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During food intake, small amounts of antioxidants are absorbed and distributed to the extracellular matrix, from which they are made available to all types of cells. They protect against various free radicals generated in the extracellular and intracellular environments. They also protect against ionising radiation or UV directly. Some of the most abundant antioxidants in food are the proanthocyanidins, a form of condensed tannin found in tea, cocoa, and grape seeds. They also bestow various other health benefits as apoptosis inducers. The present study examines the vertical and adiabatic ionisation potentials and electron affinities of flavan, (-)-epicatechin, procyanidin B2, procyanidin C1, and cinnamtannin A2, and discusses the influence of non-equilibrated solvent-solute interactions on their electronic properties. The analysis employs the M06-2x/aug-cc-pVTZ//M06-2x/6-31++G** level of theory in the aqueous phase. Procyanidin C1 was found to have the lowest ionisation potential (6.08 eV) and the highest adiabatic electron affinity (1.15 eV); also, all (-)-epicatechin derivatives demonstrated a lower IP than guanine (6.42 eV), suggesting a potential genome-protective effect. These findings were confirmed by the global reactivity descriptor, the Fukui reactivity index, and the spin density distribution. The theoretical results presented here support the experimental results which predict that nutrients can help maintain a delicate redox balance which is crucial for the extra- and intracellular matrix.

In around 50% of patients with Rapid-onset Obesity Hypothalamic dysfunction, Hypoventilation and Autonomic Dysregulation (ROHHAD) syndrome, a neuro-endocrine tumor (NET) is found. Reported NETS are (ganglio)neuroblastoma or ganglioneuroma located extracranially. Here, we report for the first time a young patient with signs and symptoms fitting the criteria of ROHHAD syndrome in whom an intracranial ganglion cell tumor was found, pathologically resembling the reported extracranial NETs. Our finding leads to the discussion of whether the NET in ROHHAD-NET syndrome should be classified as true NET or should be classified as Neural Crest Tumor (NeCT). Our case highlights the difficulty of the diagnosis of ROHHAD syndrome and the importance of screening for both extra- and intracranial Neural Crest Tumors in patients with rapid onset obesity at young age.

Reusing frying oils increases the level of oxidation products while decreasing the healthiness and quality of the frying oils. One way to improve the oxidative stability of frying oils is to use them in combination with oils rich in natural antioxidants. The aim of this study was to evaluate how enriching refined corn oil with antioxidant-rich oils affected the corn oil's behavior during deep frying over an extended period. Refined Corn Oil (COO) was blended with Black Seed Oil (BSO), Blackberry Oil (BBO), Sesame Oil (SSO), Extra Virgin Olive Oil (EVOO), and Pomegranate Oil (PMO) in a proportion of 85:15 (v/v) to obtain five blends (COO/BSO, COO/BBO, COO/SSO, COO/EVOO, COO/PMO). Each oil was used to deep-fry falafel (frying temperature: 175 ± 5 °C for 20 minutes per cycle, 36 cycles) over 12 hours. Acid Value (AV), Peroxide Value (PV), p-Anisidine Value (p-AV), total oxidation value (TOTOX), Free Fatty Acids (FFA), Fatty Acid Profile (FAP), Total Polar Compounds (TPC), and viscosity were determined. The samples were collected after the last frying cycle and stored at -20 °C until analysis. All oil blends had significantly lower values of oxidation indicators (PV, p-AV, TOTOX), FFA, and TPC than corn oil. The most significant reductions in oxidation values, TPC, and FFA were observed in the olive, pomegranate, and sesame oil blends. Based on TOTOX values, oliveand pomegranate-based blends showed the highest oxidative resistance. Deep frying reduced C18:2 and C18:3 and increased trans-C18:1 in all studied samples. The least degradation of FAP was found in the olive and pomegranate blends. Enrichment of corn oil with naturally antioxidant-rich oils may slow oxidative processes during deep frying and reduce the degradation of polyunsaturated fatty acids. The highest protective effect was observed for the pomegranate and extra virgin olive oil blends. Enrichment of corn oil with pomegranate or extra virgin olive oil significantly improved its oxidative stability during deep frying.

