Altered Brain Glymphatic Function at Diffusion-Tensor MRI in Pre-cirrhotic Metabolic Dysfunction-Associated Fatty Liver Disease.

RATIONALE AND OBJECTIVES: To evaluate glymphatic function changes and their relationships with clinical features in patients with metabolic dysfunction-associated fatty liver disease (MAFLD), thereby facilitating early intervention before this disease progresses to cirrhosis. MATERIALS AND METHODS: A cross-sectional cohort of 46 pre-cirrhotic MAFLD patients and 30 age-, sex-, and education-matched controls was enrolled, with diffusion-tensor imaging (DTI) data, laboratory and neurocognitive scores collected. The DTI analysis along the perivascular space (DTI-ALPS) index was computed for qualifying glymphatic function. Generalized linear model and partial correlation analyses were applied to evaluate relationships between the ALPS index and clinical variables. RESULTS: MAFLD group exhibited a decreased ALPS index and increased diffusivity along the y-axis in the projection fiber compared to the controls. The altered ALPS index was associated with clock drawing test (CDT) score (3.931 [0.914, 6.947], P = 0.011) and was correlated with diastolic pressure level (r = -0.315, P = 0.033) in MAFLD group. The relationships of ALPS index with CDT score (6.263 [2.069, 10.458], P = 0.003) and diastolic pressure level (r = -0.518, P = 0.014) remained in the MAFLD with metabolic syndrome (MetS) group. Furthermore, the ALPS index was even associated with Auditory Verbal Learning Test-Immediate recall score (-23.853 [-45.417, -2.289], P = 0.030) in MAFLD with MetS group. CONCLUSION: MAFLD patients may have a glymphatic dysfunction prior to cirrhosis, and this alteration may be related to cognition and diastolic pressure. Glymphatic dysfunction has a more severe impact on cognition when MAFLD patient is accompanied by MetS.

Boronic Acid-Rich Lanthanide Metal-Organic Frameworks Enable Deep Proteomics with Ultratrace Biological Samples.

Label-free proteomics is widely used to identify disease mechanism and potential therapeutic targets. However, deep proteomics with ultratrace clinical specimen remains a major technical challenge due to extensive contact loss during complex sample pretreatment. Here, a hybrid of four boronic acid-rich lanthanide metal-organic frameworks (MOFs) with high protein affinity is introduced to capture proteins in ultratrace samples jointly by nitrogen-boronate complexation, cation-π and ionic interactions. A MOFs Aided Sample Preparation (MASP) workflow that shrinks sample volume and integrates lysis, protein capture, protein digestion and peptide collection steps into a single PCR tube to minimize sample loss caused by non-specific absorption, is proposed further. MASP is validated to quantify ≈1800 proteins in 10 HEK-293T cells. MASP is applied to profile cerebrospinal fluid (CSF) proteome from cerebral stroke and brain damaged patients, and identified ≈3700 proteins in 1 µL CSF. MASP is further demonstrated to detect ≈9600 proteins in as few as 50 µg mouse brain tissues. MASP thus enables deep, scalable, and reproducible proteome on precious clinical samples with low abundant proteins.

Epidermal growth factor receptor­targeted antibody nimotuzumab combined with chemoradiotherapy improves survival in patients with locally advanced head and neck squamous cell carcinoma: a propensity score matching real-world study.

Patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) have poor survival outcomes. The real-world efficacy of nimotuzumab plus intensity modulated radiotherapy (IMRT)-based chemoradiotherapy in patients with LA-HNSCC remains unclear. A total of 25,442 HNSCC patients were screened, and 612 patients were matched by propensity score matching (PSM) (1:1). PSM was utilized to balance known confounding factors. Patients who completed at least five doses of nimotuzumab were identified as study group. The primary end point was 3-year overall survival (OS) rate. Log-rank test examined the difference between two survival curves and Cloglog transformation test was performed to compare survival at a fixed time point. The median follow-up time was 54.2 (95% confidence interval [CI]: 52.7-55.9) months. The study group was associated with improved OS (hazard ratio [HR] = 0.75, 95% CI: 0.57-0.99, p = 0.038) and progression-free survival (PFS) (HR = 0.74, 95% CI: 0.58-0.96, p = 0.021). Subgroup analysis revealed that aged 50-60 year, IV, N2, radiotherapy dose ≥ 60 Gy, without previous surgery, and neoadjuvant therapy have a trend of survival benefit with nimotuzumab. Nimotuzumab showed favorable safety, only 0.2% had nimotuzumab-related severe adverse events. Our study indicated the nimotuzumab plus chemoradiotherapy provides survival benefits and safety for LA-HNSCC patients in an IMRT era.

