Diagnostic meta-analysis of the efficacy of ultrasonography for diagnosing carpal tunnel syndrome: A comparison between Asian and non-Asian populations.

BACKGROUND: Ultrasonography is used to diagnose carpal tunnel syndrome (CTS) according to various criteria. This diagnostic meta-analysis aimed to evaluate the efficacy of ultrasonography for diagnosing CTS, focusing on the cross-sectional area (CSA) of the median nerve (MN) at the inlet of the carpal tunnel and regional variations in diagnostic thresholds between Asian and non-Asian populations. METHODS: A comprehensive literature search was conducted using PubMed, Embase, and the Cochrane Library. The risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). Patient demographic data, diagnostic "gold standards", CSA cutoff values, and diagnostic results were extracted. Meta-analysis was performed to determine the sensitivity, specificity, and optimal CSA cutoff values. RESULTS: For the 25 included studies, a combined sensitivity of 88% and specificity of 84% for CSA measurements at the carpal tunnel inlet were obtained. The Asian group had a sensitivity of 84% and specificity of 86%, while the non-Asian group had a sensitivity of 91% and specificity of 82%. The mean CSA in the Asian group was significantly lower than that in the non-Asian group (12.93 mm2 and 14.77 mm2, respectively; p = 0.042). For the Asian group, the summary receiver operating characteristic curve had an area under the curve (AUC) of 0.92 with an optimal cutoff of 10.5 mm2; for the non-Asian group, an AUC of 0.94 was obtained with a cutoff of 11.5 mm2. CONCLUSION: Ultrasonography is a reliable diagnostic method for CTS, with distinct optimal cutoff values observed between Asian and non-Asian populations. Therefore, population-specific diagnostic criteria for CTS are recommended.

A preliminary study of the effectiveness of video visitation on depression and stress in mothers with preterm infants during the pandemic.

BACKGROUND AND PURPOSE: Parents of preterm infants experience anxiety and stress in the neonatal intensive care unit (NICU). Visitation restrictions due to COVID-19 have increased maternal pressure and limited bonding opportunities. Little research exists in Taiwan on using video conferencing as a solution. This study investigates depression and stress levels in mothers of preterm infants and evaluates the effectiveness of video visitation during NICU restrictions. METHODS: This study adopts a cross-sectional design and a qualitative survey. Mothers of premature infants were recruited and they participated in the study. Interventions for video visits were scheduled on the third day of admission to the NICU (T1) and during the second week of the study (T2). After each video visit, participants completed an online survey. The study's online survey used structured questionnaires including demographics, the Edinburgh Postnatal Depression Scale (EPDS) and the Parental Stress Scale (PSS): Infant Hospitalization (IH). RESULTS: A total of 51 mothers of preterm infants participated in the study. During the T1 and T2 periods, single mothers with lower educational levels and those aged below 30 experienced depression and high levels of stress. Lower birth weight and gestational age were associated with maternal depression. Video visitation intervention led to a significant decrease in depression scores (EPDS, T1: 11.3 ± 5.5 vs. T2: 10.1 ± 5.2, p = 0.039). Positive correlations were observed between EPDS and PSS: IH scores (p < 0 .005). CONCLUSION: Video visitation intervention can reduce maternal depression in mothers with preterm infants. Since it is practical, video visitation may be applied even after the pandemic.

Regulation of candidalysin underlies Candida albicans persistence in intravascular catheters by modulating NETosis.

