Search Results (10,758)

Background/Objectives: Autism spectrum disorder (ASD) is a neurodevelopmental condition increasingly associated with dysregulated neuroimmune signaling and altered neurotrophic homeostasis. Tumor necrosis factor-alpha (TNF-α) has been implicated in ASD pathophysiology; however, the downstream effects of TNF-α blockade on cytokine–neurotrophin interactions during neurodevelopment remain insufficiently characterized. In this study, we evaluated the effects of infliximab (IFX), a monoclonal anti-TNF-α antibody, on behavioral performance, neuroinflammatory cytokine profiles, glial activation, and brain-derived neurotrophic factor (BDNF) signaling in a propionic acid (PPA)-induced experimental ASD rat model. Methods: Experimental ASD was induced by propionic acid administration in rats. Animals were divided into control and treatment groups. Behavioral performance was assessed using the Morris Water Maze, direct social interaction, and three-chamber sociability tests. Levels of TNF-α, interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and BDNF were measured in serum, hippocampal, and cerebellar tissues. Microglial and astrocytic activation were evaluated using CD11 and GFAP immunohistochemistry. Results: PPA administration resulted in pronounced impairments in learning, memory, and social behaviors, accompanied by elevated proinflammatory cytokine levels, increased BDNF expression, and marked glial activation in the hippocampus and cerebellum. Although IFX treatment significantly reduced TNF-α levels in central tissues, it did not improve behavioral deficits and was associated with persistently elevated IL-1β and IL-6 levels, sustained glial reactivity, and further alterations in BDNF levels. Conclusions: These findings suggest that TNF-α suppression alone does not normalize the disrupted cytokine–neurotrophin axis and may differentially modulate BDNF-related neuroplastic signaling during development. In conclusion, this study indicates that non-selective TNF-α blockade during neurodevelopment fails to confer behavioral benefit in experimental ASD and highlights the importance of considering cytokine–BDNF pathway interactions when designing immunomodulatory strategies for neurodevelopmental disorders. Full article

Temporomandibular disorders (TMDs) are the prevalent causes of orofacial pain and dysfunction of the temporomandibular joint (TMJ) and masticatory muscles. Previous studies have revealed that proinflammatory cytokines play a key role in promoting inflammation, pain, and degeneration within the TMJ. In this context, the present systematic review synthesizes current evidence on various cytokines involved in the pathophysiology of TMDs and evaluates their associations with clinical signs and structural TMJ damage. A PRISMA-guided search (PROSPERO: CRD420251163290) was conducted in PubMed/MEDLINE, Embase, Scopus, and the Cochrane Library to identify human-based, in vivo, and in vitro studies (January 2014 to September 2025) that assessed the roles of proinflammatory cytokines in TMDs. The following data were extracted from the identified studies: cytokine profiles, sampling methods, clinical outcomes, and TMJ structural changes. Study quality and risk of bias were systematically evaluated. A total of 15 studies (clinical, animal, and mechanistic) were included in the review. Tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-17 (IL-17) consistently emerged as the major contributors to synovitis, cartilage degradation, nociceptive sensitization, and bone resorption. Human studies showed that high levels of TNF-α, IL-1β, and IL-6 and chemokines such as C-C motif chemokine ligand 2 (CCL2) and regulated on activation, normal T-cell expressed and secreted (RANTES) were associated with TMJ pain, restricted mandibular motion, crepitus, malocclusion, and erosive changes on imaging. An increased ratio of TNF to soluble TNF receptor in synovial fluid correlated with both pain and condylar damage, suggesting that loss of cytokine control contributes to progressive joint destruction. TMDs, particularly inflammatory and degenerative subtypes, are cytokine-driven pathologies rather than purely mechanical disorders. TNF-α, IL-1β, and IL-6 are the promising candidate biomarkers of local inflammation and structural joint pathology. Standardized longitudinal studies are required to validate cytokine-based diagnostics and develop anti-cytokine therapeutics. Full article

