Search Results (2,947)

Teotihuacan, one of the most significant urban and ceremonial centers of ancient Mesoamerica, was abruptly abandoned in the mid-1st millennium AD. The cause and timing of its collapse—commonly placed between 600 and 650 AD—remain major questions in Mesoamerican archaeology. In this study, we present a new archaeomagnetic investigation of six burned structures distributed along the Street of the Dead, including sites at the Square of the Moon, the Room of Columns, the Northwest Complex of the San Juan River, the Superimposed Buildings, and the West Plaza. Magnetic analyses revealed pseudo-single-domain magnetite as the main remanence carrier and produced well-grouped paleodirections (site-mean declinations ranging from 341.1° to 1.7°, α₉₅ ≤ 3.6°) and reliable absolute paleointensities (ranging from 39.4 ± 3.4 μT to 52.5 ± 5.4 μT), obtained using the Thellier-type double-heating method. Archaeomagnetic dating using both global geomagnetic models (SHAWQ.2k) and regional secular variation curves suggests that the last heating events at these sites occurred between ~400 and 500 AD—well before the traditionally cited Metepec phase (550–650 AD) and the so-called “Great Fire.” These findings challenge the prevailing chronological framework and provide compelling evidence that major episodes of destruction and depopulation may have begun earlier than previously recognized. Full article

Fluoride prophylaxis is a cornerstone in preventing dental caries, a disease for which orthodontic patients are at high risk due to the reduced effectiveness of home oral hygiene and increased plaque accumulation. Recent evidence defines caries as polymicrobial, involving Streptococcus mutans, Lactobacilli, and emerging species such as Selenomonas sputigena. This prospective, randomized, controlled study evaluated professional topical fluoride in the form of gel and varnish in 68 patients aged 8–17 years wearing fixed orthodontic appliances. Participants were divided into three equal groups: two intervention groups and one control group. Clinical parameters (DMFT, salivary pH, PCR%) and microbiological analyses of plaque and saliva (oral Streptococci, S. mutans, S. sputigena, Lactobacilli, total bacterial count) were assessed at baseline (T0) and after 4 months (T1), following professional hygiene and fluoride application for the intervention groups. At T1, salivary pH increased in the gel group, and PCR% decreased significantly in all groups, with the most pronounced decrease observed in the varnish group. PCR analysis showed a higher rate of S. mutans and S. sputigena negativization in intervention groups. Culture-based analyses revealed reductions in oral Streptococci and Lactobacilli in intervention groups, while levels increased in controls. Overall, both clinical and microbiological variables indicated improvements in the fluoride-treated groups compared to controls, highlighting the efficacy of professional fluoride prophylaxis in orthodontic patients. Full article

Background/Objectives. Preterm birth (PTB), affecting approximately 11.1% of pregnancies globally, often results from inflammation at the maternal–fetal interface triggered by microbial or immune dysregulation. This study investigates the efficacy of cell-free supernatant derived from Bifidobacterium longum subsp. infantis CECT 7210 and Lacticaseibacillus paracasei CECT 30660 in mitigating inflammation-induced PTB in a murine model. Methods. Lipopolysaccharide (LPS) was administered to induce preterm labor and systemic inflammation, mimicking infection-related PTB. Results. The results demonstrated that combined administration of CECT 7210 and CECT 30660 cell-free supernatants reduced preterm deliveries from 85.6% to 42.8% in mice and significantly attenuated systemic and intrauterine proinflammatory cytokines, including TNF-α and IL-6, in maternal plasma and myometrial tissues. Importantly, this anti-inflammatory effect was independent of maternal progesterone or oxytocin levels, suggesting a direct modulation of immune responses in this animal model. The cell-free supernatant combination also inhibited the growth of pathogenic bacteria, including Streptococcus agalactiae, highlighting its antimicrobial potential. Conclusions. This study underscores the potential of CECT 7210 and CECT 30660 cell-free supernatants as a therapeutic strategy to reduce the risk of PTB by targeting inflammation pathways. The findings pave the way for further preclinical and clinical research to validate the efficacy of these cell-free supernatants in preventing PTB and associated complications, offering a promising alternative to traditional probiotic approaches. Full article

