The associations among peptic ulcer disease, Helicobacter pylori infection, and abdominal aortic aneurysms: A nationwide population-based cohort study.

BACKGROUND: There are overlapping risk factors and underlying molecular mechanisms for both peptic ulcer disease (PUD) and abdominal aortic aneurysm (AAA). Despite improvements in the early diagnosis and treatment of AAA, ruptured AAAs continue to cause a substantial number of deaths. Helicobacter pylori are Gram-negative, microaerophilic bacteria that are now recognized as the main cause of PUD. H. pylori infection (HPI) is associated with an increased risk of certain cardiovascular diseases. HPIs can be treated with at least two different antibiotics to prevent bacteria from developing resistance to one particular antibiotic. METHODS: We conducted a population-based cohort study using the National Health Insurance Research Database to evaluate whether associations exist among PUD, HPI, and eradication therapy for HPI and AAA. The primary outcome of this study was the cumulative incidence of AAA among patients with or without PUD and HPI during the 14-year follow-up period. RESULTS: Our analysis included 7003 patients with PUD/HPI, 7003 patients with only PUD, and another 7003 age-, sex-, and comorbidity-matched controls from the database. We found that patients with PUD/HPI had a significantly increased risk of AAA compared to those with PUD alone and matched controls. The patients who had PUD/HPI had a significantly higher cumulative risk of developing AAA than those with PUD and the comparison group (2.67 % vs. 1.41 % vs. 0.73 %, respectively, p < 0.001). Among those patients with PUD/HPI, patients who had eradication therapy had a lower incidence of AAA than those without eradication therapy (2.46 % vs. 3.88 %, p = 0.012). CONCLUSIONS: We revealed an association among PUD, HPI, and AAA, even after adjusting for age, sex, comorbidities, and annual medical follow-up visits. Notably, we found that HPI eradication therapy reduced the incidence of AAA among patients with PUD.

Acute kidney disease following COVID-19 vaccination: a single-center retrospective study.

Background: Rare cases of de novo or relapsed kidney diseases associated with vaccination against coronavirus disease 2019 (COVID-19) have been increasingly reported. The aim of this study was to report the incidence, etiologies, and outcomes of acute kidney disease (AKD) following COVID-19 vaccination. Methods: This retrospective study extracted cases from renal registry of a single medical center from 1 March 2021 to 30 April 2022, prior to the significant surge in cases of the Omicron variant of COVID-19 infection in Taiwan. Adult patients who developed AKD after COVID-19 vaccination were included. We utilized the Naranjo score as a causality assessment tool for adverse vaccination reactions and charts review by peer nephrologists to exclude other causes. The etiologies, characteristics, and outcomes of AKD were examined. Results: Twenty-seven patients (aged 23 to 80 years) with AKD were identified from 1,897 vaccines (estimated rate of 13.6 per 1000 patient-years within the renal registry). A majority (77.8%) of vaccine received messenger RNA-based regimens. Their median (IQR) Naranjo score was 8 (6-9) points, while 14 of them (51.9%) had a definite probability (Naranjo score ≥ 9). The etiologies of AKD included glomerular disease (n = 16) consisting of seven IgA nephropathy, four anti-neutrophil cytoplasmic antibodies-associated glomerulonephritis (AAN), three membranous glomerulonephritis, two minimal change diseases, and chronic kidney disease (CKD) with acute deterioration (n = 11). Extra-renal manifestations were found in four patients. Over a median (IQR) follow-up period of 42 (36.5-49.5) weeks, six patients progressed to end-stage kidney disease (ESKD). Conclusion: Besides glomerulonephritis (GN), the occurrence of AKD following COVID-19 vaccination may be more concerning in high-risk CKD patients receiving multiple doses. Patients with the development of de novo AAN, concurrent extra-renal manifestations, or pre-existing moderate to severe CKD may exhibit poorer kidney prognosis.

High-phosphate diet causes atrial remodeling and increases atrial fibrillation vulnerability via STAT3/NF-κB signaling and oxidative stress.