Candida albicans is a leading cause of intravascular catheter-related infections. The capacity for biofilm formation has been proposed to contribute to the persistence of this fungal pathogen on catheter surfaces. While efforts have been devoted to identifying microbial factors that modulate C. albicans biofilm formation in vitro, our understanding of the host factors that may shape C. albicans persistence in intravascular catheters is lacking. Here, we used multiphoton microscopy to characterize biofilms in intravascular catheters removed from candidiasis patients. We demonstrated that, NETosis, a type of neutrophil cell death with antimicrobial activity, was implicated in the interaction of immune cells with C. albicans in the catheters. The catheter isolates exhibited reduced filamentation and candidalysin gene expression, specifically in the total parenteral nutrition culture environment. Furthermore, we showed that the ablation of candidalysin expression in C. albicans reduced NETosis and conferred resistance to neutrophil-mediated fungal biofilm elimination. Our findings illustrate the role of neutrophil NETosis in modulating C. albicans biofilm persistence in an intravascular catheter, highlighting that C. albicans can benefit from reduced virulence expression to promote its persistence in an intravascular catheter.

Hippocampal proteome comparison of infant and adult Fmr1 deficiency mice reveals adult-related changes associated with postsynaptic density.

Deficiency in fragile X mental retardation 1 (Fmr1) leads to loss of its encoded protein FMRP and causes fragile X syndrome (FXS) by dysregulating its target gene expression in an age-related fashion. Using comparative proteomic analysis, this study identified 105 differentially expressed proteins (DEPs) in the hippocampus of postnatal day 7 (P7) Fmr1-/y mice and 306 DEPs of P90 Fmr1-/y mice. We found that most DEPs in P90 hippocampus were not changed in P7 hippocampus upon FMRP absence, and some P90 DEPs exhibited diverse proteophenotypes with abnormal expression of protein isoform or allele variants. Bioinformatic analyses showed that the P7 DEPs were mainly enriched in fatty acid metabolism and oxidoreductase activity and nutrient responses; whereas the P90 PEPs (especially down-regulated DEPs) were primarily enriched in postsynaptic density (PSD), neuronal projection development and synaptic plasticity. Interestingly, 25 of 30 down-regulated PSD proteins present in the most enriched protein to protein interaction network, and 6 of them (ANK3, ATP2B2, DST, GRIN1, SHANK2 and SYNGAP1) are both FMRP targets and autism candidates. Therefore, this study suggests age-dependent alterations in hippocampal proteomes upon loss of FMRP that may be associated with the pathogenesis of FXS and its related disorders. SIGNIFICANCE: It is well known that loss of FMRP resulted from Fmr1 deficiency leads to fragile X syndrome (FXS), a common neurodevelopmental disorder accompanied by intellectual disability and autism spectrum disorder (ASD). FMRP exhibits distinctly spatiotemporal patterns in the hippocampus between early development and adulthood, which lead to distinct dysregulations of gene expression upon loss of FMRP at the two age stages potentially linked to age-related phenotypes. Therefore, comparison of hippocampal proteomes between infancy and adulthood is valuable to provide insights into the early causations and adult-dependent consequences for FXS and ASD. Using a comparative proteomic analysis, this study identified 105 and 306 differentially expressed proteins (DEPs) in the hippocampi of postnatal day 7 (P7) and P90 Fmr1-/y mice, respectively. Few overlapping DEPs were identified between P7 and P90 stages, and the P7 DEPs were mainly enriched in the regulation of fatty acid metabolism and oxidoreduction, whereas the P90 DEPs were preferentially enriched in the regulation of synaptic formation and plasticity. Particularly, the up-regulated P90 proteins are primarily involved in immune responses and neurodegeneration, and the down-regulated P90 proteins are associated with postsynaptic density, neuron projection and synaptic plasticity. Our findings suggest that distinctly changed proteins in FMRP-absence hippocampus between infancy and adulthood may contribute to age-dependent pathogenesis of FXS and ASD.

MMP-9 upregulation may predict hemorrhagic transformation after endovascular thrombectomy.

