Influence Disease Progression Research Articles

Antisense oligonucleotides as a targeted therapeutic approach in model of acute myeloid leukemia.

The genetic and epigenetic alterations observed in acute myeloid leukemia (AML) contribute to its heterogeneity, influencing disease progression response to therapy, and patient outcomes. The use of antisense oligonucleotides (ASOs) technology allows for the design of oligonucleotide inhibitors based on gene sequence information alone, enabling precise targeting of key molecular pathways or specific genes implicated in AML. Midostaurin, a FLT3 specific inhibitor and ASOs targeting particular genes, exons, or mutations was conducted using AML models. This ASOs treatment was designed to bind to exon 7 of the MBNL1 (muscleblind-like) gene. Another target was the FLT3 gene, focusing on two aspects: (a) FLT3-ITD (internal tandem duplication), to inhibit the expression of this aberrant gene form, and (b) the FLT3 in general. Treated and untreated cells were analyzed using quantitative PCR (qPCR), dot blot, and Raman spectroscopy. This study contrasts midostaurin with ASOs that inhibit FLT3 protein production or its isoforms via mRNA degradation. A trend of increased FLT3 expression was observed in midostaurin-treated cells, while ASO-treated cells showed decreased expression, though these changes were not statistically significant. In AML, exon 7 of MBNL1 is involved in several cellular processes and in this study, exon 7 of MBNL1 was targeted for method optimization, with the highest block of the exon 7 gene variant observed 48h post-transfection. Midostaurin, a multitargeted kinase inhibitor, acts against the receptor tyrosine kinase FLT3, a critical molecule in AML pathogenesis. While midostaurin blocks FLT3 signaling pathways, it paradoxically increases FLT3 expression.

Precision Medicine in Prostate Cancer: Integrating Genomics, AI, and Big Data for Personalized Treatment

Prostate cancer (PCa) remains one of the most prevalent cancers among men worldwide, exhibiting significant heterogeneity in its molecular profile and clinical course. Traditional approaches to treatment have often been generalized, leading to variable outcomes and, at times, unnecessary overtreatment. Precision medicine promises to transform PCa management by leveraging genomics, artificial intelligence (AI), and big data to tailor treatments to each patient’s molecular profile. This review examines how genomics has enhanced our understanding of PCa, identifying critical genetic mutations and molecular subtypes that influence disease progression. Additionally, the application of AI and machine learning in analyzing complex datasets has proven instrumental in discovering novel biomarkers, optimizing therapeutic choices, and predicting patient responses. The integration of big data from multiple platforms, including genomics, imaging, and electronic health records (EHRs), offers an unprecedented level of insight into the nuances of PCa. We discuss key genomic biomarkers, emerging AI-based predictive models, and the role of big data in advancing PCa precision medicine. Finally, we explore the challenges of clinical implementation, including data privacy, ethical concerns, and the need for interdisciplinary collaboration. The insights from this review underscore the transformative potential of precision medicine in enhancing prostate cancer treatment outcomes and the necessity for further research to overcome existing limitations. Keywords: Prostate cancer, precision medicine, genomics, artificial intelligence, big data, personalized treatment, biomarkers, molecular subtypes, machine learning.

Harnessing machine learning and multi-omics to explore tumor evolutionary characteristics and the role of AMOTL1 in prostate cancer

Although recent advancements have shed light on the crucial role of coordinated evolution among cell subpopulations in influencing disease progression, the full potential of these insights has not yet been fully harnessed in the clinical application of personalized precision medicine for prostate cancer (PCa). In this study, we utilized single-cell sequencing to identify the evolutionary characteristics of tumoral cell states and employed comprehensive bulk RNA sequencing to evaluate their potential as prognostic indicators and therapeutic targets. Leveraging advancements in artificial intelligence, we integrated machine learning with multi-omics to develop and validate the tumor evolutionary characteristic predictive indicator (TECPI). TECPI not only demonstrated superior prognostic performance compared to traditional clinical predictors and 81 previously published models but also improved patient outcomes by accurately identifying individuals who would benefit from immunotherapy and targeted therapies. Furthermore, we experimentally validated the critical role of AMOTL1 in PCa pharmacodynamics through its interaction with AR, pivotal for modulating the sensitivity to AR antagonist. Additionally, we demonstrated the generalizability and applicability of TECPI across pan-cancers. In summary, this study emphasizes the importance of understanding cellular diversity and dynamics within the tumor microenvironment to predict PCa progression and to guide targeted therapy effectively.

