Nevin Manimala

Cureus. 2024 Dec 13;16(12):e75654. doi: 10.7759/cureus.75654. eCollection 2024 Dec.

ABSTRACT

This study investigates the safety of three different daily dosages of a liquid blend containing kava and kratom (Feel Free® Classic Tonic {FFCT}) in healthy adults over six consecutive days of supplementation. Both kava and kratom have been used traditionally for hundreds of years, but there is limited data on the combined safety of these ingredients. In this randomized, double-blind, placebo-controlled trial, the participants were assigned to receive one of three daily dosages of FFCT or placebo. Safety assessments included the monitoring of vital signs, clinical chemistry, hematology, and withdrawal symptoms using the Clinical Opiate Withdrawal Scale (COWS) and the Subjective Opiate Withdrawal Scale (SOWS). The results indicate that FFCT was safe, with mild to moderate adverse events (AEs) such as nausea, headaches, and fatigue, particularly in the high-dosage (HD) group. No significant changes in liver or kidney function were noted, and all vital signs remained within normal physiological ranges although some statistically significant changes in blood pressure (BP) and respiratory rate (RR) were observed. There were no clinically significant observations in COWS or SOWS scores despite a small but statistically significant increase in COWS total score in the high-dose group on day 7. Overall, FFCT appears safe for short-term use in healthy adults, with no significant impact on vital signs, laboratory values, or withdrawal symptoms.

PMID:39807458 | PMC:PMC11726919 | DOI:10.7759/cureus.75654

Cureus. 2024 Dec 14;16(12):e75704. doi: 10.7759/cureus.75704. eCollection 2024 Dec.

ABSTRACT

Introduction The role of the condylar position in the correct functioning of the stomatognathic system has been the center of the study. Using cone-beam computed tomography (CBCT), this study looked at the three-dimensional (3D) position of the condylar bone in patients from Class I, Class II, Division 1, and Division 2. Materials and methods This cross-sectional, retrospective study was conducted using 102 CBCT records, with 34 records allocated to each category of malocclusion classification, such as dentoskeletal Class I, skeletal Class II, and dental Class II, Division 1 and 2. CBCT scans were conducted utilizing a Carestream New Generation CBCT apparatus (Carestream Dental, Atlanta, Georgia) in accordance with a standardized protocol (operating at a voltage of 120 kV, a current of 80 mA, a seven-second scan time, a field of view (FOV) measuring 10 x 10 cm, and a resolution of 0.2 voxels, and 1-mm slice thickness). The condylar position was assessed as the superior, inferior, and medial distance of the condyle from the glenoid fossa, along with the condylar angle. The distance from the most anterior point on the anterior surface of the condyle to the articular eminence was taken as anterior condylar distance; the distance of the superior surface of the condyle from the deepest point of the glenoid fossa was taken as superior condylar distance; the distance of the posterior surface of the condyle from the glenoid fossa was taken as posterior condylar distance; the condylar angle was measured as an angle between the XY line and the FH’ line passing through X, where X is the center of the condyle; and the distance of the medial surface of the condyle from the glenoid fossa was taken as medial distance. The data were then subjected to statistical analyses. Results For anterior distance, the highest distance was noted in Class II Division 1 (3.32 ± 0.4 mm), and the lowest was seen in Class I (2.43 ± 0.26 mm). In the posterior distance, Class I exhibited the highest mean distance of 2.05 ± 0.14 mm, while Class II Division 1 showed the lowest distance of 1.83 ± 0.18 mm. For superior distance, the highest mean value was noticed in Class I patients at 2.92 ± 0.22 mm, and the lowest value was seen in Class II Division 1 at 2.61 ± 0.35 mm (p=0.001). For the condylar angle, the highest mean value was observed in Class I (30.96 ± 1.91⁰) and the lowest in Class II Division 1 (26.71 ± 1.48⁰), with p=0.001. Confirmatory factor analysis revealed that the most substantial loading was attributed to the condylar angle at -2.28, signifying its significant contribution to Fc1. Conclusion The condyle was placed anteriorly, superiorly, and medially in Class II Division 1 and posteriorly in Class II Division 2, compared to Class I patients.

PMID:39807453 | PMC:PMC11728205 | DOI:10.7759/cureus.75704

BMC Psychol. 2025 Jan 13;13(1):34. doi: 10.1186/s40359-025-02365-0.