Background: Hemorrhagic transformation (HT) is a serious complication after endovascular thrombectomy (EVT) for patients with acute ischemic stroke (AIS). We analyzed the plasma levels of MMP-9 before and after EVT and assessed the temporal changes of MMP-9 that may be associated with, and therefore predict, HT after EVT. Methods: We enrolled 30 AIS patients who received EVT, and 16 (53.3%) developed HT. The levels of MMP-9 in plasma collected from the arteries of AIS patients before and immediately after EVT were measured using ELISA. The percent change in MMP-9 after EVT (after/before) was calculated and compared between patients with and without HT. Results: The median age of the AIS patients was 70 years, and 13 patients (43.3%) were men. The median National Institutes of Health Stroke Scale (NIHSS) scores of patients with HT were 18 on admission and 18 after EVT. The median NIHSS scores of patients without HT were 17 on admission and 11 after EVT. Patients with HT demonstrated significantly greater percentage increases in arterial MMP-9 levels after EVT. Conclusion: Patients with AIS who developed HT had significantly increased arterial MMP-9 levels after EVT, suggesting that the upregulation of MMP-9 following EVT could serve as a predictive biomarker for HT.

[Improving the Rate of Palliative Care Completion in NICU Nurses].

BACKGROUND: Critically ill neonates receive care in the neonatal intensive care unit (NICU). Unfortunately, some neonates pass away in the NICU. Providing comprehensive neonatal palliative care and hospice services is crucial in supporting parents through the loss of their offspring. In our NICU, we identified that only 74.5% of nurses are able to properly recognize the need for palliative care and only 55% are able to implement the necessary procedures. PURPOSE: A project was designed and implemented to enhance the ability of nursing staff to recognize the need for and properly implement palliative care to improve the quality of this care in the NICU. RESOLUTIONS: We organized an on-the-job education and training program within our NICU with the goals of heightening awareness among nursing staff. In addition, a specialist palliative care operation flow chart, process preparation checklist, and palliative-care-related tools were created to facilitate the care process. RESULTS: After program implementation, among nursing staff in our NICU, the palliative care recognition accuracy rate rose to 100% (from 74.5%) and the implementation rate rose to 94.8% (from 55%). The quality of provided neonatal palliative care and hospice services was significantly improved. CONCLUSIONS: The developed program was shown to significantly improve nursing staff recognition and implementation of neonatal palliative care in our NICU. This experience provides a reference for improving palliative care quality and for helping families effectively manage end-of-life challenges.

Cost of Hospitalization Associated with Inpatient Goals-of-Care Program Implementation at a Comprehensive Cancer Center: A Propensity Score Analysis.

The impact of goals-of-care programs on acute hospitalization costs is unclear. We compared the hospitalization cost in an 8-month period before implementation of a multimodal interdisciplinary goals-of-care program (1 May 2019 to 31 December 2019) to an 8-month period after program implementation (1 May 2020 to 31 December 2020). Propensity score weighting was used to adjust for differences in potential covariates. The primary outcome was total direct cost during the hospital stay for each index hospitalization. This analysis included 6977 patients in 2019 and 5964 patients in 2020. The total direct cost decreased by 3% in 2020 but was not statistically significant (ratio 0.97, 95% CI 0.92, 1.03). Under individual categories, there was a significant decrease in medical oncology (ratio 0.58, 95% CI 0.50, 0.68) and pharmacy costs (ratio 0.86, 95% CI 0.79, 0.96), and an increase in room and board (ratio 1.06, 95% CI 1.01, 1.10). In subgroup analysis, ICU patients had a significant reduction in total direct cost after program implementation (ratio 0.83, 95% CI 0.72, 0.94). After accounting for the length of ICU admission, we found that the total direct cost per hospital day was no longer different between 2019 and 2020 (ratio 0.986, 95% CI 0.92, 1.05), suggesting that shorter ICU admissions likely explained much of the observed cost savings. This study provides real-world data on how "in-the-moment" GOC conversations may contribute to reduced hospitalization costs among ICU patients.

Cationic Ir(III) Complexes with 4-Fluoro-4'-pyrazolyl-(1,1'-biphenyl)-2-carbonitrile as the Cyclometalating Ligand: Synthesis, Characterizations, and Application to Ultrahigh-Efficiency Light-Emitting Electrochemical Cells.