AIM: Hyperphosphatemia is associated with adverse cardiovascular outcomes in both the general population and patients with end-stage renal disease. We evaluated whether high inorganic phosphate (Pi) intake causes atrial remodeling and increased atrial fibrillation (AF) risk. METHODS: The 5/6 nephrectomized chronic kidney disease (CKD) mice were fed a high-Pi (2%) diet for 10 weeks. AF vulnerability was evaluated through transesophageal burst atrial pacing. Phosphoproteomic, Western blotting, and immunohistochemistry were used to evaluate the effects of high Pi in atrial fibroblasts, atrial myocytes, and HL-1 myocytes. RESULTS: CKD and sham mice fed a high-Pi diet exhibited increased AF vulnerability, atrial fibrosis, and oxidative stress compared with mice fed a normal diet. Compared with normal (1 mM) Pi, high (2 mM) Pi significantly increased the activity of atrial fibroblasts and mitochondrial oxidative stress. Phosphoproteomic analysis revealed that compared with normal Pi, high Pi considerably increased the phosphorylation of intracellular proteins in atrial fibroblasts, including proteins related to NF-κB signaling and STAT3. Inhibition of NF-κB, STAT3, and Nox4 by small interfering RNA reduced the high-Pi-induced expression of collagen. In HL-1 myocytes, the high Pi induced the degradation of myofibril proteins and hyperphosphorylation of RyR2, which was abolished by Nox4 and CaMKII inhibition. Switching back to a normal-Pi diet improved the atrial abnormalities induced by high-Pi diet. CONCLUSIONS: High-Pi intake causes atrial structural and electrical remodeling and increases AF vulnerability, which is mediated through STAT3/NF-κB signaling and oxidative stress. High dietary Pi intake can exert detrimental effects on atria and may increase AF risk.

Comparison of Mitochondrial Adenosine Triphosphate-Sensitive Potassium Channel High- vs Low-Affinity Sulfonylureas and Cardiovascular Outcomes in Patients With Type 2 Diabetes Treated With Metformin.

Importance: Sulfonylureas are frequently used as add-on to metformin in type 2 diabetes (T2D), and individual sulfonylurea agents carry different risks of cardiovascular disease. Sulfonylureas' different affinities to cardiac mitochondrial adenosine triphosphate-sensitive potassium (mitoKATP) channels have been speculated to account for the intraclass difference in cardiovascular risk from in vitro and ex vivo studies; however, this hypothesis has not been assessed in a general population with diabetes receiving sulfonylureas added to metformin. Objective: To compare the risk of myocardial infarction (MI), ischemic stroke, or cardiovascular death in patients with T2D treated with mitoKATP channel high-affinity sulfonylureas and low-affinity sulfonylureas as add-on to metformin. Design, Setting, and Participants: This is a new-user, active-comparator, and propensity score-matched cohort study with analysis of the Taiwanese Diabetes Mellitus Health Database from 2006, to 2017. Data analysis was performed from August 2020 to July 2021. Exposures: Cardiac mitoKATP channel high-affinity (glyburide and glipizide) and low-affinity (gliclazide and glimepiride) sulfonylureas combined with metformin. Main Outcomes and Measures: Primary outcome was major adverse cardiovascular events (MACEs), a composite of cardiovascular death or hospitalization for either MI or ischemic stroke. Secondary outcomes included individual MACE components, heart failure, arrhythmia, all-cause mortality, and severe hypoglycemia. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs). Results: Each sulfonylurea group comprised 53 714 patients (mean [SD] age, 54.7 [12.1] years; 31 962 men [59.5%]). MitoKATP channel high-affinity sulfonylureas vs low-affinity sulfonylureas when combined with metformin were associated with an increased risk of MACE (aHR, 1.18; 95% CI, 1.03-1.34), MI (aHR, 1.34; 95% CI, 1.04-1.73), all-cause mortality (aHR, 1.27; 95% CI, 1.03-1.57), and severe hypoglycemia (aHR, 1.82; 95% CI, 1.58-2.10), but not with increased risks of ischemic stroke, cardiovascular death, arrhythmia, and heart failure. The duration analyses revealed the highest MACE risk during 1 to 90 days after initiation of mitoKATP channel high-affinity sulfonylureas (aHR, 6.06; 95% CI, 4.86-7.55). Conclusions and Relevance: Use of mitoKATP channel high-affinity sulfonylureas vs low-affinity sulfonylureas was associated with an increased MACE risk in patients with T2D concomitantly receiving metformin, suggesting that high-affinity blockage of the mitoKATP channels could account for sulfonylurea-associated MACEs.

