Category: Nevin Manimala

J Phys Chem B. 2026 Feb 6. doi: 10.1021/acs.jpcb.5c08465. Online ahead of print.

ABSTRACT

The α7-nicotinic acetylcholine receptor (α7-nAChR) is a cation-selective Cys-loop receptor involved in diverse physiological processes and is an important therapeutic target. Multiple cryo-EM structures of putative open states are now available, and their functional relevance is under active investigation. Here, we combined single-channel patch-clamp recordings with atomistic molecular dynamics (MD) simulations to assess the conductive properties of several α7-nAChR structures solved with different ligands. Simulations restrained to the respective cryo-EM structures produced only modest ion flux for all models, inconsistent with experiment, whereas fully unrestrained simulations revealed marked differences in their ability to relax into physiologically conductive ensembles. Two structures, 7KOX and ligand-bound 8V82, consistently stabilized into conductive states whose permeation properties agreed with our measured inward single-channel conductance. The conduction of 8V82 nearly stopped upon removing the ligands resolved in the PDB structures. 8V80 showed only intermittent conduction with ligands, and remained nonconductive without them. 7EKT collapsed into a nonconductive conformation upon relaxation, irrespective of whether the modeled ligands were retained or removed. 9LH5, despite having a transmembrane pore nearly identical to 7KOX’s, exhibited approximately 2-fold higher conductance, likely due to a widened extracellular vestibule. Across models, permeation events followed Poissonian statistics with a characteristic entry lag captured by a double-Poisson model. Simulations of outward currents consistently overestimated the conductance compared to experiments, perhaps reflecting the absence of the full intracellular domain in available structural models and/or the presence of current-blocking concentrations of cytosolic Mg²⁺ in patch-clamp cell-attached recordings. These results identify the conformations most compatible with the physiological open state and underscore the importance of unrestrained MD, ligand stabilization, and extracellular-vestibule geometry in shaping α7-nAChR conduction.

PMID:41650356 | DOI:10.1021/acs.jpcb.5c08465

Scand J Gastroenterol. 2026 Feb 6:1-5. doi: 10.1080/00365521.2026.2615408. Online ahead of print.

ABSTRACT

BACKGROUND: Advanced fibrosis is the main risk factor for liver-related complications in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). The first line-test for evaluating presence of advanced fibrosis, Fibrosis-4 index (FIB-4), has limitations. Here, we investigated whether the diagnostic performance of FIB-4 could be improved by incorporating commonly analyzed metabolic biomarkers, including C-reactive protein (CRP), Hemoglobin A1c (HbA1c), the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), or uric acid.

METHODS: This cross-sectional study included 276 adult (≥18 years) patients with MASLD from seven Swedish university hospitals. All patients underwent liver stiffness measurement (LSM) for assessment of advanced fibrosis, defined as LSM ≥12 kPa. The performance of FIB-4, CRP, HbA1c, HOMA-IR, and uric acid, alone and in combination, was assessed using logistic regression models. The area under the curve (AUC) was calculated.

RESULTS: An LSM value of ≥12 kPa was found in 45 patients (16%). Combining FIB-4 with CRP, HbA1c, HOMA-IR, and uric acid yielded the highest AUC (0.810; 95% confidence interval [CI] = 0.732-0.889), which was not significantly better than the AUC for FIB-4 alone (0.774, 95%CI = 0.701-0.847).

CONCLUSIONS: Adding CRP, HbA1c, HOMA-IR, or uric acid to FIB-4 did not result in any statistically significant improvement in diagnostic performance, suggesting limited additional value of these biomarkers in identifying advanced fibrosis.

PMID:41650315 | DOI:10.1080/00365521.2026.2615408

Nurs Educ Perspect. 2026 Feb 3. doi: 10.1097/01.NEP.0000000000001498. Online ahead of print.