Light-emitting electrochemical cells (LECs) promise low-cost, large-area luminescence applications with air-stabilized electrodes and a versatile fabrication that enables the use of solution processes. Nevertheless, the commercialization of LECs is still encountering many obstacles, such as low electroluminescence (EL) efficiencies of the ionic materials. In this paper, we propose five blue to yellow ionic Ir complexes possessing 4-fluoro-4'-pyrazolyl-(1,1'-biphenyl)-2-carbonitrile (ppfn) as a novel cyclometalating ligand and use them in LECs. In particular, the device within di[4-fluoro-4'-pyrazolyl-(1,1'-biphenyl)-2-carbonitrile]-4,4'-di-tert-butyl-2,2'-bipyridyl iridium(III) hexafluorophosphate (DTBP) shows a remarkable photoluminescence quantum yield (PLQY) of 70%, and by adjusting the emissive-layer thickness, the maximal external quantum efficiency (EQE) reaches 22.15% at 532 nm under the thickness of 0.51 µm, showing the state-of-the-art value for the reported blue-green LECs.

Functional bio-inspired hybrid fliers with separated ring and leading edge vortices.

Recent advances in passive flying systems inspired by wind-dispersed seeds contribute to increasing interest in their use for remote sensing applications across large spatial domains in the Lagrangian frame of reference. These concepts create possibilities for developing and studying structures with performance characteristics and operating mechanisms that lie beyond those found in nature. Here, we demonstrate a hybrid flier system, fabricated through a process of controlled buckling, to yield unusual geometries optimized for flight. Specifically, these constructs simultaneously exploit distinct fluid phenomena, including separated vortex rings from features that resemble those of dandelion seeds and the leading-edge vortices derived from behaviors of maple seeds. Advanced experimental measurements and computational simulations of the aerodynamics and induced flow physics of these hybrid fliers establish a concise, scalable analytical framework for understanding their flight mechanisms. Demonstrations with functional payloads in various forms, including bioresorbable, colorimetric, gas-sensing, and light-emitting platforms, illustrate examples with diverse capabilities in sensing and tracking.

Salmonella-induced inhibition of ß3-adrenoceptor expression in tumors and reduces tumor metastasis.

The ß3-adrenoceptor is a protein responsible for regulating the body's response to the neurotransmitter adrenaline and the hormone norepinephrine. It is critical in various physiological processes, including metabolism, thermogenesis, and cardiovascular function. Recently, researchers have discovered that the ß3-adrenoceptor is also implicated in tumor progression and metastasis. Infections caused by Salmonella can lead to gastroenteritis; however, intriguingly, Salmonella is associated with tumor inhibition. In this study, Salmonella treatment resulted in the downregulation of ß3-adrenoceptor expression and a decrease in the phosphorylation of the Protein Kinase-B (AKT)/Mammalian Target of Rapamycin (mTOR) pathway, as observed through immunoblotting in a dose-dependent manner. Notably, Salmonella treatment significantly reduced tumor cell migration, as demonstrated by wound healing and Transwell assays. Moreover, tumor-bearing mice that received Salmonella-pre-treated tumor cells exhibited improved survival rates compared to those injected with tumor cells without prior Salmonella treatment. The observed anti-metastatic effect in this study suggests that Salmonella treatment could hold promise as a potential therapeutic approach to combat tumor metastasis. Further research is warranted to explore its full therapeutic potential.

Monoclonal Antibodies as a Therapeutic Strategy against Multidrug-Resistant Bacterial Infections in a Post-COVID-19 Era.

