Angiogenic properties and intercellular communication of differentiated porcine endothelial cells in vascular therapy.

Endothelial cell dysfunction can lead to various vascular diseases. Blood flow disorder is a common symptom of vascular diseases. Regenerative angiogenesis, which involves transplanting vascular cells or stem cells into the body to shape new vasculature, can be a good therapeutic strategy. However, there are several limitations to using autologous cells from the patients themselves. We sought to investigate the new vascular cells that can play a role in the formation of angiogenesis in vivo using stem cells from alternative animals suitable for cellular therapy. Porcine is an optimal animal model for xenotransplantation owing to its physiological similarity to humans. We used differentiated porcine endothelial cells (pECs) as a therapeutic strategy to restore vessel function. Differentiated pECs formed vessel-like structures in mice, distinguishing them from stem cells. MMPs activity and migration assays indicated that differentiated pECs possessed angiogenic potential. Tube formation and 3D spheroid sprouting assays further confirmed the angiogenic phenotype of the differentiated pECs. Immunofluorescence and immunoprecipitation analyses revealed claudin-mediated tight junctions and connexin 43-mediated gap junctions between human ECs and differentiated pECs. Additionally, the movement of small RNA from human ECs to differentiated pECs was observed under co-culture conditions. Our findings demonstrated the in vivo viability and angiogenetic potential of differentiated pECs and highlighted the potential for intercellular communication between human and porcine ECs. These results suggest that transplanted cells in vascular regeneration completed after cell therapy have the potential to achieve intercellular communication within the body.

Dual-Hydrogen Bond Donor-Functionalized Carbon Nanotube Fibers: Enhancing Anion-Sensing Performance Through Functionalization Approaches.

In this study, chemiresistive anion sensors are developed using carbon nanotube fibers (CNTFs) functionalized with squaramide-based dual-hydrogen bond donors (SQ1 and SQ2) and systematically compared the sensing properties attained by two different functionalization methods. Model structures of the selectors are synthesized based on a squaramide motif incorporating an electron-withdrawing group. Anion-binding studies of SQ1 and SQ2 are conducted using UV-vis titrations to elucidate the anion-binding properties of the selectors. These studies revealed that the chemical interaction with acetate (AcO-) induced the deprotonation of both SQ1 and SQ2. Selectors are functionalized onto the CNTFs using either covalent or non-covalent functionalization. For covalent functionalization, SQ1 is chemically formed on the surface of the CNTFs, whereas SQ2 is non-covalently functionalized to the surface of the CNTFs assisted by poly(4-vinylpyridine). The results showed that non-covalently functionalized CNTFs exhibited a 3.6-fold higher sensor response toward 33.33 mm AcO- than covalently functionalized CNTFs. The selector library is expanded using diverse selectors, such as TU- and CA-based selectors, which are non-covalently functionalized on CNTFs and presented selective AcO--sensing properties. To demonstrate on-site and real-time anion detection, anion sensors are integrated into a sensor module that transferred the sensor resistance to a smartphone via wireless communication.

Clinical Manifestations, Macrolide Resistance, and Treatment Utilization Trends of Mycoplasma pneumoniae Pneumonia in Children and Adolescents in South Korea.

A resurgence of Mycoplasma pneumoniae (MP)-the leading cause of community-acquired bacterial pneumonia, particularly in children-occurred following the COVID-19 pandemic. We aimed to investigate the clinical manifestations, macrolide resistance patterns, and therapeutic approaches related to the MP pneumonia epidemic. Children and adolescents diagnosed with MP pneumonia in September-December 2023 were screened. Clinical data were retrospectively collected from 13 major hospitals using concordant microbiological criteria, including either a positive PCR result or four-fold increase in serological markers. Demographic characteristics, treatment modalities, and clinical outcomes were analyzed. Of the 474 screened patients, 374 (median age: 7.7 [IQR, 5.4-9.6] years; hospitalization rate: 88.6%) met the microbiological confirmation criteria. Most patients experienced fever (98.9%), and lobular/lobar consolidation (59.1%) was the dominant radiological finding. The macrolide resistance rate remained high at 87.0%; corticosteroids were widely used (55.6%) alongside macrolides, despite resistance. Patients with consolidation had prolonged fever (median 8 vs. 7 days, p = 0.020) and higher hospitalization rates (92.3% vs. 83.0%, p = 0.008). Macrolide resistance did not significantly influence radiological outcomes. This study highlights the ongoing challenge of macrolide resistance in MP pneumonia and need for tailored therapeutic approaches. Despite high resistance, macrolides remain commonly prescribed, often concurrently with corticosteroids.