ABSTRACT

This follow-up study was conducted to establish the preliminary psychometrics of a 12-station mental health Objective Structure Clinical Examination (OSCE). Knowledge is limited regarding OSCE use in undergraduate mental health nursing education. A convenience sample of 63 second-semester junior-level undergraduate nursing students participated. Tools included a demographic and student perceptions questionnaire. Interrater reliability and criterion validity were statistically significant. Students perceived the OSCE as beneficial and challenging. This OSCE was established as a valid, reliable tool that may be used to assess mental health nursing knowledge, skills, and attitudes in combination with existing clinical assessment methods.

PMID:41650312 | DOI:10.1097/01.NEP.0000000000001498

Anesthesiology. 2026 Feb 5. doi: 10.1097/ALN.0000000000005974. Online ahead of print.

ABSTRACT

BACKGROUND: Professionalism is a core competency in graduate medical education, yet research examining specialty-specific professionalism perceptions between trainees and faculty remains limited, particularly regarding the influence of role and institutional culture on these perceptions. This study examined how anesthesiology trainees and attendings perceive unprofessional behavior and whether these perceptions differ based on participant characteristics.

METHODS: A multi-site cross-sectional survey was conducted at five anesthesiology residency programs from February to March 2024. Participants rated degree of unprofessionalism on19 workplace vignettes depicting potentially unprofessional behaviors using a 7-point Likert scale. Vignettes were categorized into five themes: Verbal, Supervision, Quality, Time, and Engagement. Proportional odds models examined differences in ratings based on role (trainee vs. attending), adjusting for gender, race, underrepresented status, and institution.

RESULTS: Among 369 respondents (153 trainees, 216 attendings; 35.9% response rate), perceptions varied by scenario and participant characteristics. Six vignettes were more consistently rated as unprofessional (>80% unprofessional ratings), while four showed higher variability (<50% unprofessional ratings). Significant institutional differences were observed in five vignettes (Odds ratios [ORs] <0.14 or >3.7, p < 0.0001 to 0.027). Age influenced ratings of five vignettes (ORs = 0.75, 1.68, 1.63, 1.35 and 1.31 respectively, p <0.0001 to 0.027), while gender, race and underrepresented status showed no significant differences. After adjusting for demographics, trainees and attendings differed significantly in their ratings of 10 vignettes (p <0.0001 to 0.033). Attendings rated nine scenarios as more unprofessional than trainees (ORs ranging from 0.26 to 0.50), while trainees rated only one scenario as more unprofessional than attendings (OR = 2.01).

CONCLUSIONS: Perceptions of unprofessional behavior among anesthesiology professionals vary significantly by role and institution. These findings underscore the importance of context-sensitive approaches to professionalism education that acknowledge diverse perspectives and institutional cultures while maintaining core professional standards.

PMID:41650300 | DOI:10.1097/ALN.0000000000005974

J Public Health Manag Pract. 2026 Feb 6. doi: 10.1097/PHH.0000000000002339. Online ahead of print.

ABSTRACT

CONTEXT: Denominator inflation (DI) can burden long-standing immunization information systems (IIS), evident through a system having more client records than population estimates. DI underestimates IIS vaccination coverages compared to National Immunization Surveys (NIS) data. To mitigate DI, the Wisconsin Immunization Registry (WIR) implemented a dormant indicator in June 2020. Clients are presumed to have left the jurisdiction and are placed in the dormant state if they meet the following criteria: client age is at least 11 years old, no updates to the client record in at least 10 years, and the record has not been queried in the last five years. The querying component is a novel approach when compared to American Immunization Registry Association recommendations for the Patient Active/Inactive Status.

OBJECTIVE: The study purpose was to quantify how incorporating the dormant state in an adolescent population assessment impacts Wisconsin’s vaccination coverage rates compared to the NIS-Teen estimates. This study also addressed the population characteristics of adolescent dormant state and non-dormant state client records.

DESIGN: The study population included all Wisconsin adolescents, aged 13-18 years, and assessed vaccine uptake for Meningococcal ACWY , Tdap, HPV initiation, and HPV Complete. Vaccination coverage was assessed, with and without the dormant clients, and then compared to the NIS-Teen estimates. Descriptive statistics were assessed among dormant and non-dormant clients, including a regional variation assessment.

