Nevin Manimala

Metab Brain Dis. 2025 Jan 4;40(1):82. doi: 10.1007/s11011-024-01499-1.

ABSTRACT

In the acute stage of stroke, stress hyperglycemia is common in both diabetic and nondiabetic patients. The associations between stress hyperglycemia and functional outcomes, as well as stroke recurrence were heterogeneous in previous studies. We aimed to demonstrate these associations in a general population of patients with ischemic stroke and transient ischemic attack (TIA). We included patients with complete data on blood glucose and hemoglobin from The Third China National Stroke Registry. The stress hyperglycemia ratio (SHR) was calculated using fasting blood glucose (mmol/L) divided by glycosylated hemoglobin A1c (%). Outcomes included functional disability, recurrent ischemic stroke and TIA, combined vascular events, and all-cause mortality at 90 days. In total, 7186 patients were included (median age: 62 [54-70] years, male: 4864 [67.69%], TIA: 589 [8.20%]). SHR levels were significantly associated with functional disability (adjusted OR: 1.69, 95%CI: 1.22-2.33). For every 1 standard deviation increment in SHR, the risk of functional disability increased by 13%. Compared to the patients in SHR Tertile 1, those in Tertile 3 had a 1.31-fold increased risk of functional disability (95%CI: 1.08-1.60). There was a trend indicating that the risk of functional disability increased with higher SHR tertiles (P for trend = 0.0074). Stroke severity explained 42.94% of the total excess association between SHR and functional disability. However, neither SHR levels nor SHR tertiles were associated with recurrent ischemic stroke and TIA, combined vascular events, or all-cause mortality. This study found that admission stress hyperglycemia was associated with functional disability, which was partially mediated by stroke severity.

PMID:39754666 | DOI:10.1007/s11011-024-01499-1

Eur J Clin Microbiol Infect Dis. 2025 Jan 4. doi: 10.1007/s10096-024-05036-x. Online ahead of print.

ABSTRACT

BACKGROUND: High-risk human papillomavirus (HR-HPV) infection is the primary cause of cervical cancer and precancerous lesions. Approximately 35% of women with low-grade cervical intraepithelial neoplasia (CIN1) may experience persistence or progression to high-grade lesions. Yet, the dynamic characteristics of HR-HPV infection in women with CIN1 remain unclear.

METHODS: A total of 564 women diagnosed with CIN1, recruited from a community-based cohort, underwent a 24-month follow-up at 6th, 12th, and 24th month intervals. Hazard ratios (HRs) with 95% confidence interval (CI) were calculated to evaluate the risk of HR-HPV infection prognosis and their associated factors. Kaplan-Meier survival curves illustrated the dynamic changes of HR-HPV infection and association between HR-HPV infection prognosis and various influencing factors.

RESULTS: HPV16 was the predominant carcinogenic genotype, followed by HPV58 and HPV52. Over the 24-month follow-up, persistent HPV16 infection occurred in 10.6% of women, with 14.4% converting from positive to negative and 4% developing HPV16 positivity from baseline HR-HPV negativity. Rates of persistent infection for HPV58, 52, 18, and 56 decreased over time, with HPV58, 52, and 31 infections more likely to turn HR-HPV negative. Additionally, rates of positive conversion from negative for HPV58, 56, 33, and 66 increased with extended follow-up time. Variables associated with dynamic characteristics of HR-HPV infection prognosis included personal hygiene, age of first menarche, age at first sexual intercourse, educational level, age, and menopausal status (all P < 0.05).

CONCLUSIONS: These findings contribute to understanding the dynamic characteristics of HR-HPV infection prognosis in women with CIN1 and its association with non-viral factors.

PMID:39754612 | DOI:10.1007/s10096-024-05036-x

Omega (Westport). 2025 Jan 4:302228241312744. doi: 10.1177/00302228241312744. Online ahead of print.

ABSTRACT

Suicide is an important health concern. Excepting cancer, the association between physical disorders and suicidal risk is comparatively less explored. Instrumental variable analysis has been suggested as a powerful technique to deal with possible bias caused by unmeasured confounders in observational research. This population-based study set out to assess the suicidal risk of patients with major physical disorders by employing the instrumental variable analysis. Data were retrieved from the National Health Insurance Research Database and the Death Certification Registry in Taiwan (years 2010-2018). The Cox proportional hazards model with an instrumental variable estimator was performed, adjusting for comorbidities of mental disorders and other covariates. Analytical results showed that compared to their counterparts, patients with major physical disorders had an elevated risk of death by suicide within one year and three years after diagnosis of physical illness. Only did epilepsy not demonstrate a statistically significant impact on the risk of suicide.