Características clínico-epidemiológicas de los pacientes hospitalizados por COVID-19 y enfermedades crónicas durante los primeros siete meses de la pandemia en Paraguay-2020

Introduction: COVID-19, a respiratory infection caused by SARS-CoV-2, has demonstrated varying severity across populations, with approximately 20% of patients developing complications and less than 5% experiencing severe disease requiring hospitalization. The impact of chronic diseases on COVID-19 outcomes remains particularly relevant in developing countries, where healthcare resources and population characteristics differ from well-studied settings. Objective: Describe the clinical and epidemiological characteristics of patients hospitalized with COVID-19 during the first seven months of the pandemic in Paraguay, analyzing how chronic non-communicable diseases (NCDs) influenced disease progression and outcomes. Material and Methods: We conducted a cross-sectional analytical study examining medical records from patients hospitalized with confirmed SARS-CoV-2 infection across five major referral hospitals in Paraguay from March to September 2020. Using bivariate and multivariate logistic regression analyses with likelihood ratio criterion, we identified factors associated with ICU admission and mortality, considering p<0.05 statistically significant. Results: Among 1,690 hospitalized patients, 797 (47.2%) met inclusion criteria, with a median age of 51 years and male predominance (53.8%). Chronic diseases were present in 61.9% of patients, with hypertension (29.6%) and diabetes (25.6%) being most prevalent. Multivariate analysis revealed that age over 80 years (OR=7.70), presence of COPD (OR=2.58), and having three or more NCDs (OR=2.78) significantly increased mortality risk. ICU admission was required for 29.6% of patients, with an overall mortality rate of 29.1%. Conclusion: The severity of COVID-19 outcomes among hospitalized patients in Paraguay showed strong associations with advanced age, multiple chronic conditions, and specific comorbidities like COPD. These findings emphasize the need for targeted preventive strategies and enhanced monitoring of high-risk patients, particularly those with multiple NCDs.

Success Rates and Prognostic Factors in the Management of Keratoconus: A 10-Year Retrospective Cohort Study at Siriraj Hospital

Objective: To evaluate the success rates of different treatment modalities, identify prognostic factors associated with treatment outcomes and factors influencing disease progression in keratoconus patients. Materials and Methods: A retrospective cohort study of keratoconus patients at Siriraj Hospital during January 2013 to December 2023 was done. Patient characteristics, symptoms and signs related to keratoconus, outcomes of corneal topography, treatment modalities, and best-corrected visual acuity (BCVA) before and after treatment were recorded. Treatment outcome was defined as a “success” when the BCVA post-treatment was equal to or better than 6/12. Progression of keratoconus was based on the Belin ABCD progression criteria. Results: Total 119 patients (231 eyes) were analyzed. The mean age at diagnosis was 28.0 ± 9.5 years. Two hundred and sixteen eyes (93.5%) were clinical keratoconus. The overall success rate of all treatment modalities was 87.4%. Contact lenses were the most frequent treatment modality (147 eyes, 72.4%) with the highest success rate (90.5%). A worse initial BCVA, high keratometric reading and thinner cornea were risk factors for treatment failure in this group. Of 133 eyes disease progression could be evaluated (median follow-up time; 33 months) and 58 eyes(43.6%) met criteria for disease progression (median survival time; 8.8 years). No significant factors were found to be associated with disease progression. Conclusion: Success rate in keratoconus treatment at Siriraj Hospital was 87.4%. Contact lenses were most frequently applied 72.4%. Factors associated with treatment failure were found in this group but for disease progressionremained unclear due to limitations of the study.