Genome-Wide CRISPR Screen Identifies KEAP1 Perturbation as a Vulnerability of ARID1A-Deficient Cells.

ARID1A is the core DNA-binding subunit of the BAF chromatin remodeling complex and is mutated in about 8% of all cancers. The frequency of ARID1A loss varies between cancer subtypes, with clear cell ovarian carcinoma (CCOC) presenting the highest incidence at > 50% of cases. Despite a growing understanding of the consequences of ARID1A loss in cancer, there remains limited targeted therapeutic options for ARID1A-deficient cancers. Using a genome-wide CRISPR screening approach, we identify KEAP1 as a genetic dependency of ARID1A in CCOC. Depletion or chemical perturbation of KEAP1 results in selective growth inhibition of ARID1A-KO cell lines and edited primary endometrial epithelial cells. While we confirm that KEAP1-NRF2 signalling is dysregulated in ARID1A-KO cells, we suggest that this synthetic lethality is not due to aberrant NRF2 signalling. Rather, we find that KEAP1 perturbation exacerbates genome instability phenotypes associated with ARID1A deficiency. Together, our findings identify a potentially novel synthetic lethal interaction of ARID1A-deficient cells.

Genetic Diagnosis in Neonatal Encephalopathy With Hypoxic Brain Damage Using Targeted Gene Panel Sequencing.

BACKGROUND AND PURPOSE: Neonatal encephalopathy (NE) is a neurological syndrome that presents with severe neurological impairments and complications. Hypoxic-ischemic encephalopathy is a major contributor to poor outcomes, being responsible for 50%-80% of admissions to neonatal intensive care units. However, some cases of NE accompanied by hypoxic brain damage cannot be solely attributed to hypoxia-ischemia. We aimed to identify diverse pathogenic genetic variations that may be associated with cases of NE accompanied by hypoxic brain damage rather than hypoxia-ischemia. METHODS: We collected data from 34 patients diagnosed with NE accompanied by hypoxic brain damage over a 10-year period. Patients with the following specific conditions were excluded: 1) premature birth (<32 weeks), 2) no history of hypoxic events, 3) related anomalies, 4) neonatal infections, 5) antenatal or perinatal obstetrical complications, 6) severe hypoxia due to other medical conditions, and 7) early death (within 1 week). A comprehensive review of clinical and radiological features was conducted. RESULTS: A genetic diagnosis was made in 11 (32.4%) patients, with pathogenic variants being identified in the following 9 genes: CACNA1A (n=2), KCNQ2 (n=2), SCN2A (n=1), SCN8A (n=1), STXBP1 (n=1), NSD1 (n=1), PURA (n=1), ZBTB20 (n=1), and ENG (n=1). No specific treatment outcomes or clinical features other than preterm birth were associated with the results of the genetic analyses. Personalized treatments based on the results of genetic tests were attempted, such as the administration of sodium-channel blockers in patients with KCNQ2 or SCN8A variants and the implementation of a ketogenic diet in patients with STXBP1 or SCN2A mutations, which demonstrated some degree of effectiveness in these patients. CONCLUSIONS: Genetic analyses may help in diagnosing the underlying etiology of NE and concurrent hypoxic brain damage, irrespective of the initial clinical features.

Feasibility of deep learning algorithm in diagnosing lumbar central canal stenosis using abdominal CT.