The development of severe multidrug-resistant bacterial infections has recently intensified because of the COVID-19 pandemic. According to the guidelines issued by the World Health Organization (WHO), routine antibiotic administration is not recommended for patients with supposed or confirmed mild SARS-CoV-2 infection or pneumonia, unless bacterial infection is clinically suspected. However, recent studies have pointed out that the proportion of non-essential antibiotic use in patients infected with SARS-CoV-2 remains high. Therefore, the silent pandemic of antibiotic resistance remains a pressing issue regardless of the present threats presented by the COVID-19 pandemic. To prevent or delay entry into the postulated post-antibiotic era, the long-term advocacy for the rational use of antibiotics, the optimization of infection control procedures, and the development of new antibacterial agents and vaccines should be underscored as vital practices of the antibacterial toolbox. Recently, the development of vaccines and monoclonal antibodies has gradually received attention following the advancement of biotechnology as well as enhanced drug discovery and development in cancer research. Although decent progress has been made in laboratory-based research and promising results have been obtained following clinical trials of some of these products, challenges still exist in their widespread clinical applications. This article describes the current advantages of antibacterial monoclonal antibodies, the development of associated clinical trials, and some perceived future perspectives and challenges. Further, we anticipate the development of more therapeutic agents to combat drug-resistant bacterial infections as well as to increase the resilience of current or novel agents/strategies.

Suppression of presynaptic corticostriatal glutamate activity attenuates L-dopa-induced dyskinesia in 6-OHDA-lesioned Parkinson's disease mice.

A common adverse effect of Parkinson's disease (PD) treatment is L-dopa-induced dyskinesia (LID). This condition results from both dopamine (DA)-dependent and DA-independent mechanisms, as glutamate inputs from corticostriatal projection neurons impact DA-responsive medium spiny neurons in the striatum to cause the dyskinetic behaviors. In this study, we explored whether suppression of presynaptic corticostriatal glutamate inputs might affect the behavioral and biochemical outcomes associated with LID. We first established an animal model in which 6-hydroxydopamine (6-OHDA)-lesioned mice were treated daily with L-dopa (10 mg/kg, i.p.) for 2 weeks; these mice developed stereotypical abnormal involuntary movements (AIMs). When the mice were pretreated with the NMDA antagonist, amantadine, we observed suppression of AIMs and reductions of phosphorylated ERK1/2 and NR2B in the striatum. We then took an optogenetic approach to manipulate glutamatergic activity. Slc17a6 (vGluT2)-Cre mice were injected with pAAV5-Ef1a-DIO-eNpHR3.0-mCherry and received optic fiber implants in either the M1 motor cortex or dorsolateral striatum. Optogenetic inactivation at either optic fiber implant location could successfully reduce the intensity of AIMs after 6-OHDA lesioning and L-dopa treatment. Both optical manipulation strategies also suppressed phospho-ERK1/2 and phospho-NR2B signals in the striatum. Finally, we performed intrastriatal injections of LDN 212320 in the dyskenesic mice to enhance expression of glutamate uptake transporter GLT-1. Sixteen hours after the LDN 212320 treatment, L-dopa-induced AIMs were reduced along with the levels of striatal phospho-ERK1/2 and phospho-NR2B. Together, our results affirm a critical role of corticostriatal glutamate neurons in LID and strongly suggest that diminishing synaptic glutamate, either by suppression of neuronal activity or by upregulation of GLT-1, could be an effective approach for managing LID.

Tumor-educated Gr1+CD11b+ cells drive breast cancer metastasis via OSM/IL-6/JAK-induced cancer cell plasticity.

