High prevalence of xerophthalmia linked to socio-demographic and nutritional factors among vitamin A-deficient rural primary schoolchildren in Malaysia.

Vitamin A deficiency (VAD) remains a major health issue in developing nations, contributing to preventable childhood blindness. However, there is lack of recent data on xerophthalmia, especially among school-aged children in Malaysia. We hypothesized that xerophthalmia persists among rural schoolchildren in Malaysia and potentially associated with socio-demographic status and malnutrition. We conducted a cross-sectional study on 596 schoolchildren (8-12 years) from ten rural primary schools located in five states across Malaysia. Children meeting the criteria for xerophthalmia assessment included those diagnosed with vitamin A deficiency (VAD) (plasma retinol < 0.70 µmol/L) and marginal VAD (plasma retinol 0.70 to < 1.05 µmol/L). The overall prevalence of xerophthalmia was 48.8%, with the most common ocular sign being conjunctival xerosis (38.9%). The occurrence of xerophthalmia was negatively associated with retinol-binding protein 4 (RPB4) (P=0.003), alpha-carotene (P=0.04), hemoglobin (P=0.004), weight (P=0.02), body mass index (BMI) (P=0.04) and WAZ (weight-for-age z-score) (P=0.04) status. Based on multivariate logistic regression analysis, a higher risk of xerophthalmia was observed in boys (Adjusted odd ratio [AOR]: 1.7, 95% confidence interval [CI]: 1.2-2.5) and Orang Asli (OA, indigenous) schoolchildren (AOR: 2.0, 95% CI: 1.3-3.0), while schoolchildren with overweight/obesity status (AOR: 0.5, 95% CI: 0.3-0.8) were associated with a reduced risk of xerophthalmia. The present study unveils a high prevalence of xerophthalmia among vitamin A-deficient primary schoolchildren in rural areas of Malaysia, especially among the indigenous community. The identified socio-demographic and nutritional factors associated to xerophthalmia would facilitate the implementation of more targeted interventions in addressing these issues.

A challenging case of hemolytic disease of the fetus and newborn (HDFN) due to anti-Ku in a K0 (Kellnull) mother.

Hemolytic disease of the fetus and newborn (HDFN) due to an antibody in the Kell blood group system can be associated with severe fetal anemia. This case report details the challenges of managing a Kellnull mother with anti-Ku that affected her fetus/newborn. A gravida 4 para 3 woman at term underwent an emergency lower caesarean section because of fetal distress. The baby was intubated because of low oxygen saturation. An urgent request for a hematology workup showed severe anemia and erythroblastosis fetalis. Unfortunately, no compatible blood was found, and the baby died. The case was referred to the National Blood Centre, and anti-Ku was confirmed in a sample sent from the mother. When she presented with her fifth pregnancy, meticulous planning was used to manage this pregnancy. Her family screening revealed one brother with a matching phenotype. Three blood donations were planned for the brother-for freezing, for intrauterine transfusion, and for standby during delivery. Serial anti-Ku titrations of maternal samples were performed, and the fetus was monitored for anemia through middle cerebral artery Doppler scans. Although the anti-Ku titers reached as high as 1024, fetal anemia was never diagnosed. The neonate was delivered safely but was diagnosed with severe pathologic jaundice and anemia secondary to HDFN and congenital pneumonia. The baby was transfused with K0 packed red blood cells and later discharged to home.

Effect of microwave-puffed on Auricularia auricula polysaccharide and probiotic fermentation on its biotransformation and quality characteristics during storage period.

In this study, probiotics with superior fermentation performance were screened, and the mixed-bacteria fermentation was carried out with Auricularia auricula treated with microwave-puffed process as fermentation substrate, and the changes in nutritional quality under different storage conditions were investigated. The results showed that the acid and bile salt resistance of Lactiplantibacillus plantarum 21,801 and 21,805 reached 95 % and 75 % respectively, and the intestinal adhesion was superior; microwave puffing treatment had the highest retention rate of A. auricula polysaccharides and the lowest loss of polyphenols, and no effect on soluble protein. Mixed bacterial fermentation significantly increased the total polyphenols and total flavonoids of A. auricula (p < 0.05), and the DPPH and ABTS radical scavenging reached 48.31 % and 73.21 % respectively. Furthermore, the viable counts, DPPH radical scavenging, color, and sensory quality of fermented A. auricula remained stable when stored at 4 °C. In contrast, when stored at 25 °C for 7 days, the taste was unfavorable, undesirable odor and spoilage occurred; by 21 days, DPPH clearance rate dropped below 40 % and color changed significantly (△E > 2). In conclusion, the probiotic mixed fermentation and storage conditions had a significant effect on the biometabolic transformation of macromolecules and other substances in A. auricula.

