Category: Nevin Manimala

J Periodontol. 2026 Feb 28. doi: 10.1002/jper.70080. Online ahead of print.

ABSTRACT

BACKGROUND: Periodontitis, a chronic inflammatory disease, is linked to systemic conditions such as cardiovascular and kidney disease. Serum α-Klotho, an anti-aging protein with anti-inflammatory properties, has been associated with systemic diseases, but its role in periodontitis is unclear. This study evaluated the relationship between serum α-Klotho levels and periodontitis severity while accounting for confounders.

METHODS: In this cross-sectional study, data from 961 participants in the National Health and Nutrition Examination Survey (NHANES) database were analyzed. Periodontitis was classified into stages (I-IV) and grades (A-C) using the ACES (Application of the 2018 periodontal status Classification to Epidemiological Survey data) guidelines. Serum α-Klotho levels were measured via enzyme-linked immunosorbent assay (ELISA). Ordinal logistic regression assessed associations between α-Klotho levels and periodontitis, adjusting for confounders such as age, smoking, comorbidities, and oral hygiene. The number of lost teeth was analyzed as a secondary outcome.

RESULTS: In both adjusted and unadjusted regression models, no significant association was found between α-Klotho levels and periodontitis. Particularly, adjusted models revealed no significant association between α-Klotho levels and periodontitis stage (OR = 1.0001, p = 0.547, 95% CI: 0.9997-1.0006) or grade (OR = 0.9996, p = 0.144, 95% CI: 0.9991-1.0001). Age, smoking, and comorbidities significantly predicted severity. Despite a weak negative correlation between α-Klotho and tooth loss (r = -0.07, p = 0.023), this association was no longer significant after adjustment.

CONCLUSION: No significant association was found between serum α-Klotho levels and periodontitis severity. Age, smoking, and comorbidities were key predictors, highlighting the multifactorial nature of periodontitis. Further longitudinal and mechanistic studies are needed to clarify whether α-Klotho has a value as a biomarker of periodontal inflammation or disease progression.

PMID:41761827 | DOI:10.1002/jper.70080

Pak J Pharm Sci. 2026 Apr;39(4):1167-1174. doi: 10.36721/PJPS.2026.39.4.REG.15419.1.

ABSTRACT

BACKGROUND: Atrial fibrillation (AF) represents the most common type of persistent arrhythmia in older adults. This research assesses the impact of integrating sodium-glucose cotransporter 2 inhibitors (SGLT2i), specifically dapagliflozin, into standard care on atrial remodeling and the recurrence of AF in elderly patients with multiple co-existing conditions.

OBJECTIVE: The findings aim to inform improved treatment strategies for this patient population.

METHOD: The study enrolled 174 elderly persistent AF (PAF) patients, comparing 88 (research group) who received dapagliflozin plus standard care against 86 controls on standard care only. The primary endpoints were the incidence of AF recurrence and the magnitude of change in left atrial diameter (LAD) at the 12-month mark. Secondary outcomes included levels of myocardial fibrosis biomarkers (PIIINP, PICP, TGF-β1), inflammation markers (hs-CRP, IL-6), cardiac function tests (NT-proBNP, LVEF), quality of life (6MWT, ADL) and safety monitoring.

RESULTS: The research group showed a lower rate of AF recurrence at 12 months than the control group (P<0.05); this benefit was even greater in patients with diabetes (P<0.05). LAD decreased after treatment in both groups and the decrease was greater in the research group (P<0.001). The research group also achieved greater reductions in serum PIIINP, PICP, TGF-β1, hs-CRP and IL-6 compared to the control group (P<0.05). Furthermore, a more substantial drop in NT-proBNP was observed (P<0.05). LVEF remained stable in the research group but declined slightly in the control group (P<0.05). Quality of life metrics also favored the research group, which showed superior gains in both 6MWT distance and ADL scores (P<0.05). The safety profile was similar between groups, with no statistically significant difference in adverse effects (P<0.05).

CONCLUSION: These results indicate that adding dapagliflozin to standard care is a promising treatment option for PAF.

PMID:41761812 | DOI:10.36721/PJPS.2026.39.4.REG.15419.1

Pak J Pharm Sci. 2026 Apr;39(4):1112-1120. doi: 10.36721/PJPS.2026.39.4.REG.14929.1.