In the present study, using the novel quantitative susceptibility mapping technique, we aimed to systematically investigate brain iron alterations in a large group of sporadic early-stage amyotrophic lateral sclerosis patients and their correlation with clinical disability. In this study, amyotrophic lateral sclerosis patients at King's stage 1 were defined as early-stage amyotrophic lateral sclerosis patients, and 53 newly diagnosed early-stage amyotrophic lateral sclerosis patients and 50 healthy controls were included. Voxel-based whole-brain quantitative susceptibility mapping analysis was used to explore brain iron alterations. Voxel-based morphometry analysis was also performed. Longitudinal follow-up was performed in amyotrophic lateral sclerosis patients, and the follow-up progression rate was calculated. We found that, compared with healthy controls, early-stage amyotrophic lateral sclerosis patients presented significantly increased susceptibility values, mainly in the motor cortex, prefrontal cortex, hippocampus and cerebellar regions, while volumetric alterations were not detected. Moreover, motor and extra-motor cortex susceptibility values were significantly correlated with upper motor neuron scores and follow-up progression rate (r = 0.452-0.504, P < 0.01) in early-stage amyotrophic lateral sclerosis patients. We demonstrated a clear profile of early motor and extra-motor iron depositions and their important roles in early-stage amyotrophic lateral sclerosis patients. We suggest that quantitative susceptibility mapping is likely a promising neuroimaging approach for assessing early upper motor neuron damage and detecting early extra-motor alterations in amyotrophic lateral sclerosis patients.

Rapid diagnosis of drug-resistant tuberculosis (DR-TB) is very challenging, specifically in extra-pulmonary TB specimens. The current study was performed on non-sputum specimens. All specimens were subjected on Xpert MTB/RIF Ultra followed by Xpert MTB/XDR, Ziehl-Neelsen (ZN) Staining, liquid culture, line probe assay (LPA), and drug susceptibility testing (DST). Out of 1,152 non-sputum specimens, 218 were observed to be positive on Xpert MTB/RIF Ultra and were selected for further investigation. From 218 MTBC positive, Xpert MTB/XDR yielded 174 (79.8%) positive while 25 (11.5%) were negative. On comparison with reference standards, ZN smear, and culture, the sensitivity was 100% and 95.51% with specificity of 17.86% and 18.63%, respectively. DST sensitivity and specificity were 84.62% and 96.61%, 83.33% and 96.88%, 50% and 98.75%, 50% and 98.72%, and 50% and 98.75%, respectively, for isoniazid, fluoroquinolones, amikacin, kanamycin, and capreomycin in culture positive specimens. The sensitivity and specificity of Xpert MTB/XDR assay, compared with LPA (MTBDRplus and MTBDRsl), was between 94.12%-100% and 98.39%-100%, respectively. Sensitivity and specificity of Xpert MTB/XDR matched with culture-DST and LPA results for all the tested drugs. Its placement in diagnostic algorithms with Xpert MTB/RIF Ultra under National TB Programs will enhance patient outcome by providing prompt switch to a DST guided treatment regimen. This study provides crucial evidence supporting the use of Xpert MTB/XDR for rapid detection of DR-TB in non-sputum specimens including extra-pulmonary specimens, where diagnosis remains challenging due to paucibacillary in nature. By demonstrating high sensitivity and specificity compared with culture-DST and LPA, the assay shows strong potential to be integrated into the National TB Elimination Program (NTEP) diagnostic algorithm. Early detection of resistance to isoniazid, fluoroquinolones, and second-line injectables enables timely transition to DST-guided treatment, reducing delays and improving patient outcomes. The findings highlight the assay's ability to reduce dependency on conventional laboratory-based DST, shortening turnaround time and strengthening decentralized diagnostic capacity. This study provides programmatic evidence for policy-level adoption, supporting India's efforts toward DR-TB control and elimination.

