Nevin Manimala

Endocr Metab Immune Disord Drug Targets. 2025 Feb 19. doi: 10.2174/0118715303329277250120104421. Online ahead of print.

ABSTRACT

BACKGROUND: Chlorpyrifos (CPF) is an organophosphate insecticide that is mostly used in agriculture for pest control.

AIM: This investigation aimed to evaluate the possible protective role of chrysin nanocrystals on thyroid gland hormones and histology in male rats after exposure to a high dose of chlorpyrifos.

METHOD: Rats were randomly divided into 6 groups (6 rats in each group): 1. healthy control group, 2. treated with chrysin nanocrystal (5 mg/kg), 3. treated with chrysin nanocrystal (10 mg/kg), 4. treated with chrysin nanocrystal (5 mg/kg) + chlorpyrifos, 5. treated with chrysin nanocrystal (10 mg/kg) + chlorpyrifos, and 6. treated with chlorpyrifos (30 mg/kg). After 15 days of intervention, rats were anesthetized, and blood samples were taken from the heart to measure thyroid hormones. Then, the thyroid gland was isolated and stored in 10% formalin for histopathological studies. Thyroid samples were also stored at -80 ° C for measuring oxidative stress parameters.

RESULT: A significant reduction was observed in the serum concentrations of T3 and T4 in all treated groups compared with the control group (p < 0.01). In addition, hormone level examination revealed no statistically significant (p ˃ 0.05) changes in plasma TSH concentration in any of the groups. The treatment with CPF and chrysin nanocrystal did not affect the levels of oxidative biomarkers (MDA, GSH, and NO) in thyroid glands. Photomicrographs of a histological section of the thyroid gland showed vacuolar degenerated follicle epithelium and missing colloids in the histological section of the thyroid gland of all groups.

CONCLUSION: Our findings demonstrated that the oral administration of chrysin nanocrystals could not inhibit the toxic effect of a high dose of CPF on the thyroid gland in the rats.

PMID:39976093 | DOI:10.2174/0118715303329277250120104421

Curr Med Chem. 2025 Feb 18. doi: 10.2174/0109298673359149250212073143. Online ahead of print.

ABSTRACT

BACKGROUND: The precise function of DDX59 Antisense RNA 1 (DDX59- AS1) in lung adenocarcinoma (LUAD) has yet to be fully elucidated.

OBJECTIVE: This study uses bioinformatics analysis and experimental validation to investigate the association between DDX59-AS1 and LUAD.

METHODS: This study uses statistical analysis and database interrogation to investigate the potential association between DDX59-AS1 expression and various clinical characteristics, prognostic factors, regulatory networks, and immune infiltration in LUAD. The quantification of DDX59-AS1 expression in LUAD cell lines is conducted through the use of quantitative real-time polymerase chain reaction (qRT-PCR).

RESULTS: DDX59-AS1 showed significantly elevated levels of expression in patients with LUAD. High levels of DDX59-AS1 expression were found to be significantly associated with poorer overall survival (OS) in patients with LUAD (p = 0.024). Furthermore, an independent correlation was observed between high DDX59-AS1 expression (p = 0.037) and OS in LUAD patients. DDX59-AS1 was found to be involved in various pathways, including glutathione metabolism, proteasome function, and the cytosolic DNA sensing pathway, among others. A significant correlation was observed between the expression levels of DDX59-AS1 and immune cell infiltration in the context of LUAD. Notably, elevated expression of DDX59-AS1 was observed in LUAD cell lines compared to the non-cancerous Beas-2B cell line.

CONCLUSION: A significant correlation was observed between elevated DDX59-AS1 expression in patients with LUAD and adverse prognosis, alongside increased immune infiltration. These results indicate that DDX59-AS1 may function as a prognostic marker for LUAD and a potential predictor of immunotherapy response.

PMID:39976021 | DOI:10.2174/0109298673359149250212073143

Blood Coagul Fibrinolysis. 2025 Jan 23. doi: 10.1097/MBC.0000000000001342. Online ahead of print.