Curcumin ameliorates pyroptosis in diabetic seminal vesicles by upregulating TRPV6.

BACKGROUND: Diabetes damages the seminal vesicle tissues leading to a decrease in seminal fluid secretion, so investigations are ongoing to identify specific therapeutic approaches to address diabetes-induced damage to seminal vesicles. OBJECTIVE: This study investigated the secretory dysfunction of seminal vesicles and how curcumin can ameliorate this dysfunction. MATERIALS AND METHODS: First, 40 diabetic males (DM group) and 40 nondiabetic males (control group) underwent seminal vesicle ultrasound evaluation and ejaculate volume measurements. Then, the effects of curcumin on seminal vesicle function were investigated in a diabetic rat model. Fifty 8-week-old SPF-grade SD rats were categorized into five groups: control, DM (diabetes mellitus), low-dose CUR (curcumin 50 mg/kg/d), medium-dose CUR (curcumin 100 mg/kg/d), and high-dose CUR (curcumin 150 mg/kg/d). After a month-long diet with varying curcumin doses, key parameters such as body weight, blood glucose levels, seminal vesicle volume, and seminal fluid secretion were measured. Transcriptome sequencing was performed to assess differences in gene expression and structural changes in rat seminal vesicle tissues were examined by HE staining. Finally, human seminal vesicle cell lines were cultured and divided into five groups (HG-CON, HG-CUR-5 µM, HG-CUR-10 µM, HG-CUR-20 µM, and HG-CUR-50 µM) to measure the fructose levels in the seminal vesicle cell culture fluids and evaluate the expression of CASP1, GSDMD, and TRPV6. Post TRPV6 interference, variations in the gene expression of CASP1, GSDMD, and TRPV6 were monitored. RESULTS: Diabetic patients exhibited a notable reduction in seminal vesicle volume and ejaculate volume compared with the control group, with a direct correlation between the decrease in ejaculate and seminal vesicle volume. Animal studies demonstrated that curcumin supplementation significantly augmented seminal vesicle volume in diabetic rats and notably improved their seminal vesicle secretory dysfunction, particularly in the high-dose curcumin group. Transcriptome sequencing and experimental verification pinpointed the differential expression of TPRV6 and pyroptosis-associated genes (CASP1, GSDMD), with reduced TRPV6 expression but increased markers of pyroptosis (CASP1 and GSDMD) in diabetic rats. Curcumin treatment reversed these effects with an increase in TRPV6 and a decrease in GSDMD and CASP1. Cell transfection experiments indicated that TRPV6 downregulation increased GSDMD and CASP1 gene expression. CONCLUSION: Curcumin effectively activates TRPV6, thereby diminishing pyroptosis in the seminal vesicle tissues of diabetic rats. This activation not only leads to an increase in the seminal vesicle volume but also significantly ameliorates the seminal vesicle secretory dysfunction in diabetic rats.

Prevalence of subthreshold depression and its related factors in Chinese college students: A cross-sectional study.