Genetic variants in the HLA-DQ2 and HLA-DQ8 genes and their involvement in the predisposition to celiac disease

Celiac disease is a multisystem disorder that is triggered by the consumption of gluten in genetically predisposed people, particularly those who carry the HLA-DQ2 and HLA-DQ8 alleles. Environmental factors and certain epigenetic mechanisms play a fundamental role in the manifestation of the disease. It has been shown that the gut microbiome can influence disease progression to some extent. Celiac disease presents with gastrointestinal and extraintestinal symptoms that complicate the diagnosis. Classic symptoms include digestive disorders, while non-classic symptoms include anemia, osteoporosis, and unexplained fatigue. Serological antibody tests and duodenal biopsy are key to a diagnosis, especially in atypical cases. At present, the only treatment is a strict gluten-free diet, although this presents certain problems due to the high cost and nutritional deficiencies. New research is looking for alternatives such as gluten-breaking enzymes as well as immunomodulatory treatments in hopes of more comprehensive options in the future.

Strength training attenuates neuropathic pain by Preventing dendritic Spine dysgenesis through Suppressing Rac1 and inflammation in experimental autoimmune encephalomyelitis

Chronic pain is a challenge and major health problem to basic science and clinical practice. Pain is one of the worst symptoms of multiple sclerosis (MS), which has a significant impact on their quality of life. Rac1 is an important intracellular signaling molecule involved in spinal dendritic spine pathology and activation of IL-1β and TNF-α that are associated with chronic neuropathic pain. As a result, targeting Rac1 presents a promising approach to managing neuropathic pain. Clinical studies have demonstrated that physical exercise is a non-pharmacological strategy that positively influences disease progression in individuals with MS, but underlying mechanism of exercise on Rac1- induced neuropathic pain is not well understood. This study examined the effects of a 4-week strength training on Rac1 expression, IL-1B, TNF-α, TGF-β1 levels, MDA concentrations, SOD activity, dendritic spine abnormalities in the dorsal horn of the spinal cord, as well as nociceptive behaviors (formalin test) and motor function (Rotarod test) during the chronic phase of experimental autoimmune encephalomyelitis (EAE). The findings indicated that strength training increased TGF-β1 expression and SOD activity while decreasing the expression of Rac1, IL-1β, TNF-α, and MDA and reducing dendritic spine dysgenesis in the dorsal horn of the spinal cord. We observed strength training effectively reduced nociceptive behaviors and improved motor function in mice with EAE. In summary, regular physical exercise may modulate neuropathic pain through inhibition of dendritic spine dysgenesis, inflammation and oxidative stress in the dorsal horn of the spinal cord.

Therapeutic Modulation of the Microbiome in Oncology: Current Trends and Future Directions.

Cancer is a predominant cause of mortality worldwide, necessitating the development of innovative therapeutic techniques. The human microbiome, particularly the gut microbiota, has become a significant element in cancer research owing to its essential role in sustaining health and influencing disease progression. This review examines the microbiome's makeup and essential functions, including immunological modulation and metabolic regulation, which may be evaluated using sophisticated methodologies such as metagenomics and 16S rRNA sequencing. The microbiome influences cancer development by promoting inflammation, modulating the immune system, and producing carcinogenic compounds. Dysbiosis, or microbial imbalance, can undermine the epithelial barrier and facilitate cancer. The microbiome influences chemotherapy and radiation results by modifying drug metabolism, either enhancing or reducing therapeutic efficacy and contributing to side effects and toxicity. Comprehending these intricate relationships emphasises the microbiome's significance in oncology and accentuates the possibility for microbiome-targeted therapeutics. Contemporary therapeutic approaches encompass the utilisation of probiotics and dietary components to regulate the microbiome, enhance treatment efficacy, and minimise unwanted effects. Advancements in research indicate that personalised microbiome-based interventions, have the potential to transform cancer therapy, by providing more effective and customised treatment alternatives. This study aims to provide a comprehensive analysis of the microbiome's influence on the onset and treatment of cancer, while emphasising current trends and future possibilities for therapeutic intervention.

Mutations Matter: Unravelling the Genetic Blueprint of Invasive Lobular Carcinoma for Progression Insights and Treatment Strategies.

