Metformin Adherence Reduces the Risk of Dementia in Patients With Diabetes: A Population-based Cohort Study.

OBJECTIVE: Metformin is widely used as the first-line drug for type 2 diabetes mellitus and has numerous benefits apart from lowering blood glucose. However, metformin-retained regimen is challenged by newly launching, powerful glucose-lowering antiglycemic agents. This population-based cohort study examined the association between metformin adherence and the risk of dementia and Parkinson's disease (PD). METHODS: Diabetic patients with metformin-included combination antiglycemic therapy were identified from the National Health Insurance Research Database and categorized into metformin-adherent and -nonadherent groups according to the medical record of the first year prescription. Patients contraindicated with metformin, severe diabetic complications, and poor drug compliance were excluded. The study outcome was the diagnosis of dementia or PD. RESULTS: A total of 31 384 matched pairs were included after using propensity score matching and both groups were followed up for an average of 5 years. Metformin adherence was associated with a significantly lower risk of dementia (adjusted hazard risk ratio = 0.72, P < .001) but not PD (adjusted hazard risk ratio = 0.97, P = .825). Subgroup analysis revealed that the risk of dementia was significantly reduced in metformin-adherent patients, both male and female, aged >65 or ≤ 65 years, and with or without concurrent insulin treatment. This effect was not influenced by concurrent insulin treatment, which may eliminate the bias caused by the severity of diabetes mellitus. CONCLUSION: Despite the launching of numerous new oral antiglycemic agents, metformin may provide further benefit on lowering risk of dementia beyond conventional glycemic control according to the real-world evidence.

Benefits of Caregiver Counseling in Patients with Dementia: A Retrospective Observational Study.

INTRODUCTION: Patients with dementia have a 1.42 times higher risk of hospitalization than those without. Preparing and educating caregivers by counseling may attenuate the frequency of hospitalization and the financial burden on the health-care system. We conducted a retrospective observational study to verify whether caregiver counseling would benefit patients with mild cognitive impairment (MCI) or dementia. METHODS: The primary caregivers of patients with MCI or dementia at our Dementia Center from January 2017 to December 2018 were included in this study. Of the 532 caregivers who received counseling on caregiving for patients with dementia, 350 with complete data were included. The incidences of the patients' emergency department visits, hospitalizations, and durations of hospitalizations in 2 years prior to and after their caregivers received counseling were compared. A paired t test was used to test the frequency of patients' hospitalizations and emergency visits before and after counseling, and a p value of less than 0.05 was considered significant. RESULTS: The incidence of emergency visits (before counseling: 0.67 times/year, standard deviation [SD] = 0.823; after counseling: 0.25 times/year, SD = 0.549; p < 0.001) and hospitalizations (before counseling: 1.104 times/year, SD = 0.882; after counseling: 0.719 times/year, SD = 0.642; p < 0.001) decreased significantly after caregivers received counseling. The durations of hospitalization before and after counseling were 9.74 (SD = 6.940) days and 9.23 (SD = 6.908) days, respectively (p = 0.136). CONCLUSION: Counseling for caregivers of patients with MCI or dementia can significantly decrease the incidences of patients' emergency visits and hospitalizations but not durations of hospitalization. In multifaceted disease like dementia, counseling for caregivers is beneficial and reduces the burden on the health-care system. Further large-scale studies are warranted to verify this finding.

Sex Difference in the Associations among Obesity-Related Indices with Metabolic Syndrome in Patients with Type 2 Diabetes Mellitus.

Background: The aim of this study was to investigate the associations among obesity-related indices and MetS in diabetic patients, and explore sex differences in these associations. Methods: Patients with type 2 DM were included from two hospitals in southern Taiwan. The Adult Treatment Panel III criteria for an Asian population were used to define MetS. In addition, the following obesity-related indices were evaluated: waist-to-height ratio, waist-hip ratio (WHR), conicity index (CI), body mass index (BMI), body roundness index, body adiposity index, lipid accumulation product (LAP), abdominal volume index, visceral adiposity index (VAI), abdominal volume index and triglyceride-glucose index. Results: A total of 1,872 patients with type 2 DM (mean age 64.0 ± 11.3 years, 808 males and 1,064 females) were enrolled. The prevalence rates of MetS were 59.8% and 76.4% in the males and female (p < 0.001), respectively. All of the obesity-related indices were associated with MetS in both sex (all p < 0.001). LAP and BMI had the greatest areas under the receiver operating characteristic curves in both sex. In addition, the interactions between BMI and sex (p = 0.036), WHR and sex (p = 0.016), and CI and sex (p = 0.026) on MetS were statistically significant. Conclusions: In conclusion, this study demonstrated significant relationships between obesity-related indices and MetS among patients with type 2 DM. LAP and VAI were powerful predictors in both sex. The associations of BMI, WHR and CI on MetS were more significant in the men than in the women.