Peritoneal effluent MicroRNA profile for detection of encapsulating peritoneal sclerosis.

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is a catastrophic complication of peritoneal dialysis (PD) with high mortality. Our aim is to develop a novel noninvasive microRNA (miRNA) test for EPS. METHODS: We collected 142 PD effluents (EPS: 62 and non-EPS:80). MiRNA profiles of PD effluents were examined by a high-throughput real-time polymerase chain reaction (PCR) array to first screen. Candidate miRNAs were verified by single real-time PCR. The model for EPS prediction was evaluated by multiple logistic regression and machine learning. RESULTS: Seven candidate miRNAs were identified from the screening of PCR-array of 377 miRNAs. The top five area under the curve (AUC) values with 5 miRNA-ratios were selected using 127 samples (EPS: 56 vs non-EPS: 71) to produce a receiver operating characteristic curve. After considering clinical characteristics and 5 miRNA-ratios, the accuracies of the machine learning model of Random Forest and multiple logistic regression were boosted to AUC 0.97 and 0.99, respectively. Furthermore, the pathway analysis of miRNA associated targeting genes and miRNA-compound interaction network revealed that these five miRNAs played the roles in TGF-ß signaling pathway. CONCLUSION: The model-based miRNA expressions in PD effluents may help determine the probability of EPS and provide further therapeutic opinion for EPS.

Assessing the Global Impact on the Mouse Kidney After Traumatic Brain Injury: A Transcriptomic Study.

Purpose: In this study, we use animal models combined with bioinformatics strategies to investigate the potential changes in overall renal transcriptional expression after traumatic brain injury. Methods: Microarray analysis was performed after kidney acquisition using unilateral controlled cortical impact as the primary mouse TBI model. Multi-oriented gene set enrichment analysis was performed for differentially expressed genes. Results: The results showed that TBI affected the gene set associated with mitochondria function in kidney cells, and a negative enrichment of gene sets associated with immune cell migration and epidermal development was also observed. Analysis of the disease phenotype gene set revealed that differential expression of mitochondria-related genes was associated with lactate metabolism. Alternatively, activation and adhesion of immune cells associated with the complement system may promote autoinflammation in kidney tissue. The simulated immune cell infiltration analysis showed an increase in the proportion of activated memory CD4 T cells and a decrease in the proportion of resting memory CD4 T cells, suggesting that activated memory CD4 T cell infiltration may be involved in the inflammation of renal tissue and cause damage to renal cells, such as principal cells, mesangial cells and loops of Henle cells. Conclusion: This study is the first to reveal the effects of brain trauma on the kidney. TBI may affect the expression of mitochondria function-related gene sets in renal cells by increasing lactate. It may also affect renal mesangial cells by inducing increased infiltration of immune cells through mechanisms related to complement system activation or autoimmune antibodies.

Early Molecular Events Mediating Loss of Aquaporin-2 during Ureteral Obstruction in Rats.