Objective: To investigate the prevalence of subthreshold depression among Chinese college students and to explore the related factors. Methods: The research subjects were Chinese college students participating in the "2022 Psychology and Behavior Investigation of Chinese Residents (PBICR-2022)". Data on respondents' general characteristics, quality of life, perceived pressure, family communication, perceived social support, self-efficacy, and depression status were gathered. To investigate the association between each variable and the risk of subthreshold depression, statistical analyses, including chi-square tests and rank sum tests were conducted. Furthermore, a binary stepwise logistic regression was employed to establish the regression model of the factors related to subthreshold depression among Chinese college students. Results: A prevalence of subthreshold depression of about 39.7 % was found among the 8934 respondents. Logistic regression analysis revealed that respondents who are female, have chronic diseases, are in debt, experience significant impacts from epidemic control policies, have lower self-assessed quality of life, experience challenges in family communication, perceive lower social support, have lower self-efficacy, and feel higher perceived pressure are more likely to develop subthreshold depression compared to the control group. (P < 0.05). Conclusion: The prevalence rate of subthreshold depression among Chinese college students was found to be approximately 40 %. Female college students suffering from chronic diseases, with households in debt, greatly impacted by epidemic control policies, and experiencing high perceived stress, may be at risk for subthreshold depression among Chinese college students. On the other hand, strong family communication, perceived social support, and self-efficacy were identified as potential protective factors. In order to facilitate timely screening, diagnosis, and treatment of subthreshold depression in Chinese college students, it is crucial for the government, local communities, colleges, and families to prioritize the mental health of college students and implement targeted measures accordingly.

Nano/micro flexible fiber and paper-based advanced functional packaging materials.

Recently, fiber-based and functional paper food packaging has garnered significant attention for its versatility, excellent performance, and potential to provide sustainable solutions to the food packaging industry. Fiber-based food packaging is characterized by its large surface area, adjustable porosity and customizability, while functional paper-based food packaging typically exhibits good mechanical strength and barrier properties. This review summarizes the latest research progress on food packaging based on fibers and functional paper. Firstly, the raw materials used for preparing fiber and functional paper, along with their physical and chemical properties and roles in food packaging, were discussed. Subsequently, the latest advancements in the application of fiber and paper materials in food packaging were introduced. This paper also discusses future research directions and potential areas for improvement in fiber and functional paper food packaging to further enhance their effectiveness in ensuring food safety, quality, and sustainability.

Creating a bionic scaffold via light-curing liquid crystal ink to reveal the role of osteoid-like microenvironment in osteogenesis.

Osteoid plays a crucial role in directing cell behavior and osteogenesis through its unique characteristics, including viscoelasticity and liquid crystal (LC) state. Thus, integrating osteoid-like features into 3D printing scaffolds proves to be a promising approach for personalized bone repair. Despite extensive research on viscoelasticity, the role of LC state in bone repair has been largely overlooked due to the scarcity of suitable LC materials. Moreover, the intricate interplay between LC state and viscoelasticity in osteogenesis remains poorly understood. Here, we developed innovative hydrogel scaffolds with osteoid-like LC state and viscoelasticity using digital light processing with a custom LC ink. By utilizing these LC scaffolds as 3D research models, we discovered that LC state mediates high protein clustering to expose accessible RGD motifs to trigger cell-protein interactions and osteogenic differentiation, while viscoelasticity operates via mechanotransduction pathways. Additionally, our investigation revealed a synergistic effect between LC state and viscoelasticity, amplifying cell-protein interactions and osteogenic mechanotransduction processes. Furthermore, the interesting mechanochromic response observed in the LC hydrogel scaffolds suggests their potential application in mechanosensing. Our findings shed light on the mechanisms and synergistic effects of LC state and viscoelasticity in osteoid on osteogenesis, offering valuable insights for the biomimetic design of bone repair scaffolds.

A dual-template synergistic assembly strategy towards the synthesis of extra-small nitrogen-doped mesoporous carbon nanospheres with large pores.

Functional mesoporous carbon nanomaterials with large pores and small particle sizes have broad accessibility, but remain challenging to achieve. This study proposed a dual-template synergistic assembly strategy to facilely synthesize extra-small nitrogen-doped mesoporous carbon nanospheres with large pores in a low-cost manner. Directed by the synergistic effect of the combination of surfactants, sodium oleate (anionic surfactant) and triblock copolymer-P123 (nonionic surfactant) were selected as templates to construct nanomicelles (nanoemulsions), which were co-assembled with melamine-based oligomers to form composite nanomicelles, thus obtaining nitrogen-doped mesoporous polymer nanospheres (NMePS) and then nitrogen-doped mesoporous carbon nanospheres (NMeCS). Based on Schiff base chemistry, the melamine-based oligomers with self-assembly capability were synthesized as precursors, which is different from the conventional synthetic route of melamine-formaldehyde resin. The key parameters involved in the route were investigated comprehensively and correlated with the characterization results. Furthermore, the 50 nm-scale particle size and the large mesoporous size of 5.5 nm of NMeCS can facilitate effective mass transport, coupled with their high nitrogen content (15.7 wt%), contributing to their excellent performance in lithium-ion batteries.