A Real-life Study of Brexpiprazole as an Adjunctive Treatment for Major Depressive Disorder in Asian Patients in Singapore (BADA).

Objective: : To investigate the effectiveness and safety of brexpiprazole as an adjunctive treatment to antidepressant therapy (ADT) in Asian adults with major depressive disorder (MDD) and inadequate response in a real-life clinical setting in Singapore. Methods: : This was a prospective, observational 3-month study of patients with MDD who had brexpiprazole added to their existing ADT. The study was conducted at two sites in Singapore between September 2020 and October 2021. The co-primary endpoints were Patient Health Questionnaire-9 (PHQ-9) and Clinical Global Impression-Severity (CGI-S). Other endpoints included Clinical Global Impression-Improvement (CGI-I), Sheehan Disability Scale (SDS), Generalized Anxiety Disorder 7-item scale (GAD-7), and safety. Results: : Twenty patients were enrolled and 16 completed the study. There were improvements in PHQ-9, CGI-S, SDS, and GAD-7 scores from baseline at Week 12, with a mean difference of -4.8, -1.3, -8.5, and -6.2, respectively. The CGI-I score improved from baseline with a mean score of 2.3 at Week 12. One third achieved response and 25% achieved remission based on PHQ-9 scores at Week 12. Similar results were obtained using CGI-S scores (38% for both). The incidences of adverse events (AEs) and treatment-related AEs were 55% (11/20) and 50% (10/20), respectively. There were no deaths or severe AEs. Two patients withdrew brexpiprazole during the study. Conclusion: : The observed effects and safety of adjunctive brexpiprazole in Asian adults with MDD in the real-world setting in Singapore were consistent with those from clinical trials.

Omada: robust clustering of transcriptomes through multiple testing.

BACKGROUND: Cohort studies increasingly collect biosamples for molecular profiling and are observing molecular heterogeneity. High-throughput RNA sequencing is providing large datasets capable of reflecting disease mechanisms. Clustering approaches have produced a number of tools to help dissect complex heterogeneous datasets, but selecting the appropriate method and parameters to perform exploratory clustering analysis of transcriptomic data requires deep understanding of machine learning and extensive computational experimentation. Tools that assist with such decisions without prior field knowledge are nonexistent. To address this, we have developed Omada, a suite of tools aiming to automate these processes and make robust unsupervised clustering of transcriptomic data more accessible through automated machine learning-based functions. FINDINGS: The efficiency of each tool was tested with 7 datasets characterized by different expression signal strengths to capture a wide spectrum of RNA expression datasets. Our toolkit's decisions reflected the real number of stable partitions in datasets where the subgroups are discernible. Within datasets with less clear biological distinctions, our tools either formed stable subgroups with different expression profiles and robust clinical associations or revealed signs of problematic data such as biased measurements. CONCLUSIONS: In conclusion, Omada successfully automates the robust unsupervised clustering of transcriptomic data, making advanced analysis accessible and reliable even for those without extensive machine learning expertise. Implementation of Omada is available at http://bioconductor.org/packages/omada/.

Defining breast cancer-related lymphedema (BCRL) prevalence and risk factors: A pragmatic approach to lymphedema surveillance.

Introduction: We presented the key findings from Singapore's Changi General Hospital Breast Centre's lymphedema surveillance strategy that used patients' reported symptoms, standard arm circumference measurements and clinical assessment in the diagnosis of breast cancer-related lymphedema (BCRL). Our secondary aim was to highlight and discuss important elements of a surveillance strategy that can be implemented to track this outcome measure of breast cancer treatment for future research. Method: We conducted a cross-sectional study of 511 breast cancer patients to assess the prevalence of BCRL and its associated risk factors. We defined BCRL prevalence rates based on patients' self-reporting, objective arm circumference measure-ments and clinical diagnosis based on International Society of Lymphology (ISL) staging. Results: The median follow-up of patients was 88.8 months. The cumulative prevalence rate in the cohort was 30.9%. The cohort of BCRL patients were older (58.4 versus [vs] 54.9 years), had higher mean Body Mass Index (27.7 vs 25.2), higher proportion of mastectomy (77% vs 64.3%), axillary clearance, less likely breast reconstruction, higher-grade tumour, more lymph nodes excised, more advanced nodal disease, and had undergone adjuvant chemotherapy. However, clinically apparent BCRL was only 6.5% (33 out of 511 patients). The proportion of clinically significant BCRL in patients undergoing sentinel lymph node biopsy (SLNB) or axillary sampling was 1.7% compared to 9.9% in patients who had undergone axillary clearance. Majority of the BCRL were subclinical or mild in severity. Conclusion: Our study showed that our rates of BCRL were comparable to international rates and highlighted similar patient profiles who were at risk of developing the disease. Having a comprehensive lymphedema surveillance strategy is paramount in paving the way for future studies.

