Search Results (466)

Background: Childhood obesity is becoming an increasingly pressing issue on a global scale. This study aimed to explore the relationship between thyroid hormone levels and body mass index (BMI) in obese children and adolescents, an area with limited research, particularly in Bangladesh. Methods: This cross-sectional study was undertaken in Bangabandhu Sheikh Mujib Medical University, Bangladesh, from August 2018 to January 2020. We included 105 participants aged 10–18 years, divided into obese (n = 69) and normal-weight (n = 36) groups based on the CDC BMI percentiles. We conducted chi-square tests, Pearson correlation, and linear regression analyses. Results: Obese participants exhibited significantly higher mean levels of TSH (4.40 ± 3.20 µIU/mL vs. 2.26 ± 0.97 µIU/mL, p-value 0.0002) and FT3 (3.52 ± 0.71 pg/mL vs. 3.02 ± 0.48 pg/mL, p-value < 0.001) and lower FT4 levels (1.23 ± 0.21 ng/dL vs. 1.38 ± 0.30 ng/dL, p-value 0.0002) compared to normal-weight participants. We observed a positive correlation between BMI and TSH (p-value 0.002) and FT3 (p-value < 0.001), and a negative correlation between BMI and FT4 (p-value 0.003). Most of the obese children were euthyroid (71.01%), with 27.54% showing subclinical hypothyroidism and 1.45% showing overt hypothyroidism. Multivariable linear regression analysis revealed that with a one unit increase in BMI, FT3 increased by 0.032 ± 0.011 pg/mL (p-value 0.004), FT4 decreased by 0.010 ± 0.004 (p-value 0.017 ng/dL, and TSH increased by 0.104 ± 0.044 µIU/mL (p-value 0.020). Conclusions: The significant association between BMI and thyroid hormone levels underscores the necessity for routine thyroid function monitoring in obese paediatric populations. The early detection and management of thyroid dysfunction may enhance health and well-being outcomes in obese children and adolescents. Full article

Hepatocellular carcinoma (HCC) is the main leading cause of cancer-related deaths. Treatments for advanced HCC include multikinase inhibitors (Sorafenib or Lenvatinib), with limited response rates and serious side effects, or immunotherapy applicable to a small fraction of patients. Thus, new strategies are needed to improve the management of HCC. We evaluate here the efficacy and safety of XON9, a first-in-class glyco-humanized polyclonal antibody (GH-pAb). Cytotoxic activity of XON9 against Hep3B, Huh7, HepG2 or primary hepatocytes was investigated. Apoptosis, caspase activity, production of reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were evaluated. Efficacy of XON9 was then assessed in vivo in NMRI nude mice, while pharmacokinetics and safety were evaluated in a non-human primate. XON9 showed a potent complement-dependent cytotoxicity (CDC) against Hep3B and Huh7 (EC50 < 10 µg/mL), and to a less extent against HepG2. XON9 induced apoptosis of HCC cells with activation of caspases 8 and 9, increase in ROS and drop in MMP. Overall, in vitro lytic activity of XON9 was superior to that of Sorafenib. In vivo, XON9 significantly reduced tumor progression and outperformed Sorafenib. No toxicity was observed after repeated injections of XON9 in a non-human primate. XON9 represents a promising and selective immunotherapy against refractory HCC. Full article