ABSTRACT

BACKGROUND: Schizophrenia is a multifactorial disorder influenced by various biological and psychosocial factors. This study aimed to determine the characteristics and associated factors of expressed emotion (EE) among caregivers of individuals with schizophrenia.

METHODS: From May to July 2024, a cross-sectional study was conducted with caregivers of individuals with schizophrenia across multiple hospitals in Southern Thailand. The study utilized four questionnaires: (1) Demographic inquiry, (2) The Thai Expressed Emotion Scale (TEES), (3) The Thai General Health Questionnaire (GHQ-12), and (4) The Zarit Burden Interview (ZBI). Data were analyzed using descriptive statistics. The groups analyzed were compared using the Analysis of Variance (ANOVA) or Kruskal-Wallis test, the Student t-test or Wilcoxon rank sum test, and the Chi-square test. Multiple logistic regression analysis was performed.

RESULTS: In a survey of 200 caregivers, 70.5% were female. They had a median caregiving duration of 108 months, with an interquartile range (IQR) of 36 to 180 months. Notably, 51.0% of caregivers reported no mental health problems, as assessed by the GHQ-12, while 29.0% indicated experiencing severe burden. The median score on the TEES was 99.0, with an IQR of 84.7 to 109.0. Furthermore, 46.0% of caregivers reported TEES above the median score, indicating high levels of EE. There was also a significant correlation between caregiver burden and EE scores. Those experiencing severe burden had an EE score of 110.5 compared to 94.0 for those with no burden, which was statistically significant (p = 0.001). Multiple logistic regression analysis revealed that high EE among caregivers was associated with factors such as the patient’s duration of illness, caregiver occupation, and mental health status.

CONCLUSION: Nearly half of the caregivers of individuals with schizophrenia reported high levels of EE, with increased caregiver burden associated with higher EE levels. Factors such as the duration of the patient’s illness, caregiver occupation, and mental health status were also associated with higher EE. Moreover, caregivers’ emotional responses and expressions are complex and dynamic. Thus, focusing on providing support to caregivers can have a positive impact on the well-being of both caregivers and individuals with schizophrenia.

PMID:39806518 | DOI:10.1186/s40359-025-02365-0

J Health Popul Nutr. 2025 Jan 13;44(1):9. doi: 10.1186/s41043-025-00745-1.

ABSTRACT

PURPOSE: Evidence concerning the effect of cardiovascular health (CVH) on the risk of metabolic dysfunctional-associated steatotic liver disease (MASLD) is scarce. This study aimed to investigate the association between CVH and MASLD.

METHODS: 5680 adults aged ≥ 20 years from the National Health and Nutrition Examination Survey 2017-March 2020 were included. Life’s essential 8 (LE8) was applied to assess CVH. Weighted binary logistic regression was employed to calculate the odds ratio (OR) and 95% confidence interval (CI) to investigate the association of CVH with MASLD. Restricted cubic spline (RCS) was conducted to explore the dose-response association between LE8 and its subscales scores with MASLD.

RESULTS: Among 5680 participants, 724, 3901, and 1055 had low, moderate, and high CVH levels, respectively, with a MASLD diagnosis prevalence of 36.83%. In the fully adjusted logistic regression model, ORs for MASLD were 0.50 (95% CI, 0.37-0.69) for participants with moderate CVH and 0.21 (95% CI, 0.13-0.34) for those with high CVH, when compared to those with low CVH (P < 0.001 for trend). OR for MASLD was 0.68 (95% CI, 0.61-0.77) for each 10-point increase in LE8 score. RCS model demonstrated a non-linear dose-response relationship between LE8 score and health factors score with MASLD, while a linear relationship was found between health behaviors score and MASLD. Subgroup analysis showed a consistent negative correlation between LE8 score and MASLD, and sensitivity analysis validated the reliability of these findings.

CONCLUSIONS: Higher LE8 score was associated with a lower risk of MASLD. Encouraging adherence to optimal CVH levels may help mitigate the burden of MASLD.

PMID:39806517 | DOI:10.1186/s41043-025-00745-1

Syst Rev. 2025 Jan 13;14(1):11. doi: 10.1186/s13643-024-02726-7.