PMID:39754563 | DOI:10.1177/00302228241312744

Neurol Res. 2025 Jan 4:1-10. doi: 10.1080/01616412.2024.2448624. Online ahead of print.

ABSTRACT

OBJECTIVES: The aim of this study was to investigate the effect of eight weeks of aerobic training (AT) and vitamin C supplementation (VC) on apoptotic markers in hippocampus tissue of AD rats treated with trimethyltin (TMT).

MATERIALS AND METHODS: In this experimental study, 32 Sprague- Dawley rats (mean age: 14-18 months and mean weight 270-320 g) were treated with (10 mg/kg) TMT and divided into 4 groups including: 1) ADcontrol, 2) VC, 3) AT and 4) AT+VC groups. In order to investigate the effects of AD induction on research variables, 8 healthy rats selected as healthy control group (HC). Groups 3 and 4 trained for eight weeks, three sessions per week and each session lasted 15-48 minutes with an intensity of 10-24 m/min. Groups 2 and 4 received 4 mg/kg VC orally. One-way ANOVA with Tukey’s post- hoc tests were used for statistical analysis of data (p ≤ 0.05).

RESULTS: The gene expression levels of Caspase 3, FasL, Cyt-C and AP-1 in the AT, VC and AT+VC groups were significantly lower than TMT group (p ≤ 0.05); Caspase 3, FasL and Cyt-C levels were significantly lower in the AT+VC group compare to VC and ET groups (p ≤ 0.05). CytC levels in AT group were significantly lower than VC group (p = 0.002). Also, AP-1 levels in AT+VC group were significantly lower than AT group (p = 0.01).

CONCLUSIONS: It seems that AT and VC, both alone and interactively, can probably induce their anti-apoptotic effects in the hippocampus tissue of rats with AD via a common signaling pathway.

PMID:39754544 | DOI:10.1080/01616412.2024.2448624

J Physiol. 2025 Jan 4. doi: 10.1113/JP286685. Online ahead of print.

ABSTRACT

Robust preclinical models of asymmetric ventricular loading in late gestation reflecting conditions such as hypoplastic left heart syndrome are lacking. We characterized the morphometry and microvascular function of the hypoplastic left ventricle (LV) and remaining right ventricle (RV) in a sham-controlled late gestation fetal lamb model of impaired left ventricular inflow (ILVI). Singleton fetuses were instrumented at ∼120 days gestational age (dGA; term is ∼147 days) with vascular catheters, an aortic flow probe and a deflated left atrial balloon. Balloons in ILVI fetuses were inflated over the 8 day study until aortic output was eliminated; Sham balloons remained deflated. At the study end-point (∼134 dGA), cardiac function was assessed by echocardiography, microvascular perfusion of each free wall was measured by myocardial contrast echocardiography (MCE) and terminal morphometric data were collected. During the chronic study, flow through the ascending aorta of ILVI fetuses fell from 389 to -48 mL min^-1 with minimal changes to other haemodynamics or blood chemistry. End-point echocardiography and morphometry similarly showed significant and meaningful reductions in ILVI LV chamber volume and wall mass without statistically significant changes in RV size relative to Shams. MCE revealed modestly increased LV perfusion and profoundly increased RV perfusion in ILVI fetuses. Our model displays effective LV hypoplasia with preserved overall fetal health, and our finding of increased RV myocardial perfusion may indicate active vascular remodelling in response to the experimental lesion. KEY POINTS: Hypoplastic left heart syndrome can be caused by insufficient inflow of blood to the fetal left ventricle. We found that eliminating fetal left ventricular input for 8 days reduced left ventricular size and volume, with minimal effects on the right ventricle or overall fetal health. Blood and oxygen delivery increased significantly in the right ventricle and slightly in the hypoplastic left ventricle. Our results suggest functional and anatomical adaptation of the fetal coronary microvasculature to univentricular right heart conditions.