Neuroprotective Functions Through Inhibition of ER Stress by Taurine or Taurine Combination Treatments in a Rat Stroke Model.

Taurine, as a free amino acid, is found at high levels in many tissues including brain, heart and skeletal muscle and is known to demonstrate neuroprotective effects in a range of disease conditions including stroke and neurodegenerative disease. Using in vitro culture systems we have demonstrated that taurine can elicit protection against endoplasmic reticulum stress (ER stress) from glutamate excitotoxicity or from excessive reactive oxygen species in PC12 cells or rat neuronal cultures. In our current investigation we hypothesized that taurine treatment after stroke in the rat middle cerebral artery occlusion (MCAO) model would render protection against ER stress processes as reflected in decreased levels of expression of ER stress pathway components. We demonstrated that taurine elicited high level protection and inhibited both ATF-6 and IRE-1 ER stress pathway components. As ischemic stroke has a complex pathology it is likely that certain combination treatment approaches targeting multiple disease mechanisms may have excellent potential for efficacy. We have previously employed the partial NMDA antagonist DETC-MeSO to render protection against in vivo ischemic stroke using a rat cerebral ischemia model. Here we tested administration of subcutaneous administration of 0.56 mg/kg DETC-MeSO or 40 mg/kg of taurine separately or as combined treatment after a 120 min cerebral ischemia in the rat MCAO model. Neither drug alone demonstrated protection at the low doses employed. Remarkably however the combination of low dose DETC-MeSO plus low dose taurine conferred a diminished infarct size and an enhanced Neuroscore (reflecting decreased neurological deficit). Analysis of ER stress markers pPERK, peIF-2-alpha and cleaved ATF-6 all showed decreased expression demonstrating that all 3 ER stress pathways were inhibited concurrent with a synergistic protective effect by the post-stroke administration of this DETC-MeSO-taurine combination treatment.

Analysis of Neuroprotection by Taurine and Taurine Combinations in Primary Neuronal Cultures and in Neuronal Cell Lines Exposed to Glutamate Excitotoxicity and to Hypoxia/Re-oxygenation.

Ischemic stroke is one of the greatest contributors to death and long term disability in developed countries. Ischemia induced brain injury arises due to excessive release of glutamate and involves cell death due to apoptosis and endoplasmic reticulum (ER) stress responses. Despite major research efforts there are currently no effective treatments for stroke. Taurine, a free amino acid found in high concentrations in many invertebrate and vertebrate systems can provide protection against a range of neurological disorders. Here we demonstrate that taurine can combat ER stress responses induced by glutamate or by hypoxia/re-oxygenation in neuronal cell lines and primary neuronal cultures. Taurine decreased expression of ER stress markers GRP78, CHOP, Bim and caspase 12 in primary neuronal cultures exposed to hypoxia/re-oxygenation. In analyzing individual ER stress pathways we demonstrated that taurine treatment can result in reduced levels of cleaved ATF6 and decreased p-IRE1 levels. We hypothesized that because of the complex nature of stroke a combination therapy approach may be optimal. For this reason we proceeded to test combination therapies using taurine plus low dose administration of an additional drug: either granulocyte colony stimulating factor (G-CSF) or sulindac a non-steroidal anti-inflammatory drug with potent protective functions through signaling via ischemic preconditioning pathways. When primary neurons were pretreated with 25 mM taurine and 25 ng/mL G-CSF for I hour and then exposed to high levels of glutamate, the taurine/G-CSF combination increased the protective effect against glutamate toxicity to 88% cell survival compared to 75% cell survival from an individual treatment with taurine or G-CSF alone. Pre-exposure of PC12 cells to 5 mM taurine or 25 µM sulindac did not protect the cells from hypoxia/re-oxygenation stress whereas at these concentrations the combination of taurine plus sulindac provided significant protection. In summary we have demonstrated the protective effect of taurine in primary neuronal cultures against hypoxia with re-oxygenation through inhibition of ATF6 or p-IRE-1 pathway but not the PERK pathway of ER stress. Furthermore the combinations of taurine plus an additional drug (either G-CSF or sulindac) can show enhanced potency for protecting PC 12 cells from glutamate toxicity or hypoxia/re-oxygenation through inhibition of ER stress responses.

