Nevin Manimala

Transl Psychiatry. 2025 Jan 4;15(1):1. doi: 10.1038/s41398-024-03197-z.

ABSTRACT

Experiencing a traumatic event may lead to Posttraumatic Stress Disorder (PTSD), including symptoms such as flashbacks and hyperarousal. Individuals suffering from PTSD are at increased risk of cardiovascular disease (CVD), but it is unclear why. This study assesses shared genetic liability and potential causal pathways between PTSD and CVD. We leveraged summary-level data of genome-wide association studies (PTSD: N = 1,222,882; atrial fibrillation (AF): N = 482,409; coronary artery disease (CAD): N = 1,165,690; hypertension (HT): N = 458,554; heart failure (HF): N = 977,323). First, we estimated genetic correlations and utilized genomic structural equation modeling to identify a common genetic factor for PTSD and CVD. Next, we assessed biological, behavioural, and psychosocial factors as potential mediators. Finally, we employed multivariable Mendelian randomization to examine causal pathways between PTSD and CVD, incorporating the same potential mediators. Significant genetic correlations were found between PTSD and CAD, HT, and HF (r_g = 0.21-0.32, p ≤ 3.08 · 10^-16), but not between PTSD and AF. Insomnia, smoking, alcohol dependence, waist-to-hip ratio, and inflammation (IL6, C-reactive protein) partly mediated these associations. Mendelian randomization indicated that PTSD causally increases CAD (IVW OR = 1.53, 95% CIs = 1.19-1.96, p = 0.001), HF (OR = 1.44, CIs = 1.08-1.92, p = 0.012), and to a lesser degree HT (OR = 1.25, CIs = 1.05-1.49, p = 0.012). While insomnia, smoking, alcohol, and inflammation were important mediators, independent causal effects also remained. In addition to shared genetic liability between PTSD and CVD, we present strong evidence for causal effects of PTSD on CVD. Crucially, we implicate specific lifestyle and biological mediators (insomnia, substance use, inflammation) which has important implications for interventions to prevent CVD in PTSD patients.

PMID:39755697 | DOI:10.1038/s41398-024-03197-z

Sci Rep. 2025 Jan 4;15(1):824. doi: 10.1038/s41598-024-79600-y.

ABSTRACT

Real-world data on treatment outcomes or the quality of large-scale chronic hepatitis B (CHB) treatment programs in sub-Saharan Africa (SSA) is extremely difficult to obtain. In this study, we aimed to provide data on the prevalence and incidence of mortality, loss to follow-up (LFTU), and their associated factors in patients with CHB in three treatment centres in Eritrea. Additional information includes baseline clinical profiles of CHB patients initiated on nucleos(t)ide analogue (NUCs) along with a comparison of treatment with Tenofovir disoproxil fumarate (TDF) vs. TDF + Lamuvudine (LAM) using specific biochemical, haematological and virologic parameters. A multicenter retrospective cohort study was conducted on CHB patients in Asmara, Eritrea (2018-2021). Demographic, clinical, and laboratory information was collected from medical records using a structured checklist. Relevant parametric and nonparametric statistics were employed to explore treatment outcomes and to evaluate differences between groups. Where appropriate, Kaplan-Meier (KM) curves and univariate and multivariate Cox regression models were implemented. A two-sided p-value < 0.05 was considered significant. A total of 413 patients with HBV (median age (IQR) at diagnosis: 39 (IQR: 28-50 years; females: 118(28.6%); followed for a total of 22,921 person days) were studied. HBV/HIV co-infection was observed in 15(3.6%) and baseline ALT and AST were elevated in 99(31.2%) and 101(32.8%), respectively. The Fibrosis-4 (FIB-4) index estimates suggested that cirrhosis was highly likely in 33 (14%) patients with 49 (20.8%) patients in the indeterminate FIB-4 score category. During the follow-up period, 4.6% (95% CI: 2.5-6.6%) died, while 23.9% (95% CI: 19.8-28%) were LTFU. In the adjusted Cox proportional hazards model, LTFU were independently associated with baseline serum HBV DNA (IU/mL) (aHR = 1.3, 95% CI 1.04-1.7; p-value = 0.02); Not initiated on NUC (aHR = 3.9, 95% CI: 1.1-13.7, p-value = 0.02); and FIB-4 Score (aHR = 1.05, 95% CI: 1-1.1; p-value = 0.01). Of the 413 patients enrolled in the study, 98 cases (23.73%) were initiated on treatment. In the head-to-head comparison of the results in TDF and TDF + LAM after 12 weeks of treatment, VR was observed in 14(45.2%) vs. 17(54.8%), respectively, translating into an overall VR of 60.7% (95% CI 46.9-74.6). Furthermore, VR in TDF vs. TDF + LAM were similar, 14(45.2%) vs. 17(54.4%) respectively, p-value = 0.3). This study uncovered multiple systems- and patient-centered gaps in the three HBV treatment programs in Asmara, Eritrea. These include late presentation, high incidence of LTFU, inconsistencies in routine data, and poor data management. Interventions should target improvements in laboratory infrastructure, adherence to patient monitoring guidelines, HBV literacy, better tracking of patients, and documentation of patient’s information.