Four centrosome-related genes to predict the prognosis and drug sensitivity of patients with colon cancer.

BACKGROUND: As the primary microtubule organizing center in animal cells, centrosome abnormalities are involved in human colon cancer. AIM: To explore the role of centrosome-related genes (CRGs) in colon cancer. METHODS: CRGs were collected from public databases. Consensus clustering analysis was performed to separate the Cancer Genome Atlas cohort. Univariate Cox and least absolute shrinkage selection operator regression analyses were performed to identify candidate prognostic CRGs and construct a centrosome-related signature (CRS) to score colon cancer patients. A nomogram was developed to evaluate the CRS risk in colon cancer patients. An integrated bioinformatics analysis was conducted to explore the correlation between the CRS and tumor immune microenvironment and response to immunotherapy, chemotherapy, and targeted therapy. Single-cell transcriptome analysis was conducted to examine the immune cell landscape of core prognostic genes. RESULTS: A total of 726 CRGs were collected from public databases. A CRS was constructed, which consisted of the following four genes: TSC1, AXIN2, COPS7A, and MTUS1. Colon cancer patients with a high-risk signature had poor survival. Patients with a high-risk signature exhibited decreased levels of plasma cells and activated memory CD4+ T cells. Regarding treatment response, patients with a high-risk signature were resistant to immunotherapy, chemotherapy, and targeted therapy. COPS7A expression was relatively high in endothelial cells and fibroblasts. MTUS1 expression was high in endothelial cells, fibroblasts, and malignant cells. CONCLUSION: We constructed a centrosome-related prognostic signature that can accurately predict the prognosis of colon cancer patients, contributing to the development of individualized treatment for colon cancer.

Decellularised plant scaffolds facilitate porcine skeletal muscle tissue engineering for cultivated meat biomanufacturing.

Cultivated meat (CM) offers a sustainable and ethical alternative to conventional animal agriculture, involving cell maturation in a controlled environment. To emulate the structural complexity of traditional meat, the development of animal-free and edible scaffolds is crucial, providing vital physical and biological support during tissue development. The aligned vascular bundles of the decellularised asparagus scaffold were selected to facilitate the attachment and alignment of murine myoblasts (C2C12) and porcine adipose-derived mesenchymal stem cells (pADMSCs). Muscle differentiation was assessed through immunofluorescence staining with muscle markers, including Myosin heavy chain (MHC), Myogenin (MYOG), and Desmin. The metabolic activity of Creatine Kinase in C2C12 differentiated cells significantly increased compared to proliferated cells. Quantitative PCR analysis revealed a significant increase in Myosin Heavy Polypeptide 1 (MYH1) and MYOG expression compared to Day 0. These results highlight the application of decellularised plant scaffold (DPS) as a promising, edible material conducive to cell attachment, proliferation, and differentiation into muscle tissue. To create a CM prototype with biological mimicry, pADMSC-derived muscle and fat cells were also co-cultured on the same scaffold. The co-culture was confirmed through immunofluorescence staining of muscle markers and LipidTOX staining, revealing distinct muscle fibres and adipocytes containing lipid droplets respectively. Texture profile analysis conducted on uncooked CM prototypes and pork loin showed no significant differences in textural values. However, the pan-fried CM prototype differed significantly in hardness and chewiness compared to pork loin. Understanding the scaffolds' textural profile enhances our insight into the potential sensory attributes of CM products. DPS shows potential for advancing CM biomanufacturing.

Coupling hyperspectral imaging with machine learning algorithms for detecting polyethylene (PE) and polyamide (PA) in soils.