Triple-negative breast cancer (TNBC) is an aggressive, heterogeneous subtype of breast cancer. miRNAs play an essential role in TNBC pathogenesis and prognosis. Obesity is linked with an increased risk for several cancers, including breast cancer. Obesity is also related to the dysregulation of miRNA expression in adipose tissues. However, there is limited knowledge about race- and obesity-specific differential miRNA expression in TNBC. We performed miRNA sequencing of 48 samples (24 tumor and 24 adjacent non-tumor tissues) and RNA sequencing of 24 tumors samples from Black (AA) and White (EA) TNBC patients with or without obesity. We identified 55 miRNAs exclusively associated with tumors in obese EA patients and 33 miRNAs in obese AA patients, each capable of distinguishing tumor tissues from obese from lean individuals within their respective racial groups. In EA, we detected 41 significant miRNA–mRNA correlations. Notably, miR-181b-5p and miR-877-5p acted as negative regulators of tumor-suppressor genes (e.g., HEY2, MCL2, HAND2), while miR-204-5p and miR-143-3p appeared to indirectly target oncogenes (e.g., RAB10, DR1, PTBP3, NCBP1). Among AA patients, we found 28 significant miRNA–mRNA interactions. miR-195-5p, miR-130a-3p, miR-130a-5p, miR-424-5p, miR-148a-3p, miR-374-5p, and miR-30a-5p each potentially downregulated two or more genes (e.g., CLCN4, PLCB1, CDC25B, AEBP2, ERBB4). Pathway enrichment analysis highlighted KRAS, ESR1, ESR2, RAB10, TNRC6C, and NCAN as the most commonly differentially expressed in EA, whereas ERBB4, PLCB1, and SERPINE1 were most frequently in AA. These findings highlight the importance of considering race-specific miRNA–mRNA signatures in understanding TNBC in the context of obesity, offering insights into biomarker-driven patient stratification for targeted therapeutic strategies. Full article

Background: Various studies have demonstrated fucoidan’s immunomodulatory effects. A previous study reported the anticancer effects of Durvillaea antarctica fucoidan (DAF) via immune activation in mice. Methods: In this study, we confirmed the DAF’s pulmonary immune activation ability by nasal administration of the dendritic cells (DCs) and T cells. Furthermore, we examined its ability to enhance the efficacy of lung cancer treatment by combining it with anti-PD-L1 antibodies to activate the lung immune response. Results: Nasal DAF administration increased C-C chemokine receptor type 7 expression in DCs and promoted DC migration to the mediastinal lymph nodes (mLN). Specifically, DAF increased conventional DC type 1 (cDC1) and cDC2 numbers in mLN and potently activated cDC1. Furthermore, the nasal administration of DAF increased the production of inflammatory cytokines in the lungs and peripheral blood. Repeated intranasal administration of DAF induced T-cell activation, resulting in the enhanced production of interferon-gamma and tumor necrosis factor-alpha in CD4 T and CD8 T cells. CD8 T cells also showed increased secretion of cytotoxic mediators after DAF treatment, and the proportion of Tregs expressing FoxP3 decreased in the mLN. DAF inhibited lung cancer growth in Lewis lung carcinoma 2 cells, which was enhanced by combining it with an anti-programmed death-ligand 1 antibody. Finally, the anticancer effects of DAF were not observed in mice with depleted CD4-positive and CD8-positive cells. Conclusions: Nasal administration of DAF may inhibit lung cancer growth by inducing lung immune activation and is expected to be helpful as an immune activator for nasal administration. Full article

Background: Clostridium difficile colonization (CDC) represents a clinical concern in oncology patients undergoing abdominopelvic surgery, particularly regarding the potential role of prophylactic antibiotics in preventing progression to active infection. Methods: We performed a single-center, retrospective, case-matched observational study of oncology patients with CDC who underwent abdominopelvic surgery between 2018 and 2023. Patients were divided into two cohorts: those who received prophylactic antibiotics and those who did not. Postoperative outcomes were compared using propensity score matching (PSM). Logistic regression and ROC curve analysis were applied to assess the predictive value of antibiotics relative to other comorbidities. Results: Ninety patients were included (62 with antibiotics; 28 without). In the unmatched cohort, patients receiving antibiotics showed a non-significant trend toward higher morbidity (32.2% vs. 21.4%, p = 0.327) and surgical site infection rates (9.6% vs. 0%, p = 0.171). After PSM (26 patients per group), morbidity remained comparable between cohorts (30.7% vs. 23.0%, p = 0.538). Notably, no patient developed active C. difficile infection during follow-up, regardless of antibiotic use. Antibiotic therapy was not an independent predictor of postoperative morbidity (OR 1.746, p = 0.297; AUC 0.549, 95% CI 0.405–0.687). Conclusions: In this study, prophylactic antibiotic use in CDC patients undergoing abdominopelvic oncology surgery was not associated with improved postoperative outcomes. While no progression to active infection was observed, the potential benefits of prophylaxis remain uncertain. Larger, prospective studies are needed to clarify the clinical role of antibiotics in this setting. Full article