Horse chestnut (Aesculus hippocastanum L.) is a widely planted ornamental and urban tree valued for its aesthetic and ecological functions. In recent years, declining health of horse chestnut in urban environments has been increasingly reported, often associated with a complex of biotic and abiotic stressors. During a health survey of A. hippocastanum trees growing along an urban road corridor in Warsaw, Poland, extensive bark necrosis and branch dieback were observed. The aim of this study was to identify the causal agent of these symptoms using morphological, cultural, molecular (ITS rDNA), and pathogenicity tests under controlled conditions. Fungal isolates were obtained from necrotic tissues and were consistently identified as Kalmusia variispora based on ITS sequence analysis (99.0–99.6% similarity to GenBank references) and characteristic morphology. Pathogenicity tests fulfilled Koch’s postulates, reproducing necrotic lesions and cambial damage similar to those observed in the field. To our knowledge, this is the first documented report worldwide of K. variispora infecting A. hippocastanum. The findings expand the known host range of this opportunistic Didymosphaeriaceae species and highlight its potential role in bark and wood disease complexes of urban trees. Further research is needed to assess its distribution, genetic diversity, and epidemiological significance in urban forest ecosystems. Full article

Environmental DNA (eDNA) offers a promising, non-invasive approach for monitoring infectious agents in aquaculture. While molecular techniques for detecting shrimp pathogens are well established in host tissues, there is a lack of standardized protocols for pathogen detection from environmental samples using conventional PCR. In this study, we developed and validated a universal conventional PCR protocol for monitoring DNA from major viral and bacterial shrimp pathogens within pond water and sediment samples. The method was applied to two commercial shrimp farms in Mexico, where eDNA was extracted from field-collected water and sediment. Using published primer sets, we successfully amplified DNA sequences corresponding to six key pathogens—Infectious hypodermal and hematopoietic necrosis virus (IHHNV), Baculovirus penaei (BP), Monodon baculovirus (MBV), Shrimp hemocyte iridescent virus (SHIV), Candidatus Hepatobacter penaei (NHP-B), and Acute hepatopancreatic necrosis disease (AHPND)-causing Vibrio spp.—in environmental samples. Sequencing of PCR amplicons confirmed 93–100% identity to previously reported pathogen strains, highlighting the method’s reliability. Pathogen detection rates varied by site, sample type, and date, with the percentage of positive samples ranging from 11.1% to 77.7%. Notably, this is the first report of SHIV DNA detection from environmental samples in the Americas, highlighting its value for pathogen surveillance even in the absence of documented outbreaks. This protocol offers a cost-effective and scalable tool for pathogen surveillance in shrimp aquaculture, enhancing early disease detection and contributing to improved biosecurity and risk assessment frameworks. Full article

Background/Objectives: Obesity is characterized by chronic low-grade inflammation, and bariatric surgery promotes substantial metabolic and inflammatory improvement. However, residual obesity and microvascular complications may persist in some individuals, suggesting potential genetic influences on postoperative outcomes. This exploratory pilot study investigated the association between inflammatory cytokine gene polymorphisms and clinical, metabolic, and inflammatory outcomes in older women one year after bariatric surgery. Methods: This cross-sectional, hypothesis-generating pilot study included 21 women aged ≥50 years (mean 61.6 ± 5.0) who underwent Roux-en-Y gastric bypass at a public bariatric center in Brazil. Anthropometry, body composition, biochemical markers, and serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were assessed 12 months postoperatively. Genotyping for IL6-174G/C (rs1800795) and TNFA-308G/A (rs1800629) was performed using PCR-RFLP. Associations were analyzed using non-parametric statistical tests. Results: Notably, the IL6-174CC genotype was associated with persistent obesity, whereas carriers of the TNFA-308A allele showed a higher prevalence of diabetic retinopathy. These results highlight genotype-specific postoperative outcomes. No significant genotype-related differences were observed for most anthropometric, biochemical, or inflammatory parameters, indicating substantial overall metabolic improvement after surgery regardless of genetic background. However, the observed associations were based on a small sample and should be interpreted cautiously. Conclusions: This exploratory pilot study revealed associations between inflammatory cytokine gene polymorphisms and selected postoperative outcomes, particularly persistent obesity and diabetic retinopathy, in older women one year after bariatric surgery. These hypothesis-generating findings emphasize the need for larger, longitudinal studies to clarify the role of genetic factors in postoperative heterogeneity after bariatric surgery. Full article