Soil, particularly in agricultural regions, has been recognized as one of the significant reservoirs for the emerging contaminant of MPs. Therefore, developing a rapid and efficient method is critical for their identification in soil. Here, we coupled HSI systems [i.e., VNIR (400-1000 nm), InGaAs (800-1600 nm), and MCT (1000-2500 nm)] with machine learning algorithms to distinguish soils spiked with white PE and PA (average size of 50 and 300 µm, respectively). The soil-normalized SWIR spectra unveiled significant spectral differences not only between control soil and pure MPs (i.e., PE 100% and PA 100%) but also among five soil-MPs mixtures (i.e., PE 1.6%, PE 6.9%, PA 5.0%, and PA 11.3%). This was primarily attributable to the 1st-3rd overtones and combination bands of C-H groups in MPs. Feature reductions visually demonstrated the separability of seven sample types by SWIR and the inseparability of five soil-MPs mixtures by VNIR. The detection models achieved higher accuracies using InGaAs (92-100%) and MCT (97-100%) compared to VNIR (44-87%), classifying 7 sample types. Our study indicated the feasibility of InGaAs and MCT HSI systems in detecting PE (as low as 1.6%) and PA (as low as 5.0%) in soil. SYNOPSIS: One of two SWIR HSI systems (i.e., InGaAs and MCT) with a sample imaging surface area of 3.6 mm² per grid cell was sufficient for detecting PE (as low as 1.6%) and PA (as low as 5.0%) in soils without the digestion and separation procedures.

Impact of polyphenol-loaded edible starch nanomaterials on antioxidant capacity and gut microbiota.

Starch nanoparticles (SNPs) have the capability to adsorb polyphenol components from apple pomace efficiently, forming bound polyphenols (P-SNPs). These bound polyphenols may have potential bioactivities to affect human health positively. Therefore, in-depth in vivo observation of the antioxidant activity and evaluation of its gut microbiota regulatory function are essential. The results revealed that P-SNPs indicated significant scavenging abilities against DPPH, ABTS, and hydroxyl radicals. Furthermore, the nanomaterials exhibited non-toxic properties, devoid of hepatorenal and intestinal damage, while concurrently stimulating the production of short-chain fatty acids (SCFAs) within the gastrointestinal tract. Notably, P-SNPs significantly enhanced antioxidant capacity in serum, liver, and kidney tissues, fostering the proliferation of beneficial bacteria (Lactobacillus, Bacillus, norank_f__Muribaculaceae) while suppressing pathogenic bacterial growth (Helicobacter, Odoribacter). This study proposes a novel research concept for the scientific use of polyphenols in promoting gut health.

Intrinsic statistical separation of subpopulations in heterogeneous collective motion via dimensionality reduction.

Collective motion of locally interacting agents is found ubiquitously throughout nature. The inability to probe individuals has driven longstanding interest in the development of methods for inferring the underlying interactions. In the context of heterogeneous collectives, where the population consists of individuals driven by different interactions, existing approaches require some knowledge about the heterogeneities or underlying interactions. Here, we investigate the feasibility of identifying the identities in a heterogeneous collective without such prior knowledge. We numerically explore the behavior of a heterogeneous Vicsek model and find sufficiently long trajectories intrinsically cluster in a principal component analysis-based dimensionally reduced model-agnostic description of the data. We identify how heterogeneities in each parameter in the model (interaction radius, noise, population proportions) dictate this clustering. Finally, we show the generality of this phenomenon by finding similar behavior in a heterogeneous D'Orsogna model. Altogether, our results establish and quantify the intrinsic model-agnostic statistical disentanglement of identities in heterogeneous collectives.

Elevated remnant cholesterol and non-HDL cholesterol concentrations from real-world laboratory results: a cross-sectional study in Southeast Asians.