Intravenous immunoglobulin for postpolio syndrome: a systematic review and meta-analysis.

BACKGROUND: Postpolio syndrome (PPS) is characterized by progressive disabilities that develop decades after prior paralytic poliomyelitis. Because chronic inflammation may be the process underlying the development of PPS, immunomodulatory management, such as intravenous immunoglobulin (IVIg) administration, may be beneficial. METHODS: We performed a systematic review and meta-analysis of published randomized controlled trials (RCTs) and prospective studies that evaluated the efficacy of IVIg in managing PPS. Electronic databases, including PubMed, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials, were searched for articles on PPS published before December 2014. The primary outcomes were pain severity, fatigue scores, and muscle strength. The secondary outcomes were physical performance, quality of life (QoL), and cytokine expression levels. RESULTS: We identified 3 RCTs involving 241 patients and 5 prospective studies involving 267 patients. The meta-analysis of pain severity (weighted mean difference [WMD] = -1.02, 95% confidence interval [CI] = -2.51 to 0.47), fatigue scores (WMD = 0.28, 95% CI -0.56 to 1.12), and muscle strength revealed no significant differences between the IVIg and the placebo group. Regarding QoL, the RCTs yielded controversial outcomes, with improvement in only certain domains of the Short Form 36 (SF-36). Moreover, one prospective study reported significant improvement on SF-36, particularly in patients aged younger than 65 years, those with paresis of the lower limbs, and high pain intensity. CONCLUSION: The present review indicated that IVIg is unlikely to produce significant improvements in pain, fatigue, or muscle strength. Thus, routinely administering IVIg to patients with PPS is not recommended based on RCTs. However, a potential effect in younger patients with lower limbs weakness and intense pain requires confirmation from further well-structured trials.

Pro-Angiogenic Effects of Chalcone Derivatives in Zebrafish Embryos in Vivo.

The aim of this study was to investigate novel chalcones with potent angiogenic activities in vivo. Chalcone-based derivatives were evaluated using a transgenic zebrafish line with fluorescent vessels to real-time monitor the effect on angiogenesis. Results showed that the chalcone analogues did not possess anti-angiogenic effect on zebrafish vasculatures; instead, some of them displayed potent pro-angiogenic effects on the formation of the sub-intestinal vein. Similar pro-angiogenic effects can also be seen on wild type zebrafish embryos. Moreover, the expression of vegfa, the major regulator for angiogenesis, was also upregulated in their treatment. Taken together, we have synthesized and identified a series of novel chalcone-based derivatives as potent in vivo pro-angiogenic compounds. These novel compounds hold potential for therapeutic angiogenesis.

Randomized comparison trial of balance training by using exergaming and conventional weight-shift therapy in patients with chronic stroke.