Background/Objectives: Pediatric intussusception, a condition where part of the intestine telescopes into an adjacent segment, predominantly affects children aged 6–18 months. Prompt diagnosis and management are crucial to prevent serious complications such as ischemia or necrosis. This systematic review aims to comprehensively evaluate and synthesize existing research on predictive and prognostic biomarkers associated with pediatric intussusception that can aid in early diagnosis, severity assessment, outcome prediction, and treatment. Methods: A comprehensive literature search was conducted across PubMed, Scopus, and Web of Science using specific MeSH and free-text terms related to intussusception, biomarkers, and the pediatric population. The review followed PRISMA guidelines, with independent screening, data extraction, and quality assessment using the Joanna Briggs Institute critical appraisal tools. A total of 47 studies, mostly retrospective cohorts from diverse countries, with over 20,000 patients, were included. Results: The studies identified numerous biomarkers associated with disease severity, including hematological markers and indices (e.g., WBC counts and neutrophil-to-lymphocyte ratio), inflammatory markers (CRP and cytokines), biochemical markers (serum lactate, D-dimer, and electrolytes), and novel molecular markers (I-FABP, MCP-1, and transfer RNA fragments). Elevated inflammatory markers and derived ratios consistently predicted bowel necrosis, ischemia, and need for surgery. Biochemical markers like serum lactate and D-dimer correlated with ischemic severity. Emerging molecular biomarkers show promise for early, non-invasive risk stratification. However, heterogeneity in study designs, assay methods, and cutoff values currently limits immediate clinical application. Conclusions: Biomarker research offers valuable tools for improving pediatric intussusception management, with the potential to enhance early diagnosis and outcome prediction. While traditional markers are useful, novel molecular and protein biomarkers hold promise for more specific and rapid assessment. Validation through multicenter, prospective studies and standardized protocols is essential before routine implementation. Integrating biomarkers with clinical and imaging data could refine decision-making, ultimately reducing morbidity and improving prognosis in affected children. Full article

Background: Pre-pectoral direct-to-implant breast reconstruction is increasingly adopted after mastectomy because it avoids pectoralis major dissection, reduces postoperative pain, and eliminates animation deformity. However, reconstruction in patients with large or markedly ptotic breasts remains challenging because of skin envelope management, nipple–areola complex (NAC) viability, and implant stability. This study evaluated batwing skin-reducing mastectomy with immediate pre-pectoral polyurethane-coated implant reconstruction. Methods: We conducted a retrospective single-center study of consecutive patients who underwent batwing skin-reducing mastectomy with immediate pre-pectoral polyurethane-coated implant reconstruction between November 2022 and January 2025. Demographic, oncologic, operative, postoperative, and BREAST-Q data were collected. Primary outcomes included complications, oncologic events, and 12-month patient-reported outcomes. Results: Thirteen patients underwent reconstruction, accounting for 18 breasts, with a mean follow-up of 12.85 months. Mean age was 54.5 ± 9.7 years, mean body mass index was 27.0 ± 3.4 kg/m², and mean Regnault ptosis grade was 3.46 ± 0.52. No seromas or oncologic recurrences were observed. One hematoma and one late infection requiring implant removal occurred. Superficial NAC/central flap epidermolysis developed in four patients and resolved conservatively; no full-thickness NAC necrosis occurred. BREAST-Q scores improved significantly in all domains at 12 months, including satisfaction with breasts, psychosocial well-being, physical well-being, and sexual well-being (all p < 0.05). Conclusions: Batwing skin-reducing mastectomy with immediate pre-pectoral polyurethane implant reconstruction appears safe and reproducible in selected patients with advanced ptosis, with acceptable complication rates and significant improvement in patient-reported outcomes. Full article

