Tag: nevin manimala

Saudi Pharm J. 2025 Aug 25;33(5):30. doi: 10.1007/s44446-025-00035-1.

ABSTRACT

BACKGROUND: Limited research has explored the genetic variability of CYP3A4 and CYP3A5 in the Saudi population, particularly concerning tacrolimus (Tac) therapy among Saudi kidney transplant patients (SKTP).

OBJECTIVES: To investigate specific CYP3A4 and CYP3A5 polymorphisms in SKTP and evaluate their influence on Tac dose requirements and trough levels.

METHODS: A total of 251 Saudi participants were recruited, comprising 129 kidney transplant patients and 122 healthy volunteers. Genomic DNA was extracted, and polymorphisms in CYP3A4 (*1B, *6, *18, *22) and CYP3A5 (*2, *3, *4) were analyzed using real-time PCR and allele-specific sequencing. Genotype frequencies and minor allele frequencies (MAF) were calculated, and the impact of CYP3A variants on Tac dosing and trough levels (C0) was assessed in SKTP.

RESULTS: The CYP3A41B polymorphism was absent, with all participants being homozygous wild type (G/G). For CYP3A5*3, 98.4% of participants carried the mutant genotype (*3/*3), while 1.6% carried the wild-type genotype (*1/*1). Patients with the wild-type allele (*1/*1) required significantly higher Tac doses and exhibited lower trough concentrations (C0) compared to those with the mutant genotype (*3/3). Other polymorphisms, such as CYP3A4*22, were rare, with approximately 90% of participants carrying the wild-type allele.

CONCLUSION: This study highlights the high prevalence of the CYP3A5*3/*3 genotype and wild-type CYP3A4 alleles in the Saudi population. The genetic variability significantly affects Tac trough levels and dosing requirements necessary to achieve therapeutic targets. These findings underscore the importance of pharmacogeneticguided Tac dosing to optimize therapeutic outcomes in SKTP.

PMID:40853585 | DOI:10.1007/s44446-025-00035-1

J Epidemiol Glob Health. 2025 Aug 25;15(1):110. doi: 10.1007/s44197-025-00450-6.

ABSTRACT

OBJECTIVE: This study aims to analyze the epidemiological characteristics, spatial and temporal distribution patterns, and trends in the evolution of scrub typhus (ST) in Jiangsu Province from 2006 to 2023. Scrub typhus was chosen for this study due to its increasing incidence in Jiangsu Province, its substantial health burden on rural populations, and its relevance as a vector-borne disease influenced by environmental and seasonal factors.

METHODS: Data on ST cases in Jiangsu Province from 2006 to 2023 were obtained from the China Disease Control and Prevention Information System. Descriptive statistics were used to summarize the overall epidemiological trends. Spatial autocorrelation analysis (Global and Local Moran’s I) assessed the overall and local distribution patterns of ST cases. while spatial-temporal hotspot analysis identified regions with significant clustering of cases over time, providing insights into potential high-risk areas.

RESULTS: A total of 16,998 ST cases were reported in Jiangsu Province, with an average annual incidence rate of 1.13 per 100,000. The gender distribution showed a male-to-female ratio of 1:1.20. The ages of affected individuals ranged from 3 months to 97 years, with a mean age of 60 years. Farmers represented the largest occupational group, accounting for 84.68% of the cases. The incidence rate showed a significant upward trend (χ²trend = 8484.517, p < 0.001). Peak incidence occurred primarily between October and November. The global Moran’s I index ranged from 0.071 to 0.345. Local autocorrelation analysis revealed that Yancheng and Nantong cities were high-high clustering areas. Spatial-temporal hotspot analysis revealed that hotspots were predominantly located in the northern and central regions of Jiangsu, while the southern region was identified as a cold spot. These hotspots displayed oscillating patterns, with new hotspots emerging in specific areas. Standard deviation ellipse analysis indicated that the epidemic spread continued to expand along the north-south axis, while the east-west axis showed relative stability. Spatial-temporal scanning analysis identified four high-incidence spatial-temporal clustering zones.