Introduction: Triglyceride-rich remnant lipoproteins (TRLs) are considered atherogenic due to the presence of remnant cholesterol, which is transported by apolipoprotein B. In clinical practice, the concentration of TRLs can be estimated by calculating remnant cholesterol or non-HDL cholesterol levels. Aim: This study aims to investigate the proportion of patients who have low LDL cholesterol (LDL-C) concentration but elevated remnant cholesterol concentration, stratified by the presence of hypertriglyceridaemia and ethnicity, using real-world hospital data. Our secondary aim is to investigate the proportion of patients with elevated non-HDL cholesterol levels using guideline-recommended goals. Methods: A 2-year retrospective study was conducted at a single centre, analyzing lipid blood tests of all patients, including directly measured LDL-C. Fasting for blood tests was not mandatory. Results: The study included a total of 21,605 consecutive patients with plasma lipid profiles analyzed in our hospital laboratory. The median age was 61 years. In patients with ASCVD (n = 14,704), 23.7% had an LDL-C level of <1.8 mmol/L, 11.3% had elevated remnant cholesterol concentrations at ≥0.65 mmol/L, and 48.8% were at the non-high-density lipoprotein cholesterol (non-HDL-C) goal (<2.6 mmol/L). Among patients diagnosed with atherosclerotic cardiovascular disease (ASCVD) with LDL-C levels of <1.8 mmol/L (n = 3,484), only 11.9% had high levels of remnant cholesterol, but 96% of the ASCVD patients also achieved the recommended non-HDL-C target of <2.6 mmol/L. When the LDL-C level was <1.8 mmol/L, the mean concentration of remnant cholesterol was 0.214 mmol/L when the triglyceride level was <1.7 mmol/L (n = 3,380), vs. 0.70 mmol/L when the triglyceride level was elevated (n = 724), p < 0.001. Among patients with a triglyceride level of ≥1.7 mmol/L and an LDL-C level of <.8 mmol/L, there were 254 patients with elevated remnant cholesterol concentration and 71 patients with suboptimal non-HDL levels. Malays had a higher mean remnant cholesterol concentration compared with both Chinese and Indians across all LDL-C levels, particularly in the presence of hypertriglyceridaemia. Conclusions: An elevated remnant cholesterol concentration of >0.65 mmol/L was present in 11% of all patients. The current guideline-recommended non-HDL-C goal, which uses a 0.8 mmol/L estimate of remnant cholesterol concentration, was achieved in >92% of patients, suggesting that it is unlikely to be clinically useful for the majority of our patient population except where there is concomitant hypertriglyceridaemia. Further studies are needed to establish the appropriate non-HDL-C goal or calculated remnant cholesterol concentration, paired with the LDL-C goal or otherwise, in a Southeast Asian population.

Canthin-6-One Inhibits Developmental and Tumour-Associated Angiogenesis in Zebrafish.

Tumour-associated angiogenesis play key roles in tumour growth and cancer metastasis. Consequently, several anti-angiogenic drugs such as sunitinib and axitinib have been approved for use as anti-cancer therapies. However, the majority of these drugs target the vascular endothelial growth factor A (VEGFA)/VEGF receptor 2 (VEGFR2) pathway and have shown mixed outcome, largely due to development of resistances and increased tumour aggressiveness. In this study, we used the zebrafish model to screen for novel anti-angiogenic molecules from a library of compounds derived from natural products. From this, we identified canthin-6-one, an indole alkaloid, which inhibited zebrafish intersegmental vessel (ISV) and sub-intestinal vessel development. Further characterisation revealed that treatment of canthin-6-one reduced ISV endothelial cell number and inhibited proliferation of human umbilical vein endothelial cells (HUVECs), suggesting that canthin-6-one inhibits endothelial cell proliferation. Of note, canthin-6-one did not inhibit VEGFA-induced phosphorylation of VEGFR2 in HUVECs and downstream phosphorylation of extracellular signal-regulated kinase (Erk) in leading ISV endothelial cells in zebrafish, suggesting that canthin-6-one inhibits angiogenesis independent of the VEGFA/VEGFR2 pathway. Importantly, we found that canthin-6-one impairs tumour-associated angiogenesis in a zebrafish B16F10 melanoma cell xenograft model and synergises with VEGFR inhibitor sunitinib malate to inhibit developmental angiogenesis. In summary, we showed that canthin-6-one exhibits anti-angiogenic properties in both developmental and pathological contexts in zebrafish, independent of the VEGFA/VEGFR2 pathway and demonstrate that canthin-6-one may hold value for further development as a novel anti-angiogenic drug.

Supplementation of red palm olein-enriched biscuits improves levels of provitamin A carotenes, iron, and erythropoiesis in vitamin A-deficient primary schoolchildren: a double-blinded randomised controlled trial.