Invasive Lobular Carcinoma (ILC) presents a distinct subtype of breast cancer, representing 10-15% of cases, with unique clinical and molecular features. Characterized by a non-cohesive, single-file invasion pattern, ILC is typically estrogen receptor (ER)- and progesterone receptor (PR)-positive but human epidermal growth factor receptor 2 (HER2)-negative. Despite favorable prognostic features, its highly metastatic nature and predilection for atypical sites contribute to lower long-term survival compared to invasive breast carcinoma of no special type (NST). ILC's genetic landscape includes mutations in various genes (CDH1, BRCA2, ATM, etc.) and signaling pathways that impact treatment responses, especially in endocrine treatment. Furthermore, the diverse ILC subtypes complicate its management. Current challenges in chemotherapy, along with the targeted therapies, are also discussed. The present article aims to comprehensively review the recent literature, focusing on the pathological and molecular aspects of ILC, including associated genetic mutations influencing disease progression and drug resistance.

Characterization of the T-cell receptor repertoire associated with lymph node metastasis in colorectal cancer.

Colorectal cancer (CRC) is a leading cause of cancer-related mortality worldwide, with lymph node (LN) metastasis playing a pivotal role in disease progression. This study aimed to explore the T-cell receptor (TCR) repertoire among CRC patients, distinguishing those with LN metastasis from those without, in order to uncover potential biomarkers for predicting metastasis. We analyzed the TCR repertoire in CRC patients with and without LN metastasis. A classification model utilizing random forest analysis was developed to assess the predictive potential of the TCR repertoire. The findings demonstrated a significant increase in the number of V-J combinations and immune CDR3 sequences in patients with LN metastasis compared to the control group. The classification model achieved high accuracy in differentiating patients with LN metastasis, with AUC values ranging from 0.514 to 0.794. Specific V-J combinations and CDR3 sequences were identified as significant predictors of the model's predictive accuracy. These results suggest that the TCR repertoire is altered in CRC patients exhibiting LN metastasis, potentially influencing disease progression. This study highlights the importance of TCR repertoire analysis as a non-invasive biomarker for predicting LN metastasis in CRC patients.

Spatial and Single Cell Analyses Reveal Heterogeneity of DNAM-1 Receptor-Ligand Interactions that Instructs Intratumoral γδT-Cell Activity.

The dynamic interplay between tumor cells and γδT cells within the tumor microenvironment (TME) significantly influences disease progression and immunotherapy outcome. Here, we delved into the modulation of γδT-cell activation by tumor cell ligands CD112 and CD155, which interact with the activating receptor DNAM-1 on γδT cells. Spatial and single cell RNA sequencing (scRNA-seq), as well as spatial metabolome analysis, from neuroblastoma (NB) revealed that the expression levels and localization of CD112 and CD155 varied across and within tumors, correlating with differentiation status, metabolic pathways, and ultimately disease prognosis and patient survival. Both in vivo tumor xenograft experiments and in vitro co-culture experiments demonstrated that a high CD112/CD155 expression ratio in tumors enhanced γδT-cell-mediated cytotoxicity, while a low-ratio fostered tumor resistance. Mechanistically, CD112 sustained DNAM-1-mediated γδT-cell activation, whereas CD155 downregulated DNAM-1 expression via TRIM21-mediated ubiquitin proteasomal degradation. By interacting with tumor cells differentially expressing CD112 and CD155, intratumoral γδT cells exhibited varying degrees of activation and DNAM-1 expression, representing three major functional subsets. This study underscores the complexity of tumor-immune crosstalk, offering insights into how tumor heterogeneity shapes the immune landscape.