CONCLUSION: The incidence of ST in Jiangsu Province exhibited a significant upward trend, with distinct seasonal peaks between October and November. The epidemic demonstrated a pronounced transmission along the north-south axis, spatial-temporal clustering, and a shifting center of gravity. It is recommended to strengthen surveillance in high-risk areas and implement targeted prevention and control measures during high-risk seasons, particularly for vulnerable populations, to effectively curb the spread of the epidemic.

PMID:40853578 | DOI:10.1007/s44197-025-00450-6

Int Ophthalmol. 2025 Aug 25;45(1):351. doi: 10.1007/s10792-025-03715-y.

ABSTRACT

BACKGROUND/OBJECTIVES: To determine the proportion of eyes with optical coherence tomography (OCT) features of polypoidal choroidal vasculopathy (PCV) among patients diagnosed as neovascular age-related macular degeneration (nAMD) based on Asia-Pacific Ocular Imaging Society (APOIS) Diagnostic Criteria.

METHODS: This study was a retrospective cross-sectional review of OCT images. Medical records of treatment-naïve nAMD patients between January 2018 and June 2023 were reviewed. Clinical and demographic profile at presentation was collected. OCT scans were reviewed for presence of APOIS Diagnostic Criteria. Eyes were classified as having PCV features (PCV) based on the presence of ≥ 2 major OCT APOIS diagnostic criteria and then compared with eyes not having these features (non-PCV).

RESULTS: OCT scans of 45 eyes of 38 patients diagnosed with nAMD were analyzed. Mean age was 69.4 years old (range 53-83), 71.1% of patients were female, and 81.6% had unilateral disease. There was no statistically significant difference among clinical and demographic characteristics between PCV and non-PCV groups. Twenty-four eyes (53.3%) had ≥ 2 major APOIS criteria for PCV. Among PCV eyes, sub-RPE ring-like lesion and double-layer sign were the most common major (87.5%) and minor OCT criteria (100%), respectively. Sharp-peaked PED (p < 0.001), sub-RPE ring-like lesion (p < 0.001), en face OCT complex RPE elevation (p = 0.005) and double-layer sign criteria (p = 0.007) were more frequent in the PCV than in the non-PCV group.

CONCLUSION: More than half of Filipino eyes diagnosed with nAMD fulfill the OCT criteria for PCV. The APOIS PCV Workgroup Criteria helps identify patients who will benefit from additional confirmatory and treatment options.

PMID:40853572 | DOI:10.1007/s10792-025-03715-y

Urolithiasis. 2025 Aug 25;53(1):163. doi: 10.1007/s00240-025-01831-z.

ABSTRACT

Infections are common postoperative complications associated with the use of medical implants such as ureteric double-J stents. However, bacterial resistance to antibiotics poses serious risks to human health. These complications highlight the need for novel antibacterial agents. This study aimed to synthesize ionic liquids (ILs) with antibacterial potential, namely, 1-benzyl-3-(2-nitrobenzoyl)-1 H-imidazol-3-ium chloride (OM-1) and 4-(dimethyl amino)-1-(4-nitrobenzoyl) pyridin-1-ium chloride (OM-2), for use as biocompatible coating materials on double-J stents. The chemical structures of the synthesized ILs were confirmed by Nuclear Magnetic Resonance (NMR) and Fourier Transform Infrared (FTIR) spectroscopy. The antibacterial properties were evaluated using the Kirby-Bauer Disk Diffusion method on Klebsiella pneumoniae and Escherichia coli. Cytotoxicity was evaluated in a human skin fibroblast cell line (HFF-1) using a 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2 H tetrazolium (MTS) assay. Molecular docking and ADMETox analyses were also performed to calculate binding affinities and pharmacokinetic properties. At 50 µg/mL, OM-1 and OM-2 exhibited significant activity against Klebsiella pneumoniae (p = 0.04), with OM-1 differing significantly from Gentamicin (p = 0.017). In Escherichia coli, both ILs exhibited significant differences compared to piperacillin/tazobactam (p < 0.001 and p = 0.002, respectively). At 100 µg/mL, both ILs demonstrated statistically significant differences compared to Ceftazidime and Piperacillin/Tazobactam. The IC₅₀ values for OM-1 and OM-2 in HFF-1 cells were calculated as 260.90 µg/mL and 216.35 µg/mL, respectively. Docking studies performed on OM-1 revealed stronger binding affinity as antifungal and antioxidant, while OM-2 was a stronger candidate for antibacterial applications due to its ADMETox profile. These findings, supported by both experimental and computational studies, confirm the biocoating potential of OM-1 and OM-2 for double-J stents.