A two-tier feature selection method for predicting mortality risk in ICU patients with acute kidney injury.

Acute kidney injury (AKI) is one of the most important lethal factors for patients admitted to intensive care units (ICUs), and timely high-risk prognostic assessment and intervention are essential to improving patient prognosis. In this study, a stacking model using the MIMIC-III dataset with a two-tier feature selection approach was developed to predict the risk of in-hospital mortality in ICU patients admitted for AKI. External validation was performed using separate MIMIC-IV and eICU-CRD. The area under the curve (AUC) was calculated using the stacking model, and features were selected using the Boruta and XGBoost feature selection methods. This study compares the performance of a stacking model using two-tier feature selection with a model using single-tier feature selection (XGBoost: 85; Boruta: 83; two-tier: 0.91). The predictive effectiveness of the stacking model was further validated by using different datasets (Validation 1: 0.83; Validation 2: 0.85) and comparing it with a simpler model and traditional clinical scores (SOFA: 0.65; APACH IV: 0.61). In addition, this study combined interpretable techniques and causal inference to analyze the causal relationship between features and predicted outcomes.

Abnormally glymphatic system functional in patients with migraine: a diffusion kurtosis imaging study.

BACKGROUND: The diffusion tensor imaging analysis along the perivascular space (DTI-ALPS) method has been used to evaluate glymphatic system function in patients with migraine. However, since the diffusion tensor model cannot accurately describe the diffusion coefficient of the nerve fibre crossing region, we proposed a diffusion kurtosis imaging ALPS (DKI-ALPS) method to evaluate glymphatic system function in patients with migraine. METHODS: The study included 29 healthy controls and 37 patients with migraine. We used diffusion imaging data from a 3T MRI scanner to calculate DTI-ALPS and DKI-ALPS indices of the two groups. We compared the DTI-ALPS and DKI-ALPS indices between the two groups using a two-sample t-test and performed correlation analyses with clinical variables. RESULTS: There was no significant difference in DTI-ALPS index between the two groups. Patients with migraine showed a significantly increased right DKI-ALPS index compared to healthy controls (1.6858 vs. 1.5729; p = 0.0301). There was no significant correlation between ALPS indices and clinical variables. CONCLUSIONS: DKI-ALPS is a potential method to assess glymphatic system function and patients with migraine do not have impaired glymphatic system function.

Rhythmic gamma frequency light flickering ameliorates stress-related behaviors and cognitive deficits by modulating neuroinflammatory response through IL-12-Mediated cytokines production in chronic stress-induced mice.