Legionella is widespread in natural aquatic habitats and can contaminate man-made water systems. Due to public-health risks, measuring microbial load in water samples is essential. This study compared a new lipopolysaccharide bioprobe method (Microcolony Counter Analysis-MICA), which detects and counts Legionella pneumophila in 2&#x2009;days, with the standard culture method (ISO 11731:2017), which may take up to 10&#x2009;days. Our results on 108 water samples showed 82.4% agreement. Fifteen were ISO+/MICA- and four ISO-/MICA+; MICA sensitivity was 67.4%. Analysis of culture-media factors (Legionella inhibition by contaminating flora; culture on Glycine Vancomycin Polymyxin Cycloheximide agar (GVPC) and MICA factors (possible killing/growth inhibition due to acid treatment) showed that (a) ISO counts tended to be higher than MICA, with little difference whether GVPC results or the maximum yield between Buffered Charcoal Yeast Extract agar (BCYE) and GVPC were used. (b) Acid-treated MICA samples tended to yield higher counts than untreated ones, especially at high MICA counts. Considering what has been disclosed, a short 48-h incubation may reduce MICA recovery for some wild L. pneumophila strains, affecting click-based detection. With refinement, MICA could be a practical, user-friendly diagnostic tool, simpler sample prep, no large-volume filtration, no colony isolation or extra confirmation and provides confirmed results in 2&#x2009;days versus &#x2265;&#x2009;10&#x2009;days for ISO culture.

To assess the knowledge, understanding, clinical practices, and challenges of physicians in Pakistan concerning Gastroesophageal reflux disease (GERD), and to identify areas for improvement to enhance patient outcomes. This cross-sectional survey was conducted among 435 physicians across Pakistan, including general practitioners, gastroenterologists, and internal medicine specialists. A structured, self-administered questionnaire collected data on demographics, knowledge of GERD risk factors and symptoms, diagnostic practices, management approaches, and perceived challenges. Among 435 surveyed physicians, 80.2% reported being very familiar with GERD diagnosis and management, yet there were notable gaps in recognizing atypical and extra-esophageal symptoms. While acid regurgitation (91.5%) and heartburn (82.8%) were the most commonly recognized symptoms, less frequent acknowledgment was found for dysphagia (42.8%), cough (47.6%), and sore throat (37.7%). Only 14.0% of respondents consistently considered extra-esophageal symptoms in the context of GERD. Additionally, risk factors such as diet (82.3%), obesity (78.9%), and smoking (77.5%) were widely recognized, but challenges like poor treatment adherence (73.1%) and medication costs (46.0%) were reported. A majority of respondents requested more training (61.8%) and availability of updated national guidelines (57.2%). These findings highlight gaps in symptom recognition and the need for enhanced education and research to improve GERD diagnosis and management practices. While most physicians demonstrated adequate knowledge of GERD, significant gaps in recognizing atypical symptoms, utilization of advanced diagnostics, and addressing management challenges were noted. Tailored interventions, including updated national GERD guidelines, focused training programs, and enhanced access to diagnostic and management tools, are essential to improving care quality and patient outcomes in Pakistan.

Stretch-mediated tissue expansion is commonly used to grow extra skin for reconstructive surgeries. To ensure harmonious growth, the two main skin compartments, the epidermis and the dermis, must both expand in a coordinated manner. How fibroblasts respond to stretch-mediated tissue expansion in supporting keratinocyte proliferation remains unclear. Here we map the fibroblast transcriptional response to stretching in vivo and demonstrate that stretching forces fibroblasts to exit their quiescent state and restart proliferation. Concurrently, fibroblasts reduce collagen production and upregulate extracellular matrix remodelling factors, adopting a more embryonic-like program. Because embryonic fibroblasts are widely used as feeder layers to support the expansion of epidermal stem cells for clinical application, we leveraged this model to show that a low collagen state enhances epidermal stem cell self-renewal, thereby coordinating epidermal and dermal responses during skin expansion. These findings provide valuable insights to guide the design of in vivo stretch-mediated tissue expansion protocols and the production of in vitro skin grafts for clinical application.