PMID:40853571 | DOI:10.1007/s00240-025-01831-z

JAMA. 2025 Aug 25. doi: 10.1001/jama.2025.13074. Online ahead of print.

ABSTRACT

IMPORTANCE: Melanoma, the fifth most common cancer in the US, has increased from 8.8 per 100 000 in 1975 to 28.42 per 100 000 in 2022. Cutaneous melanoma comprises 94% of cases, with 104 960 US cases projected for 2025.

OBSERVATIONS: Cutaneous melanoma presents as a new, changing, or irregularly pigmented skin lesion. Cutaneous melanoma subtypes include superficial spreading (≈70%), lentigo maligna (≈15%), nodular (≈5%), desmoplastic (≈4%), amelanotic (2%-8%), spitzoid (<2%), and acral (≈1%). Risk factors for cutaneous melanoma include UV radiation exposure, skin type (eg, skin that always burns, never tans), presence of benign and atypical nevi, and personal or family history of melanoma. Primary prevention consists of avoiding direct sunlight and indoor tanning, and photoprotection (sunscreen and sun-protective clothing). Based on United States Cancer Statistics data from 1999 to 2021, 77% of patients with cutaneous melanoma had localized disease (involving only the primary site), 9.5% had regional (nodal) disease, 4.7% had distant metastasis, and 8.8% were unstaged. Melanoma staging, which includes tumor thickness and ulceration and presence of lymph node or distant metastasis, ranges from stage 0 (melanoma in situ) to stage IV (distant metastasis). Localized melanoma (stage IA-IIA) is surgically excised, with margins of 0.5 cm to 2 cm based on depth of invasion. Sentinel lymph node biopsy is recommended for cutaneous melanoma that is ulcerated or 0.8 mm or more thick. Following surgery, patients with stage IIB-C melanoma have improved recurrence-free survival with adjuvant anti-PD-1 immunotherapy compared with placebo (hazard ratio [HR] for recurrence or death, 0.62 [95% CI, 0.49-0.79] for pembrolizumab and 0.42 [95% CI, 0.30-0.59] for nivolumab). For stage III disease, recurrence risk is decreased with nivolumab (HR, 0.72 [95% CI, 0.60-0.86]), pembrolizumab (HR, 0.61 [95% CI, 0.51-0.72]), or BRAF + MEK inhibitor therapy (dabrafenib + trametinib) (HR, 0.52 [95% CI, 0.43-0.63]). First-line treatment for distant metastatic or unresectable melanoma is dual checkpoint blockade with ipilimumab (anti-CTLA-4) and nivolumab. In 2017, 10-year melanoma-specific survival rates were 98% to 94% for stage IA-B, 88% to 75% for stage IIA-C, 88% for stage IIIA, 77% to 60% for stage IIIB-C, and 24% for stage IIID. In 2024, patients with distant metastatic or unresectable melanoma treated with ipilimumab and nivolumab had a 10-year overall survival rate of 43%.

CONCLUSIONS AND RELEVANCE: Melanoma is a common cancer in the US. Treatment for stage IA-IIA melanoma is surgical resection. Anti-PD-1 immunotherapy after surgical excision improves recurrence-free survival in stages IIB-C melanoma. For stage III melanoma, anti-PD-1 immunotherapy or BRAF + MEK inhibitor therapy decreases risk of melanoma recurrence. First-line therapy for metastatic melanoma is dual checkpoint blockade with ipilimumab and nivolumab.