BACKGROUND: Ureteral obstruction is marked by disappearance of the vasopressin-dependent water channel aquaporin-2 (AQP2) in the renal collecting duct and polyuria upon reversal. Most studies of unilateral ureteral obstruction (UUO) models have examined late time points, obscuring the early signals that trigger loss of AQP2. METHODS: We performed RNA-Seq on microdissected rat cortical collecting ducts (CCDs) to identify early signaling pathways after establishment of UUO. RESULTS: Vasopressin V2 receptor (AVPR2) mRNA was decreased 3 hours after UUO, identifying one cause of AQP2 loss. Collecting duct principal cell differentiation markers were lost, including many not regulated by vasopressin. Immediate early genes in CCDs were widely induced 3 hours after UUO, including Myc, Atf3, and Fos (confirmed at the protein level). Simultaneously, expression of NF-κB signaling response genes known to repress Aqp2 increased. RNA-Seq for CCDs at an even earlier time point (30 minutes) showed widespread mRNA loss, indicating a "stunned" profile. Immunocytochemical labeling of markers of mRNA-degrading P-bodies DDX6 and 4E-T indicated an increase in P-body formation within 30 minutes. CONCLUSIONS: Immediately after establishment of UUO, collecting ducts manifest a stunned state with broad disappearance of mRNAs. Within 3 hours, there is upregulation of immediate early and inflammatory genes and disappearance of the V2 vasopressin receptor, resulting in loss of AQP2 (confirmed by lipopolysaccharide administration). The inflammatory response seen rapidly after UUO establishment may be relevant to both UUO-induced polyuria and long-term development of fibrosis in UUO kidneys.

Novel CNNM2 Mutation Responsible for Autosomal-Dominant Hypomagnesemia With Seizure.

CNNM2 is primarily expressed in the brain and distal convoluted tubule (DCT) of the kidney. Mutations in CNNM2 have been reported to cause hypomagnesemia, seizure, and intellectual disability (HSMR) syndrome. However, the clinical and functional effect of CNNM2 mutations remains incompletely understood. We report our clinical encounter with a 1-year-old infant with HSMR features. Mutation screening for this trio family was performed using next-generation sequencing (NGS)-based whole exome sequencing (WES) with the identified mutation verified by Sanger sequencing. We identified a de novo heterozygous mutation c.G1439T (R480L) in the essential cystathionine ß-synthase (CBS) domain of CNNM2 encoding CNNM2 (cyclin M2) without any other gene mutations related to hypomagnesemia. The amino acid involved in this missense mutation was conserved in different species. It was also found to be pathogenic based on the different software prediction models and ACGME criteria. In vitro studies revealed a higher expression of the CNNM2-R480L mutant protein compared to that of the wild-type CNNM2. Like the CNNM2-wild type, proper localization of CNNM2-R480L was shown on immunocytochemistry images. The Mg2+ efflux assay in murine DCT (mDCT) cells revealed a significant increase in intracellular Mg2+ green in CNNM2-R480L compared to that in CNNM2-WT. By using a simulation model, we illustrate that the R480L mutation impaired the interaction between CNNM2 and ATP-Mg2+. We propose that this novel R480L mutation in the CNNM2 gene led to impaired binding between Mg2+-ATP and CNNM2 and diminished Mg2+ efflux, manifesting clinically as refractory hypomagnesemia.

Correlation between Physical Activity and Psychological Distress in Patients Receiving Hemodialysis with Comorbidities: A Cross-Sectional Study.

Comorbidities cause psychological distress to patients on hemodialysis and cause their physical function to deteriorate. This study aims to examine whether physical patterns are associated with anxiety, depression and fatigue among patients with and without comorbidities who are on hemodialysis. To this end, a cross-sectional survey was administered to 120 patients on hemodialysis. Data were collected using the International Physical Activity Questionnaire­Short Form, Beck Depression Inventory­Second Edition, Beck Anxiety Inventory, and Brief Fatigue Inventory­Taiwan Version. An independent sample t test and generalized linear model analyses were conducted. The results revealed that patients with comorbidities exhibited more severe levels of depression (p < 0.001), anxiety (p < 0.001), and fatigue (p = 0.010) than patients without comorbidities. Additionally, patients on hemodialysis with a high physical activity level (≥600 metabolic equivalent of task per min/week) exhibited less depression (B = −4.03; p < 0.001; 95% confidence interval [CI] = −6.04, −2.03) and anxiety (B = −2.64; p = 0.002; 95% CI = −4.27, −1.00) severity than those with a low physical activity level; those who engaged in weekly physical activities exhibited less fatigue severity (B = −1.17; p = 0.001; 95% CI = −1.84, −0.49) and fatigue interference (B = −0.61; p = 0.015; 95% CI = −1.10, −0.12). For patients on hemodialysis, having comorbidities was correlated with more severe levels of depression, anxiety, and fatigue. Weekly moderate-intensity physical activities were revealed to be correlated with less severity levels of depression, anxiety, and fatigue. The study findings aid the development of interventions for promoting physical activity among patients on hemodialysis to prevent the exacerbation of complications caused by comorbidities and psychological distress.