PMID:39755688 | DOI:10.1038/s41598-024-79600-y

Nat Commun. 2025 Jan 4;16(1):389. doi: 10.1038/s41467-024-55214-w.

ABSTRACT

Spatial protein expression technologies can map cellular content and organization by simultaneously quantifying the expression of >40 proteins at subcellular resolution within intact tissue sections and cell lines. However, necessary image segmentation to single cells is challenging and error prone, easily confounding the interpretation of cellular phenotypes and cell clusters. To address these limitations, we present STARLING, a probabilistic machine learning model designed to quantify cell populations from spatial protein expression data while accounting for segmentation errors. To evaluate performance, we develop a comprehensive benchmarking workflow by generating highly multiplexed imaging data of cell line pellet standards with controlled cell content and marker expression and additionally established a score to quantify the biological plausibility of discovered cellular phenotypes on patient-derived tissue sections. Moreover, we generate spatial expression data of the human tonsil-a densely packed tissue prone to segmentation errors-and demonstrate cellular states captured by STARLING identify known cell types not visible with other methods and enable quantification of intra- and inter- individual heterogeneity.

PMID:39755686 | DOI:10.1038/s41467-024-55214-w

J Ultrasound Med. 2025 Jan 4. doi: 10.1002/jum.16641. Online ahead of print.

ABSTRACT

OBJECTIVES: The pathogenesis of premature ovarian insufficiency (POI) not only affects the ovarian structure and function but also gives rise to complications such as osteoporosis and dyslipidemia. Although low-intensity pulsed ultrasound (LIPUS) has been proven effective in treating POI, its impact on the associated complications remains unexplored. Therefore, this study aims to investigate the effects of LIPUS irradiation on osteoporosis and dyslipidemia in a mouse model of POI.

METHODS: The post-treatment complications following LIPUS cessation were monitored in POI rats at 30 and 120 days in this trial conducted by us. The secretion of follicle-stimulating hormone (FSH) was assessed using enzyme-linked immunosorbent assay (ELISA) at different time points in POI rats. Pathological changes in the liver and femur were observed through HE staining. Blood lipid and bone metabolism indexes were measured via blood biochemical testing. Osteoporosis was evaluated using MicroCT and Masson staining techniques. The expression level of inflammatory factors in bone tissue was detected by Western blot (WB) test.

RESULTS: The serum FSH content showed a significant decrease in the LIPUS group on day 0, day 15, and day 30 (P < .05). On the 30th day following LIPUS treatment, TC, TG, and LDL-C decreased in the LIPUS group while HDL-C increased with no statistically significant differences (P > .05); the indexes of femur parameters (BS/TV, BV/TV, Tb.Th, BMD, and TMD) were increased (P > .05). On the 120th day after LIPUS treatment, TC content demonstrated a significant decrease (P < .05), and TG and LDL-C displayed a downward trend (P > .05) while HDL-C content increased (P < .05); the femur parameters were significantly reduced (P < .05). The LIPUS group exhibited an increased presence of new fibrillar fibers. Levels of IL-6 and IL-1β significantly decreased with LIPUS treatment, whereas osteocalcin (OCN) expression notably increased (P < .05).

CONCLUSIONS: The application of LIPUS demonstrates potential in mitigating complications associated with POI in rats through the reduction of FSH secretion levels and inhibition of tissue inflammation, thereby presenting a promising avenue for women with POI to explore more efficacious treatment alternatives.

PMID:39754744 | DOI:10.1002/jum.16641

ARP Rheumatol. 2024 Oct-Dec;3(4):277-287.

ABSTRACT

AIMS: ultrasound (US) diagnosis of enthesitis is burdened of low specificity, especially when it is performed in patients with psoriasis (PsO) but without clinical psoriatic arthritis (PsA), because of mechanical, dysmetabolic and age-related concurrent enthesopatic changes. We propose a novel US score to quantify the cortical-entheseal bone remodeling burden of several peripheral entheses, aiming to improve the specificity of US for PsA-related enthesitis, and to evaluate its diagnostic value in PsO patients with subsequent diagnosis of psoriatic arthritis (PsO/PsA).