PMID:40853557 | DOI:10.1001/jama.2025.13074

J Ultrasound. 2025 Aug 25. doi: 10.1007/s40477-025-01069-w. Online ahead of print.

ABSTRACT

PURPOSE: To evaluate the inter- and intra-assessor reliability of ultrasonographic assessment of swallowing-related muscle indices in healthy young adults.

METHODS: Three examiners conducted ultrasonographic evaluations on healthy young adults (n = 34, age: ≥ 20 years) examining the thickness and area of the geniohyoid muscle, anterior belly of the digastric muscle, tongue, and the mylohyoid, masseter, and depressor anguli oris muscles. To assess inter-rater reliability, each examiner evaluated each assessment item for one subject three times on the same day. Intra-rater reliability was assessed by rater No. 3 re-evaluating the participants 4-7 days after the initial measurement, using the retest method. Image analysis was conducted by a single examiner utilizing an ultrasonography measurement tool. Statistical analysis was performed using intraclass correlation coefficients (ICCs) for intra- and inter-rater reliability.

RESULTS: The study included 34 participants (male: 17, female: 17; age: 25 ± 2 years, body mass index: 20.3 ± 1.7 kg/m²). For intra-rater reliability for thickness of the geniohyoid muscle, ICC = 0.94 [95% CI (0.89, 0.97)], and ICC = 0.90 [95% CI (0.81, 0.93)] for the area of the anterior belly of the digastric muscle. For inter-rater reliability, ICC = 0.93 [95% CI (0.88, 0.96)] and 0.86 [95% CI (0.77, 0.92)] for the thickness of the geniohyoid muscle, and area of the anterior belly of the digastric muscle, respectively.

CONCLUSIONS: The inter- and intra-assessor reliability of ultrasound assessments of swallowing-related indices in young healthy subjects was good, exhibiting particularly high accuracy for the geniohyoid muscle and the anterior belly of the digastric muscle.

PMID:40853540 | DOI:10.1007/s40477-025-01069-w

Neurol Sci. 2025 Aug 25. doi: 10.1007/s10072-025-08443-w. Online ahead of print.

ABSTRACT

Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by slowly progressive degeneration of upper motor neurons (UMNs) and lower motor neurons (LMNs). Although the pathogenesis of sporadic form of ALS has not been fully elucidated, the initial damage mostly leads to hyperexcitability of the central and peripheral motor neuron. The results of our study aimed to confirm the changes in the excitability of the peripheral motor axon and contribute to the emergence of these measurements as potential biomarkers for disease progression. A total of 56 ALS patients [24 women (43%), median age 62.5 (interquartile range: 53.75-70.25) years] were finally included in the study. Twenty-four healthy controls that were age- and sex-matched to the cases [12 women (50%), mean age 58.46 ± 8.84] were recruited. The first main finding of our study is the fact that abnormalities of the voltage gated K⁺ ion channels were constantly present in ALS patients than in the controls. The multivariate analysis revealed that Superexcitability 7ms lower than – 21.06%, related to shorter survival. Additionally using receiver operating characteristic (ROC) curves, the c-statistic showed Superexcitability 7ms moderate predictive ability. The clinical significance of our results is that Superexcitability 7ms can be used as a biomarker not only for survival but also for disease progression.

PMID:40853517 | DOI:10.1007/s10072-025-08443-w

Pediatr Cardiol. 2025 Aug 25. doi: 10.1007/s00246-025-03925-2. Online ahead of print.