The necrotrophic pathogen Sclerotinia sclerotiorum compromises the physiological and anatomical integrity of cotton, leading to substantial economic losses due to rapid tissue necrosis, stem blight, boll rot, and leaf wilting. In this context, the use of endophytic microorganisms emerges as a promising strategy for the biocontrol of white mold. This study tested the hypothesis that endophytic fungal strains isolated from the roots of Butia purpurascens, a palm tree endemic to the Cerrado biome, could mitigate disease symptoms in Gossypium hirsutum L. To evaluate this, cotton plants were subjected to biotic stress imposed by S. sclerotiorum to assess the effectiveness of seven fungal strains in attenuating disease. The impact of the pathogen was monitored through growth variables, gas exchange, leaf temperature, chlorophyll a fluorescence, antioxidant enzyme activity, proline and malondialdehyde (MDA) levels, and the incidence of rot in petioles, leaves, and flower buds. Overall, inoculation with endophytic fungi significantly alleviated the effects of the phytopathogen, promoting vegetative growth and optimizing physiological performance. Treated plants exhibited alleviated stress in primary photochemistry, reduced non-photochemical energy dissipation, and stable carbon fixation. Additionally, efficient modulation of the antioxidant system and preservation of anatomical structures were observed, minimizing the severe symptoms of white mold. Notably, the non-pathogenic strains BP10EF (Gibberella moniliformis), BP16EF (Penicillium purpurogenum), and BP33EF (Hamigera insecticola) acted as potent physiological modulators, yielding responses similar to those of healthy plants. These results highlight the biotechnological potential of these endophytic strains, which can be explored as both growth promoters and resistance inducers in cotton against white mold. Full article

Non-infectious cardiac failure in feedyard cattle has become more frequently diagnosed. There is limited research assessing gross and histologic lesions in grossly abnormal hearts of harvested cattle. Cases were stratified by heart score (HS) using a scale of 1–5, with 1 representing a normal heart and 5 representing severely remodeled ventricles. Cattle were evaluated for gross lesions of the heart, lung, and liver. Samples collected from each animal for histology included cardiac (n = 4), pulmonary (n = 4), and hepatic (n = 1) tissues. Histologic evaluation scored cardiac and hepatic fibrosis and necrosis, embedded myocardial protozoal cysts (EMPCs) were quantified, and pulmonary lesions were categorized based on histologic patterns. Of 103 cases, 40 had normal HSs (NHSs) (1 or 2), and 63 had abnormal HSs (AHSs) (3, 4, or 5). There were 64 cases with normal lung deflation scores, and 39 cases with abnormal lung deflation scores. At least one cardiac section contained EMPCs in 67 cases. Cattle with abnormal lung deflation scores were more likely to have an AHS (0.76 ± 0.07, p ≤ 0.01) compared with cattle with normal deflation scores (0.52 ± 0.06). Cattle with EMPCs present in at least one cardiac section were more likely to also have an AHS (0.73 ± 0.05, p ≤ 0.1) compared with cattle without EMPCs (0.39 ± 0.08). No histological findings for the lungs or liver were associated with abnormal heart score; however, lung deflation and EMPCs were associated with abnormal heart score. Full article