RESULTS: Initial results showed an increase in adolescent vaccination rates for all vaccines and series when excluding dormant clients and suggest a more accurate assessment in line with NIS-Teen estimates. Dormant clients had a higher proportion of unknown and missing data fields for race, sex, and ethnicity.

CONCLUSION: At this time, removing dormant client records is an effective strategy for reducing DI in WIR, with opportunities for further refinement.

PMID:41650293 | DOI:10.1097/PHH.0000000000002339

Stat Med. 2026 Feb;45(3-5):e70351. doi: 10.1002/sim.70351.

ABSTRACT

Mediation analysis aims to identify and estimate the effect of an exposure on an outcome that is mediated through one or more intermediate variables. In the presence of multiple intermediate variables, two pertinent methodological questions arise: estimating mediated effects when mediators are correlated, and performing high-dimensional mediation analyses when the number of mediators exceeds the sample size. This paper presents a two-step procedure for high-dimensional mediation analyses. The first step selects a reduced number of candidate mediators using an ad-hoc lasso penalty. The second step applies a procedure we previously developed to estimate the mediated effects, accounting for the correlation structure among the retained candidate mediators. We compare the performance of the proposed two-step procedure with state-of-the-art methods using simulated data. Additionally, we demonstrate its practical application by estimating the causal role of DNA methylation (DNAm) in the pathway between smoking and rheumatoid arthritis (RA) using real data.

PMID:41646011 | DOI:10.1002/sim.70351

J Vasc Access. 2026 Feb 6:11297298261415955. doi: 10.1177/11297298261415955. Online ahead of print.

ABSTRACT

BACKGROUND: Arterial blood gas (ABG) analysis is essential in the emergency department (ED) for the rapid assessment of acid-base status, oxygenation, and metabolic disturbances in critically ill patients. The distal forearm (DF) is the conventional site for radial arterial puncture. Recent studies in interventional cardiology have explored the anatomical snuffbox (ASB) approach as an alternative vascular access site; however, its utility for ABG sampling in the ED remains unclear.

METHODS: In this single-center, randomized controlled non-inferiority trial conducted from May 2022 to October 2023, 356 adult patients requiring ABG analysis in the ED were randomized in a 1:1 ratio to undergo sampling via either the ASB or DF approach. Eligible patients had a palpable radial pulse at both access sites, while those with hypotension, local site abnormalities, or a positive Allen’s test were excluded. The primary outcome was the first-pass success rate; secondary outcomes included the number of attempts, failure rates (defined as failure to obtain a sample after three attempts), and procedure-related complications observed during a 12-h ED stay.

RESULTS: The DF approach demonstrated a significantly higher first-pass success rate (74.7%) compared with the ASB approach (60.7%; p = 0.006). The failure rate was lower in the DF group (5.1%) relative to the ASB group (21.3%; p < 0.001). Although minor complications such as hematoma, arterial spasm, and bleeding were noted in both groups, there were no statistically significant differences in overall complication rates.

CONCLUSIONS: Although the anatomical snuffbox (ASB) approach has been proposed as an alternative access site based on potential benefits in other procedural settings, this trial found that it did not meet non-inferiority compared with the conventional distal forearm (DF) method for ABG sampling in the ED. Given the higher failure rate with the ASB approach, the DF method remains the preferred sampling site in this setting.

TRIAL REGISTRATION: The Clinical Trials Registry – India (CTRI/2022/07/044216).

PMID:41646008 | DOI:10.1177/11297298261415955

Natl Med J India. 2026 Jan-Feb;39(1):23-29. doi: 10.25259/NMJI_295_2023.