ABSTRACT

OBJECTIVES: Concomitant use of cytochrome P-450 and P-glycoprotein (CYP 3A4/P-gp) inducing antiseizure medications and direct oral anticoagulants (DOAC) may result in reduced DOAC effectiveness, but study results are inconsistent and of variable quality. The purpose of this study was to assess the safety of concomitant CYP 3A4/P-gp inducing antiseizure medications and DOAC use.

METHODS: This was a retrospective cohort study of adult patients who were newly, concomitantly receiving a DOAC (apixaban, dabigatran, or rivaroxaban) and either a CYP 3A4/P-gp inducer (carbamazepine, phenytoin, phenobarbital, or primidone) or noninducer (gabapentin). The primary outcome was the occurrence of a thromboembolic complication, defined as the composite of ischemic stroke and systemic embolism (S/SE) and venous thromboembolism (VTE). Secondary outcomes included the components of the primary composite as well as all-cause mortality and clinically relevant bleeding. Adjusted multivariate proportional hazards modeling was used to compare outcomes for each DOAC individually in the inducer and noninducer groups.

RESULTS: There were 1843 and 14 647 patients who received a DOAC plus a CYP3A4/P-gp inducer and noninducer, respectively. Overall, patients were primarily older, white, had atrial fibrillation, and were dispensed dabigatran. After adjustment, there were no statistically significant differences in the primary outcome between the groups (P > 0.05); however, concomitant inducer and DOAC use was associated with an increased risk of all-cause mortality (P < 0.05).

CONCLUSIONS: No excess risk of thrombosis during concomitant use of DOACs with CYP3A4/P-gp inducing antiseizure medications compared to use with gabapentin was identified. Further research is needed to confirm an association with excess all-cause mortality.

PMID:39976008 | DOI:10.1097/MBC.0000000000001342

Eur J Gastroenterol Hepatol. 2025 Feb 21. doi: 10.1097/MEG.0000000000002949. Online ahead of print.

ABSTRACT

BACKGROUND: Excessive alcohol consumption is a major risk factor for liver disease, with significant variations in its impact across populations. BMI has been identified as a potential mediator in alcohol-related liver damage. This study aimed to examine the association between alcohol consumption and liver function and to explore the mediating role of BMI in a population from India, where both are rising public health concerns.

MATERIALS AND METHODS: A cross-sectional study was conducted using data from adult participants. Liver function was assessed using serum levels of gamma-glutamyl transferase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). Alcohol consumption was self-reported, and BMI was calculated AST from height and weight measurements. Multiple linear regression models were used to evaluate the relationship between alcohol consumption and liver enzymes while adjusting for BMI as a mediator. Statistical significance was set at P < 0.05.

RESULTS: The results indicated that higher alcohol consumption was significantly associated with elevated levels of GGT, ALT, and AST. BMI was found to mediate this relationship, with individuals having higher BMI showing a greater increase in liver enzyme levels in response to alcohol consumption. However, no significant association was observed for ALP. BMI also independently correlated with higher levels of GGT, ALT, and AST.

CONCLUSION: This study highlights the mediating role of BMI in alcohol-induced liver dysfunction in the Indian population. Public health interventions focusing on both reducing alcohol intake and managing obesity may help mitigate the risk of liver disease in this high-risk population.

PMID:39975998 | DOI:10.1097/MEG.0000000000002949

Neuroreport. 2025 Jan 14. doi: 10.1097/WNR.0000000000002138. Online ahead of print.