Background: The introduction of prophylactic HPV vaccination has transformed cervical cancer prevention worldwide, yet many low- and middle-income countries face persistent challenges in implementation, coverage gaps, and vaccine hesitancy. This article presents a narrative review of global and Brazilian HPV vaccination programs, highlighting achievements, pitfalls, and lessons for future strategies. Methods: We reviewed peer-reviewed literature and official reports from WHO, PAHO, CDC, Brazilian institutions, and others, focusing on programmatic performance, coverage trends, and vaccine acceptance. Results: In high-income settings such as Australia and the United Kingdom, school-based vaccination programs have driven sharp declines in HPV prevalence, genital warts, and precancerous lesions, in some cases approaching elimination thresholds. The United States has made progress but continues to struggle with disparities in uptake linked to socioeconomic and cultural factors. In India and several African nations, recent evidence supports single-dose regimens as a cost-effective and logistically feasible strategy. In Brazil, HPV vaccination was introduced in 2014 via the National Immunization Program (PNI), initially targeting girls aged 9–13 years through school campaigns. First-dose coverage exceeded 80% in the first year but subsequently declined, with full-schedule completion rates dropping below 60%. Contributing factors include misinformation, weakening of school-based delivery, and pandemic-related disruptions. Brazil later expanded eligibility to boys and immunocompromised populations and, more recently, extended catch-up vaccination to older adolescents. Conclusions: HPV vaccination has the potential to substantially reduce cervical cancer incidence globally. However, sustained impact depends not only on infrastructure and universal access but also on consistent school-based delivery, adaptive policies such as single-dose regimens, and robust communication strategies to counter misinformation. Brazil’s experience offers both inspiration and caution, providing lessons for countries striving to meet the WHO 90-70-90 targets. Full article

Background: Solute carrier organic anion transporter family member 1B1 (SLCO1B1) mediates statin uptake into hepatocytes, the primary sites of cholesterol production. While the impact of SLCO1B1 variation on statin-associated muscle symptoms (SAMS) is well-documented, its role in LDL-C reduction remains understudied. This single-center, retrospective cohort study evaluated whether SLCO1B1 variation affects statin effectiveness in 213 adults. Methods: The SLCO1B1 variant rs4149056 (NM_006446.5:c.521T>C) was tested to categorize patients by their SLCO1B1 function: normal, decreased, or poor. The primary endpoint was percent change in LDL-C from baseline to follow-up (≥6 weeks post-statin initiation), with secondary endpoints of SAMS occurrence and statin adherence. Results: Overall, the average LDL-C decreased by 32% across all groups. No significant difference in LDL-C reduction was observed between SLCO1B1 phenotypes (p = 0.24). Conclusions: SLCO1B1 variation did not significantly affect LDL-C reduction, SAMS occurrence, or statin adherence. However, the retrospective design and limited adherence data in this study represent important limitations warranting prospective validation studies. Full article

Background/Objectives: Because of the chronic course of the disease, clinicians managing IBD frequently encounter patients with a prior or newly diagnosed cancer. This can be related to the specific background cancer risk in that subject, aging, familial/genetic factors, or ongoing chronic inflammation. However, a potential influence of some therapeutic agents should also be considered. This setting, in the absence of controlled trials and few open series reports available, raises issues such as correct screening, prevention, and surveillance, but also eventual modification or adaptation of the medical management. Methods and Results: Few consensus guidelines and studies are available on the management of IBD patients with a history of cancer, and therefore, we aim to review the recommendations of the current guidelines and the evidence reported in the most recent real-world cohorts. Conclusions: This review will offer (a) an understanding of the background of cancer risk in IBD patients; (b) analysis and discussion of the risk of cancer related to IBD therapy; and, finally, (c) some clues for the management of IBD in patients with a previous or current history of cancer. Full article