Background/Objectives: Symptoms of autonomic dysfunction are common in infection-associated chronic conditions and illnesses (IACCIs), including myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). This study aimed to evaluate autonomic symptoms and their impact on ME/CFS illness severity. Methods: Data came from a multi-site study conducted in seven ME/CFS specialty clinics during 2012–2020. Autonomic dysfunction was assessed using the Composite Autonomic Symptom Scale 31 (COMPASS-31), medical history, and a lean test originally described by the National Aeronautics and Space Administration (NASA). Illness severity was assessed using Patient-Reported Outcomes Measurement Information System measures, the 36-item short-form, as well as the CDC Symptom Inventory. This analysis included 442 participants who completed the baseline COMPASS-31 assessment, comprising 301 individuals with ME/CFS and 141 healthy controls (HC). Results: ME/CFS participants reported higher autonomic symptom burden than HC across three assessment tools (all p < 0.0001), including the COMPASS-31 total score (34.1 vs. 6.8) and medical history indicators [dizziness or vertigo (42.6% vs. 2.8%), cold extremities (38.6% vs. 5.7%), and orthostatic intolerance (OI, 33.9% vs. 0.7%)]. Among ME/CFS participants, 97% had at least one autonomic symptom. Those with symptoms in the OI, gastrointestinal, and pupillomotor domains had significantly higher illness severity than those without these symptoms. Conclusions: ME/CFS patients exhibit a substantial autonomic symptom burden that correlates with greater illness severity. Individualized care strategies targeting dysautonomia assessment and intervention may offer meaningful improvements in symptom management and quality of life for those with ME/CFS and similar chronic conditions. Full article

The X-linked TLR7 rs179008 T allele has been associated with altered antiviral immunity. Given their shared inflammatory pathways and higher pediatric mortality rates in Brazil during the pandemic, we investigated their association with multisystem inflammatory syndrome in children (MIS-C) together with Kawasaki disease (KS) following SARS-CoV-2 infection. A cross-sectional study (2021–2022) analyzed 73 hospitalized children (<13 years) with confirmed COVID-19. Genotyping for TLR7 rs179008, TLR8 (rs3764879, rs2407992), and TLR3 rs3775291 was performed via PCR and Sanger sequencing. MIS-C/KS cases were identified using CDC criteria, with severity classified by the need for ICU care. Statistical analysis included Fisher’s exact test and relative risk (RR) calculations. Hemizygous boys carrying the TLR7 T allele had a 1.87-fold higher risk of MIS-C/KS (p = 0.007) and a 1.75-fold increased risk of severe or critical outcomes. The T allele frequency was 2.6× higher in MIS-C/KS cases versus other COVID-19 presentations. All fatalities occurred in boys (3/8 MIS-C cases) with one T-allele carrier. No associations were found for TLR8 or TLR3 variants. The TLR7 rs179008 T allele is a potential genetic risk factor for severe post-COVID-19 inflammatory syndromes in boys, likely due to impaired immune signaling. These findings highlight its utility as a biomarker for risk stratification in pediatric populations. Full article