Aberrant overexpression of HOTAIR inhibits abdominal adipogenesis through remodelling of genome-wide DNA methylation and transcription.

OBJECTIVE: Abdominal adiposity is strongly associated with diabetic and cardiovascular comorbidities. The long noncoding RNA HOTAIR (HOX Transcript Antisense Intergenic RNA) is an important epigenetic regulator with fat depot-specific expression. Its functional roles and epigenetic regulation in abdominal adipogenesis remain uncertain. METHODS: We collected different fat depots from healthy, severely obese, and uraemic subjects to measure fat-depot specific gene expression and quantify regional adiposity via dual-energy X-ray absorptiometry (DXA). HOTAIR was overexpressed to evaluate its functional roles. Reduced representation bisulfite sequencing (RRBS), RNA-sequencing, real-time qPCR and RNA/chromatin immunoprecipitation were performed to analyse HOTAIR-mediated epigenetic regulation. RESULTS: A negative correlation between adipose tissue HOTAIR expression (arm or abdominal subcutaneous fat depots) and regional adiposity under the status of severe obesity or uraemia was observed. HOTAIR overexpression using human immortalized abdominal preadipocytes further revealed its anti-adipogenic effects. Integrative analysis of genome-wide DNA methylation by reduced representation bisulfite sequencing (RRBS) and gene expression was performed. Overall, the differentially methylated genes were functionally enriched for nervous system development, suggesting that HOTAIR may be epigenetically associated with cell lineage commitment. We specifically found that HOTAIR-mediated genes showed strong changes in both DNA methylation and gene expression during abdominal adipogenesis. We observed that two HOTAIR-repressed genes, SLITRK4 and PITPNC1, present an obesity-driven fat-depot specific expression pattern that is positively correlated with the central body fat distribution. CONCLUSIONS: Our study indicated that HOTAIR is a key regulator of abdominal adipogenesis via intricate DNA methylation and is likely to be associated with the transcriptional regulation of genes involved in nervous system development and lipid metabolism, such as SLITRK4 and PITPNC1.

Association Between Specificity of Sulfonylureas to Cardiac Mitochondrial KATP Channels and the Risk of Major Adverse Cardiovascular Events in Type 2 Diabetes.

OBJECTIVE: Previous studies have revealed an intraclass difference in major adverse cardiovascular events (MACE) among sulfonylureas. In vitro and ex vivo studies reported several sulfonylureas to exhibit high-affinity blockage of cardiac mitochondrial ATP-sensitive potassium (mitoKATP) channels and could interfere with ischemic preconditioning, the most important mechanism of self-cardiac protection. However, no studies have examined whether these varying binding affinities of sulfonylureas could account for their intraclass difference in MACE. We compared mitoKATP channel high-affinity versus low-affinity sulfonylureas regarding the MACE risk in real-world settings. RESEARCH DESIGN AND METHODS: Using the Taiwan nationwide health care claims database, patients with type 2 diabetes initiating sulfonylurea monotherapy between 2007 and 2016 were included in the cohort study. A total of 33,727 new mitoKATP channel high-affinity (glyburide and glipizide) and low-affinity (gliclazide and glimepiride) sulfonylurea users, respectively, were identified after 1:1 propensity score matching. Cox proportional hazard models were used to estimate adjusted hazard ratios (aHRs) and 95% CI. RESULTS: MitoKATP channel high-affinity sulfonylureas were associated with a significantly increased risk of three-point MACE (aHR 1.21 [95% CI 1.03-1.44]), ischemic stroke (aHR 1.23 [95% CI 1.02-1.50]), and cardiovascular death (aHR 2.61 [95% CI 1.31-5.20]), but not with that of myocardial infarction (aHR 1.04 [95% CI 0.75-1.46]). The duration-response analyses revealed the highest MACE risk to be within 90 days of therapy (aHR 4.67 [95% CI 3.61-6.06]). CONCLUSIONS: Cardiac mitoKATP channel high-affinity sulfonylureas were associated with an increased MACE risk compared with low-affinity sulfonylureas in a nationwide population with diabetes.