Chronic stress enhances the risk for psychiatric disorders and induces depression and cognitive impairment. Gamma oscillations are essential for neurocircuit function, emotion, and cognition. However, the influence of gamma entrainment by sensory stimuli on specific aspects of chronic stress-induced responses remains unclear. Mice were subjected to corticosterone (CORT) administration and chronic restraint stress (CRS) for weeks, followed by rhythmic gamma frequency light flickering exposure. Local field potentials (LFPs) were recorded from the V1, CA1, and PFC regions to verify the light flicker on gamma oscillations. Behavioral tests were used to examine stress-related and memory-related behaviors. Golgi staining was performed to observe changes in spine morphology. Synaptosomes were isolated to determine the expression of synapse-related proteins through immunoblotting. RNA sequencing (RNA-seq) was applied to explore specific changes in the transcriptome. Immunofluorescence staining, real-time quantitative polymerase chain reaction (qPCR), and ELISA were used to evaluate microglial activation and cytokine levels. In this study, we demonstrated that rhythmic 40 Hz LF attenuated stress-related behavior and cognitive impairments by ameliorating the microstructural alterations in spine morphology and increasing the expression of GluN2A and GluA1 in chronically stressed mice. Transcriptome analysis revealed that significantly downregulated genes in LF-exposed CRS mice were enriched in neuroimmune-related signaling pathways. Rhythmic 40 Hz LF exposure significantly decreased the number of Iba1-positive microglia in the PFC and hippocampus, and the expression levels of the M1 markers of microglia iNOS and CD68 were reduced significantly in CRS mice. In addition, 40 Hz LF exposure suppressed the secretion of cytokines IL-12, which could regulate the production of IFN-γ and IL-10 in stressed mice. Our results demonstrate that exposure to rhythmic 40 Hz LF induces the neuroimmune response and downregulation of neuroinflammation with attenuated stress-related behaviors and cognitive function in CRS-induced mice. Our findings highlight the importance of sensory-evoked gamma entrainment as a potential therapeutic strategy for stress-related disorders treatment. Abbreviations: CORT, Chronic corticosterone treatment; CRS, Chronic restraint stress; IACUC, Institutional Animal Care and Use Committee; LF, light flickers; FST, Forced swim test; NSFT, Novelty-suppressed feeding test; SPT, Sucrose preference test; NSFT, Novelty-suppressed feeding; qPCR, Quantitative real-time polymerase chain reaction; SDS-PAGE, sodium dodecyl sulfate-polyacrylamide gel electrophoresis; PVDF, polyvinylidene fluoride; PBS, phosphate-buffered saline; PBS-T, phosphate-buffered saline plus 0.1% Tween 20; PVDF, polyvinylidene fluoride; GFAP, Glial fibrillary acidic protein; DAPI, 4',6-Diamid- ino-2-phenylindole; Iba1, Ionized calcium-binding adaptor molecule 1; iNOS, Inducible nitric oxide synthase; IL-10, Interleukin-10; IL6, Interleukin 6; IL-1ß, Interleukin 1ß; IL-12, Interleukin 12; TNF-α, Tumor necrosis factor alpha; IFN-γ, Interferon-gamma; TLR6 and 9, Toll-like Receptor 6 and 9.

"Top-down" overexpression optimization of butelase-1 in Escherichia coli and its application in anti-tumor peptides.

Butelase-1, the fastest known Asn/Asp-specific peptide ligase capable of catalyzing peptide ligation and cyclization, holds promising application prospects in the fields of food and biology. However, limited research exists on its recombinant expression and potential applications in peptide drugs. In this study, the activity of recombinantly-produced butelase-1 was enhanced by co-expressing it with a molecular chaperone in the SHuffle T7 strain. By introducing single or multiple synonymous rare codons at the beginning of the coding regions of beta-strand or alpha-helix, in combination with ribosomal binding site engineering, the activity of butelase-1 could be further improved. Consequently, the butelase-1 with a specific activity of 386.93 U/mg and a catalytic efficiency of 11,048 M-1 s-1 was successfully prepared in E. coli, resulting in a total activity of 8183.54 U/L and a yield of about 100 mg/L. This optimized butelase-1 was then used to efficiently cyclize the redesigned anti-cancer peptide lunasin, leading to enhanced bioavailability and anti-cancer effects. Overall, this study not only provided valuable biotechnology strategies for improving the recombinant expression of butelase-1 but also demonstrated a successful application for enhancing the biological efficacy of anti-cancer peptides.

Bifurcation detection in intravascular optical coherence tomography using vision transformer based deep learning.

Objective. Bifurcation detection in intravascular optical coherence tomography (IVOCT) images plays a significant role in guiding optimal revascularization strategies for percutaneous coronary intervention (PCI). We propose a bifurcation detection method using vision transformer (ViT) based deep learning in IVOCT.Approach. Instead of relying on lumen segmentation, the proposed method identifies the bifurcation image using a ViT-based classification model and then estimate bifurcation ostium points by a ViT-based landmark detection model.Main results. By processing 8640 clinical images, the Accuracy and F1-score of bifurcation identification by the proposed ViT-based model are 2.54% and 16.08% higher than that of traditional non-deep learning methods, are similar to the best performance of convolutional neural networks (CNNs) based methods, respectively. The ostium distance error of the ViT-based model is 0.305 mm, which is reduced 68.5% compared with the traditional non-deep learning method and reduced 24.81% compared with the best performance of CNNs based methods. The results also show that the proposed ViT-based method achieves the highest success detection rate are 11.3% and 29.2% higher than the non-deep learning method, and 4.6% and 2.5% higher than the best performance of CNNs based methods when the distance section is 0.1 and 0.2 mm, respectively.Significance. The proposed ViT-based method enhances the performance of bifurcation detection of IVOCT images, which maintains a high correlation and consistency between the automatic detection results and the expert manual results. It is of great significance in guiding the selection of PCI treatment strategies.