METHODS: clinical and US data of 119 consecutive patients with moderate/severe PsO and nonspecific musculoskeletal symptoms, were included in this retrospective study. PsO patients underwent a multi-joint US examination and a subsequent rheumatologic visit to evaluate concurrent PsA clinical diagnosis, in a scenario of real clinical practice. The cortical-entheseal bone remodeling has been evaluated with a morphologic gray-scale US score named “CERTUS” (Cortical-Entheseal Remodeling Tuscany Ultrasonographic Score, range 0-36), grading the combination of both enthesophytes and erosions in a semiquantitative scale. A variant of CERTUS, with Power Doppler (PD), was calculated too (CERTUS-PD, range 0-48), scoring PD signals into erosions. The sum of the scores obtained for 12 peripheral entheses was used as global score for statistic aims. The new bone formation at extensor tendon entheses at distal inter-phalangeal (DIP) joints were also recorded.

RESULTS: a clinical diagnosis of PsO/PsA was made in 48/119 PsO patients (40.3%), showing older age (p<0.001), higher BMI (p=0.015), prevalence of metabolic syndrome (p=0.014) and smoking habit (p<0.001). CERTUS (AUROC 0.814) showed a highest specificity cut-off=11 (sensitivity 41.4%, specificity 100%), whereas CERTUS-PD (AUROC 0.828) showed a highest specificity cut-off=13 (sensitivity 37.9%, specificity 100%). CERTUS and CERTUS-PD correlated with both other validated US scores as Belgrade Ultrasound Enthesitis Score (BUSES) (p<0.001), DACTylitis glObal Sonographic (DACTOS) score (p=0.05 and p=0.031 respectively), amount of synovitis (p=0.036 and p=0.04 respectively), enthesitis (p<0.001) and entheseal new bone formation on DIP joints (p=0.029 and p=0.031 respectively).

CONCLUSIONS: the scoring system named CERTUS (and its variant with PD) is a quick tool to quantify cortico-entheseal bone remodeling burden in PsO patients, improving the specificity of US to diagnose patients with subclinical PsA-related enthesitis.

PMID:39754729

Vet Rec. 2025 Jan 4:e4908. doi: 10.1002/vetr.4908. Online ahead of print.

ABSTRACT

BACKGROUND: This study aimed to evaluate the effects of administering flunixin meglumine (FM) and meloxicam (M) on specific days post-mating on progesterone (P4), total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), pregnancy-specific protein B (PSPB), pregnancy-associated glycoprotein (PAG) concentrations and fertility parameters in Awassi sheep.

METHODS: Seventy-five Awassi sheep were divided into three groups of 25: control, M and FM. On days 9 and 10 post-mating, the control group received saline, the M group received 0.5 mg/kg M and the FM group received 2.2 mg/kg FM. Blood samples were collected on days 8, 9, 10, 11, 12 and 17 post-mating.

RESULTS: Statistically significant time-dependent differences in P4, TAS, TOS, OSI, PSPB and PAG concentrations were found between the groups (p < 0.001). TAS was highest in the M group and lowest in the control group (p < 0.001). TOS was higher in the control group and lower in the M group (p < 0.001). PSPB and PAG were highest in the control group and lowest in the M group (p < 0.05).

LIMITATION: Further studies with larger sample sizes are needed to confirm the findings.

CONCLUSION: FM and M significantly affected oxidative stress parameters and early pregnancy factors but not fertility parameters.

PMID:39754716 | DOI:10.1002/vetr.4908

Diagnosis (Berl). 2025 Jan 6. doi: 10.1515/dx-2024-0181. Online ahead of print.

ABSTRACT

OBJECTIVES: Published clinical reasoning curricula are limited, and measuring curricular impact has proven difficult. This study aims to evaluate the impact of a broad-reaching, multi-level reasoning curricula by measuring utilization of clinical reasoning terminology in published abstracts.

METHODS: In 2014, the University of Pittsburgh Medical Center (UPMC) created a clinical reasoning curriculum with interventions at the student, resident, and faculty levels with the goal of bringing reasoning education to the forefront. This study was a retrospective analysis of published clinical vignettes of the Society of General Internal Medicine prior to local curricular intervention (2014), post-curricular intervention (2018), and on follow-up (2022). UPMC-affiliated abstracts were compared to abstracts containing reasoning terms from all other institutions, at each time point.

RESULTS: There was a statistically significant increase in the use of clinical reasoning terms by UPMC-affiliated participants from 2014 to 2018. Non-UPMC submissions, saw a smaller, but still significant increase in the use of clinical reasoning terms. There was a decline in clinical reasoning term use from 2018 to 2022, both at UPMC and nationally.

CONCLUSIONS: This study demonstrates that widespread clinical reasoning curricula can increase interest in and use of clinical reasoning terminology. Further work is needed to develop creative assessment tools for reasoning curricula.

PMID:39754715 | DOI:10.1515/dx-2024-0181

J Relig Health. 2025 Jan 4. doi: 10.1007/s10943-024-02239-6. Online ahead of print.