Cancer cell plasticity contributes to therapy resistance and metastasis, which represent the main causes of cancer-related death, including in breast cancer. The tumor microenvironment drives cancer cell plasticity and metastasis, and unraveling the underlying cues may provide novel strategies for managing metastatic disease. Using breast cancer experimental models and transcriptomic analyses, we show that stem cell antigen-1 positive (SCA1+) murine breast cancer cells enriched during tumor progression and metastasis had higher in vitro cancer stem cell-like properties, enhanced in vivo metastatic ability, and generated tumors rich in Gr1hiLy6G+CD11b+ cells. In turn, tumor-educated Gr1+CD11b+ (Tu-Gr1+CD11b+) cells rapidly and transiently converted low metastatic SCA1- cells into highly metastatic SCA1+ cells via secreted oncostatin M (OSM) and IL-6. JAK inhibition prevented OSM/IL-6-induced SCA1+ population enrichment, while OSM/IL-6 depletion suppressed Tu-Gr1+CD11b+-induced SCA1+ population enrichment in vitro and metastasis in vivo. Moreover, chemotherapy-selected highly metastatic 4T1 cells maintained high SCA1+ positivity through autocrine IL-6 production, and in vitro JAK inhibition blunted SCA1 positivity and metastatic capacity. Importantly, Tu-Gr1+CD11b+ cells invoked a gene signature in tumor cells predicting shorter overall survival (OS), relapse-free survival (RFS), and lung metastasis in breast cancer patients. Collectively, our data identified OSM/IL-6/JAK as a clinically relevant paracrine/autocrine axis instigating breast cancer cell plasticity and triggering metastasis.

Hippocampal proteomic changes in high-fat diet-induced obese mice associated with memory decline.

Substantial evidence suggest that chronic consumption of high-fat diets (HFDs) can lead to obesity, abnormal metabolism, as well as cognitive impairment. Molecular and cellular changes regarding hippocampal dysfunctions have been identified in multiple HFD animal models. Therefore, in-depth identification of expression changes of hippocampal proteins is critical for understanding the mechanism of HFD-induced cognitive deficits. In this study, we fed 3-week-old male mice with HFD for 3 months to generate obese mice who exhibit systemic metabolic abnormality and learning and memory decline. Using an iTRAQ-labeled proteomic analysis, we identified a total of 82 differentially expressed proteins (DEPs) in the hippocampus upon HFD with 35 up-regulated proteins and 47 down-regulated proteins. Functional enrichment indicated that these DEPs were predominantly enriched in regulation of catabolic process, dendritic shaft, neuron projection morphogenesis and GTPase regulator activity. Protein-protein interaction enrichment showed that the DEPs are mostly enriched in postsynaptic functions; and of them, six proteins (i.e., DLG3, SYNGAP1, DCLK1, GRIA4, GRIP1, and ARHGAP32) were involved in several functional assemblies of the postsynaptic density including G-protein signaling, scaffolding and adaptor, kinase and AMPA signaling, respectively. Collectively, our findings suggest that these DEPs upon HFD might contribute to memory decline by disturbing neuronal and postsynaptic functions in the hippocampus.

Determining the Electron Scattering from Interfacial Coulomb Scatterers in Two-Dimensional Transistors.

Two-dimensional (2D) transistors are promising for potential applications in next-generation semiconductor chips. Owing to the atomically thin thickness of 2D materials, the carrier scattering from interfacial Coulomb scatterers greatly suppresses the carrier mobility and hampers transistor performance. However, a feasible method to quantitatively determine relevant Coulomb scattering parameters from interfacial long-range scatterers is largely lacking. Here, we demonstrate a method to determine the Coulomb scattering strength and the density of Coulomb scattering centers in InSe transistors by comprehensively analyzing the low-frequency noise and transport characteristics. Moreover, the relative contributions from long-range and short-range scattering in the InSe transistors can be distinguished. This method is employed to make InSe transistors consisting of various interfaces a model system, revealing the profound effects of different scattering sources on transport characteristics and low-frequency noise. Quantitatively accessing the scattering parameters of 2D transistors provides valuable insight into engineering the interfaces of a wide spectrum of ultrathin-body transistors for high-performance electronics.

Differential item functioning for the Tendency of Avoiding Physical Activity and Sport Scale across two subculture samples: Taiwanese and mainland Chinese university students.