Background/Objectives: Hispanics living in the United States have higher rates of diagnosis and mortality from certain kinds of cancers, including human papillomavirus (HPV)-related cancers. HPV vaccines can prevent 90% of HPV-associated cancers. Methods: The purpose of this study was to recruit a sample of Hispanic parents to investigate trusted sources of HPV vaccine information. An online survey was used to collect data from Hispanic parents who reported having children between the ages of 11 and 17. Results: Parents of children 11–17 years of age (n = 203, M_age = (38, SD = 6.97; female 85.1%) were included. The top five trusted sources of HPV vaccine information were medical doctors (95.1%), registered nurses (54.2%), the CDC (47.8%), the WHO (45.3%), and pharmacists (25.6%). The two least trusted sources were the president of the U.S. (7.9%) and religious leaders (3%). Hierarchical linear regression models revealed that HPV vaccine acceptance was associated with trusting registered nurses (p < 0.001) and the CDC (p = 0.026) in recommending the HPV vaccine. Importantly, the family-held belief that vaccines cause autism was strongly correlated with personal beliefs that vaccines cause autism (r = 0.58; p < 0.001). Conclusions: Findings from this study have clinical implications for the development of interventions and health communication strategies that leverage trusted sources of information including medical doctors and registered nurses to encourage preventive health behaviors. Additionally, our findings support that pharmacists should be included in these interventions as they are often an underused resource and are trusted by their patients for vaccine information. Full article

Optimal treatment for non-critically ill multisystem inflammatory syndrome in children (MIS-C) remains unclear. We evaluated short-term outcomes in mild to moderately ill hospitalized MIS-C patients fulfilling CDC 2020 and CDC/CTSE 2023 criteria and treated between April 2020 and March 2022 with either intravenous immunoglobulin (IVIG) monotherapy (Group A, n = 17) or IVIG plus corticosteroids (GC) (Group B, n = 22). Cardiovascular clinical parameters, inflammatory markers, and cardiac imaging were compared on days 1, 3, and 5 relative to day 0. The two groups had no significant differences in demographics or illness severity. Group B showed improvement in heart rate (17.8; 95% CI [9.74, 25.8]), mean blood pressure (5.63 [1.61, 9.64]), and body temperature (1.45 [0.94, 1.95]) by day 1, followed by improvement in albumin (0.43 [0.2, 0.84]), CRP (7.56 [3.0, 12.11]), D-dimer (2344 [488.7, 4200.2]), ferritin (1448 [−609.4, 3505.5]), fibrinogen (110 [44.4, 176]), lymphocyte count (1006 [63.5, 1948]), and NT-proBNP (2901 [−349.3, 6153]) by day 3 and left ventricular ejection fraction by day 4–5 (3.84 [0.55, 8.23]). All results were statistically significant (p < 0.05). Group A required more additional therapies, with no difference in hospital stay. Our study concludes that combined IVIG and GC therapy yielded better short-term outcomes than IVIG monotherapy in this patient population, with improvement in cardiovascular clinical parameters preceding changes in inflammatory markers and cardiac imaging. Full article

Limited surveillance and laboratory testing for non-influenza viruses remains a challenge in Uganda. The World Health Organization (WHO) designated National Influenza Center (NIC) tested samples from patients with influenza-like illness (ILI) and severe acute respiratory infections (SARIs) during August 2022–February 2023. We leveraged the influenza sentinel surveillance system to detect other respiratory viruses (ORVs). Samples were tested using the US Centers for Disease Control and Prevention (CDC) influenza and SARS-CoV-2 multiplex and the FTD^TM Respiratory Pathogens 21 assays using real-time reverse transcription polymerase chain reaction (RT-qPCR). A total of 687 (ILI = 471 (68.6%) and SARI = 216 (31.4%) samples were tested. The median age was 2 years (IQR: 1–25) for ILI and 6 years (IQR: 1–18) for SARI case definitions (p-value = 0.045). One or more respiratory pathogens were detected in 38.7% (n = 266) of all samples; 33 (12.4%) were selected for metagenomics sequencing and 8 (3%) for SARS-CoV-2 targeted sequencing. Respiratory pathogens were detected by sequencing in 23 of 33 (69.7%) samples. Our study provides insight into the usefulness of this surveillance system in conducting virological testing for other viruses and provides tools and evidence to monitor patterns and characteristics of viruses causing ILI/SARI, which will guide public health decisions and interventions in Uganda. Full article