ABSTRACT

BACKGROUND: Acute pancreatitis (AP) is a common gastrointestinal emergency characterized by unpredictable severity. Early identification of patients at risk for severe disease is essential for timely intervention and improved outcomes, yet reliable prognostic markers remain limited, particularly in Central Asian clinical settings.

OBJECTIVE: To identify early clinical, laboratory, and demographic predictors of acute pancreatitis (AP) severity using statistical and machine learning approaches, to improve early risk stratification and guide prompt clinical management.

METHODS: This retrospective case series analysed 40 patients diagnosed with AP between 2022 and 2024 at tertiary hospitals in Bishkek, Kyrgyzstan. Admission data, including demographic characteristics, clinical symptoms, and laboratory values, were collected and evaluated using the revised Atlanta criteria. Statistical analyses included correlation testing, subgroup comparisons, and logistic regression, while a machine-learning-based feature importance analysis was used to identify key predictors of severe AP.

RESULTS: Several variables were significantly associated with severe AP. Serum amylase >500 U/L (OR = 5.2, p 7lt; 0.001), WBC count >15×10⁹/L (OR = 4.7, p <0.001), and BMI ≥30 (OR = 3.4, p = 0.003) emerged as strong predictors of severity. A strong correlation was observed between total bilirubin and jaundice (r = 0.62, p < 0.001). Obese patients had longer hospital stays compared with non-obese patients (median 12 vs. 7 days; p = 0.021). Machine learning analysis confirmed serum amylase, WBC count, and BMI as the most influential predictors.

CONCLUSION: Serum amylase, WBC count and BMI are practical, easily accessible markers that can support early prediction of AP severity. Incorporating these indicators into initial assessment protocols may enhance risk stratification and optimize clinical decision-making. Prospective multicentre studies are needed to validate these findings and refine AP severity prediction models.

PMID:41761807 | DOI:10.36721/PJPS.2026.39.4.REG.14929.1

Pak J Pharm Sci. 2026 Apr;39(4):990-998. doi: 10.36721/PJPS.2026.39.4.REG.13681.1.

ABSTRACT

BACKGROUND: Depression is a common mental disorder. Patients with treatment-resistant depression (TRD) often experience sleep disorders (SD), which interact with each other and aggravate the deterioration of the disease.

OBJECTIVE: In this study, we analyzed the effect of paroxetine combined with low-dose quetiapine on patients with treatment-resistant depression complicated by sleep disorders.

METHODS: We divided treatment-resistant depression + sleep disorders 120 patients into a control group treated with paroxetine and a research group treated with paroxetine + low-dose-quetiapine. Hamilton Depression Scale (HAMD-17), Self-rating Anxiety and Depression Scale (SAS/SDS), Pittsburgh Sleep Quality Index (PSQI) and serum indexes (cortisol, epinephrine, thyroid hormone, etc.) were used to analyze the data.

RESULTS: In terms of clinical efficacy, the research group demonstrated superior efficacy. Besides, the research group showed lower self-rating anxiety/depression scale scores than the control group after treatment (P<0.05). In terms of sleep quality, the Pittsburgh Sleep Quality Index of the research group also decreased more significantly compared with the control group (P<0.05). Moreover, better stress injury alleviation and endocrine function improvement were determined in the research group (P<0.05). The two groups were not statistically different in treatment compliance and adverse reactions (P>0.05).

CONCLUSION: Paroxetine combined with a low dose of quetiapine is a clinically effective approach for treatment-resistant depression with sleep disorders and is recommended for clinical use.

PMID:41761797 | DOI:10.36721/PJPS.2026.39.4.REG.13681.1

Pak J Pharm Sci. 2026 Apr;39(4):970-978. doi: 10.36721/PJPS.2026.39.4.REG.15414.1.

ABSTRACT

BACKGROUND: Hepatocarcinogenesis arising from liver cirrhosis is a major contributor to hepatocellular carcinoma (HCC), but effective interventions remain limited Objective: This study aimed to elucidate the molecular mechanism by which icariin suppresses cirrhosis-to-cancer progression through the ROS/NLRP3/miR-145 axis.

METHODS: Fifty Sprague-Dawley rats were randomly assigned to five groups: control, model, low-dose icariin (ICA-L), high-dose icariin (ICA-H), and positive control. In vitro, SMMC-7721 and HepG2 cells were treated with TGF-β1 and various concentrations of icariin to assess their effects on hepatocellular carcinoma cell activity.