Molecular characterization of PANoptosis-related genes associated with immune infiltration and prognosis in idiopathic pulmonary fibrosis

Idiopathic pulmonary fibrosis (IPF) is a chronic pulmonary disease with unknown pathogenesis and poor prognosis. PANoptosis, a newly identified form of inflammatory programmed cell death, has been implicated in various inflammatory lung diseases. This study aimed to identify differentially expressed PANoptosis-related genes (PRDEGs) associated with immune infiltration and prognosis in IPF, while also establishing a novel prognostic prediction model. A total of 63 PRDEGs were identified from GSE110147 dataset, with 31 exhibiting consistent expression trends in GSE213001. Enrichment analysis indicated that the majority of these PRDEGs were enriched in inflammatory and immune-related pathways. Three key PRDEGs—NLRP3, ATM, and VEGFA—were selected through univariate and multivariable Cox regression analyses. The prognostic prediction model developed from these key PRDEGs demonstrated robust predictive performance. Furthermore, the expression of most PRDEGs was positively correlated with pro-inflammatory immune cells, including macrophages, neutrophils, and CD4+ T cells. Validation of the expression levels of these key PRDEGs was conducted in fibrotic mouse lung tissue. This study suggests that PANoptosis plays a role in IPF, potentially linked to the infiltration of pro-inflammatory immune cells, and may influence disease progression through the regulation of inflammatory immune signaling pathway. A new prognostic prediction model for IPF based on PRDEGs was successfully developed.

Identification of Novel Genetic Loci Affecting Age at Onset of Parkinson's Disease: A Genome-wide Association Study.

The age at onset (AAO) of Parkinson's disease (PD) varies widely among individuals and significantly influences disease progression and prognosis. However, few genome-wide association studies (GWASs) have investigated genetic variants determining AAO, particularly in East Asian populations. To identify single-nucleotide polymorphisms (SNPs) affecting AAO of PD in Korean patients. We conducted a GWAS on AAO of PD in 1048 Korean patients using sex-adjusted linear regression models. Additionally, we conducted downstream analyses of our primary GWAS results. rs2134545 demonstrated genome-wide significance (β = -2.459; standard error [SE] = 0.851; P = 1.898 × 10-8) and is an intergenic SNP near the ALCAM gene associated with an average AAO reduction of 3.47 years. Additionally, rs4366309 (LYST; MIR1537) demonstrated suggestive significance (β = 2.949; SE = 1.072; P = 8.68 × 10-8) and was associated with an average delay of 3.05 years. The polygenic risk score based on known PD risk loci also affected the AAO for European and Korean PD risk loci, respectively (β = -0.149; P < 0.001 and β = -0.096; P = 0.002). However, the proportion of variance was small (r2 = 0.022 and 0.009, respectively). We identified a novel SNP associated with the AAO of PD near the ALCAM gene, distinct from previously reported PD risk loci. These findings need further functional validation; however, they suggest unique genetic pathways influencing the AAO of PD and highlight the need for further research in diverse populations. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Transforming Cardiotoxicity Detection in Cancer Therapies: The Promise of MicroRNAs as Precision Biomarkers.

Cardiotoxicity (CDTX) is a critical side effect of many cancer therapies, leading to increased morbidity and mortality if not addressed. Early detection of CDTX is essential, and while echocardiographic measures like global longitudinal strain offer promise in identifying early myocardial dysfunction, the search for reliable biomarkers continues. MicroRNAs (miRNAs) are emerging as important non-coding RNA molecules that regulate gene expression post-transcriptionally, influencing key biological processes such as the cell cycle, apoptosis, and stress responses. In cardiovascular diseases, miRNAs have demonstrated potential as biomarkers due to their stability in circulation and specific expression patterns that reflect pathological changes. Certain miRNAs have been linked to CDTX and hold promise for early detection, prognosis, and therapeutic targeting. These miRNAs not only assist in identifying early cardiac injury, but also offer opportunities for personalized interventions by modulating their expression to influence disease progression. As research advances, integrating miRNA profiling with traditional diagnostic methods could enhance the management of CDTX in cancer patients, paving the way for improved patient outcomes and more tailored therapeutic strategies. Further clinical studies are essential to validate the clinical utility of miRNAs in managing CDTX.

Immunometabolism: signaling pathways, homeostasis, and therapeutic targets.