OBJECTIVE: To compare the effects of exergaming with conventional weight-shift training on balance function in patients with chronic stroke. DESIGN: Single-blind randomized controlled trial. SETTING: Medical center. PARTICIPANTS: Patients (N=30) with chronic stroke and balance deficits. INTERVENTIONS: Twelve weeks of Wii Fit training or conventional weight-shift training. MAIN OUTCOME MEASURES: Static balance was assessed using posturography. We recorded the stability index and percentage of weight bearing on the affected leg in 8 positions. We also used the timed Up and Go and forward reach tests for dynamic balance evaluation, Falls Efficacy Scale-International for fear of falling assessment, and Physical Activity Enjoyment Scale for estimating the enjoyment of training. RESULTS: The exergaming group showed more improvement in stability index than the control group in head straight with eyes open while standing on a foam surface, eyes closed while standing on a solid surface with head turned 30° to the left, and eyes closed while standing on a solid surface with head turned up positions (time-group interaction P=.02, .04, and .03, respectively); however, the effects were not maintained. At 3-month follow-up, the control group showed more improvement in weight-bearing symmetry in the head straight with eyes open while standing on a solid surface position than the exergaming group (time-group interaction P=.03). Both groups showed improvement in the timed Up and Go test, forward reach test, and fear of falling. The improvement in fear of falling was not maintained. The exergaming group enjoyed training more than the control group (P=.03). CONCLUSIONS: Exergaming is enjoyable and effective for patients with chronic stroke.

Miniaturized 3D-printed hand-operable dispersive sample pretreatment device with replaceable chitosan/polydopamine thin film metal sorbent for enhanced metal analysis.

To address the increasing demand for sensitive and selective sample preparation methods for metal analysis; preconcentration of intended analyte from complex sample matrices before analysis is required to improve the performance of analysis instruments. In this study, we have engineered a sustainable and portable syringe-based hand-operable three-dimensionally (3D) printed sample pretreatment apparatus equipped with a replaceable bio-based thin- film metal sorbent. This device effectively addresses the challenges of sample matrix interference in metal analysis. A metal sorbent film composed of chitosan (CS) and polydopamine (PDA) leveraged the diverse functional groups in the CS/PDA matrix to significantly enhance the extraction efficiency for various metals. Our approach demonstrated excellent analytical performance, with coefficients of determination (R2) of 0.9982 for copper (Cu) and 0.996 for chromium (Cr). The method achieved low limits of detection (LOD) of 0.3 µg L-1 for Cr and 0.7 µg L-1 for Cu. Precision and practicality assessments using actual urine samples yielded satisfactory relative standard deviations (RSD%) ranging from of 1.6 %-8.5 % for both metals, indicating minimal interference from the sample matrix. Moreover, our approach exhibited robust performance even after seven consecutive extraction and desorption cycles, highlighting its sustainability and practical applicability for laboratory and on-site sample pretreatment.

A new potential therapeutic approach for ALS: A case report with NGS analysis.

RATIONALE: Amyotrophic lateral sclerosis (ALS) poses a significant clinical challenge due to its rapid progression and limited treatment options, often leading to deadly outcomes. Looking for effective therapeutic interventions is critical to improve patient outcomes in ALS. PATIENT CONCERNS: The patient, a 75-year-old East Asian male, manifested an insidious onset of right-hand weakness advancing with dysarthria. Comprehensive Next-generation sequencing analysis identified variants in specific genes consistent with ALS diagnosis. DIAGNOSES: ALS diagnosis is based on El Escorial diagnostic criteria. INTERVENTIONS: This study introduces a novel therapeutic approach using artificial intelligence phenotypic response surface (AI-PRS) technology to customize personalized drug-dose combinations for ALS. The patient underwent a series of phases of AI-PRS-assisted trials, initially incorporating a 4-drug combination of Ibudilast, Riluzole, Tamoxifen, and Ropinirole. Biomarkers and regular clinical assessments, including nerve conduction velocity, F-wave, H-reflex, electromyography, and motor unit action potential, were monitored to comprehensively evaluate treatment efficacy. OUTCOMES: Neurophysiological assessments supported the ALS diagnosis and revealed the co-presence of diabetic polyneuropathy. Hypotension during the trial necessitated an adaptation to a 2-drug combinational trial (ibudilast and riluzole). Disease progression assessment shifted exclusively to clinical tests of muscle strength, aligning with the patient's well-being. LESSONS: The study raises the significance of personalized therapeutic strategies in ALS by AI-PRS. It also emphasizes the adaptability of interventions based on patient-specific responses. The encountered hypotension incident highlights the importance of attentive monitoring and personalized adjustments in treatment plans. The described therapy using AI-PRS, offering personalized drug-dose combinations technology is a potential approach in treating ALS. The promising outcomes warrant further evaluation in clinical trials for searching a personalized, more effective combinational treatment for ALS patients.