PMID:39754538 | DOI:10.1113/JP286685

J Atten Disord. 2025 Jan 4:10870547241307680. doi: 10.1177/10870547241307680. Online ahead of print.

ABSTRACT

OBJECTIVE: ADHD is one of the most common neurodevelopmental disorders, seen in children and adolescents, and is often treated with various pharmacological agents, especially methylphenidate. There are differing opinions in the literature regarding the cardiovascular safety of long-term methylphenidate use. Studies suggest that the drug may increase the risk of hypertension, myocardial infarction, ventricular arrhythmia, sudden cardiac death, cardiomyopathy, heart failure (HF), pulmonary hypertension, and stroke. This study aimed to compare the clinical and echocardiographic characteristics of patients diagnosed with ADHD who have been using long-acting methylphenidate for an extended period with age-gender matched healthy volunteers.

MATERIALS AND METHODS: A total of 70 patients diagnosed with ADHD, who had been using long-acting methylphenidate for 2 years or more, and 51 healthy volunteers, who were referred to our clinic, were included in our study. Patients were evaluated with basic and advanced techniques such as Motion Mode (M-mode), two-dimensional (2D), Doppler, and 2D-Speckle Tracking (STE) using transthoracic echocardiography. All other data were evaluated instantly after the processing with the strain images analysis program.

RESULTS: Statistically significant differences were observed between the case and control groups in terms of body mass index (BMI) and systolic blood pressure (SBP), with BMI negatively correlated and SBP positively correlated with methylphenidate use duration. There was no significant difference between the groups in apical four-chamber, three-chamber, two-chamber, and global longitudinal strain (GLS) values obtained by 2D-STE technique indicating early deterioration. The Left Ventricular (LV) lateral E’ value, which indicates diastolic dysfunction, was lower in the drug group, but still within normal limits. The lateral LV E’, Right Ventricular (RV) E’, and RV A’ values showed a significant negative correlation with the duration of drug use and remained within normal limits. Other parameters evaluating systolic/diastolic function such as E/E’, left ventricular ejection fraction (LVEF), myocardial performance index (MPI), and tricuspid/mitral annular plane systolic excursion (TAPSE/MAPSE) did not differ significantly between the groups and were within normal limits. Valve structures and regurgitations were also not significantly different between the two groups.

CONCLUSION: Considering all parameters, we conclude that long-term use of long-acting methylphenidate does not cause cardiovascular dysfunction in late adolescent and early adult individuals. The observed differences in the E’ lateral value between the case and control groups, as well as the slight correlation of lateral LV E’, RV E’, and RV A’ values with the duration of use, do not directly indicate cardiac dysfunction.

PMID:39754497 | DOI:10.1177/10870547241307680

Clin Pharmacol Ther. 2025 Jan 4. doi: 10.1002/cpt.3531. Online ahead of print.

ABSTRACT

Two observational studies were conducted to support an initiative to qualify translational kidney safety biomarkers as clinical drug development tools that identify tubular injury prior to changes in estimated glomerular filtration rate (eGFR). Normal healthy volunteers provided three morning spot urine collections over 4 weeks. Patients undergoing surgical resection and intrathoracic cisplatin for malignant pleural mesothelioma provided urine samples pre- and postoperatively at 4, 8, and 12 hours and daily for 6 days. Using receiver-operating characteristics curves, “statistically significant thresholds” established peak longitudinal changes for 8 biomarkers to differentiate mesothelioma patients who developed acute kidney injury (AKI) from normal healthy volunteers. We also assessed “medically significant thresholds” to differentiate mesothelioma patients who did vs. did not develop AKI. Statistically and medically significant thresholds for a fold-change from baseline of urine creatinine (UCr)-normalized values were established for 6 biomarkers: clusterin (2.2, 5.1); osteopontin (3.1, 7.1); N-acetyl-ß-D-glucosaminidase (2.7, 8.1); kidney injury molecule-1 (4.3, 7.5); cystatin C (1.8, 4.5); neutrophil gelatinase-associated lipocalin (2.9, 7.8). For urine albumin and total protein, thresholds were established based on UCr-normalized absolute values: (> upper limit normal, > 10× upper limit normal). Statistically significant thresholds for all biomarkers outperformed eGFR at discriminating mesothelioma subjects exposed to cisplatin from healthy volunteers, demonstrating their utility for enhancing safe drug development. Medically significant thresholds provide perspective on when patients begin to exhibit AKI. These studies have established guideposts for confirmatory studies with additional cohorts and nephrotoxicants to formally qualify the selected biomarkers with worldwide regulatory authorities.