Background/Objectives: Prior studies using administrative data have found that antenatal anemia is a risk factor for severe maternal morbidity (SMM). However, administrative definitions, including the commonly used definition from the Centers for Disease Control and Prevention (CDC), have a poor positive predictive value for some SMM components. We tested the relationship between hemoglobin level at delivery admission and SMM, as defined by gold-standard chart review. Methods: This was a retrospective case–control study of deliveries at a high-acuity hospital in Los Angeles, California, from 2016 to 2019. Administrative data were screened to identify patients with CDC SMM. Control-patients were selected at random from screen-negative individuals. Medical records for all individuals were reviewed for gold-standard SMM criteria, and clinical data were abstracted. Confirmed-positive and confirmed-negative patients were compared using bivariate analyses. Multiple logistic regression models were developed to test the relationship between admission hemoglobin level and gold-standard SMM. Results: Of 4202 eligible individuals, 275 (6.5%) screened positive for SMM. Of these, 107 (38.5%) met gold-standard SMM criteria; 285 confirmed-negative controls were retained for analysis. Case-patients were more likely than control-patients to have anemia on delivery admission (43.9% vs. 24.2%, p < 0.01) and had lower admission hemoglobin levels (11.2 ± 1.7 g/dL vs. 11.9 ± 1.3 g/dL, p < 0.01). After controlling for covariates, admission hemoglobin was independently and inversely associated with gold-standard SMM (aOR = 0.76, 95% CI 0.60–0.96, p = 0.02). Conclusions: Lower hemoglobin level at delivery admission was associated with an increased risk of developing gold-standard SMM. Full article

Background/Objective: Pediatric obesity negatively impacts metabolic and musculoskeletal health, particularly muscle quality and function. Ultrasound-derived measures like muscle thickness and echo intensity, combined with body composition data, provide a more comprehensive assessment of muscle status in this population. The purpose of our study was to examine the relationship between anthropometric measurements, muscle strength, and bioelectrical impedance estimations with ultrasound-derived indicators such as subcutaneous fat and quadriceps femoris thickness, as well as muscle quality, through EI. Methods: This cross-sectional study included Hispanic children aged 6 to under 18 years with overweight or obesity (BMI ≥ 85th percentile per CDC standards). Participants were recruited consecutively from outpatient visits. All eligible children were invited for a standardized nutritional assessment, and those who consented were included. Results: The study included 294 children and adolescents (153 boys, 141 girls) with overweight or obesity, showing significant sex differences in anthropometric and body composition variables. Girls had higher intramuscular adipose tissue (IMAT) (p < 0.001), while boys had more lean and musculoskeletal mass. Body fat percentage was significantly correlated with muscle echo intensity (EI corrected: R² = 0.264, p < 0.001; EI uncorrected: R² = 0.242, p < 0.001) and with IMAT (R² = 0.268, p < 0.001). These associations were stronger in girls. Linear models identified body fat and BMI percentile as key predictors of muscle quality indicators (p < 0.001). Conclusions: This study found that higher body fat in children and adolescents with overweight or obesity is linked to poorer muscle quality, and especially increased echo intensity and intramuscular fat. Ultrasound proves useful for early, non-invasive detection of musculoskeletal changes, emphasizing the need to assess both muscle size and quality. Full article