Physical Activity and Health-Related Quality of Life of Patients on Hemodialysis with Comorbidities: A Cross-Sectional Study.

Patients on hemodialysis with multiple comorbidities have limited physical activity, resulting in poor health, low activity participation, and low quality of life. Accordingly, the nursing care provided to such patients should include regular physical activity training programs. Therefore, this cross-sectional descriptive study investigated whether patients on hemodialysis with and without comorbidities have different levels of physical activity and health-related quality of life (HRQoL); the correlations among the comorbidities, physical activity, and HRQoL of the two cohorts were also assessed. The 36-Item Short-Form Health Survey version 2 and International Physical Activity Questionnaire were employed to collect data from 120 patients on hemodialysis. An independent samples t-test and univariate and multivariate linear regression analyses were conducted. The overall HRQoL of patients with comorbidities was lower than that of patients without comorbidities (p = 0.008). Compared with patients who participated in low-intensity physical activity, the overall HRQoL of patients who participated in moderate-intensity physical activity was higher (p < 0.001). The overall HRQoL of patients with comorbidities who participated in low-intensity physical activity was lower than that of those who participated in moderate-intensity physical activity (p < 0.001). Moderate-intensity physical activity was correlated with higher HRQoL for patients with comorbidities. This finding supports the implementation of effective physical activity intervention measures. Furthermore, it supports the promotion of patient self-management and the implementation of regular exercise programs and lifestyle changes, and patients on hemodialysis can benefit from the future management of physical activities.

Mortality rate of end-stage kidney disease patients in Taiwan.

BACKGROUND/PURPOSE: End-stage kidney disease (ESKD) is a global burden that reflects each country's unique condition. We used the National Health Insurance Research Database (NHIRD) of Taiwan to decipher changes in the mortality and international survival rates and to determine the effectiveness of the pre-end-stage renal disease care program (pre-ESRD care program) to guide future health policies for ESKD. METHODS: We conducted a retrospective cohort analysis of the NHIRD data along with records from the catastrophic illness certificate program of ESKD patients from 2010 to 2018. RESULTS: From 2010 to 2018, the annual dialysis-related mortality rate in Taiwan increased from 10.6 to 11.8 deaths per hundred patient-years. The mortality rate for patients below 40 years appears to be decreasing, reflecting the improved quality of care for ESKD patients. Patients above 75 years showed increasing mortality, indicating the prolonged survival and aging of the ESKD population. Patients undergoing dialysis who participated in the pre-ESRD care program had a higher post-dialysis initiation life expectancy than those who did not participate. Among the program enrollees, the post-dialysis initiation life expectancy was higher in patients who had participated for more than one year. Taiwan has one of the highest ESKD patient survival rates globally. CONCLUSION: From 2010 to 2018, the reduced mortality in young patients and aging of the ESKD population might indicate that the quality of care in Taiwan for ESKD has improved. Furthermore, a better survival rate after dialysis initiation was observed in the pre-ESRD care program participants.

miR-424/322 protects against abdominal aortic aneurysm formation by modulating the Smad2/3/runt-related transcription factor 2 axis.