Anti-inflammatory and cytotoxicity nitrogenous merosesquiterpenoids from the sponge Pseudoceratina purpurea.

Fourteen undescribed nitrogenous merosesquiterpenoids, purpurols A-D (1-4) and puraminones A-J (5-14), along with three known related compounds (15-17) were isolated from the sponge Pseudoceratina purpurea collected in the South China Sea. Their structures and absolute configurations were unambiguously elucidated by a combination of spectroscopic data, X-ray diffraction analysis, electronic circular dichroism calculations, and chemical derivatization. Purpurols A-D (1-4) incorporated nitrogenous heterocycles, compounds 1 and 2 feature an unusual benzothiazole ring, while 3 and 4 feature benzoxazole ring. Puraminones A-J (5-14) represent sesquiterpenoid aminoquinones with different amine and amino acid side chains at C-20. Additionally, twenty unreported sesquiterpenoid aminoquinone analogues were obtained through chemical derivatization. It is worth noting that all compounds are featured with unusual rearranged 4,9-friedodrimane subunit. In the bioassays, purpurols A and B showed weak anti-inflammation in zebrafish, as well as some compounds showed activities against tumor cells, therefore, preliminary structure-cytotoxicity relationships are also discussed.

Synergistic Effect of Microconvex Texture and Particle Medium on the Tribological Property of the Rubber Sliding Interface.

In this study, we examined how surface topography and particle medium interact to affect the tribological performance of rubber sliding interfaces, uncovering the mechanisms of particle lubrication under various conditions. We found that microtextured surfaces, created using a mold transfer method, modestly reduced the friction coefficient of rubber under both dry and lubricated states, primarily by altering the real contact area. Additionally, the presence of different microconvex textures on the surface topography significantly influenced rubber's tribological properties. Our three-dimensional morphological analysis revealed that microtextured rubber surfaces with higher Sa, Sku, and Sal and lower Str values consistently showed lower friction coefficients during sliding. The friction mechanism was attributed to the combined effects of the material properties, surface topography, and contact area. With the addition of a particle medium, the dry friction coefficient of the rubber interface decreased but exhibited an initial increase, followed by a decrease with increasing particle diameter. When particles were mixed with a water-based cutting fluid, the concentration, diameter, and wettability of the particles significantly impacted the tribological properties due to the synergistic effects of surface topography and particle lubrication. This work enhances our understanding of tribological control for viscoelastic materials through surface design, providing a theoretical basis for the tribological optimization of rubber surfaces.

Sphingobacterium tenebrionis sp. nov., isolated from intestine of mealworm.

A bacterial strain designated PU5-4T was isolated from the mealworm (the larvae of Tenebrio molitor) intestines. It was identified to be Gram-stain-negative, strictly aerobic, rod-shaped, non-motile, and non-spore-forming. Strain PU5-4T was observed to grow at 10-40 °C, at pH 7.0-10.0, and in the presence of 0-3.0 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain PU5-4T should be assigned to the genus Sphingobacterium. The 16S rRNA gene sequence similarity analysis showed that strain PU5-4T was closely related to the type strains of Sphingobacterium lactis DSM 22361T (98.49 %), Sphingobacterium endophyticum NYYP31T (98.11 %), Sphingobacterium soli NCCP 698T (97.69 %) and Sphingobacterium olei HAL-9T (95.73 %). The predominant isoprenoid quinone is MK-7. The major fatty acids were identified as iso-C15 : 0, iso-C17 : 03-OH and summed feature 3 (C16 : 1 ω7c and/or C16 : 1 ω6c) and summed feature 9 (iso-C17 : 0 ω9c). The polar lipids are phosphatidylethanolamine, one unidentified phospholipid, and six unidentified lipids. The genomic DNA G+C content of strain PU5-4T is 40.24 mol%. The average nucleotide identity of strain PU5-4T exhibited respective values of 73.88, 73.37, 73.36 and 70.84 % comparing to the type strains of S. lactis DSM 22361T, S. soli NCCP 698T, S. endophyticum NYYP31T and S. olei HAL-9T, which are below the cut-off level (95-96 %) for species delineation. Based on the above results, strain PU5-4T represents a novel species of the genus Sphingobacterium, for which the name Sphingobacterium temoinsis sp. nov. is proposed. The type strain is PU5-4T (=CGMCC 1.61908T=JCM 36663T).