ABSTRACT

Background There is minimal literature on the spectrum and long-term outcomes of acute kidney injury (AKI) from tropical countries. Methods Patients with AKI without underlying chronic kidney disease (CKD), were recruited from March 2017 to December 2018 to assess their outcomes. Survivors were followed for a year post-discharge. A linear model with fixed effects was created to compare the estimated glomerular filtration rate (eGFR) trajectories of patients with and without CKD at the end of follow-up. Results A total of 529 patients with AKI were recruited, of which 288 (54.4%) were hospital-acquired AKI. Infections and sepsis were the most common aetiologies for community-acquired AKI and hospital-acquired AKI. The overall mortality rate was 42.9% (n=227). The ICU stay (HR 1.78; 95% CI 1.08-2.93), mechanical ventilation (HR 1.98; 95% CI 1.09-3.54), and the requirement for inotropic support (HR 2.36; 95% CI 1.65-3.39) were independent risk factors of in-hospital mortality. Among 156 subjects with long-term follow-up, 70 (44.9%) developed CKD after a median follow-up of 12 months. Age (p<0.001) and hospital-acquired AKI (p=0.014) were significant predictors, whereas ICU stay and comorbid conditions did not influence the GFR trajectories. CKD patients showed a lower eGFR from the first follow-up (p<0.001). Conclusions AKI is associated with significant mortality. Even after an apparent recovery, around half the survivors progress to CKD at the end of 1 year.

PMID:41645992 | DOI:10.25259/NMJI_295_2023

Natl Med J India. 2026 Jan-Feb;39(1):19-22. doi: 10.25259/NMJI_222_2023.

ABSTRACT

Background Long-term Covid-19 symptoms have the potential to negatively impact health and quality of life. We evaluated the incidence and predictors of long Covid-19 among hospitalized patients. Methods We prospectively collected clinical data of 393 patients diagnosed as Covid-19 positive and admitted to our hospital. At 1-year follow-up, all vital parameters and laboratory investigations were recorded. A multiple logistic regression model was used to determine predictors of long Covid-19. Results Long Covid-19 was found in 34.4% of patients at 1-year follow-up. Most commonly reported symptoms were joint pain (40%), fatigue (33%), and dyspnoea (22.9%). Severity of disease at the time of admission (1.5; 95% Confidence Interval [CI] 1.09-2.2; p=0.01), high body-mass index (BMI) (1.1; 95% CI 1.03-1.13; p=0.003) and increased age (1.02; 95% CI 1.00-1.04; p=0.02) were independent predictors of long Covid-19 on follow-up. Conclusion Almost one-third of patients were diagnosed with long Covid-19 at 1-year follow-up. Severity of disease at the time of admission, increased BMI, and increased age were independent predictors of long Covid-19.

PMID:41645987 | DOI:10.25259/NMJI_222_2023

Natl Med J India. 2025 Nov-Dec;38(6):339-343. doi: 10.25259/NMJI_364_2023.

ABSTRACT

Background Integration of smart mobile devices (SMD) like smartphones and digital tablets into medical practice continues to be hindered despite the benefits of access to guidelines at the point of care and patient safety. The barriers include administrator attitudes, perceptions about how patients would receive it, shyness about accessing it in the presence of coworkers, and perceived attrition in medical education. We aimed to understand the perceptions of doctors, medical students, and patients about the use of SMDs in patient care areas. Methods A cross-sectional survey of doctors, medical students, and patients across multiple states in India was conducted. Data were collected using a validated questionnaire after ethical clearance and participant consent. A sample size of 385 was estimated for each group (95% confidence interval, alpha error 0.5, power 80%). Results 406 doctors, 425 medical students, and 418 patients responded to the survey. 92% doctors, 96% medical students, and 57% patients owned an SMD. 81% doctors had used an SMD for patient care, with a little over 50% having used it in front of their juniors, and only 34% approved the use in patient contact areas. 99% medical students used SMD for studying; 93% advocated it to their juniors for learning, but only 68% used it in front of their juniors, and 29% in front of their patients. About 90% patients were ready for doctors to use SMDs in front of them, with over 75% agreeing that SMD use will lead to better and safer care. Conclusions SMDs are widely used in the patient care area and for medical education. Some perceived barriers such as patient perceptions about doctors require behavioural change and acceptance of changing times.

PMID:41645985 | DOI:10.25259/NMJI_364_2023