ABSTRACT

Cardiac remodeling has been reported in HIV-exposed but uninfected (HEU) infants. Inflammatory biomarkers have also been observed to be associated with cardiac remodeling in older HEU children but have not been widely studied in infants. We identified left ventricular (LV) cardiac changes in HEU infants exposed to current ARV therapy in utero and determined their association with the inflammatory biomarkers, C-reactive protein (CRP), and cardiac troponin. This comparative cross-sectional study included 196 HEU infants and 198 matched HIV-unexposed controls. We evaluated LV structure and function using echocardiography and tested blood samples using highly sensitive CRP (hsCRP) and cardiac troponin I (cTnI-plus) measurements. Data were analyzed using the R statistical software package; p values of < 0.05 were considered statistically significant. The HEU infants had thicker LV posterior walls and interventricular septa in diastole (median difference 0.55 and 0.30, 95% CI 0.22-0.89 and 0.13-0.54, respectively, p < 0.001), higher left ventricular mass index (median difference 3.8, 95% CI 1.2-6.9, p < 0.001), and left ventricular wall thickness-to-diameter ratio (median difference 0.02, 95% CI 0.01-0.03, p < 0.001) compared with controls. The interventricular septa Z score was significantly thicker in HEU infants with elevated hsCRP levels (AOR 2.3, 95% CI 1.22-3.36, p = 0.006). Cardiac remodeling is present in HEU infants exposed to current ARV regimens in utero. Longitudinal studies are required to identify infants who may require cardiac evaluation and further explore biomarkers associated with cardiac remodeling in HEU infants.

PMID:40853460 | DOI:10.1007/s00246-025-03925-2

J Pak Med Assoc. 2025 Aug;75(8):1320-1326. doi: 10.47391/JPMA.21001.

ABSTRACT

OBJECTIVE: To assess the frequency of anxiety and its coping mechanism among medical and engineering students.

METHODS: The comparative cross-sectional study was conducted from April to September 2023 in Faisalabad, Pakistan, and comprised students from two medical and two engineering education institutions. Within the two subsets, one was a public-sector institution and the other was in the private sector. Data was collected using Generalised Anxiety Disorder-7 and Brief Cope Inventory. Data was Analysed using SPSS 27.

RESULTS: Study subjects ranged between 17-26 years of age and 144(36%) of them were females. Of the 400 subjects, 200(50%) were medical students and the rest were engineering students uniformly representing all years of education. Also, 200(50%) responses were from private-sector institutions and the rest were from public-sector institutions. Mild anxiety was present in 220(55%) subjects, more in engineering students. Moderate anxiety was found in 98(24.5%) students, most in public-sector medical institutions. Minimal and severe anxiety were noted in 56(14%) and 26(6.50%) subjects, respectively. Medical and engineering students showed the same patterns of coping mechanisms, with planning (2.55±0.69) being the most adopted, and substance abuse (1.78±0.68) the least.

CONCLUSIONS: Except for mild anxiety, all other groups of anxiety levels were found to be higher among medical students. In terms of coping behaviour, there was no difference between medical and engineering students.

PMID:40851158 | DOI:10.47391/JPMA.21001

J Pak Med Assoc. 2025 Aug;75(8):1267-1270. doi: 10.47391/JPMA.20788.

ABSTRACT

The retrospective, observational study was planned to present the clinical manifestations of obstructive nephropathy secondary to urolithiasis, and its effect on long-term renal function. The sample comprised patients diagnosed with obstructive nephropathy secondary to stones admitted to the Department of Urology and Renal Transplant, Lahore General Hospital, Lahore, Pakistan, between January 1, 2018, and December 31, 2021. Data was analysed using SPSS 20. Of the 76 patients with a mean age of 50.06±13.42 years, 56(73.7%) were males and 20(26.3%) were females. The most frequent clinical cause was bilateral ureteric obstruction in 39 (51.3%) patients. The most common emergency procedure performed was unilateral percutaneous nephrostomy. It took an average of 10.8±2.3 days for patients to have a nadir value of creatinine. On follow-up, diabetes, presence of lower urinary tract symptoms and a higher value of creatinine at admission were significantly related to poorer outcomes (p<0.05).

PMID:40851138 | DOI:10.47391/JPMA.20788