ABSTRACT

Cannabinoid type 1 receptors (CB1Rs) play important roles in regulating neurotransmitter release, synaptic plasticity, cell differentiation, and survival. CB1R is coupled via pertussis toxin (PTX)-sensitive Gαi/o proteins to the activation of extracellular regulated kinase (ERK) signaling. However, there are multiple Gαi/o isoforms, and it is unknown which of these isoforms is responsible for CB1R-induced phosphorylation of ERK. The purpose of this study was to determine which Gαi/o isoform(s) couple CB1R to ERK phosphorylation. HEK293 cells stably expressing the mouse CB1R (CB1R-HEK cells) were transfected with either pcDNA3.1 or pcDNA3.1 encoding PTX-insensitive mutants of Gαo, Gαi1, Gαi2, or Gαi3. PTX was used to inactivate endogenous Gαi/o isoforms before cells were treated with vehicle, delta-9-tetrahydrocannabinol (∆9-THC), or CP55940 and ERK phosphorylation was measured by western blotting. CP55940 induced robust phosphorylation of ERK in cells transfected with vector alone. This effect was completely abolished by PTX treatment. CP55940-induced ERK phosphorylation was rescued by expression of PTX-insensitive forms of Gαo, Gαi1, Gαi2, or Gαi3, indicating that the CB1 receptor can couple to ERK phosphorylation through each of these Gαi/o isoforms. Consistent with its actions as a partial agonist, ∆9-THC induced nominal (two to four-fold) increases in ERK phosphorylation that did not reach statistical significance except in cells transfected with PTX-insensitive Gαi3. These data demonstrate that CB1R can couple to ERK phosphorylation through Gαo, Gαi1, Gαi2, or Gαi3 when stimulated with CP55940 (full agonist). However, ∆9-THC (partial agonist)-induced ERK activation might require high levels of Gαi3 expression.

PMID:39975996 | DOI:10.1097/WNR.0000000000002138

Front Neurosci. 2025 Feb 5;19:1533799. doi: 10.3389/fnins.2025.1533799. eCollection 2025.

ABSTRACT

OBJECTIVES: Early diagnostic separation between glioblastoma (GBM) and solitary metastases (MET) is important for patient management but remains challenging when based on imaging only. The objective of this study was to assess whether amide proton transfer weighted (APTw) MRI alone or combined with dynamic susceptibility contrast (DSC) MRI parameters, including cerebral blood volume (CBV), cerebral blood flow (CBF), and leakage parameter (K2) measurements, can differentiate GBM from MET.

METHODS: APTw MRI and DSC-MRI were performed on 18 patients diagnosed with GBM (N = 10) or MET (N = 8). Quantitative parameter maps were calculated, and regions-of-interest (ROIs) were placed in whole tumor, contrast-enhanced tumor (ET), edema, necrosis and normal-appearing white matter (NAWM). The mean and max of the APTw signal, CBF, leakage-corrected CBV and K2 were obtained from each ROI. Except for K2, all were normalized to NAWM (nAPTw_mean/max, nCBF_mean/max, ncCBV_mean/max,). Receiver Operating Characteristic (ROC) curves and area-under-the-curve (AUC) were assessed for different parameter combinations. Statistical analyses were performed using Mann-Whitney U test.

RESULTS: When comparing GBM to MET, nAPT_max, nCBF_max, ncCBV_max and ncCBV_mean were significantly increased (p < 0.05) in ET with AUC being 0.81, 0.83, 0.85, and 0.83, respectively. Combinations of nAPTw_max + ncCBV_max, nAPTw_mean + ncCBV_mean, nAPTw_max + nCBF_max, nAPTw_max + K2_max and nAPTw_max + ncCBV_max + K2_max in ET showed significant prediction in differentiating GBM and MET (AUC = 0.92, 0.82, 0.92, 0.85, and 0.92 respectively).

CONCLUSION: When assessed in Gd-enhanced tumor areas, nAPTw MRI signal intensity alone or combined with DSC-MRI parameters, was an excellent predictor for differentiating GBM and MET. However, the small cohort warrants future studies.

PMID:39975970 | PMC:PMC11836003 | DOI:10.3389/fnins.2025.1533799

Front Psychiatry. 2025 Feb 5;16:1508791. doi: 10.3389/fpsyt.2025.1508791. eCollection 2025.

ABSTRACT

INTRODUCTION: Medical students are exposed to various stressors. Among the many factors that determine the possibility of a mental crisis, there is also a personality profile and a sense of meaning in life.

MATERIALS AND METHODS: Sets of anonymous surveys were distributed among medical students of different years studying at the Medical University of Lodz. The set of surveys included a sociodemographic survey, Beck’s Depression Inventory version II (BDI-II), the NEO Five Factory Inventory (NEO-FFI), Reker’s Life Attitude Profile – Revised questionnaire (LAP-R), Osman’s Suicidal Behavior Questionnaire (SBQ-R).