ABSTRACT

BACKGROUND: Impaired intrauterine growth, a significant global health problem, contributes to a higher burden of infant morbidity and mortality, mainly in resource-poor settings. Maternal anemia and undernutrition, two important causes of impaired intrauterine growth, are prioritized by global nutrition targets of 2030. We synthesized the evidence on the role of preconception nutrition supplements in reducing maternal anemia and improving intrauterine growth.

METHODS: We undertook a review of the randomized controlled trials (RCTs) assessing the effect of preconception nutrition supplements on maternal hemoglobin, an indicator to estimate maternal anemia, and markers of intrauterine growth including birth weight, length, head circumference, and small for gestational age. Additionally, we examined preterm birth as an important perinatal outcome. We searched PubMed, CINAHL, Web of Science, Cochrane Central, and Embase. We computed summary mean differences and risk ratios (RR) with 95% confidence intervals (CIs) using random-effect models. We employed I² and Cochran’s Q test statistics to assess heterogeneity. We used a revised Cochrane risk-of-bias (RoB version 2.0) and GRADE (grading of recommendations, assessment, development, and evaluation) tools to assess the risk of bias and quality of evidence of eligible RCTs, respectively.

RESULTS: We identified 20 eligible RCTs (n = 27,659 women). Preconception nutrition supplements (iron and folic acid, multiple micronutrients, and a lipid-based nutrient supplement) overall increased maternal hemoglobin by 0.30 g/dL ((0.03, 0.57); I² = 79%; n=9). However, we did not find a significant effect of the supplements on birth weight (12.25 gm ((- 22.66, 47.16); I² = 55%; n=10)), length (0.15 cm (- 0.26, 0.56); I² = 68%; n = 5), head circumference (- 0.23 cm (- 0.88, 0.43); I² = 84%; n=4), small for gestational age (RR 0.91 (0.80, 1.04); I² = 31%; n=8), or preterm birth (RR 0.93 (0.69,1.25); I² = 57%; n=12). In general, the quality of evidence was assessed as very low to moderate.

CONCLUSION: Preconception nutrition supplements studied to date appear to reduce maternal anemia. However, it is uncertain whether there are beneficial effects of the supplements on intrauterine growth. Low quality of evidence warrants future well-designed RCTs to produce solid scientific data, particularly of a more comprehensive package of preconception nutrition supplements that include both macro- and micronutrients.

SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42023464966.

PMID:39806515 | DOI:10.1186/s13643-024-02726-7

Skelet Muscle. 2025 Jan 13;15(1):2. doi: 10.1186/s13395-024-00371-1.

ABSTRACT

BACKGROUND: Duchenne muscular dystrophy (DMD) is a prevalent, fatal degenerative muscle disease with no effective treatments. Mdx mouse model of DMD exhibits impaired muscle performance, oxidative stress, and dysfunctional autophagy. Although antioxidant treatments may improve the mdx phenotype, the precise molecular mechanisms remain unclear. This study investigates the effects of aminoguanidine hemisulfate (AGH), an inhibitor of reactive oxygen species (ROS), on mitochondrial autophagy, oxidative stress, and muscle force in mdx mice.

METHODS: Male wild-type (WT) and mdx mice were divided into three groups: WT, mdx, and AGH-treated mdx mice (40 mg/kg intraperitoneally for two weeks) at 6 weeks of age. Gene expression, western blotting, H&E staining, immunofluorescence, ROS assays, TUNEL apoptosis, glutathione activity, and muscle force measurements were performed. Statistical comparisons used one-way ANOVA.

RESULTS: AGH treatment significantly reduced the protein levels of LC3, and p62 in mdx mice, indicating improved autophagy activity and the ability to clear damaged mitochondria. AGH restored the expression of mitophagy-related genes Pink1 and Parkin and increased Mfn1, rebalancing mitochondrial dynamics. It also increased Pgc1α and mtTFA levels, promoting mitochondrial biogenesis. ROS levels were reduced, with higher Prdx3 and MnSOD expression, improving mitochondrial antioxidant defenses. AGH normalized the GSSG/GSH ratio and decreased glutathione reductase and peroxidase activities, further improving redox homeostasis. Additionally, AGH reduced apoptosis, shown by fewer TUNEL-positive cells and lower caspase-3 expression. Histological analysis revealed decreased muscle damage and fewer embryonic and neonatal myosin-expressing fibers. AGH altered fiber composition, decreasing MyH7 while increasing MyH4 and MyH2. Muscle force improved significantly, with greater twitch and tetanic forces. Mechanistically, AGH modulated the AKT/FOXO1 pathway, decreasing myogenin and Foxo1 while increasing MyoD.