PMID:39754474 | DOI:10.1002/cpt.3531

Orthod Craniofac Res. 2025 Jan 4. doi: 10.1111/ocr.12895. Online ahead of print.

ABSTRACT

OBJECTIVE: This retrospective study aimed to evaluate morphometric changes in mandibular condyles of patients with skeletal Class III malocclusion following two-jaw orthognathic surgery planned using virtual surgical planning (VSP) and analysed with automated three-dimensional (3D) image analysis based on deep-learning techniques.

MATERIALS AND METHODS: Pre-operative (T1) and 12-18 months post-operative (T2) Cone-Beam Computed Tomography (CBCT) scans of 17 patients (mean age: 24.8 ± 3.5 years) were analysed using 3DSlicer software. Deep-learning algorithms automated CBCT orientation, registration, bone segmentation, and landmark identification. By utilising voxel-based superimposition of pre- and post-operative CBCT scans and shape correspondence, the overall changes in condylar morphology were assessed, with a focus on bone resorption and apposition at specific regions (superior, lateral and medial poles). The correlation between these modifications and the extent of actual condylar movements post-surgery was investigated. Statistical analysis was conducted with a significance level of α = 0.05.

RESULTS: Overall condylar remodelling was minimal, with mean changes of < 1 mm. Small but statistically significant bone resorption occurred at the condylar superior articular surface, while bone apposition was primarily observed at the lateral pole. The bone apposition at the lateral pole and resorption at the superior articular surface were significantly correlated with medial condylar displacement (p < 0.05).

CONCLUSION: The automated 3D analysis revealed distinct patterns of condylar remodelling following orthognathic surgery in skeletal Class III patients, with minimal overall changes but significant regional variations. The correlation between condylar displacements and remodelling patterns highlights the need for precise pre-operative planning to optimise condylar positioning, potentially minimising harmful remodelling and enhancing stability.

PMID:39754473 | DOI:10.1111/ocr.12895

Nonlinear Dynamics Psychol Life Sci. 2025 Jan;29(1):59-111.

ABSTRACT

Emergent phenomena exhibit interesting dynamics when considered individually. The present article examines two emergent processes that could be occurring simultaneously in an intense team interaction: the emergence of leaders and the emergence of autonomic synchrony within teams making dynamic decisions. In the framework of panarchy theory and related studies on complex systems, autonomic synchrony would be a fast dynamic that is shaped or controlled by leadership emergence, which is a slower dynamic. The present study outlines three distinct statistical distributions – the swallowtail catastrophe model for phase shifts, inverse power laws that indicate fractal processes, and lognormal distributions – that are known to characterize emergent processes of different types. The objective was to determine the extent to which the two emergent processes reflected the same dynamics. Research participants were 136 undergraduates who were organized into teams of three to five members playing the computer-game Counter-Strike while wearing GSR sensors to measure autonomic arousal levels in a steady stream. After approximately two hours of interaction, team members rated each other on leadership behaviors. Autonomic synchrony was analyzed as a driver-empath process that produced individual driver scores (the total influence of one person on the rest of the group) and empath scores (the total influence of the group on one person). Results showed that leadership emergence displayed the swallowtail configuration that was consistent with prior studies. Autonomic synchrony started as a simpler process and unfolded into a swallowtail catastrophe toward the end of the experimental session. Lognormal distributions were second-best representations of all variables. Inverse power laws were least descriptive of any of the research variables. The implications of the temporal dynamics of the co-emerging processes for training and team development are discussed.

PMID:39754464

Nonlinear Dynamics Psychol Life Sci. 2025 Jan;29(1):1-4.

ABSTRACT

The articles in this special issue examine the contributions of Jeffrey A. Goldstein to the understanding of emergence as a formal group of processes. Applications include work teams, organizations, ecologies of organizations, and societies. Prominent methodologies include agent-based modeling, qualitative analysis of publicly available business and governmental reports, structured analyses of team discussions, and nonlinear statistical analysis of time series data.

PMID:39754461