OBJECTIVE: To develop a deep learning algorithm for diagnosing lumbar central canal stenosis (LCCS) using abdominal CT (ACT) and lumbar spine CT (LCT). MATERIALS AND METHODS: This retrospective study involved 109 patients undergoing LCTs and ACTs between January 2014 and July 2021. The dural sac on CT images was manually segmented and classified as normal or stenosed (dural sac cross-sectional area ≥ 100 mm2 or < 100 mm2, respectively). A deep learning model based on U-Net architecture was developed to automatically segment the dural sac and classify the central canal stenosis. The classification performance of the model was compared on a testing set (990 images from 9 patients). The accuracy, sensitivity, and specificity of automatic segmentation were quantitatively evaluated by comparing its Dice similarity coefficient (DSC) and intraclass correlation coefficient (ICC) with those of manual segmentation. RESULTS: In total, 990 CT images from nine patients (mean age ± standard deviation, 77 ± 7 years; six men) were evaluated. The algorithm achieved high segmentation performance with a DSC of 0.85 ± 0.10 and ICC of 0.82 (95% confidence interval [CI]: 0.80,0.85). The ICC between ACTs and LCTs on the deep learning algorithm was 0.89 (95%CI: 0.87,0.91). The accuracy of the algorithm in diagnosing LCCS with dichotomous classification was 84%(95%CI: 0.82,0.86). In dataset analysis, the accuracy of ACTs and LCTs was 85%(95%CI: 0.82,0.88) and 83%(95%CI: 0.79,0.86), respectively. The model showed better accuracy for ACT than LCT. CONCLUSION: The deep learning algorithm automatically diagnosed LCCS on LCTs and ACTs. ACT had a diagnostic performance for LCCS comparable to that of LCT.

A Bone Health Optimization Framework for Malaysia: a position paper by the Malaysian Bone Health Optimization Network (MyBONe).

This position paper aims to establish and standardise Bone Health Optimization (BHO) strategies for older patients undergoing elective orthopaedic surgeries in Malaysia. It emphasises pre-, intra-, and post-operative assessments and tailored management. Adopting the "5IQ" approach, it proposes clinical standards and a registry to improve surgical outcomes and patient care. PURPOSE: Osteoporosis and osteopenia are highly prevalent among older patients scheduled for elective arthroplasties and spinal surgeries. This position paper aims to establish, promote, and standardise effective Bone Health Optimization (BHO) strategies for such patients within orthopaedic practices in Malaysia. It emphasises the need for bone health assessments to be undertaken at the pre-operative, intra-operative, and post-operative stages, with tailored management strategies to meet individual patient needs. METHODOLOGY: A comprehensive literature review was conducted, focusing on articles published from 2019 to 2024. Twelve broad themes were defined including definitions and importance of BHO, epidemiological data, assessment techniques, risk stratification, management strategies, and outcome metrics. RESULTS: Elective surgeries on patients with poor bone health are associated with adverse outcomes, such as periprosthetic fractures, aseptic loosening of implants, and complications after spinal surgeries. This position paper advocates for routine bone health assessments and monitoring during the pre-operative, intra-operative, and post-operative phases. It provides summaries of imaging modalities, risk assessment tools, and techniques for each phase. By adapting the successful "5IQ" approach from secondary fracture prevention, we propose 5IQ-based Clinical Standards for BHO, including 18 Key Performance Indicators. A Malaysian BHO Registry is proposed to benchmark care in real-time and support a national quality improvement programme. Practical resources, such as a BHO algorithm and key practice points, are included. CONCLUSION: This position paper proposes a paradigm shift in the management of bone health for patients undergoing elective orthopaedic surgery in Malaysia, aiming to improve surgical outcomes and patient care through standardised BHO strategies.