Role of cognitive parameters in dengue hemorrhagic fever and dengue shock syndrome.

Dengue is becoming recognized as one of the most important vector-borne human diseases. It is predominant in tropical and subtropical zones but its geographical distribution is progressively expanding, making it an escalating global health problem of today. Dengue presents with spectrum of clinical manifestations, ranging from asymptomatic, undifferentiated mild fever, dengue fever (DF), to dengue hemorrhagic fever (DHF) with or without shock (DSS), a life-threatening illness characterized by plasma leakage due to increased vascular permeability. Currently, there are no antiviral modalities or vaccines available to treat and prevent dengue. Supportive care with close monitoring is the standard clinical practice. The mechanisms leading to DHF/DSS remains poorly understood. Multiple factors have been attributed to the pathological mechanism, but only a couple of these hypotheses are popular in scientific circles. The current discussion focuses on underappreciated factors, temperature, natural IgM, and endotoxin, which may be critical components playing roles in dengue pathogenesis.

Association between cerebral lesions and emotional changes in acute ischemic stroke patients.

Controversies and interest are present in the associations between specific brain locations and depression or anxiety. This study investigated the association between stroke location and emotional changes in stroke patients. This prospective observational study analyzed the neuroimages and neuropsychiatric conditions of 26 patients with acute middle cerebral artery infarction. Each patient's neurological and psychiatric condition was evaluated 1 week as well as 1 month after the stroke. We found that the right superior and middle temporal gyrus was associated with anxiety at 1 month after stroke. Moreover, better mentality is associated with deterioration of anxiety within 1 month after stroke, and larger lesion volume is associated with deterioration of depression within 1 month after stroke.

Taurine exerts robust protection against hypoxia and oxygen/glucose deprivation in human neuroblastoma cell culture.

Stroke is one of the leading causes of mortality and disability worldwide. There is no effective treatment for stroke despite extensive research. Taurine is a free amino acid which is present at high concentrations in a range of organs including the brain, heart, and retina in mammalian systems. It had been shown that taurine can significantly increase cell survival under stroke conditions using both in vivo and in vitro models. Recently, we have found that several agents including granulocyte colony-stimulating factor (G-CSF), a stem cell enhancer and facilitator;S-methyl-N-diethylthiolcarbamate sulfoxide (DETC-MeSO), an NMDA receptor partial antagonist; sulindac, a potent antioxidant; and taurine, a neuroprotectant and calcium regulator, are effective in protecting against stroke-induced neuronal injury when used alone or in combination in both animal and tissue/cell culture models. In this chapter, we demonstrate that taurine can protect human neuroblastoma cells measured by ATP assay under conditions of hypoxia or oxygen/glucose deprivation (OGD). In addition, we found that taurine exerts its protective function by suppressing the OGD-induced upregulation of endoplasmic reticulum (ER) stress markers and proapoptotic proteins. A model depicting the mode of action of taurine in protecting neuroblastoma cells under OGD conditions is presented.

The mechanism of taurine protection against endoplasmic reticulum stress in an animal stroke model of cerebral artery occlusion and stroke-related conditions in primary neuronal cell culture.

Taurine is an inhibitory neurotransmitter and is one of the most abundant amino acids present in the mammalian nervous system. Taurine has been shown to provide protection against neurological diseases, such as Huntington's disease, Alzheimer's disease, and stroke. Ischemic stroke is one of the leading causes of death and disability in the world. It is generally believed that ischemia-induced brain injury is largely due to excessive release of glutamate resulting in excitotoxicity and cell death. Despite extensive research, there are still no effective interventions for stroke. Recently, we have shown that taurine can provide effective protection against endoplasmic reticulum (ER) stress induced by excitotoxicity or oxidative stress in PC12 cell line or primary neuronal cell cultures. In this study, we employed hypoxia/reoxygenation conditions for primary cortical neuronal cell cultures as an in vitro model of stroke as well as the in vivo model of rat focal middle cerebral artery occlusion (MCAO). Our data showed that when primary neuronal cultures were first subjected to hypoxic conditions (0.3%, 24 h) followed by reoxygenation (21%, 24-48 h), the cell viability was greatly reduced. In the animal model of stroke (MCAO), we found that 2 h ischemia followed by 4 days reperfusion resulted in an infarct of 47.42 ± 9.86% in sections 6 mm from the frontal pole. Using taurine greatly increased cell viability in primary neuronal cell culture and decreased the infarct area of sections at 6 mm to 26.76 ± 6.91% in the MCAO model. Furthermore, levels of the ER stress protein markers GRP78, caspase-12, CHOP, and p-IRE-1 which were markedly increased in both the in vitro and in vivo models significantly declined after taurine administration, suggesting that taurine may exert neuroprotection functions in both models. Moreover, taurine could downregulate the ratio of cleaved ATF6 and full-length ATF6 in both models. In the animal model of stroke, taurine induced an upregulation of the Bcl-2/Bax ratio and downregulation of caspase-3 protein activity indicating that it attenuates apoptosis in the core of the ischemic infarct. Our results show not only taurine elicits neuroprotection through the activation of the ATF6 and the IRE1 pathways, but also it can reduce apoptosis in these models.