Background: Neoadjuvant chemotherapy (NAC) is widely used in the management of stage I–III breast cancer, with tumor regression serving as an important surrogate for long-term outcome. Identifying reliable pathological biomarkers predictive of residual disease remains clinically relevant. Methods: We conducted a retrospective cohort study of 165 patients with non-metastatic breast cancer treated with neoadjuvant chemotherapy followed by surgery between 2019 and 2022. Pathological response was assessed using the Residual Cancer Burden (RCB) index. The primary study endpoint was extensive residual disease (RCB-III), defined as the poorest category of tumor regression, indicating treatment resistance. Associations between the Nottingham Score together with other histopathological parameters, immunohistochemical markers (ER, PR, HER2), Ki67 proliferation index, and RCB were analyzed using univariate and multivariable logistic regression. Results: In univariate analysis, higher Nottingham scores (OR = 1.807, p = 0.0017), negative ER expression (OR = 3.017, p = 0.0255), the absence of lymphovascular invasion (OR = 0.1877, p = 0.0069) and elevated Ki67 (OR = 1.034, p = 0.0003) were significantly associated with RCB III. In multivariable analysis, only Ki67 and lymphovascular invasion remained independent predictors of RCB III, while Nottingham score and ER expression lost statistical significance. Correlation analysis demonstrated strong associations between Nottingham score, Ki67, hormone receptor loss, and tumoral necrosis. Conclusions: Ki67 is an independent predictor of poor tumor regression following neoadjuvant chemotherapy and appears to capture much of the prognostic information traditionally attributed to histologic grade and Nottingham score. However, the absence of lymphovascular invasion remains a significant positive prognostic factor. These observations support further investigation into the integration of proliferation markers into multivariable predictive models to improve response stratification in breast cancer. Full article

Background and Clinical Significance: Multiligamentous knee injuries (MLKIs) are uncommon but severe injuries associated with instability, neurovascular compromise, and long-term functional impairment. Irreducible knee dislocations are a distinct subgroup requiring urgent intervention because soft-tissue interposition may prevent closed reduction and place the limb at risk of skin necrosis and vascular compromise. This report reviews current concepts in MLKI management and presents a complex KD-IV irreducible knee dislocation treated with a staged surgical strategy. Case Presentation: A 56-year-old woman presented 24 h after a skiing injury with a grossly deformed knee, multidirectional instability, and an anteromedial “pucker sign”. Magnetic resonance imaging demonstrated a KD-IV injury with complete rupture of the anterior cruciate ligament, posterior cruciate ligament, and medial collateral ligament, associated with capsular disruption and intra-articular soft-tissue interposition causing irreducibility. Urgent open reduction was performed. The first stage included reduction of the incarcerated capsule, capsular repair, and reconstruction of the posteromedial corner and medial collateral ligament using a semitendinosus autograft. Delayed reassessment at 6 months demonstrated satisfactory stability, minimal residual anterior laxity, and no subjective instability; therefore, anterior cruciate ligament reconstruction was not performed. At final follow-up, the patient had near-full range of motion, no significant valgus instability, and no arthrofibrosis or vascular complications. Conclusions: Management of MLKIs should be individualized according to reducibility, soft-tissue condition, neurovascular status, and functional demands. Irreducible KD-IV dislocations with a pucker sign require urgent open reduction. In selected patients, staged reconstruction may reduce postoperative stiffness and allow selective omission of cruciate ligament reconstruction when satisfactory functional stability is achieved. Full article

Background/Objectives: Glioblastoma remains the most lethal primary brain tumor in adults, and progress in oncolytic virotherapy is limited by the lack of immunocompetent models permissive to human-tropic viruses. Methods: Here, murine CT-2A and GL261 glioma and B16 melanoma cell lines were engineered to express human Coxsackievirus and Adenovirus Receptor (CXADR) fused to tagBFP, generating “humanized” tumors that preserve parental growth characteristics while acquiring high susceptibility to group B Coxsackieviruses (CVBs) and adenovirus serotype 5. Results: CXADR expression in CT-2A, GL261, and B16 cells markedly enhanced binding, internalization, and replication of CVBs in vitro, with the strongest effect observed for LEV14 (attenuated CVB5), which reached up to 10⁵-fold higher viral titers in humanized cells compared with parental cells. Unchanged sensitivity to vesicular stomatitis virus indicated receptor-specific effects. Humanized CT-2A-CXADR-BFP and GL261-CXADR-BFP cells initiated aggressive subcutaneous and intracranial tumors in syngeneic C57BL/6 mice without signs of immune rejection, and histology and MRI confirmed invasive high-grade glioma phenotypes. In intracranial CT-2A-CXADR-BFP tumors, repeated intratumoral LEV14 administration induced extensive tumor necrosis and prolonged survival despite the rapid development of neutralizing antibodies. Systemic intravenous LEV14 dosing produced strong oncolytic activity against subcutaneous CT-2A-CXADR-BFP tumors, as demonstrated by pronounced tumor growth inhibition, long-lasting regression in a subset of animals with gliomas, and improved overall survival. Conclusions: Collectively, these data establish CXADR-humanized models as versatile, immunocompetent platforms for evaluation of CXADR-dependent oncolytic enteroviruses. Full article

