenior medical students and newly-graduated doctors compare themselves with peers and near-peers in terms of prior learning and current performance to evaluate and understand their own performance at work. Future studies need to examine further how the feeling of preparedness or unpreparedness generated from social comparisons may affect subsequent clinical performance and professional development.</jats:sec

Operative management of acute abdomen after bariatric surgery in the emergency setting: the OBA guidelines

Background: Patients presenting with acute abdominal pain that occurs after months or years following bariatric surgery may present for assessment and management in the local emergency units. Due to the large variety of surgical bariatric techniques, emergency surgeons have to be aware of the main functional outcomes and long-term surgical complications following the most performed bariatric surgical procedures. The purpose of these evidence-based guidelines is to present a consensus position from members of the WSES in collaboration with IFSO bariatric experienced surgeons, on the management of acute abdomen after bariatric surgery focusing on long-term complications in patients who have undergone laparoscopic sleeve gastrectomy and laparoscopic Roux-en-Y gastric bypass. Method: A working group of experienced general, acute care, and bariatric surgeons was created to carry out a systematic review of the literature following the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols (PRISMA-P) and to answer the PICO questions formulated after the Operative management in bariatric acute abdomen survey. The literature search was limited to late/long-term complications following laparoscopic sleeve gastrectomy and laparoscopic Roux-en-Y gastric bypass. Conclusions: The acute abdomen after bariatric surgery is a common cause of admission in emergency departments. Knowledge of the most common late/long-term complications (&gt; 4&nbsp;weeks after surgical procedure) following sleeve gastrectomy and Roux-en-Y gastric bypass and their anatomy leads to a focused management in the emergency setting with good outcomes and decreased morbidity and mortality rates. A close collaboration between emergency surgeons, radiologists, endoscopists, and anesthesiologists is mandatory in the management of this group of patients in the emergency setting

Legumes as food ingredient: characterization, processing, and applications

Editores: Jiménez-López, José Carlos (CSIC); Clemente, Alfonso (CSIC

Probing Chemical Space with Alkaloid-Inspired Libraries

Screening of small molecule libraries is an important aspect of probe and drug discovery science. Numerous authors have suggested that bioactive natural products are attractive starting points for such libraries, due to their structural complexity and sp3-rich character. Here, we describe the construction of a screening library based on representative members of four families of biologically active alkaloids (Stemonaceae, the structurally related cyclindricine and lepadiformine families, lupin, and Amaryllidaceae). In each case, scaffolds were based on structures of the naturally occurring compounds or a close derivative. Scaffold preparation was pursued following the development of appropriate enabling chemical methods. Diversification provided 686 new compounds suitable for screening. The libraries thus prepared had structural characteristics, including sp3 content, comparable to a basis set of representative natural products and were highly rule-of-five compliant

Identifying Regulators for EAG1 Channels with a Novel Electrophysiology and Tryptophan Fluorescence Based Screen

Ether-à-go-go (EAG) channels are expressed throughout the central nervous system and are also crucial regulators of cell cycle and tumor progression. The large intracellular amino- and carboxy- terminal domains of EAG1 each share similarity with known ligand binding motifs in other proteins, yet EAG1 channels have no known regulatory ligands.Here we screened a library of small biologically relevant molecules against EAG1 channels with a novel two-pronged screen to identify channel regulators. In one arm of the screen we used electrophysiology to assess the functional effects of the library compounds on full-length EAG1 channels. In an orthogonal arm, we used tryptophan fluorescence to screen for binding of the library compounds to the isolated C-terminal region.Several compounds from the flavonoid, indole and benzofuran chemical families emerged as binding partners and/or regulators of EAG1 channels. The two-prong screen can aid ligand and drug discovery for ligand-binding domains of other ion channels