PURPOSE: Vitamin A deficiency (VAD) remains a significant contributor to childhood morbidity and mortality in developing countries; therefore, the implementation of sustainable and cost-effective approaches to control VAD is of utmost pertinence. This study aims to investigate the efficacy of red palm olein (RPO)-enriched biscuit supplementation in improving vitamin A, haematological, iron, and inflammatory status among vitamin A-deficient schoolchildren. METHODS: We conducted a double-blinded, randomised controlled trial involving 651 rural primary schoolchildren (8-12 years) with VAD in Malaysia. The schoolchildren were randomised to receive either RPO-enriched biscuits (experimental group, n = 334) or palm olein-enriched biscuits (control group, n = 317) for 6-month duration. RESULTS: Significant improvements in retinol and retinol-binding protein 4 levels were observed in both groups after supplementation (P < 0.001). The improvement in retinol levels were similar across groups among subjects with confirmed VAD (P = 0.40). Among those with marginal VAD, greater improvement in retinol levels was recorded in the control group (P < 0.001) but lacked clinical significance. The levels of α- and ß-carotenes, haematological parameters (haemoglobin, packed cell volume, mean corpuscular volume and mean corpuscular haemoglobin) and iron enhanced more significantly in the experimental group (P < 0.05). The significant reduction in the prevalence of microcytic anaemia (- 21.8%) and high inflammation (- 8.1%) was only observed in the experimental group. CONCLUSION: The supplementation of RPO-enriched biscuits enhanced levels of provitamin A carotenes, iron, and erythropoiesis, and exhibited anti-inflammatory effects. Therefore, the incorporation of RPO into National Nutritional Intervention Programs may be a potential measure to improve the health status of vitamin A-deficient children, among various other interventions. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT03256123).

Investigation the nutritional properties of Auricularia auricula pulp fermented with Lactobacillus strains and their effects on gut microbiota.

BACKGROUND: Auricularia auricula is rich in bioactive components, and microbial fermentation can further dramatically increase its content and bioavailability. However, there are few studies on the relationship between fermented A. auricula pulp (FAAP) and gut microbiota. In this study, standard strains Lactobacillus plantarum 21801 and 21805 purchased from the China Center of Industrial Culture Collection were used to ferment A. auricula pulp at a ratio of 2:1, with an inoculum of 5%, a fermentation temperature of 31 °C, and a fermentation time of 22 h. The nutritional properties, aroma, and color of FAAP and their effects on the body characteristics of mice and the structure and abundance of gut microbiota are discussed. RESULTS: The results showed that, compared with A. auricula pulp, FAAP significantly increased the nutritional properties while maintaining favorable sensory quality and flavor profiles. Among them, the content of total polyphenols and total flavonoids reached 22.04 µg mL-1 and 20.56 µg mL-1 respectively, and the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid free-radical scavenging rate increased to 73.21%. The consumption of FAAP had no negative effects on weight or liver and kidney function in mice and dramatically enhanced the antioxidant capacity in the liver and serum. The production of short-chain fatty acids in the gut was promoted, the relative abundance of beneficial bacteria (Lactobacillus, Bifidobacterium, norank_f__Muribaculaceae and unclassified_f__Lachnospiraceae) increased, and the growth of some pathogenic bacteria (Helicobacter, Mucispirillum, and Alloprevotella) was inhibited. CONCLUSION: These findings demonstrate that FAAP is rich in nutrients and has unique functional properties that promote host health and regulate the gut microbiota. © 2023 Society of Chemical Industry.

Astragaloside IV (ASIV) Mediates Endothelial Progenitor Cell (EPC) Exosomal LINC01963 to Inhibit Pyroptosis and Oxidative Stress in High Glucose-impaired Endothelial Cells.