Immunometabolism plays a central role in sustaining immune system functionality and preserving physiological homeostasis within the organism. During the differentiation and activation, immune cells undergo metabolic reprogramming mediated by complex signaling pathways. Immune cells maintain homeostasis and are influenced by metabolic microenvironmental cues. A series of immunometabolic enzymes modulate immune cell function by metabolizing nutrients and accumulating metabolic products. These enzymes reverse immune cells' differentiation, disrupt intracellular signaling pathways, and regulate immune responses, thereby influencing disease progression. The huge population of immune metabolic enzymes, the ubiquity, and the complexity of metabolic regulation have kept the immune metabolic mechanisms related to many diseases from being discovered, and what has been revealed so far is only the tip of the iceberg. This review comprehensively summarized the immune metabolic enzymes' role in multiple immune cells such as T cells, macrophages, natural killer cells, and dendritic cells. By classifying and dissecting the immunometabolism mechanisms and the implications in diseases, summarizing and analyzing advancements in research and clinical applications of the inhibitors targeting these enzymes, this review is intended to provide a new perspective concerning immune metabolic enzymes for understanding the immune system, and offer novel insight into future therapeutic interventions.

Modification of asthma treatment efficacy by healthcare access: A reanalysis of AsthmaNet Step-Up Yellow Zone Inhaled Corticosteroids to Prevent Exacerbations (STICS) clinical trial

BackgroundWhile randomized controlled trials (RCTs) in asthma management are designed to balance known and unknown variables across treatment groups, including social and environmental co-exposures, it remains important to consider how these co-exposures influence disease progression and treatment outcomes. The importance of considering socio-environmental co-exposures in the context of asthma is twofold: 1) asthma disproportionately affects low-income urban communities, where air pollution and chronic stress are pervasive; and 2) despite the wide range of asthma treatments, inadequate disease control persists. MethodsIn the present ancillary study of the Step-Up Yellow Zone Inhaled Corticosteroids to Prevent Exacerbations (STICS) RCT, we investigated how socio-environmental factors, such as air pollution exposure and healthcare access, modify the effect of inhaled corticosteroid (ICS) therapy in children with asthma. The original STICS RCT evaluated the efficacy and safety of increasing the dose of inhaled glucocorticoids from a baseline daily low dose to five times the daily dose for 7 days in school-age children with mild -to-moderate persistent asthma who began to have short-term loss of asthma control (Jackson et al., 2018 Mar 8) [1]. Our study adds onto those findings by incorporating residential level particulate matter 2.5 μg/m3 (PM2.5) and geographic health provider shortage areas (HPSA) as potential modifiers. ResultsConsistent with the main trial results, we did not find a difference in the number of exacerbations between treatment arms. However, we found the effect of receiving 5xICS, as compared with 1xICS on the time to prednisone was significantly different for children living in areas a shortage of health professionals (HR: 2.09; 95 % CI: 0.74, 5.95) than for children living in no shortage areas (HR: 0.40; 95 % CI: 0.21, 0.77). ConclusionThis finding underscores the importance of considering environmental and social factors in asthma treatment. Trial registrationClinicalTrials.gov ID NCT02066129 https://clinicaltrials.gov/study/NCT02066129.

Patient-derived tumor organoid and fibroblast assembloid models for interrogation of the tumor microenvironment in esophageal adenocarcinoma.

The tumor microenvironment (TME) comprises all non-tumor elements of cancer and strongly influences disease progression and phenotype. To understand tumor biology and accurately test new therapeutic strategies, representative models should contain both tumor cells and normal cells of the TME. Here, we describe and characterize co-culture tumor-derived organoids and cancer-associated fibroblasts (CAFs), a major component of the TME, in matrix-embedded assembloid models of esophageal adenocarcinoma (EAC). We demonstrate that the assembloid models faithfully recapitulate the differentiation status of EAC and different CAF phenotypes found in the EAC patient TME. We evaluate cell phenotypes by combining tissue-clearing techniques with whole-mount immunofluorescence and histology, providing a practical framework for the characterization of cancer assembloids.

A Novel Cyanine-Based Fluorescent Dye for Targeted Mitochondrial Imaging in Neurotoxic Conditions and In Vivo Brain Studies.