Background: The candidate therapeutic peptide TnP demonstrates broad, system-level regulatory capacity, revealed through integrated network analysis from transcriptomic data in zebrafish. Our study primarily identifies TnP as a multifaceted modulator of drug metabolism, wound healing, proteolytic activity, and pigmentation pathways. Results: Transcriptomic profiling of TnP-treated larvae following tail fin amputation revealed 558 differentially expressed genes (DEGs), categorized into four functional networks: (1) drug-metabolizing enzymes (cyp3a65, cyp1a) and transporters (SLC/ABC families), where TnP alters xenobiotic processing through Phase I/II modulation; (2) cellular trafficking and immune regulation, with upregulated myosin genes (myhb/mylz3) enhancing wound repair and tlr5-cdc42 signaling fine-tuning inflammation; (3) proteolytic cascades (c6ast4, prss1) coupled to autophagy (ulk1a, atg2a) and metabolic rewiring (g6pca.1-tg axis); and (4) melanogenesis-circadian networks (pmela/dct-fbxl3l) linked to ubiquitin-mediated protein turnover. Key findings highlight TnP’s unique coordination of rapid (protease activation) and sustained (metabolic adaptation) responses, enabled by short network path lengths (1.6–2.1 edges). Hub genes, such as nr1i2 (pxr), ppara, and bcl6aa/b, mediate crosstalk between these systems, while potential risks—including muscle hypercontractility (myhb overexpression) or cardiovascular effects (ace2-ppp3ccb)—underscore the need for targeted delivery. The zebrafish model validated TnP-conserved mechanisms with human relevance, particularly in drug metabolism and tissue repair. TnP’s ability to synchronize extracellular matrix remodeling, immune resolution, and metabolic homeostasis supports its development for the treatment of fibrosis, metabolic disorders, and inflammatory conditions. Conclusions: Future work should focus on optimizing tissue-specific delivery and assessing genetic variability to advance clinical translation. This system-level analysis positions TnP as a model example for next-generation multi-pathway therapeutics. Full article

The 2025 avian influenza A(H5N1) outbreak has highlighted the urgent need for rapidly generated health communication materials during public health emergencies. Artificial intelligence (AI) systems offer transformative potential to accelerate content development pipelines while maintaining scientific accuracy and impact. We evaluated an AI-generated health communication material on bird flu precautions among 100 U.S. adults. The material was developed using ChatGPT for text generation based on CDC guidelines and Leonardo.AI for illustrations. Participants rated perceived message effectiveness, quality, realism, relevance, attractiveness, and visual informativeness. The AI-generated health communication material received favorable ratings across all dimensions: perceived message effectiveness (3.83/5, 77%), perceived message quality (3.84/5, 77%), realism (3.72/5, 74%), relevance (3.68/5, 74%), attractiveness (3.62/5, 74%), and visual informativeness (3.35/5 67%). Linear regression analysis revealed that all features significantly predicted perceived message effectiveness in unadjusted and adjusted models (p < 0.0001), e.g., multivariate analysis of outcome on perceived visual informativeness showed β = 0.51, 95% CI: 0.37–0.66, p < 0.0001. Also, mediation analysis revealed that visual informativeness accounted for 23.8% of the relationship between material attractiveness and perceived effectiveness. AI tools can enable real-time adaptation of prevention guidance during epidemiological emergencies while maintaining effective risk communication. Full article

Background: Broad-spectrum antibiotics are often used for suspected infections in patients with hematologic malignancies due to the risk of severe infections. Although antibiotic use can lead to antimicrobial resistance and microbiome dysbiosis, the effects of antibiotics on the microbiome and resistome in patients with acute myeloid leukemia (AML) undergoing remission induction chemotherapy (RIC) are not well understood. Methods: Various statistical models were utilized to examine the effects of antibiotic administration on the microbiome and resistome over time, as well as differences in AR-infection (ARI) and colonization (ARC) by important CDC-threats in 119 AML patients. Results: A greater number of unique antibiotic classes administered correlated with a loss of unique antibiotic resistance genes (ARGs) (R = −0.39, p = 0.008). Specifically, although a greater number of oxazolidinone administrations was correlated with a greater loss of diversity (R = −0.58, p < 0.001), each additional day of linezolid reduced the risk of ARC by ~30% (HR: 0.663, p = 0.047) and decreased the odds of acquiring genes predicted to confer macrolide (HR: 0.50, p = 0.026) resistance. Conclusions: The number of antibiotic administrations and the types of antibiotics used can influence the risk of antibiotic resistance gene (ARG) expansion and ARC events in AML patients undergoing RIC. While certain antibiotics may reduce microbial diversity, they are not always linked to an increase in ARGs or ARC events. Full article