Cancer is a major global health concern. Head and neck cancers are the sixth most prevalent type of cancer globally; it has been suggested that these cancers can be caused due to pesticide exposure during agricultural activities. In this study, we aimed to investigate whether agricultural labor is associated with an increased risk of head and neck cancers. A case–control study was performed in Ocean Road Cancer Institute in Tanzania: a national, specialized cancer hospital. A total of 298 head and neck cases and 305 controls were included. Occupational history and information about lifestyle factors and diet were obtained by interview. Using logistic regression analyses and adjusting for lifestyle and diet, an increased risk of head and neck cancer was found among workers with a history of agricultural work, with an odds ratio of 2.6 and a 95% confidence interval of 1.60–4.37. When including only non-smokers and non-alcohol users (n = 363), a similar estimate was found. Participants with over 10 years (n = 481) of agricultural work experience, after adjusting for lifestyle and diet, exhibited an odds ratio of 5.1, with a 95% confidence interval of 2.56–9.94. Our findings indicate that agricultural work is associated with the risk of head and neck cancer. Carcinogens in agriculture should be examined in future studies. Full article

Treatment paradigms for B-cell lymphomas have evolved significantly in the last decades. Nevertheless, the widespread clinical use of immunotherapy has demonstrated that it invariably leads to the development of resistance. This review outlines the underlying molecular mechanisms of resistance associated with emerging immunotherapeutic strategies, including Chimeric Antigen Receptor (CAR) T cell therapy and bispecific antibodies (BsAbs). In high-grade B-cell lymphomas, nearly 50% of patients progress following CAR T treatment due to host-related factors affecting CAR T cell proliferation and persistence, as well as tumor-intrinsic factors, such as loss of CD19 epitope expression, trogocytosis, and other genomic alterations (e.g., CD19 mutations, chromothripsis, APOBEC mutational activity, and deletions of RHOA). Additional genomic and epigenetic events, including mutations, alternative splicing of CD19, and aberrant promoter methylation, further contribute to resistance. BsAbs, representing an off-the-shelf T-cell-redirecting strategy, have recently shown promising single-agent efficacy with a manageable toxicity profile, predominantly characterized by T cell overactivation syndromes. Similarly to CAR T cell therapy, BsAb resistance arises through diverse mechanisms, such as antigen loss, T cell dysfunction (exhaustion and regulatory T cell activation), tumor-intrinsic alterations (e.g., TP53 mutations and MYC amplifications), and immunosuppressive influences from the tumor microenvironment. These findings underscore the complexity of immune evasion in B-cell lymphomas and highlight the ongoing need to optimize immunotherapeutic strategies and develop combination approaches to overcome resistance. Full article

Exposure to heavy metals from mining activities has been consistently associated with disruptions in hematologic homeostasis, adversely affecting children’s overall development. We aimed to determine population-specific distributions of hematological markers and to compare anemic and nonanemic children in a mining-exposed highland community. A cross-sectional study was conducted with 156 children aged 3 to 7 years from the Peruvian highlands, using non-probability sampling and following CLSI C28-A3 guidelines for this population. Inclusion criteria were children with complete blood count results and residency in mining-contaminated areas. Blood samples were collected via venipuncture and analyzed with a 3-part Sysmex differential hematology analyzer. The mean WBC count was 10.42 ± 1.76 × 10³/µL, with no significant differences between males and females (p = 0.770). Hematological indices, including RBC, hemoglobin, and hematocrit levels, were consistent between sexes. However, significant differences were noted between anemic and nonanemic 3–4-year-old children for RBC (5.56 ± 0.47 vs. 7.06 ± 0.96 × 10⁶/µL) and HCT (33.97 ± 6.89 vs. 35.64 ± 5%) (each p < 0.00001), with lower values in anemic subjects. Also, anemic and nonanemic 5–7-year-old children had significant differences in RBC (5.87 ± 1.02 vs. 7.36 ± 0.79 × 10⁶/µL) and HCT (31.13 ± 1.73 vs. 36.54 ± 4) (each p < 0.00001). Our findings reveal variations in hematological parameter distributions, emphasizing the importance of personalized blood assessments for mining-exposed populations. This approach could enable earlier diagnosis and intervention for anemia among vulnerable pediatric groups. Full article