Focused Perioperative Nutritional Supplementation Reduces Wound Complications in Patients Undergoing Spinal Fusion Surgery.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: To evaluate intensive postoperative nutritional supplementation on wound healing complications and outcomes after spinal fusion surgery. BACKGROUND: Poor nutritional status leads to inferior postoperative outcomes by increasing mortality and predisposing patients to infection and wound healing complications. While perioperative nutritional supplementation has shown promise in mitigating these risks, there is a paucity of literature regarding specific nutritional routines in spinal fusion surgery. METHODS: A retrospective analysis was conducted on patients who underwent spinal fusion surgery between 2019 and 2022. Demographic and nutritional data, including preoperative prealbumin levels (PAB) and postoperative supplemental diet, were examined. Primary endpoints included wound complications, with secondary outcomes assessing Oswestry Disability Index (ODI) and Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Health (PH) scores. Statistical analyses included unpaired t-tests and Chi-squared/Fischer's exact tests with significance set at P<0.05. RESULTS: Patients receiving the supplemental diet (n=229) demonstrated fewer wound complications (7% vs. 21%, P=0.004) and reoperations (3% vs. 11%, P=0.016) compared to those without supplementation (n=56). No significant differences were observed in preoperative or postoperative PROMIS PH or ODI scores. Patients with normal preoperative PAB had more wound complications without the supplemental diet (5% vs. 18%, P=0.025). A similar trend was seen in the patients with low preoperative PAB (12% vs. 26%, P=0.12). CONCLUSION: Postoperative nutritional supplementation significantly reduces wound complications after spinal fusion surgery in a cost-effective manner. This study underscores the modifiability of certain perioperative risk factors and suggests that nutritional strategies can mitigate potential complications.

Analytical performance evaluation of the GreenCare A1c and Cera-Stat HbA1c point-of-care testing assays.

BACKGROUND: The escalating prevalence of diabetes underscores the need for precise diagnostic tools to facilitate effective management. Hemoglobin A1c (HbA1c) is a crucial biomarker for long-term glycemic control in diabetic patients. Point-of-care testing (POCT) for HbA1c offers rapid, accessible alternatives to conventional laboratory methods, but uncertainties persist regarding the accuracy and reliability of POCT assays. METHODS: This study evaluates the analytical performance of two boronate-affinity based HbA1c POCT assays, the GreenCare A1c and Cera-Stat HbA1c. Various analytical parameters including precision, linearity, comparison, and accuracy are assessed following guidelines from Clinical and Laboratory Standards Institute (CLSI), with results applied to certification criteria from the National Glycohemoglobin Standardization Program (NGSP) and International Federation of Clinical Chemistry and Laboratory Medicine (IFCC). Furthermore, 52 and 13 frozen EDTA whole blood samples were respectively used for additional evaluation of accuracy and interference due to Hb variants for the GreenCare A1c assay. RESULTS: Both GreenCare and Cera-Stat demonstrated good precision (repeatability CV% 1.5-1.9 and total imprecision CV% 1.6-2.2), linearity (R2 = 0.9996 & 0.9990), and correlation (r = 0.982 & 0.978) with an established HbA1c analyzer, the Bio-Rad D100. The GreenCare also exhibited good accuracy with frozen EDTA samples with known HbA1c values. Both assays met the certification criteria from NGSP and IFCC, classifying them as "standard" according to IFCC model for quality targets for HbA1c. CONCLUSIONS: This evaluation affirms the reliability of GreenCare and Cera-Stat POCT assays for HbA1c measurements, which can potentially reduce unnecessary referrals and enhance the overall quality of diabetes diagnosis and treatment.

Detecting M-Protein via Mass Spectrometry and Affinity Beads: Enrichment With Mixed Kappa-Lambda Beads Enables Prompt Application in Clinical Laboratories.