BACKGROUND: Hyperglycemia is widespread in the world's population, increasing the risk of many diseases. This study aimed to explore the regulatory effect and mechanism of astragaloside IV (ASIV)-mediated endothelial progenitor cells (EPCs) exosomal LINC01963 in endothelial cells (HUVECs) impaired by high glucose. METHODS: Morphologies of exosomes were observed by light microscope and electron microscope. Immunofluorescence was used to identify EPCs and detect the expressions of caspase-1. LINC01963 was detected by quantitative reverse transcription PCR. NLRP3, ASC, and caspase-3 were detected by Western Blot. Nanoparticle tracking analysis was carried out to analyze the exosome diameter. High-throughput sequencing was applied to screen target lncRNAs. The proliferation of endothelial cells was measured by cell counting kit-8 assay. The apoptosis level of HUVECs was detected by flow cytometry and TdT-mediated dUTP Nick-End labeling. The levels of IL- 1ß, IL-18, ROS, SOD, MDA, and LDH were measured by enzyme-linked immunosorbent assay. RESULTS: ASIV could promote the secretion of the EPC exosome. LINC01963 was obtained by high-throughput sequencing. It was observed that high glucose could inhibit the proliferation, reduce the level of SOD, the expression of NLRP3, ASC, and caspase- 1, increase the levels of IL-1ß, IL-18, ROS, MDA, and LDH, and promote apoptosis of HUVECs. Whereas LINC01963 could inhibit the apoptosis of HUVECs, the increase the expression of NLRP3, ASC, and caspase-1, and decrease the levels of IL-1ß, IL-18, ROS, MDA, and LDH. CONCLUSION: EPCs exosomal LINC01963 play an inhibitory role in high glucoseinduced pyroptosis and oxidative stress of HUVECs. This study provides new ideas and directions for treating hyperglycemia and researching exosomal lncRNAs.

Evaluation of the microbiological efficacy of cleaning agents for tracheostomy inner cannulas.

PURPOSE: Biofilms are a significant cause of morbidity in patients with indwelling medical devices. Biofilms pose a potential risk with reusable inner cannulas by increasing the risk of infections. Effective decontamination is thus vital in decreasing bioburden. The current guidelines for cleaning inner cannulas are varied, with multiple techniques being recommended, which are not supported by strong evidence. This randomized, controlled, cross-over study attempted to enumerate the bacterial count of inner cannulas used in tracheostomy patients (n = 60) pre-and post-decontamination with detergent (A) or sterile water (B). MATERIALS AND METHODS: The patients were randomly allocated to sequence A > B or B > A in 1:1 fashion. The saline flushing of the inner cannulas was plated on trypticase soy agar with 5 % sheep blood to enumerate the bacterial count. RESULTS: The mean ratio [Log (CFU)post/Log (CFU)pre]A/[Log (CFU)post/Log (CFU)pre]B based on 53 samples was 0.918 ± 0.470, two-sided 90 % confidence interval (CI) 0.812, 1.024. The equivalence criterion was met as the mean ratio after cleaning fell within the equivalence region of 0.8 and 1.25. CONCLUSION: This study demonstrated the microbiological efficacy of both detergent and sterile water in the decontamination of inner cannulas, and that sterile water was not less effective than detergent in reducing the bacterial load for safe re-use of inner cannulas. This has the potential to promote cost savings for patients with tracheostomy, both in the hospital and the community. The study findings may also be relevant in formulating tracheostomy care policies.

Mental Health for All: The Case for Investing in Digital Mental Health to Improve Global Outcomes, Access, and Innovation in Low-Resource Settings.

Mental health disorders are an increasing global public health concern that contribute to morbidity, mortality, disability, and healthcare costs across the world. Biomedical and psychological research has come a long way in identifying the importance of mental health and its impact on behavioral risk factors, physiological health, and overall quality of life. Despite this, access to psychological and psychiatric services remains widely unavailable and is a challenge for many healthcare systems, particularly those in developing countries. This review article highlights the strengths and opportunities brought forward by digital mental health in narrowing this divide. Further, it points to the economic and societal benefits of effectively managing mental illness, making a case for investing resources into mental healthcare as a larger priority for large non-governmental organizations and individual nations across the globe.

Dynamic circulating tumor DNA during chemoradiotherapy predicts clinical outcomes for locally advanced non-small cell lung cancer patients.

The value of circulating tumor DNA (ctDNA) during chemoradiotherapy (CRT) remains unclear but is critical for detecting molecular residual disease (MRD). In this prospective study, we sequenced 761 blood samples from 139 patients with locally advanced non-small cell lung cancer treated with definitive radiation therapy (RT). ctDNA concentrations showed a significantly declining trend as CRT progressed at on-RT and after-RT time points versus baseline. Thirty-eight (27.3%) patients with early undetectable ctDNA at both on-RT (RT reached 40 Gy) and after-RT time points, indicating early response to CRT, had better survival outcomes for both with or without consolidation immune checkpoint inhibitors. Longitudinal undetectable MRD was found in 20.1% patients. The 2-year cancer-specific progression-free survival of these patients was 88.4%, corresponding to a potentially cured population. Further analysis revealed that pretreatment ctDNA variants serve as an essential MRD informed source. These data provide clinical insights for ctDNA-MRD detection.