RESULTS: Compared with the model group, icariin significantly reduced the liver index, serum AFP levels, Ki-67 positivity, and hepatic ROS levels in rats, suppressed NLRP3 expression, upregulated miR-145, and effectively ameliorated liver fibrosis and dysplasia (P<0.05). In SMMC-7721 cells, icariin inhibited TGF-β1-induced proliferation, migration and invasion, promoted apoptosis and G0/G1 phase arrest, while concurrently increasing exosomal miR-145 levels (P<0.05). Further mechanism verification confirmed that miR-145 directly targets and inhibits NLRP3 expression.

CONCLUSION: Icariin effectively inhibits cirrhosis-associated carcinogenesis by suppressing the ROS-NLRP3 pathway and upregulating miR-145, providing a theoretical basis for the prevention and treatment of cirrhosis and hepatocellular carcinoma.

PMID:41761795 | DOI:10.36721/PJPS.2026.39.4.REG.15414.1

Neurorehabil Neural Repair. 2026 Feb 28:15459683261418670. doi: 10.1177/15459683261418670. Online ahead of print.

ABSTRACT

BackgroundThe Time to Walking Independently after Stroke (TWIST) prediction tool is designed to predict the number of post-stroke weeks at which patients are expected to achieve walking independence. The external validation of the TWIST tool’s clinical applicability and generalizability has been desired.ObjectiveWe performed a geographic external validation of TWIST prediction in a multicenter prospective cohort.Patients and MethodsAdult post-stroke patients with lower-limb weakness and inability to walk independently were enrolled. Each patient’s TWIST score (max. score: 4 points) was calculated using age, knee-extension strength, and the Berg Balance Scale score at 1 week post-stroke. The TWIST score predicts independent walking by 4, 6, 9, 16, or 26 weeks post-stroke, and we calculated the overall fit, calibration, and discrimination at each of these timepoints to assess the model’s performance.ResultsThe validation cohort consisted of 145 patients (median age 73 years, 44% women, 36% moderate-severe stroke). At 9 and 26 post-stroke weeks, 60.7% and 72.4% of the patients achieved walking independence. The overall fit explained a moderate proportion of the outcome’s variance (Nagelkerke R² = 0.28-0.49), and the discrimination performance was good (c-statistic >0.75). Calibration performance showed over-prediction at all timepoints (calibration-in-the-large = -1.62 to -0.34). Higher TWIST scores (3 or 4 points) over-predicted early post-stroke; lower TWIST scores (1 or 2 points) became increasingly over-predictive over time.ConclusionsThe TWIST prediction tool optimistically predicted walking independence in Japanese patients with stroke. Further validation studies are necessary to assess this tool’s precise clinical impact and generalizability.Clinical Trial Registration URL:https://www.umin.ac.jp/UMIN000050588.

PMID:41761786 | DOI:10.1177/15459683261418670

Lang Speech. 2026 Feb 28:238309261419120. doi: 10.1177/00238309261419120. Online ahead of print.

ABSTRACT

This tutorial paper introduces two approaches to modeling tongue contour data obtained with DeepLabCut using multivariate generalized additive models (MGAMs) and multivariate functional principal component analysis (MFPCA). For each method, we present a fully commented analysis of two illustrative data sets: VC coarticulation in Italian and Polish, and consonant emphaticness in Lebanese Arabic. All the materials (inlcuding data and code) are available in the research compendium of the tutorial at https://github.com/stefanocoretta/mv_uti. We conclude by discussing advantages and disadvantages of the two methods (MGAM and MFPCA) and we recommend researchers to prefer MFPCA over MGAM as an initial step for modeling tongue contours.

PMID:41761784 | DOI:10.1177/00238309261419120

Leuk Lymphoma. 2026 Feb 28:1-11. doi: 10.1080/10428194.2026.2633180. Online ahead of print.

ABSTRACT

In a Norwegian national cross-sectional survey, we assessed the burden of selected late effects (LEs) by a 95-item questionnaire in tumor-free Hodgkin lymphoma survivors (HLSs) diagnosed at age ≥60 years. Responses were compared to age- and sex-matched controls. A total of 290 older HLSs diagnosed 2000-2021 received the questionnaire, 193 (67%) were included. Median age at survey was 76 years (range 63-92) and median time since diagnosis 7 years (2-23). Compared to controls, HLSs reported significantly higher rates of heart failure (10% vs. 6%), atrial fibrillation (19% vs. 14%), memory problems (48% vs. 37%), other cognitive difficulties (34% vs. 17%) and chronic fatigue (29% vs. 13%). HLSs scored lower on physical and mental health-related quality of life (HRQoL) and more often reported needing help with basic (P-ADL) and instrumental activities of daily living (I-ADL). However, differences were small, only for fatigue and dependence in I-ADL did the difference reach moderate statistical effect size.