Background: Detecting monoclonal protein (M-protein), a hallmark of plasma cell disorders, traditionally relies on methods such as protein electrophoresis, immune-electrophoresis, and immunofixation electrophoresis (IFE). Mass spectrometry (MS)-based methods, such as matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) and electrospray ionization-quadrupole time-of-flight (ESI-qTOF) MS, have emerged as sensitive methods. We explored the M-protein-detection efficacies of different MS techniques. Methods: To isolate immunoglobulin and light chain proteins, six types of beads (IgG, IgA, IgM, kappa, lambda, and mixed kappa and lambda) were used to prepare samples along with CaptureSelect nanobody affinity beads (NBs). After purification, both MALDI-TOF MS and liquid chromatography coupled with Synapt G2 ESI-qTOF high-resolution MS analysis were performed. We purified 25 normal and 25 abnormal IFE samples using NBs and MALDI-TOF MS (NB-MALDI-TOF). Results: Abnormal samples showed monoclonal peaks, whereas normal samples showed polyclonal peaks. The IgG and mixed kappa and lambda beads showed monoclonal peaks following the use of daratumumab (an IgG/kappa type of monoclonal antibody) with both MALDI-TOF and ESI-qTOF MS analysis. The limits of detection for MALDI-TOF MS and ESI-qTOF MS were established as 0.1 g/dL and 0.025 g/dL, respectively. NB-MALDI-TOF and IFE exhibited comparable sensitivity and specificity (92% and 92%, respectively). Conclusions: NBs for M-protein detection, particularly with mixed kappa-lambda beads, identified monoclonal peaks with both MALDI-TOF and ESI-qTOF analyses. Qualitative analysis using MALDI-TOF yielded results comparable with that of IFE. NB-MALDI-TOF might be used as an alternative method to replace conventional tests (such as IFE) to detect M-protein with high sensitivity.

Using Domain Adaptation and Inductive Transfer Learning to Improve Patient Outcome Prediction in the Intensive Care Unit: Retrospective Observational Study.

BACKGROUND: Accurate patient outcome prediction in the intensive care unit (ICU) can potentially lead to more effective and efficient patient care. Deep learning models are capable of learning from data to accurately predict patient outcomes, but they typically require large amounts of data and computational resources. Transfer learning (TL) can help in scenarios where data and computational resources are scarce by leveraging pretrained models. While TL has been widely used in medical imaging and natural language processing, it has been rare in electronic health record (EHR) analysis. Furthermore, domain adaptation (DA) has been the most common TL method in general, whereas inductive transfer learning (ITL) has been rare. To the best of our knowledge, DA and ITL have never been studied in-depth in the context of EHR-based ICU patient outcome prediction. OBJECTIVE: This study investigated DA, as well as rarely researched ITL, in EHR-based ICU patient outcome prediction under simulated, varying levels of data scarcity. METHODS: Two patient cohorts were used in this study: (1) eCritical, a multicenter ICU data from 55,689 unique admission records from 48,672 unique patients admitted to 15 medical-surgical ICUs in Alberta, Canada, between March 2013 and December 2019, and (2) Medical Information Mart for Intensive Care III, a single-center, publicly available ICU data set from Boston, Massachusetts, acquired between 2001 and 2012 containing 61,532 admission records from 46,476 patients. We compared DA and ITL models with baseline models (without TL) of fully connected neural networks, logistic regression, and lasso regression in the prediction of 30-day mortality, acute kidney injury, ICU length of stay, and hospital length of stay. Random subsets of training data, ranging from 1% to 75%, as well as the full data set, were used to compare the performances of DA and ITL with the baseline models at various levels of data scarcity. RESULTS: Overall, the ITL models outperformed the baseline models in 55 of 56 comparisons (all P values <.001). The DA models outperformed the baseline models in 45 of 56 comparisons (all P values <.001). ITL resulted in better performance than DA in terms of the number of times and the margin with which it outperformed the baseline models. In 11 of 16 cases (8 of 8 for ITL and 3 of 8 for DA), TL models outperformed baseline models when trained using 1% data subset. CONCLUSIONS: TL-based ICU patient outcome prediction models are useful in data-scarce scenarios. The results of this study can be used to estimate ICU outcome prediction performance at different levels of data scarcity, with and without TL. The publicly available pretrained models from this study can serve as building blocks in further research for the development and validation of models in other ICU cohorts and outcomes.

Optimization of Sodium Iodide-Based Root Filling Material for Clinical Applications: Enhancing Physicochemical Properties.