Epidemiology and analysis of SARS-CoV-2 Omicron subvariants BA.1 and 2 in Taiwan.

The Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), first detected in October 2021, possessed many mutations compared to previous variants. We aimed to identify and analyze SARS-CoV-2 Omicron subvariants among coronavirus disease 2019 (COVID-19) patients between January 2022 and September 2022 in Taiwan. The results revealed that BA.2.3.7, featuring K97E and G1251V in the spike protein compared with BA.2, emerged in March 2022 and persistently dominated between April 2022 and August 2022, resulting in the largest COVID-19 outbreak since 2020. The accumulation of amino acid (AA) variations, mainly AA substitution, in the spike protein was accompanied by increasing severity in Omicron-related COVID-19 between April 2022 and January 2023. Older patients were more likely to have severe COVID-19, and comorbidity was a risk factor for COVID-19-related mortality. The accumulated case fatality rate (CFR) dropped drastically after Omicron variants, mainly BA.2.3.7, entered Taiwan after April 2022, and the CFR was 0.16% in Taiwan, which was lower than that worldwide (0.31%) between April 2021 and January 2023. The relatively low CFR in Omicron-related COVID-19 patients can be attributed to adjustments to public health policies, promotion of vaccination programs, effective antiviral drugs, and the lower severity of the Omicron variant.

Logistic regression and artificial neural network-based simple predicting models for obstructive sleep apnea by age, sex, and body mass index.

Age, sex, and body mass index (BMI) were associated with obstructive sleep apnea (OSA). Although various methods have been used in OSA prediction, this study aimed to develop predictions using simple and general predictors incorporating machine learning algorithms. This single-center, retrospective observational study assessed the diagnostic relevance of age, sex, and BMI for OSA in a cohort of 9, 422 patients who had undergone polysomnography (PSG) between 2015 and 2020. The participants were randomly divided into training, testing, and independent validation groups. Multivariable logistic regression (LR) and artificial neural network (ANN) algorithms used age, sex, and BMI as predictors to develop risk-predicting models for moderate-and-severe OSA. The training-testing dataset was used to assess the model generalizability through five-fold cross-validation. We calculated the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of the independent validation set to assess the performance of the model. The results showed that age, sex, and BMI were significantly associated with OSA. The validation AUCs of the generated LR and ANN models were 0.806 and 0.807, respectively. The independent validation set's accuracy, sensitivity, specificity, PPV, and NPV were 76.3%, 87.5%, 57.0%, 77.7%, and 72.7% for the LR model, and 76.4%, 87.7%, 56.9%, 77.7%, and 73.0% respectively, for the ANN model. The LR- and ANN-boosted models with the three simple parameters effectively predicted OSA in patients referred for PSG examination and improved insight into risk stratification for OSA diagnosis.

Role of Fracture Risk Assessment Tool and Bone Turnover Markers in Predicting All-Cause and Cardiovascular Mortality in Hemodialysis Patients.