ABSTRACT

Spirituality is widely recognized as a potential moderator of the adverse effects of hemodialysis on mental health. Understanding its impact on mental health in Saudi Arabia and the Arab world, however, remains a significant research gap. Hence, this study aims to explore the correlations between spirituality, anxiety, and depression among Saudi Arabian patients undergoing hemodialysis. Using a cross-sectional design, 121 hemodialysis patients were recruited. Self-administered surveys were employed to capture demographic data, as well as a Depression and Anxiety Scale, and a Spiritual Well-being Scale. Descriptive and inferential statistics, along with multivariate regression, were utilized to analyze the data. Results show that the majority of respondents (77.7-87.6%) report moderate levels of religious well-being (RBW) and existential well-being (EWB), while 76.8-15.7% showed low-to-moderate levels of depression, respectively. Additionally, 20.7% of patients experienced moderate-to-severe anxiety. Significant negative correlations were found between RWB/EWB and depression (r = – 0.459, r = – 0.601, p < 0.001, respectively) and between RWB / EWB and anxiety (r = – 0.341, r = – 0.536, p < 0.001). The RWB accounted for 54.9% of the religious score variance, showing a strong correlation with existential score (β = 0.655, p < 0.001), but not with anxiety or depression. Similarly, the EWB accounted for 63.7% of the EWB variance, showing a correlation with religious score (β = 0.528, p < 0.001) and anxiety score (β = – 0.199, p < 0.05), but not with depression. In contrast, the depression explained 71.2% of the variation in depression scores, as well as showing strong correlations with anxiety (β = 0.663, p < 0.05). The anxiety accounted for 66.8% of the variance in anxiety scores, with depression being a significant predictor (β = 0.763, p < 0.001). This study highlights the importance of integrating spirituality into holistic care for hemodialysis patients because its presence positively influences both mental and physical health outcomes.

PMID:39754693 | DOI:10.1007/s10943-024-02239-6

Ir J Med Sci. 2025 Jan 4. doi: 10.1007/s11845-024-03860-w. Online ahead of print.

ABSTRACT

AIM: This study aimed to investigate the effect of the COVID-19 pandemic on the clinical and pathological stages of patients diagnosed with breast cancer.

METHOD: In this retrospective study, a total of 298 male and female patients over the age of 18 who were diagnosed with breast cancer and who were continuing surgical and oncologic treatment were included.

RESULTS: Of the 298 patients diagnosed with breast cancer, 186 (62.4%) belonged to the pre-COVID period and 112 (37.6%) to the COVID period, and there was a 39.7% decrease in the number of diagnosed patients. Statistical analyzes revealed significant differences in family history, smoking, histopathologic grade, disease stage, type of surgery performed and Cerb-B2 ovarian expression (p = 0.005, p = 0.001, p = 0.018, p = 0.035, p < 0.001, p = 0.047). During the pandemic period, tumor size (T), axillary lymph node metastasis rate, neoadjuvant chemotherapy rate, and distant metastasis rate increased, but there was no statistically significant difference (p = 0.535, p = 0.070, p = 0.148, p = 0.153, respectively).

CONCLUSIONS: In pandemic situations such as COVID-19, restrictions in social life and fear of contamination can prolong the time of admission to the hospital. This may cause delays in the diagnosis of malignant diseases such as breast cancer and progression in the disease stage. In these and similar outbreaks, public awareness should be raised, and the public should be encouraged to comply with screening and follow-up programs in order to continue outpatient clinic activities and screening programs without interruption by taking contamination measures.

PMID:39754685 | DOI:10.1007/s11845-024-03860-w

Indian J Pediatr. 2025 Jan 4. doi: 10.1007/s12098-024-05392-8. Online ahead of print.

ABSTRACT

This hospital-based cross-sectional study aimed to screen newborns for sickle cell anemia immediately after birth and validate dried blood spot (DBS) samples against conventional venous blood samples (CBS) for hemoglobin variant analysis by HPLC. Among 751 newborns, 2.93% were found to have sickle cell trait. Hemoglobin variants were analyzed in both DBS and CBS samples, showing good agreement with 100% sensitivity and 100% specificity. Passing Bablok regression indicated minimal proportional bias, while Bland-Altman analysis showed a bias of 0.67, but the line of equality within the 95% CI of the bias indicated acceptable minimal systematic bias. The concordance correlation coefficient was 0.91 (p < 0.0001), Pearson’s ρ (precision measure) was 0.967, and Cohen’s kappa statistics gave a weighted kappa of 0.93, confirming no significant differences between the two methods. This study supports DBS as a reliable method for universal neonatal screening for sickle cell disease, demonstrating its potential for widespread clinical use.

PMID:39754675 | DOI:10.1007/s12098-024-05392-8