Endometriosis is a common gynecologic condition, but extra-pelvic manifestations are rare and often pose significant diagnostic challenges. Thoracic and abdominal endometriosis may present with nonspecific respiratory and abdominal symptoms that closely mimic pulmonary tuberculosis, particularly in TB-endemic regions, leading to delayed or incorrect diagnosis. We report the case of a 40-year-old Tanzanian&#xa0;woman with a previous history of treated pulmonary tuberculosis who presented with a 6-month history of progressive shortness of breath, right-sided chest pain, and abdominal distension. Imaging revealed a massive right hydropneumothorax with near-total lung collapse and ascites, initially raising concern for post-tuberculous disease. Pleural fluid cytology demonstrated a hemorrhagic effusion. Diagnostic laparoscopy revealed hemorrhagic ascites, mesenteric nodular lesions, and extensive uterine adhesions. Histopathological examination of the mesenteric nodules confirmed endometriosis. The patient was treated with gonadotropin-releasing hormone agonist therapy (goserelin) and underwent pleurodesis, with subsequent clinical improvement and resolution of symptoms. This case highlights thoracoabdominal endometriosis as an important differential diagnosis in women of reproductive age presenting with unexplained respiratory symptoms in TB-endemic settings. Awareness of this rare entity is essential to avoid misdiagnosis and unnecessary anti-tuberculous therapy. Early consideration of extra-pelvic endometriosis and timely histological confirmation can facilitate appropriate management and improve patient outcomes.

Intensive care units (ICU) account for a disproportionate share of hospital costs. Retrospectively identifying high-need, high-cost (HNHC) ICU patients using machine learning (ML) may inform structured cost auditing and more efficient healthcare resource allocation. This retrospective study included adult patients with ICU admission (&#x2265;24&#x202f;h) from multiple specialty ICUs in a Chinese tertiary hospital (2018-2024). HNHC patients were defined as the top 5% of annual ICU costs. Clinical, laboratory, and resource-use variables were extracted and preprocessed. Six ML models were developed using feature selection, class balancing, cross-validation, and Bayesian optimization, with performance evaluated by area under the receiver operating characteristic curve (AUC) and related metrics. Shapley Additive Explanations (SHAP) was applied for model interpretability. Among 51,056 ICU patients, 2,556 (5.0%) were classified as HNHC. HNHC patients had longer ICU stays, greater disease complexity, and substantially higher use and duration of intensive therapies, resulting in markedly increased total and ICU-related costs. After correlation and Boruta feature selection, 19 variables were retained for model development. Among six ML models, the random forest (RF) achieved the highest discriminative performance in the independent test set, with an AUC of 0.942 (95% CI 0.931-0.952), followed by Extra Trees and LightGBM. The random forest model showed a favorable balance between sensitivity and F1 score in this highly imbalanced population. Decision curve analysis demonstrated stable net benefit across clinically relevant threshold probabilities. SHAP interpretation identified ICU length of stay and mechanical ventilation duration as the strongest contributors, revealing pronounced nonlinear effects, while diagnosis-related group (DRG) reform did not substantially alter the contribution patterns of key features. Stratified analyses confirmed that model performance and feature contribution patterns remained stable across the pre- and post-DRG reform periods. High ICU costs were primarily associated with intensive resource use rather than demographics alone. A RF model reliably classified HNHC patients and remained stable across DRG reform, supporting its use as a tool for retrospective risk stratification, identification of cost drivers, and more efficient allocation of critical care resources.

Tobacco use disorder (TUD) is a major public health issue with significant individual differences. A deeper understanding of its neurobiology and reliable biomarkers is needed. This study investigated whether inter-subject variability in resting-state brain functional connectivity (IVFC) could serve as such a marker for TUD. Resting-state fMRI data from 123 male TUD patients and 123 healthy controls (HCs) were collected and analyzed. IVFC was computed within seven major brain lobes. Five machine learning models (random forest, gradient boosting, extra trees, multi-layer perceptron, and support vector machine) were trained to classify the groups based on IVFC features. Univariate regression was conducted with each lobe's IVFC predicting clinical scores. Multivariate stepwise regression was then performed to identify the best combination of IVFC predictors for dependence severity. TUD showed significantly altered IVFC in six brain lobes compared to controls, with the largest difference in the insular lobe. The machine learning models, particularly the extra trees classifier, achieved high accuracy (up to 88&#xa0;%) in classifying TUD, primarily utilizing features from the temporal and limbic lobes. Univariate regression showed that higher IVFC in frontal, insular, limbic, and temporal lobes was associated with lower nicotine dependence severity. Multivariate stepwise regression identified insular lobe IVFC as the sole independent predictor. These findings suggest that widespread alterations in IVFC may characterize TUD and relate to its clinical severity, indicating the potential value of this measure as a neurobiological marker. The combination of IVFC analysis with machine learning appears to offer a promising approach for distinguishing TUD, which could contribute to advancing our understanding of its underlying brain mechanisms.