Background: Fracture Risk Assessment Tool (FRAX) and bone turnover markers (BTMs) predict fractures in the general population. However, the role of FRAX and BTMs in predicting mortality remains uncertain in hemodialysis (HD) patients. Methods: One hundred and sixty-four HD patients stratified by low or high risk of 10-year fracture probability using FRAX. High risk of fracture was defined as 10-year probability of hip fracture ≥3% or major osteoporotic fracture ≥20%. The association of high risk of fracture and BTMs with all-cause mortality and cardiovascular (CV) mortality were evaluated using multivariate-adjusted Cox regression analysis. Results: Eighty-five (51.8%) patients were classified as high risk of fracture based on FRAX among 164 HD patients. During a mean follow-up period of 3.5 ± 1.0 years, there were 39 all-cause deaths and 23 CV deaths. In multivariate-adjusted Cox regression, high risk of fracture based on FRAX was independently associated with all-cause mortality [hazard ratio (HR): 2.493, 95% confidence interval (CI): 1.026-6.056, p = 0.044) but not with CV mortality (HR: 2.129, 95% CI: 0.677-6.700, p = 0.196). There were no associations between BTMs and mortality risk. Furthermore, lower geriatric nutritional risk index (GNRI) was significantly associated with increased CV mortality (HR: 0.888, 95% CI: 0.802-0.983, p = 0.022) after adjusting by confounding variables. Conclusion: High risk of fracture using FRAX was an independent predictor of all-cause mortality in patients undergoing HD. FRAX, rather than BTMs, has an important role of prognostic significance in HD patients.

Transmembrane stem cell factor protein therapeutics enhance revascularization in ischemia without mast cell activation.

Stem cell factor (SCF) is a cytokine that regulates hematopoiesis and other biological processes. While clinical treatments using SCF would be highly beneficial, these have been limited by toxicity related to mast cell activation. Transmembrane SCF (tmSCF) has differential activity from soluble SCF and has not been explored as a therapeutic agent. We created novel therapeutics using tmSCF embedded in proteoliposomes or lipid nanodiscs. Mouse models of anaphylaxis and ischemia revealed the tmSCF-based therapies did not activate mast cells and improved the revascularization in the ischemic hind limb. Proteoliposomal tmSCF preferentially acted on endothelial cells to induce angiogenesis while tmSCF nanodiscs had greater activity in inducing stem cell mobilization and recruitment to the site of injury. The type of lipid nanocarrier used altered the relative cellular uptake pathways and signaling in a cell type dependent manner. Overall, we found that tmSCF-based therapies can provide therapeutic benefits without off target effects.

Defect Inspection Techniques in SiC.

With the increasing demand of silicon carbide (SiC) power devices that outperform the silicon-based devices, high cost and low yield of SiC manufacturing process are the most urgent issues yet to be solved. It has been shown that the performance of SiC devices is largely influenced by the presence of so-called killer defects, formed during the process of crystal growth. In parallel to the improvement of the growth techniques for reducing defect density, a post-growth inspection technique capable of identifying and locating defects has become a crucial necessity of the manufacturing process. In this review article, we provide an outlook on SiC defect inspection technologies and the impact of defects on SiC devices. This review also discusses the potential solutions to improve the existing inspection technologies and approaches to reduce the defect density, which are beneficial to mass production of high-quality SiC devices.

Association between stroke and patients with pelvic inflammatory disease: a nationwide population-based study in Taiwan.

BACKGROUND AND PURPOSE: The aim of this study is to estimate the risk of stroke in a 3-year period after pelvic inflammatory disease (PID) using a nationwide population-based study. METHODS: Our study cohort consisted of all patients with a diagnosis of PID (N = 64,515) between 2004 and 2005 with a control cohort (1:2) of age-matched controls (N = 129, 030). Each patient was tracked from hospitalization until the end of 2006. Cox regressions were performed to compute the 3-year stroke-free survival rates after adjusting for possible confounding factors. RESULTS: We found that women with PID were more likely to have strokes than the control population. After adjusting for potential confounding factors, the adjusted hazard ratio of stroke was 1.63 (95% CI, 1.45-1.85) for PID patients as compared to the general population cohort. Sensitivity analysis using a bootstrap approach further ensured the validity of the results of our study. CONCLUSIONS: We concluded that patients with PID have an association with stroke. Further research is necessary to investigate the pathophysiology between PID and stroke.