Premature loss of root canal-treated primary teeth has long been a concern in dentistry. To address this, researchers developed a sodium iodide-based root canal-filling material as an alternative to traditional iodoform-based materials. The goal of this study was to improve the physicochemical properties of the sodium iodide-based material to meet clinical use standards. To resolve high solubility issues in the initial formulation, researchers adjusted component ratios and added new ingredients, resulting in a new paste called L5. This study compared L5 with L0 (identical composition minus lanolin) and Vitapex as controls, conducting physicochemical and antibacterial tests. Results showed that L5 met all ISO 6876 standards, demonstrated easier injection and irrigation properties than Vitapex, and exhibited comparable antibacterial efficacy to Vitapex, which is currently used clinically. The researchers conclude that if biological stability is further verified, L5 could potentially be presented as a new option for root canal-filling materials in primary teeth.

The efficacy of adipose stem cell-derived exosomes in hair regeneration based on a preclinical and clinical study.

BACKGROUND: Androgenetic alopecia (AGA) is a prevalent hair loss disorder with psychological repercussions. Traditional treatments have limitations, leading to the exploration of regenerative therapies such as exosomes derived from adipose tissue stem cells (ASC-Exosomes). METHODS: First, using human hair follicle (HF) dermal papilla cells (hDPCs) treated with ASC-Exosomes, ALP, VCAN, ß-catenin, and LEF-1 levels with RT-PCR and p-GSK3ß, GSK3ß, ß-catenin, ALP, and ß-actin levels with western blot analysis were assessed. Hair shaft elongation test and assay for ALP, Ki-67, and ß-catenin were done using human HF organ culture. Patients with AGA had ASC-Exosomes treatment and were evaluated for hair counts, photographic assessments, subjective satisfaction, and safety profiles. RESULTS: ASC-Exosomes impact hDPCs, increasing proliferation and the upregulation of hair growth-related genes, including ALP, VCAN, ß-catenin, and LEF-1. The Wnt/ß-catenin pathway was activated, indicating their role in promoting hair growth. ASC-Exosomes also promoted hair shaft elongation and ALP activity, suggesting a potential for hair regeneration. Thirty participants with AGA enrolled and treated over 24 weeks. The subjects experienced a significant increase in total hair density, improved global photographic assessments, and reported higher subjective satisfaction without severe adverse reactions. CONCLUSION: This research contributes to the growing body of evidence supporting the use of exosomes in hair loss treatment, offering a safe and effective alternative for individuals with AGA.

Intraoperative detection of parathyroid glands using artificial intelligence: optimizing medical image training with data augmentation methods.

BACKGROUND: Postoperative hypoparathyroidism is a major complication of thyroidectomy, occurring when the parathyroid glands are inadvertently damaged during surgery. Although intraoperative images are rarely used to train artificial intelligence (AI) because of its complex nature, AI may be trained to intraoperatively detect parathyroid glands using various augmentation methods. The purpose of this study was to train an effective AI model to detect parathyroid glands during thyroidectomy. METHODS: Video clips of the parathyroid gland were collected during thyroid lobectomy procedures. Confirmed parathyroid images were used to train three types of datasets according to augmentation status: baseline, geometric transformation, and generative adversarial network-based image inpainting. The primary outcome was the average precision of the performance of AI in detecting parathyroid glands. RESULTS: 152 Fine-needle aspiration-confirmed parathyroid gland images were acquired from 150 patients who underwent unilateral lobectomy. The average precision of the AI model in detecting parathyroid glands based on baseline data was 77%. This performance was enhanced by applying both geometric transformation and image inpainting augmentation methods, with the geometric transformation data augmentation dataset showing a higher average precision (79%) than the image inpainting model (78.6%). When this model was subjected to external validation using a completely different thyroidectomy approach, the image inpainting method was more effective (46%) than both the geometric transformation (37%) and baseline (33%) methods. CONCLUSION: This AI model was found to be an effective and generalizable tool in the intraoperative identification of parathyroid glands during thyroidectomy, especially when aided by appropriate augmentation methods. Additional studies comparing model performance and surgeon identification, however, are needed to assess the true clinical relevance of this AI model.