Purpose: Ankyloglossia (tongue-tie) can lead to oromyofascial dysfunction which affects breathing, swallowing, speech, and posture. This study presents the evolution and outcomes of a refined lingual frenuloplasty protocol that integrates individualized myofunctional therapy to address compensatory patterns. Methods: A prospective cohort of 445 patients (≥4 years) was treated between 2021 and 2023 using a fascia-preserving CO₂ laser protocol with structured pre- and postoperative myofunctional therapy. Patients were stratified as pediatric (<12 years) or adolescent/adult (≥12 years). Key refinements included fascia-sparing dissection, reduced suture tension with cyanoacrylate adhesive, defined functional endpoints, structured myofunctional therapy, and standardized wound-healing strategies. Results: Among 379 patients (85% response) with >2 months follow-up, the 2025 protocol achieved an 86% satisfaction rate and significantly fewer complications compared with 2019 (pain 3.7% vs. 15.8%; bleeding 1% vs. 13%; revision 2.1% vs. 6.6%). Deeper genioglossus dissection increased swelling risk (OR = 4.0, p < 0.0001) but did not affect satisfaction. Conclusions: The refined 2025 protocol represents an outcome-tracked advancement in ankyloglossia management. By emphasizing fascia preservation, functional diagnostics, and integrated myofunctional therapy, the approach improves safety, efficacy, and patient-centered outcomes. Full article

Rural communities have a close-knit social structure, hindering the disclosure of mental disorders due to fear of negative societal perception. The study aimed to explore the experiences of both clubhouse members and staff with stigma and to examine how the Clubhouse addresses stigma in rural Wyoming through semi-structured interviews. Semi-structured interviews were conducted with 16 participants (12 clubhouse members and 4 staff members). The data analysis was performed in NVivo using reflexive thematic analysis. Three main themes were generated: “mental health prejudices,” where participants reported being perceived as dangerous, unintelligent, incompetent, and attention seekers. The second main theme, “the root causes of mental health stigma,” has three subthemes: “mental health illiteracy”, “the media,” and “personal struggles and background.” The third main theme, “clubhouse effort to address stigma,” encompasses two subthemes: “the unique clubhouse environment for self-stigma recovery” and “advocacy and community outreach.” The study findings highlight the emotional challenges individuals with mental illness face due to stigma from the media and the public. However, the clubhouse provides a non-judgmental environment that addresses both self- and public stigma. The findings also support expanding clubhouses, especially in rural areas, to improve mental health outcomes. Full article

Background/Objectives: Excessive weight gain is a growing concern among people living with HIV (PWH) receiving integrase strand transfer inhibitor (INSTI)-based regimens as first-line antiretroviral therapy (ART), as it may contribute to multimorbidity. The mechanisms driving weight gain in INSTI users are not fully understood but are thought to be multifactorial. This study examines the plasma metabolome associated with weight gain in PWH on INSTI-based regimens. Methods: We conducted a nested case–control study within the randomized clinical trial MICTLAN (NCT06629480). Sixty-six participants were randomized to receive INSTI-based regimens, either bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) or dolutegravir/abacavir/lamivudine (DTG/ABC/3TC), and followed for 18 months. Weight gain >10% relative to baseline was considered a primary endpoint and used as a criterium to categorize cases (n = 28) and controls (n = 38). Anthropometric and clinical measurements, plasma insulin, and metabolomic profiles were assessed at baseline and 18 months post-ART. Plasma untargeted metabolomics was performed using liquid chromatography–mass spectrometry (LC-MS/MS) to identify metabolomic changes linked to weight gain. Bioinformatic tools, including Partial Least Squares Discriminant Analysis (PLS-DA), volcano plots, and KEGG pathway enrichment analysis, were used to analyze plasma metabolomes and identify significant differential metabolites. Results: Weight gain at 18 months in PWH on INSTI-based ART was associated with insulin resistance, as measured by HOMA-IR (OR 3.23; 95% CI 1.14–9.10; p = 0.023), and visceral adipose tissue thickness > 4 cm (OR 4.50; 95% CI 1.60–13.03; 9.10; p = 0.004), and hypertriglyceridemia (OR 3.9; 95% CI 1.38–10.94; p = 0.008). Baseline HIV RNA viral load >50,000 copies/mL (OR 8.05; 95% CI 2.65–24.43; p = 0.0002) was identified as a baseline predictor of weight gain (aOR 6.58 (1.83–23.58); p = 0.004). In addition, accumulation of circulating medium-chain acylcarnitines, indicative of mitochondrial dysfunction, and insulin resistance were linked to weight gain in PWH on INSTI-based regimens after 18 months of therapy. Conclusions: This metabolomic study identified metabolites reflecting mitochondrial dysfunction, dysregulated lipid metabolism, and altered amino acid metabolism as key mechanisms underlying insulin resistance and weight gain in PWH on INSTI-based ART. Full article