PMID:41761714 | DOI:10.1080/10428194.2026.2633180

J Neurotrauma. 2026 Feb 28:8977151261424703. doi: 10.1177/08977151261424703. Online ahead of print.

ABSTRACT

Individuals experiencing severe polytrauma are typically transported to the highest level of care as soon as possible, including helicopter evacuation from remote and/or rural environments. However, several recent preclinical and clinical studies have suggested that aeromedical evacuation exacerbates central nervous system injury and inflammation, and potentially results in increased mortality, questioning the right time and conditions under which to fly. Twenty-four swine with moderate-to-severe rotational traumatic brain injury (TBI) and ∼40% blood loss were randomly assigned to standard (∼8500 feet), tactical (evasive maneuvering), or mock (stationary on ground) helicopter (U.S. Army Black Hawk; HH-60M model) evacuation 2 h post-injury, with standard recommended therapies initiated in-flight. Results indicated that tactical evacuation was associated with increased cerebral perfusion pressure and inflammation (IL-6) post-flight relative to the standard and mock evacuation profiles, even after statistically controlling for pre-flight trauma procedures. Although the overall mortality rate was ∼25%, indicating severe polytrauma, no differences in mortality were observed as a function of aeromedical evacuation scenarios. Primary biomarkers of hemorrhagic shock, traumatic brain injury, lung and kidney pathology were also negative for aeromedical evacuation effects. In summary, the medical benefits associated with immediate (i.e., within a few hours of injury) helicopter evacuation of severe polytrauma patients likely outweigh the few increased complications associated with flight, as the latter may only be present during more extreme helicopter evacuation scenarios. Additional studies are needed to address potential adjunctive therapies that can be administered pre-flight to minimize the potential adverse effects of tactical flight.

PMID:41761707 | DOI:10.1177/08977151261424703

Eur J Neurol. 2026 Mar;33(3):e70527. doi: 10.1111/ene.70527.

ABSTRACT

BACKGROUND: Insulin resistance and impaired insulin secretion are hallmarks of type 2 diabetes (T2D) and may influence risks of complications including dementia. We investigated dementia risk across T2D subgroups defined by beta-cell function and insulin sensitivity.

METHODS: We used Homeostasis Model Assessment-2 indices of beta-cell function (HOMA2-B) and insulin sensitivity (HOMA2-S) to classify 7221 individuals with recently diagnosed T2D into insulinopenic (low HOMA2-B, high HOMA2-S), classical (low HOMA2-B, low HOMA2-S), and hyperinsulinemic (high HOMA2-B, low HOMA2-S) subgroups. Incident dementia was ascertained by validated hospital diagnosis codes and dementia-specific medication over 13 years. Absolute risks were estimated using the Aalen-Johansen estimator and adjusted hazard ratios (aHRs) using Cox regression.

RESULTS: Over a median follow-up of 9 years, 179 (2.5%) developed dementia. The 10-year risk (95% CI) was 3.8% (2.4%-5.8%) in the insulinopenic subgroup versus 2.8% in both classical (2.3%-3.5%) and hyperinsulinemic (2.0%-3.8%) subgroups. Compared with classical T2D, aHRs (95% CI) were 1.31 (0.83-2.09) for insulinopenic and 1.10 (0.78-1.54) for hyperinsulinemic T2D. No robust associations with dementia were observed with insulin resistance (HOMA-IR) or C-peptide levels, although compared to the lowest C-peptide levels (quartile 1), aHRs (95% CI) were decreased at 0.67 (0.45-1.01) in quartile 2, 0.73 (0.48-1.09) in quartile 3, and 0.89 (0.59-1.33) in quartile 4.

CONCLUSIONS: We found no clear associations between T2D subgroup, insulin resistance, or C-peptide level at T2D diagnosis and dementia risk. The numerically higher risk in those with lower insulin secretion was statistically imprecise and warrants further study.

PMID:41761701 | DOI:10.1111/ene.70527