Plant proteins, peptides, and non-protein amino acids: Toxicity, sources, and analysis.

Plants have evolved various mechanisms to synthesize diverse range of substances that contribute to their survival against pests, pathogens, predators, and adverse environmental conditions. Although several plant metabolites possess therapeutic potential, some can be potentially harmful to human and animal health when consumed in large proportion. Proteins, peptides, and non-protein amino acids are products of plant biochemical pathways with proven beneficial and nutritional effects. Despite these benefits, the in vivo toxicities associated with certain plant-derived proteins, peptides, and non-protein amino acids pose a significant risk to humans and animals. Symptoms of poisoning include nausea, vomiting, diarrhea, hair and weight loss, goiter, cataracts, and infertility. Even though plant processing methods such as soaking and drying can reduce the amount of toxin contained in plants, complete riddance is often impossible. As such, food regulatory bodies need to prevent uncontrolled consumption of the listed and many other toxin-containing plant species to keep the public safe. For this purpose, this review collates crucial insights into the sources, and in vivo toxicity associated with certain plant-derived proteins, peptides, and non-protein amino acids that have the clear potential to adversely affect human health. Additionally, this review provides information on analytical methods suitable for the detection of these substances in plants.

A review of food contamination with nitrated and oxygenated polycyclic aromatic hydrocarbons: toxicity, analysis, occurrence, and risk assessment.

Prolonged exposure to polycyclic aromatic hydrocarbons (PAHs) and their derivatives, particularly nitrated polycyclic aromatic hydrocarbons (NPAHs) and oxygenated polycyclic aromatic hydrocarbons (OPAHs), can result in adverse health effects and may carry higher toxicity risks compared to PAHs alone. Various extraction methods have been utilized for PAHs derivatives from food samples. The analytes are then analyzed using gas chromatography/mass spectrometry and high-performance liquid chromatography techniques. PAHs derivatives are increasingly being detected in the environment, prompting scrutiny from numerous researchers. Similarly, their presence in food is becoming a significant concern. The elevated levels of PAH derivatives found in smoked food may result in detrimental dietary exposure and pose potential health hazards. Furthermore, investigating the level of exposure to these contaminants in food is imperative, as their consumption by humans carries inherent risks. Consequently, this review concentrates on the toxicity, analysis, occurrence, and risk evaluation of NPAHs and OPAHs present in food sources.

Genotypic and phenotypic analysis of Korean patients with tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is a rare autosomal dominant disorder caused by mutations in the TSC1 or TSC2 gene. The aim of this study was to analyze the genotypes and phenotypes of Korean patients diagnosed with TSC and expand our understanding of this disorder. This retrospective observational study included 331 patients clinically diagnosed with TSC between November 1990 and April 2023 at Severance Children's Hospital, Seoul, South Korea. The demographic and clinical characteristics of the patients were investigated. Thirty novel variants were identified. Of the 331 patients, 188 underwent genetic testing, and genotype-phenotype variation was analyzed according to the type of gene mutation and functional domain. Fourty-nine patients (49/188, 26%) were had TSC1 mutations, 103 (55%) had TSC2 mutations, and 36 (19%) had no mutation identified (NMI). Hotspots were identified in exons 8 of TSC1 and exons 35 and 41 of TSC2. Patients with TSC2 mutations exhibited a significantly younger age at the time of seizure onset and had refractory epilepsy. Infantile epileptic spasms syndrome (IESS) was more common in the middle mutation domain of TSC2 than in the hamartin domain. Additionally, retinal hamartoma, cardiac rhabdomyoma, and renal abnormalities were significantly associated with TSC2 compared with other gene types. This study contributes to our understanding of TSC by expanding the genotypic spectrum with novel variants and providing insights into the clinical spectrum of patients with TSC in Korea.