Crosstalk between gastrointestinal tract disorders and obstructive sleep apnea.

PURPOSE: Clinical studies suggested associations between obstructive sleep apnea (OSA) and gastrointestinal tract disorders. This study aims to investigate the genetic causal relationship between OSA and gastrointestinal tract disorders, specifically gastroesophageal reflux disease (GERD) and inflammatory bowel disease (IBD). METHODS: In this study, we employed two-sample Mendelian Randomization (MR) analysis to investigate the potential relationships between OSA and GERD, and between OSA and IBD. More specifically, the primary analysis utilized inverse variance weighting (IVW). Weighted median, MR Egger, and MR PRESSO were applied to complicate potential violations of MR assumptions. Also, sensitivity analysis was evaluated and similar analysis was performed again after outliers were removed. Additionally, multivariable MR (MVMR) was conducted for associated pairs to adjust for obesity. RESULTS: Genetically predicted risk of GERD increased OSA risk by approximately 60% (ORIVW = 1.62, 95%CI = [1.43,1.84]) which was also stable by other complicated approaches, and even with BMI adjusted by MVMR (ORadjBMI[95%CI] = 1.26 [1.15,1.37]). Besides, OSA showed a mild causal effect on increased GERD risk after adjusting for obesity (ORadjBMI[95%CI] = 1.05 [1.02,1.08]). Additionally, OSA increased the risks for IBD (ORIVW[95%CI] = 1.36 [1.12,1.65]), including a higher risk of CD (ORIVW[95%CI] = 1.41 [1.08,1.83]), and a trend for increasing UC risk (ORIVW[95%CI] = 1.29 [0.99,1.67]). CONCLUSION: GERD exerts a substantial causality on increasing the risk of OSA. Conversely, the potential for a causal relationship that OSA contributes to the development of GERD or IBD remains probable. These findings support the crosstalk between gastrointestinal tract disorders and OSA.

Trend in Prescription Medication Utilization for Opioid Use Disorder and Alcohol Use Disorder From 2015 to 2021: A Population-wide Study in a Canadian Province.

OBJECTIVE: To examine the quarterly incidence and prevalence of medications for opioid use disorder (OUD) and alcohol use disorder (AUD) from 2015 to 2021. METHODS: A retrospective population-wide observational study in Manitoba, Canada, was conducted using administrative claims data from the Manitoba Centre for Health Policy to examine the incidence and prevalence of OUD (methadone, buprenorphine-naloxone, buprenorphine) or AUD medications (naltrexone, acamprosate, disulfiram) per 10,000 individuals in each quarter between January 1, 2015, and December 31, 2021. RESULTS: There were 1179 and 451 individuals who received at least one prescription for OUD and AUD, respectively, in the first quarter of 2020. The prevalence of OUD medications more than doubled from 6.3 to 14.3 per 10,000 from January 1, 2015, to December 31, 2021. Likewise, AUD medication prevalence increased almost 10-fold from 0.68 to 6.5 per 10,000 from January 1, 2015, to December 31, 2021, primarily due to naltrexone. The incidence of AUD prescription use increased 8.6-fold from 0.29 to 2.51 per 10,000 during the study period. In contrast, the incidence of opioid agonist therapy declined from 2.1 per 10,000 in the first quarter of 2015 to 0.53 per 10,000 the first quarter of 2016, primarily due to methadone. Whereas methadone incidence declined, buprenorphine-naloxone incidence increased almost 15-fold during the study period. CONCLUSION: An increase in both AUD medication prevalence and incidence in addition to an increase in buprenorphine-naloxone incidence was observed. These findings reflect an increase in the uptake of medications for treating AUD and OUD following changes to improve coverage and access to these medications.