Aims: The aims of the study were to examine the differential item functioning (DIF) of the Tendency of Avoiding Physical Activity and Sport Scale (TAPAS) among three subgroups (gender, weight status, and region) and to test the construct and concurrent validities of the scale. Methods: Using an online survey, university students (608 Taiwanese and 2319 mainland Chinese) completed the TAPAS. Rasch analysis examined if all the 10 TAPAS items fitted the same construct and displayed no substantial DIF across three subgroups: gender (male vs. female), weight status (overweight vs. non-overweight), and region (Taiwan vs. China). Concurrent validity was examined using the scores on the Weight Self-Stigma Questionnaire (WSSQ) and Weight Bias Internalization Scale (WBIS). Results: All TAPAS items, except for Item 10 ("Prefer to participate in physical activity in a more private setting"), fitted the same construct. None of the TAPAS items displayed DIF in any of the subgroups except for Item 10 across participants from Taiwan and China (DIF contrast = -1.41). Conclusion: The TAPAS can appropriately assess the tendency to avoid physical activity and sport among both Taiwanese and mainland Chinese university students. However, Item 10 may need to be further examined.

Better Detection of Peripheral Arterial Disease with Toe-Brachial Index Compared to Ankle-Brachial Index among Taiwanese Patients with Diabetic Kidney Disease.

BACKGROUND: Ankle-brachial index (ABI) is a simple method for diagnosing peripheral artery disease (PAD) but has limited reliability in patients with diabetes mellitus (DM) because of medial artery calcification. Our study aims to investigate whether the toe brachial index (TBI) or the cardio-ankle vascular index (CAVI) has a better detection over the ABI for diagnosing PAD in diabetic kidney disease (DKD). MATERIALS AND METHODS: A cohort of 368 patients (mean age 68.59 ± 13.14 years, 190 males and 178 females) with type 2 DM underwent ABI, TBI, and CAVI measurements at our outpatient clinic. RESULTS: Of all enrolled patients, the TBI is significant in evaluating PAD, especially in patients whose chronic kidney disease (CKD) stage 3a with adjusted odds ratio (AOR) = 6.50, 95% confidence interval (CI) 1.63-25.97, p = 0.0080, stage 3b AOR = 7.47, 95% CI 1.52-36.81, p = 0.0135, and stage 4-5 AOR = 20.13, 95% CI 1.34-94.24, p = 0.0116. CAVI is also significant in CKD stage 1 with AOR = 0.16, 95% CI 0.03-0.77, p = 0.0223, stage 2 with AOR = 0.18, 95% CI 0.04-0.74, p = 0.0180, and stage 3a AOR = 0.31, 95% CI 0.10-0.93, p = 0.0375. CONCLUSION: TBI has a better yield of detection of PAD compared to ABI among Taiwanese patients with DKD. CAVI may play a role in the early stage of DKD.

Chemical Redox Cycling in an Organic Photoelectrochemical Transistor: Toward Dual Chemical and Electronic Amplification for Bioanalysis.

The organic photoelectrochemical transistor (OPECT) has been proven to be a promising platform to study the rich light-matter-bio interplay toward advanced biomolecular detection, yet current OPECT is highly restrained to its intrinsic electronic amplification. Herein, this work first combines chemical amplification with electronic amplification in OPECT for dual-amplified bioanalytics with high current gain, which is exemplified by human immunoglobulin G (HIgG)-dependent sandwich immunorecognition and subsequent alkaline phosphatase (ALP)-mediated chemical redox cycling (CRC) on a metal-organic framework (MOF)-derived BiVO4/WO3 gate. The target-dependent redox cycling of ascorbic acid (AA) acting as an effective electron donor could lead to an amplified modulation against the polymer channel, as indicated by the channel current. The as-developed bioanalysis could achieve sensitive HIgG detection with a good analytical performance. This work features the dual chemical and electronic amplification for OPECT bioanalysis and is expected to stimulate further interest in the design of CRC-assisted OPECT bioassays.

Physiologically based mechanistic insight into differential risk of valproate hepatotoxicity between children and adults: A focus on ontogeny impact.