Structural basis of positive allosteric modulation of metabotropic glutamate receptor activation and internalization.

The metabotropic glutamate receptors (mGluRs) are neuromodulatory family C G protein coupled receptors which assemble as dimers and allosterically couple extracellular ligand binding domains (LBDs) to transmembrane domains (TMDs) to drive intracellular signaling. Pharmacologically, mGluRs can be targeted at the LBDs by glutamate and synthetic orthosteric compounds or at the TMDs by allosteric modulators. Despite the potential of allosteric compounds as therapeutics, an understanding of the functional and structural basis of their effects is limited. Here we use multiple approaches to dissect the functional and structural effects of orthosteric versus allosteric ligands. We find, using electrophysiological and live cell imaging assays, that both agonists and positive allosteric modulators (PAMs) can drive activation and internalization of group II and III mGluRs. The effects of PAMs are pleiotropic, boosting the maximal response to orthosteric agonists and serving independently as internalization-biased agonists across mGluR subtypes. Motivated by this and intersubunit FRET analyses, we determine cryo-electron microscopy structures of mGluR3 in the presence of either an agonist or antagonist alone or in combination with a PAM. These structures reveal PAM-driven re-shaping of intra- and inter-subunit conformations and provide evidence for a rolling TMD dimer interface activation pathway that controls G protein and beta-arrestin coupling.

Detection of foreign bodies in the canine stomach using capsule endoscopy: a randomized trial.

Introduction: This study aimed to assess the effectiveness of capsule endoscopy in detecting gastric foreign bodies in normal dogs, considering variations in the number of foreign bodies and the gastric environment. Methods: Five healthy male beagles were administered virtual, non-harmful foreign objects that maintained their shape in the stomach. Capsule endoscopy was performed and the images were evaluated by veterinarians and non-veterinarians. Results: The overall sensitivity and specificity of capsule endoscopy were 99.1 and 90.4%, respectively. Sensitivity and specificity were comparable between veterinarians and non-veterinarians. Sensitivity and specificity in the veterinarian group were 98.7 and 91.2%, respectively, whereas those in the non-veterinarian group were 100 and 88.5%, respectively. Discussion: Capsule endoscopy is a valuable alternative diagnostic tool for identifying foreign bodies in the stomach, particularly in challenging cases in which conventional imaging or invasive approaches have limitations.

Glycemic Burden and Clinical Outcomes of Early Stage Hepatocellular Carcinoma after Curative Treatment.

Early-stage hepatocellular carcinoma (HCC) is still difficult to cure for its high recurrence rate. This study aimed to examine whether glycemic burden management could be one way to improve outcomes of early-stage HCC. A total of 137 very early or early-stage HCC patients who underwent resection or ablation at Samsung Medical Center and had glycemic burden assessment were analyzed. Glycemic burden was assessed using hemoglobin A1c (HbA1c) level. Outcomes were recurrence and overall survival. Risks of recurrence and overall survival were compared according to glycemic burden using a cut-off point of 6.5% or two cut-off points of 6.0% and 7.5%. Overall, 51 (37.2%) patients experienced HCC recurrence. The adjusted hazard ratio (aHR) for recurrence comparing patients with HbA1c > 6.5% to those with HbA1c ≤ 6.5% was 2.66 (95% CI: 1.26-5.78). The risk of recurrence increased in a dose-dependent manner by glycemic burden; aHR for 6.0 < HbA1c ≤ 7.5%: 2.00 (95% CI: 0.78-5.55); aHR for HbA1c > 7.5%: 6.05 (95% CI: 2.31-17.5). Mortality was observed in 16 (11.7%) patients. The risk of mortality was higher for HbA1c > 6.5% than for HbA1c ≤ 6.5% (aHR: 2.33; 95% CI: 1.10-5.08). There was also a dose-response relationship between overall survival and glycemic burden. Glycemic burden assessed using HbA1c level was significantly associated with outcomes of early-stage HCC patients. Good glycemic control could be a therapeutic goal to improve clinical outcomes in these populations.