CONCLUSIONS: AGH treatment restored mitochondrial autophagy, reduced oxidative stress, apoptosis, and altered muscle fiber composition via the AKT/FOXO1 pathway, collectively improving muscle force in mdx mice. We propose AGH as a potential therapeutic strategy for DMD and related muscle disorders.

PMID:39806512 | DOI:10.1186/s13395-024-00371-1

Virol J. 2025 Jan 13;22(1):10. doi: 10.1186/s12985-025-02626-9.

ABSTRACT

BACKGROUND: Mycoplasma pneumoniae (MP) is a common pathogen for respiratory infections in children. Previous studies have reported respiratory tract microbial disturbances associated with MP infection (MPI); however, since the COVID-19 pandemic, respiratory virome data in school-aged children with MPI remains insufficient. This study aims to explore the changes in the respiratory virome caused by MPI after the COVID-19 pandemic to enrich local epidemiological data.

METHODS: Clinical samples from 70 children with MPI (70 throat swab samples and 70 bronchoalveolar lavage fluid (BALF) samples) and 78 healthy controls (78 throat swab samples) were analyzed using viral metagenomics. Virus reads were calculated and normalized using MEGAN.6, followed by statistical analysis.

RESULTS: Principal Coordinate Analysis (PCoA) showed that viral community diversity is a significant difference between disease cohorts and healthy controls. After MPI, the number of virus species in the upper respiratory tract (URT) increased obviously, and the abundance of families Poxviridae, Retroviridae, and Iridoviridae, which infect vertebrates, rose evidently, particularly the species BeAn 58,085 virus (BAV). Meanwhile, phage alterations in the disease cohorts were predominantly characterized by increased Myoviridae and Ackermannviridae families and decreased Siphoviridae and Salasmaviridae families (p < 0.01). In addition, some new viruses, such as rhinovirus, respirovirus, dependoparvovirus, and a novel gemykibvirus, were also detected in the BALF of the disease cohort.

CONCLUSIONS: This cross-sectional research highlighted the respiratory virome characteristics of school-aged children with MPI after the COVID-19 outbreak and provided important epidemiological information. Further investigation into the impact of various microorganisms on diseases will aid in developing clinical treatment strategies.

PMID:39806507 | DOI:10.1186/s12985-025-02626-9

J Cardiovasc Imaging. 2025 Jan 13;33(1):1. doi: 10.1186/s44348-024-00043-0.

ABSTRACT

BACKGROUND: There are insufficient studies to determine whether sodium-glucose cotransporter type 2 inhibitors (SGLT2i) will help reduce early diabetic cardiomyopathy, especially in patients without documented cardiovascular disease.

METHODS: We performed a single center, prospective observation study. A total of 90 patients with type 2 diabetes patients without established heart failure or atherosclerotic cardiovascular disease were enrolled. Echocardiography, cardiac enzyme, and glucose-control data were examined before and 3 months after the administration of SGLT2i (dapagliflozin 10 mg per day). Cardiovascular risk factors included hypertension, smoking, obesity, dyslipidemia, and old age. The primary end point was the change of E/e’ before and after administration of SGLT2i.

RESULTS: Most patients (86.7%) had three or more cardiovascular risk factors, and about 32% had all five risk factors. Although the decrease in E/e’ after the administration of SGLT2i was observed in 20% of enrolled patients, there was no significant difference in average E/e’ value or left atrial volume index before and after the SGLT2i medication. Even in patients with all known risk factors including old age, E/e’ value did not decrease after adding SGLT2i (8.9 ± 2.4 vs. 8.7 ± 3.2). There was a statistically significant difference in E/e’ change after the SGLT2i administration between patients younger than 60 years and those older than 60 years (-0.7 ± 2.2 vs. 1.1 ± 2.8, P = 0.002).

CONCLUSIONS: In type 2 diabetes patients without documented cardiovascular disease including heart failure, administration of SGLT2i showed no improvement in diastolic function profile. Further large-scale randomized studies are needed to determine who will benefit from potential cardiovascular events with early addition of SGLT2i.

PMID:39806504 | DOI:10.1186/s44348-024-00043-0

Int J Retina Vitreous. 2025 Jan 13;11(1):6. doi: 10.1186/s40942-025-00628-x.