Introduction: Major Depressive Disorder (MDD) has been increasingly associated with inflammatory dysregulation, particularly involving tumor necrosis factor-alpha (TNF-α). Genetic polymorphisms within the TNFA promoter region have been investigated as potential modulators of depressive susceptibility, symptom expression, treatment response, and inflammatory comorbidity. However, findings remain inconsistent across populations and clinical contexts. Methods: This systematic review adhered to PRISMA 2020 guidelines and was registered in PROSPERO (CRD420251242724). Observational and interventional studies evaluating associations between TNFA polymorphisms—specifically rs1800629 (−308 G/A), rs1799724 (−857 C/T), and rs1799964 (−1031 T/C)—and MDD-related outcomes in adults were included. Data extraction and methodological quality assessment were performed independently using an adapted GRIPS framework. Results: Eleven studies met the inclusion criteria, with eight investigating MDD without cardiovascular comorbidity and three assessing cardiovascular populations. Across diverse cohorts, rs1800629 and rs1799724 did not demonstrate consistent associations with MDD susceptibility. Although isolated population-specific findings were reported, genotype and allele distributions were generally comparable between cases and controls. Rs1799724 was associated with symptom dimensions and altered TNF-α expression in two cohorts. Rs1799964 was not linked to disease occurrence but showed potential association with antidepressant response and adverse cardiovascular outcomes in patients with chronic heart failure and comorbid depression. Overall, findings were heterogeneous and influenced by population characteristics, sample size, and clinical context. Conclusions: Current evidence does not support a robust etiological role for TNFA promoter polymorphisms in major depressive disorder. These variants may exert context-dependent modulatory effects on symptom expression, treatment response, or inflammatory-cardiovascular interactions rather than serving as primary susceptibility determinants. Larger, ethnically diverse studies integrating genetic, inflammatory, and clinical data are required to clarify the contribution of inflammatory genetic variability in depressive disorders. Full article

Diseases of the nasal cavity have a diverse etiology and cause severe disorders in animals. Conidiobolomycosis is a type of zygomycosis caused by the fungus Conidiobolus spp., occurring more frequently in sheep. The objective of this study is to describe the clinical and epidemiological characteristics, as well as microbiological and histopathological findings, of an outbreak of conidiobolomycosis in sheep. A total of 12 animals out of a herd of 70 were affected, representing a morbidity of 17.1%; mortality and lethality were 11.4% (8/70) and 66.6% (8/12), respectively, of which 4 sheep died spontaneously and 4 were euthanized for diagnostic purposes due to the severity of the clinical condition. Necropsy was performed on 4 (33.3%) of the 12 affected animals, and after opening the skull in the sagittal section, a friable mass with coloration ranging from whitish-yellow to gray-green, as well as areas of necrosis, were evident in regions such as the nasal meatus, conchae, nasopharynx, hard palate, cribriform plate, meninges, and frontal lobe of the brain. Conidiobolus lamprauges was isolated from samples collected from 6 animals from nasal discharge, fungal granuloma, and intranasal swab. Reproductive structures consistent as kind of zygospores with C. lamprauges and C. incongruus were also identified. Regarding the clinical form, animals 1, 2, 3, and 4 presented manifestations of the nasopharyngeal form, with the first three progressing to the rhinocerebral form; in animal 5, the clinical form found was rhinofacial. It is concluded that clinical signs may vary with the presentation of the disease as well as the involved agent. Early diagnostic alternatives such as fungal isolation from material collected from intranasal swabs can be useful and employed in affected herds, enabling earlier intervention. Full article