RESULTS: The study cohort comprised of 276 students (mean age 21.7 years). According to the BDI-II, 79 participants (28.4%) were identified as having depressive symptoms. Additionally, 80 participants (28.9%) were assessed to be at significant risk of suicide according to the SBQ-R scale. Based on the results of these questionnaires, we identified four groups: 1. Participants with depressive symptoms (D). 2. Participants with suicide risk (SR), 3. Participants with both depressive symptoms with suicide risk (D and SR), 4. A control group. Students from D and D and SR groups, exhibited higher neuroticism scores compared to those with suicide risk alone (SR) and the control group. In terms of extroversion, the control and SR groups scored higher compared to the D with SR group. Participants with SR and those with D and SR had higher openness scores compared to the D and control groups. D and SR group obtained statistical lower score then control group in the terms of conscientiousness. In life control score, participants in D and D with SR group has significant lower score then SR and control group. The conditions: personal meaning index and life attitude balance in the control group achieved significantly higher values compared to all other groups.

CONCLUSION: People with depressive symptoms, suicide risk and both of these variables simultaneously differed in terms of personality profile and components influencing the meaning of life.

PMID:39975950 | PMC:PMC11836027 | DOI:10.3389/fpsyt.2025.1508791

Front Psychiatry. 2025 Feb 5;16:1538267. doi: 10.3389/fpsyt.2025.1538267. eCollection 2025.

ABSTRACT

INTRODUCTION: Childhood traumatization can result in physical and mental health problems in adulthood, such as post-traumatic stress disorder (PTSD), which negatively influences quality of life and social functioning. Although evidence based trauma treatments benefit clients with PTSD after childhood abuse and comorbid personality disorders, they are less effective than in clients who were traumatized in adulthood, and drop-out is substantial. The current study aims to assess the effects of inpatient dialectical behavior therapy combined with prolonged exposure (DBT-PTSD) on severity of PTSD, dissociation, parasuicidal behavior and borderline personality disorder (BPD) in clients with severe PTSD and comorbid psychiatric disorders. Secondary outcomes are social functioning, quality of life, borderline and cluster C personality disorder symptoms as treatment predictors, treatment trajectories, clients’ experiences and health economic consequences.

METHODS: The naturalistic, longitudinal Trauma Therapy Study is conducted from January 2019 until May 2025 in a mental healthcare center in the Netherlands. Clients with severe PTSD and comorbid conditions who are referred to inpatient DBT-PTSD are included into the study. Based on power analyses a total sample size of N=56 is needed. Measurements take place before the waiting list period, at pre- and posttreatment and at six- and twelve-months follow-up. Clients fill in a daily DBT-PTSD diary, which gives insight into individual symptom trajectories.

RESULTS: Statistical analyses include two-sided paired samples t-tests, linear mixed model analyses and cost-effectiveness analyses. Qualitative interviews are conducted within two years posttreatment and analyzed using a phenomenological approach. We correct for chance capitalization by using a conservative α-level of.01. Multiple imputation is used to handle missing data.

DISCUSSION: Research on the effects of integrated treatment programs for clients with severe PTSD and co-morbid conditions is scarce. This study extends current knowledge on the effects of inpatient DBT-PTSD on PTSD and BPD symptoms, clients’ social functioning and quality of life. In addition, it provides insight into individual symptom trajectories and experiences, inspiring future treatment improvements for clients with severe psychopathology.

TRIAL REGISTRATION: Medical Ethical Committee approval (NL669060018, RTPO1044/01.10.2018). Preregistration: Dutch registration database Centrale Commissie Mensgebonden Onderzoek and International Clinical Trials Registry Platform (NL-OMON46167/01.10.2018/https://trialsearch.who.int/Trial2.aspx?TrialID=NL-OMON46167).

PMID:39975947 | PMC:PMC11836029 | DOI:10.3389/fpsyt.2025.1538267

Res Sq [Preprint]. 2025 Jan 31:rs.3.rs-5927600. doi: 10.21203/rs.3.rs-5927600/v1.