Ceramide kinase (CerK) catalyzes the phosphorylation of ceramide to ceramide-1-phosphate (C1P), a bioactive sphingolipid with diverse signaling roles. While CerK has been identified in several cellular compartments, its presence and functional significance in kidney proximal tubules remain unexplored. Herein, we report the first characterization of CerK activity in basolateral membranes (BLMs) from porcine proximal tubule cells. We demonstrate that BLM fractions contain neutral and acidic sphingomyelinases, providing local substrate for CerK, which efficiently generates C1P under physiological pH (6.5–7.2) and temperature (30–37 °C) conditions. Enzyme activity was stimulated by cAMP in a protein kinase A-dependent manner but was not affected by angiotensin II. Lipidomic analysis confirmed the presence of C1P in human proximal tubule (HK-2) cells under basal conditions and revealed changes during ischemic stress. Transcriptomic analysis of kidney biopsies from patients with chronic kidney disease (CKD) further uncovered coordinated remodeling of sphingolipid metabolism genes, with increased expression of ceramidases (ASAH1 and NAAA) and downregulation of ceramide synthases (CERS4, CERS5), consistent with adaptive regulation of the Cer/CerK/C1P axis. Together, these findings identify for the very first time CerK activity in renal BLM, establish its biochemical requirements, and highlight its potential role in modulating transporter function and sphingolipid signaling in physiology and kidney disease. Full article

The prevalence of students with Autism Spectrum Disorder (ASD) has steadily increased, posing new challenges for inclusive education and teacher preparation. Teaching competence, understood as a multidimensional construct integrating cognitive, attitudinal, motivational, and practical components, is key to ensuring high-quality educational responses. This study developed and preliminarily validated DocenTEA, a questionnaire designed to assess five interrelated dimensions of inclusive competence: training, knowledge, experience, socio-emotional skills, and inclusive pedagogical practices. The instrument, consisting of 25 Likert-type items (0–4), was administered to 270 teachers across different educational levels in Spain. Content validity was examined through expert judgment and Aiken’s V coefficient (≥0.70), while construct validity was assessed via exploratory factor analysis using ULS estimation and Promax rotation. The five-factor solution explained 60.43% of the variance and showed adequate reliability (α and ω ≥ 0.70). Overall, DocenTEA emerges as a useful tool to identify teachers’ strengths and training needs, and to guide professional development programs and inclusive practices aimed at supporting students with ASD. Full article

Quantitative reliability evaluation is essential for optimizing control policies and maintenance strategies in complex industrial systems. While Reliability Block Diagrams (RBDs) are a natural formalism for modeling these hierarchical systems, modern applications require highly efficient, online reliability assessment on resource-constrained embedded hardware. This demand presents two fundamental challenges: developing algorithmically efficient RBD evaluation methods that can handle diverse custom distributions while preserving numerical accuracy, and ensuring platform-agnostic performance across diverse multicore architectures. This paper investigates these issues by developing a new version of the librbd open-source RBD library. This version includes advances in efficiency of evaluation algorithms, as well as restructured computation sequences, cache-aware data structures to minimize memory overhead, and an adaptive parallelization framework that scales automatically from embedded processors to high-performance systems. Comprehensive validation demonstrates that these advances significantly reduce computational complexity and improve performance over the original implementation, enabling real-time analysis of substantially larger systems. Full article