The anticonvulsant valproic acid (VPA) despite complex pharmacokinetics has been in clinical use for nearly 6 decades. Previous reports indicated neonates, infants, and toddlers/preschoolers had higher risk of valproate hepatotoxicity than adults. However, dosing recommendations for those less than 10 years of age are lacking. To decipher clinical puzzles, physiologically-based pharmacokinetic (PBPK) models of VPA and its hepatotoxic metabolite 4-ene-VPA were constructed and simulated with particularly integrated information of drug-metabolizing enzyme ontogeny. Adult and pediatric PK data of VPA (n = 143 subjects) and 4-ene-VPA (n = 8 subjects) collected from previous reports were used for model development and validation. Sensitivity analyses were performed to characterize ontogeny impacts of CYP2C9 and UGT2B7 on dispositions of VPA and 4-ene-VPA across age groups. Optimal VPA dosing for each pediatric age group was also predicted and objectively judged by ensuring VPA efficacy and avoiding 4-ene-VPA hepatotoxicity. The study revealed UGT2B7 ontogeny was quite influential on VPA clearance even in neonates and small children. Intrinsic clearance of CYP2C9 was the most prominent determinant for areas under the concentration-time curve of VPA and 4-ene-VPA in infants, and toddlers/preschoolers, reflecting higher hepatotoxicity risk due to noxious 4-ene-VPA accumulation in these groups. The ontogeny-based PBPK approach complements conventional allometric methods in dosing estimation for the young by providing more mechanistic insight of the processes changing with age. The established ontogeny-based PBPK approach for VPA therapy deserves further corroboration by real-world therapeutic data to affirm its clinical applicability.

Rural-urban disparities in the incidence and treatment intensity of periodontal disease among patients with diabetes.

Background: Diabetes threatens population health, especially in rural areas. Diabetes and periodontal diseases have a bidirectional relationship. A persistence of rural-urban disparities in diabetes may indicate a rural-urban difference in periodontal disease among patients with diabetes; however, the evidence is lacking. This retrospective study aimed to investigate rural-urban discrepancies in the incidence and treatment intensity of periodontal disease among patients who were newly diagnosed with type 2 diabetes in the year 2010. Methods: The present study was a retrospective cohort design, with two study samples: patients with type 2 diabetes and those who were further diagnosed with periodontal disease. The data sources included the 2010 Diabetes Mellitus Health Database at the patient level, the National Geographic Information Standardization Platform and the Department of Statistics, Ministry of Health and Welfare in Taiwan at the township level. Two dependent variables were a time-to-event outcome for periodontal disease among patients with type 2 diabetes and the treatment intensity measured for patients who were further diagnosed with periodontal disease. The key independent variables are two dummy variables, representing rural and suburban areas, with urban areas as the reference group. The Cox and Poisson regression models were applied for analyses. Results: Of 68,365 qualified patients, 49% of them had periodontal disease within 10 years after patients were diagnosed with diabetes. Compared to urban patients with diabetes, rural (HR = 0.83, 95% CI: 0.75-0.91) and suburban patients (HR = 0.86, 95% CI: 0.83-0.89) had a lower incidence of periodontal disease. Among 33,612 patients with periodontal disease, rural patients received less treatment intensity of dental care (Rural: RR = 0.87, 95% CI: 0.83, 0.92; suburban: RR = 0.93, 95% CI: 0.92, 0.95) than urban patients. Conclusion: Given the underutilization of dental care among rural patients with diabetes, a low incidence of periodontal disease indicates potentially undiagnosed periodontal disease, and low treatment intensity signals potentially unmet dental needs. Our findings provide a potential explanation for the persistence of rural-urban disparities in poor diabetes outcomes. Policy interventions to enhance the likelihood of identifying periodontal disease at the early stage for proper treatment would ease the burden of diabetes care and narrow rural-urban discrepancies in diabetes outcomes.