ABSTRACT

BACKGROUND: Management of Diabetic Macular edema (DME) requires repeated injections. Therefore newer Anti-VEGFs like Brolucizumab with longer durability have been introduced. We compared two different dosages of Brolucizumab, 6.0 mg and 3.6 mg, for their safety & efficacy in treatment of DME, in treatment naïve patients over 52 weeks.

METHOD: A prospective, pilot randomised controlled, single centre, double blinded, two arm comparative study was conducted between Dec 2022 to Apr 2024. The study recruited 82 patients of DME who were randomised into two groups of 41 patients each, one group to be treated with Brolucizumab 6.0 mg in 50 μL and the other to receive 3.6 mg in 30 μL. All patients received the first dose of Brolucizumab at 0 week and were then followed up at every 4 weeks for detailed ophthalmic and OCT macula examination. Those who met the pre-defined re-treatment criteria were re-injected with Brolucizumab, the dose being fixed for each group throughout the study. All patient receiving an injection were further followed up on Day 1, Day 7 and Day 28 to look for any adverse reactions. The efficacy parameters included change in best corrected visusal acuity (BCVA), contrast and central macular thickness (CMT) on Optical Coherence Tomography. The average number of injections recd in each group were also calculated.

RESULTS: The change in BCVA from baseline in 6.0 mg group was 0.54 LogMAR units and 3.6 mg group was 0.59 LogMAR units, which was not statistically significant. The reduction in CMT from baseline in 6.0 mg group was 133.2 µm (μ) and 3.6 mg group was 110.6 μ, which was not statistically significant. The improvement in contrast from baseline in 6.0 mg group was 0.74 and 3.6 mg group was 0.95, with p value of 0.0002. The re-injection interval was 14.21 weeks in 6.0 mg group and 15.56 weeks for 3.6 mg subgroup. The total number of adverse events in both groups were similar at 70 in 6.0 mg group and 47 in 3.6 mg group with only one grade 4 adverse event occurring in each group.

CONCLUSION: The results of present study show that the safety and efficacy of both doses of Brolucizumab, i.e. 6.0 mg and 3.6 mg, for treating diabetic macular edema is similar. Trial registration Study was registered with Clinical trials registry of India (CTRI ref no. CTRI/2023/06/054105), registered on 14 Nov 2022.

PMID:39806501 | DOI:10.1186/s40942-025-00628-x

Int J Retina Vitreous. 2025 Jan 13;11(1):5. doi: 10.1186/s40942-025-00630-3.

ABSTRACT

PURPOSE: To evaluate the predictive accuracy of various machine learning (ML) statistical models in forecasting postoperative visual acuity (VA) outcomes following macular hole (MH) surgery using preoperative optical coherence tomography (OCT) parameters.

METHODS: This retrospective study included 158 eyes (151 patients) with full-thickness MHs treated between 2017 and 2023 by the same surgeon and using the same intraoperative surgical technique. Data from electronic medical records and OCT scans were extracted, with OCT-derived qualitative and quantitative MH characteristics recorded. Six supervised ML models-ANCOVA, Random Forest (RF) regression, K-Nearest Neighbor, Support Vector Machine, Extreme Gradient Boosting, and Lasso regression-were trained using an 80:20 training-to-testing split. Model performance was evaluated on an independent testing dataset using the XLSTAT software. In total, the ML statistical models were trained and tested on 14,652 OCT data points from 1332 OCT images.

RESULTS: Overall, 91% achieved MH closure post-surgery, with a median VA gain of -0.3 logMAR units. The RF regression model outperformed other ML models, achieving the lowest mean square error (MSE = 0.038) on internal validation. The most significant predictors of VA were postoperative MH closure status (variable importance = 43.078) and MH area index (21.328). The model accurately predicted the post-operative VA within 0.1, 0.2 and 0.3 logMAR units in 61%, 78%, and 87% of OCT images, respectively.

CONCLUSION: The RF regression model demonstrated superior predictive accuracy for forecasting postoperative VA, suggesting ML-driven approaches may improve surgical planning and patient counselling by providing reliable insights into expected visual outcomes based on pre-operative OCT features.

CLINICAL TRIAL REGISTRATION NUMBER: Not applicable.

PMID:39806497 | DOI:10.1186/s40942-025-00630-3