ABSTRACT

Background: Substance use can negatively impact treatment adherence and health outcomes, thus exacerbating the burden of the disease. This study determined the prevalence and factors associated with substance use among patients with TB disease in Kampala, Uganda. Methods: This was a cross-sectional study of 144 patients with drug-susceptible TB enrolled from July 2020 to March 2021 across five health facilities in Kampala. Eligible participants were 18-65 years old, diagnosed with TB, and had initiated treatment for <= one month. Exclusions included drug-resistant TB, severe illness, or impairments affecting study participation. Data on socio-demographics, substance use, and clinical characteristics were collected using a semi-structured questionnaire. Self-reported substance use was the outcome of interest. Descriptive statistics and simple logistic regression analyses were performed for factors associated with substance use. Stata version 18.0 was used for analysis. Results: The participants had a median age of 34 years (IQR: 25.5 – 45.0); 50% were female and 31.9% were HIV infected. The prevalence of any substance use was 20.8% among TB patients. Alcohol use was the predominant substance (18.1%), followed by marijuana (2.8%) and tobacco (2.1%). Males were more likely than females to use any substances (COR: 2.38, 95% CI: 1.02 – 5.56, p=0.055), as were HIV-infected persons (COR: 3.20, 95% CI: 1.40 – 7.34, p=0.006), and those affiliated with the Catholic religion (COR: 3.50, 95% CI: 1.06 – 11.60, p=0.040). Conclusion: Our study found a relatively high level of substance use among persons with TB. TB-HIV co-infected persons should be particularly targeted with interventions to minimize the negative health effects of substance use.

PMID:39975935 | PMC:PMC11838757 | DOI:10.21203/rs.3.rs-5927600/v1

Res Sq [Preprint]. 2025 Feb 3:rs.3.rs-5867126. doi: 10.21203/rs.3.rs-5867126/v1.

ABSTRACT

Background Globally, stroke is one of the top three leading causes of death and disability. Although several stroke risk factors are modifiable, including hypertension, factors associated with stroke among older patients with hypertension in Uganda remain underexplored. This study assessed the prevalence and factors associated with stroke among older patients with hypertension in public healthcare facilities in the Greater Kampala Metropolitan Area, Uganda. Methods A cross-sectional study was conducted among 383 older patients with hypertension. Systematic sampling was used to recruit study participants, and STATA 15.0 was used for analysis. Descriptive statistics were used to present continuous variables, while frequencies and proportions were used to present categorical data. Bivariate analyses identified associations between independent variables and stroke. Multivariable analyses controlled for confounders. A modified Poisson regression analysis with robust standard errors estimated prevalence ratios. Results Of the 383 respondents, 71.0% (272/383) were aged 60-69 years (mean age 66.8 ± 7.1), 80.9% (310/383) were female, and 42.8% (164/383) had a primary education level (1-7 years). About 31.9% (122/383) exercised regularly, 94.8% (363/383) consumed carbohydrates frequently, 5.2% (20/383) had ever smoked, and 42.0% (151/383) had ever consumed alcohol. The prevalence of stroke was 18.3% (70/383). The factors associated with stroke included being aged 80 years and above (APR = 2.68, 95% CI: 1.59-4.51), having 8-13 years of formal education (secondary education)(APR = 0.37, 95% CI: 0.14-0.98), possessing health insurance (APR = 3.34, 95% CI: 1.19-9.37), having high knowledge of stroke (APR = 24.72, 95% CI: 6.20-98.55), and receiving stroke-related health information (APR = 1.78, 95% CI: 1.05-3.02). Conclusion and recommendation: This study demonstrated a high prevalence of stroke among older patients with hypertension. Public health education and community outreach should be expanded to underserved populations, while age-specific hypertension management and affordable healthcare services are essential. Engaging men and leveraging stroke survivors as peer educators can further strengthen prevention efforts. Future research should explore barriers to prevention and develop tailored interventions for diverse populations.

PMID:39975928 | PMC:PMC11838758 | DOI:10.21203/rs.3.rs-5867126/v1