Mitochondrial dysfunction is a key feature of neurodegenerative diseases, often preceding symptoms and influencing disease progression. However, real-time in vivo imaging of mitochondria in the brain is limited by existing dyes like MitoTrackers, which struggle with poor tissue penetration, phototoxicity, and inability to cross the blood-brain barrier (BBB). This study introduces Cy5-PEG4, a novel mitochondrial-targeting dye that overcomes these limitations, enabling high-resolution, non-invasive imaging of mitochondrial dynamics. Cy5-PEG4 effectively labels mitochondria in primary neuronal cells exposed to the SARS-CoV-2 RNYIAQVD peptide, revealing dose-dependent alterations in mitochondrial function that may contribute to COVID-19-related neurodegeneration. Importantly, Cy5-PEG4 crosses the BBB without causing neuroinflammation or toxicity, making it a safe tool for in vivo brain imaging and detailed studies of mitochondrial responses. In 3D cultured cells, Cy5-PEG4 captures dynamic changes in mitochondrial distribution and morphology as cell structures mature, highlighting its potential in neurobiological research, diagnostics, and therapeutic development. These findings support Cy5-PEG4 as a powerful tool for studying disease progression, identifying early biomarkers, and evaluating therapeutic strategies in neurodegenerative disorders and COVID-19.

Gluten Unraveled: Latest Insights on Terminology, Diagnosis, Pathophysiology, Dietary Strategies, and Intestinal Microbiota Modulations-A Decade in Review.

A decade of research on gluten-related disorders (GRDs) is reviewed in this study, with a particular emphasis on celiac disease (CD) and non-celiac gluten sensitivity (NCGS). GRDs are triggered by the ingestion of gluten and gluten-like proteins found in wheat, barley, and rye. These proteins lead to intestinal damage in celiac disease, an autoimmune condition characterized by villous atrophy and a variety of gastrointestinal and extraintestinal symptoms. More enigmatic and less understood, NCGS involves symptoms similar to CD but without the immunological reaction or intestinal damage. Recent years have seen advances in the understanding of GRDs, particularly in connection to how intestinal microbiota influences disease progression and patient outcomes. The gluten-free diet (GFD) is still the standard therapy recommended for GRDs despite significant challenges, as discussed in this article. Precise diagnostic methods, patient education and dietary counseling are critical for improving patients' quality of life. The purpose of this review is to provide a more clear and up-to-date understanding of GRDs, and to help further research on this important topic.

Reevaluating Pediatric Osteomyelitis with Osteoarticular Tuberculosis: Addressing Diagnostic Delays and Improving Treatment Outcomes.

Pediatric osteoarticular tuberculosis (TB) remains a significant global health challenge, particularly in resource-limited settings, where delayed diagnosis and treatment frequently lead to severe long-term complications. Despite advancements in TB control, skeletal TB in children is often misdiagnosed due to its non-specific clinical presentation, contributing to poor outcomes such as joint deformities, growth disturbances, and chronic pain. The complexity of diagnosing osteoarticular TB is further exacerbated by the limited sensitivity of conventional diagnostic tools and the overlap with other musculoskeletal conditions. This study seeks to evaluate the impact of early detection and multidisciplinary management on treatment outcomes in pediatric patients with osteoarticular TB. A retrospective review was conducted at the Pediatric Orthopedics Department of the "Grigore Alexandrescu" Children's Hospital in Romania from 2009 to 2023. Case data included clinical, imaging, and microbiological findings, and treatment outcomes in children aged 0-18 years diagnosed with tuberculous osteomyelitis. The study identified varied clinical presentations, with delayed diagnosis often linked to misinterpretation of symptoms as non-TB infections. Multimodal diagnostic approaches combining imaging, microbiological testing, and histopathology improved diagnostic accuracy. Early surgical intervention alongside anti-TB therapy proved effective in reducing long-term complications. Timely, accurate diagnosis and multidisciplinary treatment are critical to improving outcomes in pediatric osteoarticular TB. Vaccination status and comprehensive diagnostic tools significantly influence disease progression and treatment success. The study underscores the need for enhanced screening and diagnostic methods to prevent delays in treatment.