Rupture of abdominal aortic aneurysms (AAAs) is one of the leading causes of sudden death in the elderly population. The osteogenic transcription factor runt-related gene (RUNX) encodes multifunctional mediators of intracellular signal transduction pathways in vascular remodeling and inflammation. We aimed to evaluate the roles of RUNX2 and its putative downstream target miR-424/322 in the modulation of several AAA progression-related key molecules, such as matrix metalloproteinases and vascular endothelial growth factor. In the GEO database, we found that male patients with AAAs had higher RUNX2 expression than did control patients. Several risk factors for aneurysm induced the overexpression of MMPs through RUNX2 transactivation, and this was dependent on Smad2/3 upregulation in human aortic smooth muscle cells. miR-424 was overexpressed through RUNX2 after angiotensin II (AngII) challenge. The administration of siRUNX2 and miR-424 mimics attenuated the activation of the Smad/RUNX2 axis and the overexpression of several AAA progression-related molecules in vitro. Compared to their littermates, miR-322 KO mice were susceptible to AngII-induced AAA, whereas the silencing of RUNX2 and the administration of exogenous miR-322 mimics ameliorated the AngII-induced AAA in ApoE KO mice. Overall, we established the roles of the Smad/RUNX2/miR-424/322 axis in AAA pathogenesis. We demonstrated the therapeutic potentials of miR-424/322 mimics and RUNX2 inhibitor for AAA progression.

A Reconfigurable Differential-to-Single-Ended Autonomous Current Adaptation Buffer Amplifier Suitable for Biomedical Applications.

A reconfigurable differential-to-single-ended autonomous current adaptation buffer amplifier (ACABA) is proposed. The ACABA, based on floating-gate technologies, is a capacitive circuit, of which output DC level and bandwidth can be adjusted by programming charges on floating nodes. The gain is variable by switching different amounts of capacitors without altering the output DC level. Without extra sensing and control circuitries, the current consumption of the proposed ACABA increases spontaneously when the input signal is fast or large, achieving a high slew rate. The supply current dwindles back to the low quiescent level autonomously when the output voltage reaches equilibrium. Therefore, the proposed ACABA is power-efficient and suitable for processing physiological signals. A prototype ACABA has been designed and fabricated in a [Formula: see text] CMOS process occupying an area of [Formula: see text]. When loaded by a [Formula: see text] capacitor, it consumes [Formula: see text] to achieve a unity-gain bandwidth of [Formula: see text] with a measured IIP2 value of [Formula: see text] and a slew rate of [Formula: see text].

Pharmacological Activation Of Aldehyde Dehydrogenase 2 Protects Against Heatstroke-Induced Acute Lung Injury by Modulating Oxidative Stress and Endothelial Dysfunction.

Heatstroke (HS) can cause acute lung injury (ALI). Heat stress induces inflammation and apoptosis via reactive oxygen species (ROS) and endogenous reactive aldehydes. Endothelial dysfunction also plays a crucial role in HS-induced ALI. Aldehyde dehydrogenase 2 (ALDH2) is a mitochondrial enzyme that detoxifies aldehydes such as 4-hydroxy-2-nonenal (4-HNE) protein adducts. A single point mutation in ALDH2 at E487K (ALDH2*2) intrinsically lowers the activity of ALDH2. Alda-1, an ALDH2 activator, attenuates the formation of 4-HNE protein adducts and ROS in several disease models. We hypothesized that ALDH2 can protect against heat stress-induced vascular inflammation and the accumulation of ROS and toxic aldehydes. Homozygous ALDH2*2 knock-in (KI) mice on a C57BL/6J background and C57BL/6J mice were used for the animal experiments. Human umbilical vein endothelial cells (HUVECs) were used for the in vitro experiment. The mice were directly subjected to whole-body heating (WBH, 42°C) for 1 h at 80% relative humidity. Alda-1 (16 mg/kg) was administered intraperitoneally prior to WBH. The severity of ALI was assessed by analyzing the protein levels and cell counts in the bronchoalveolar lavage fluid, the wet/dry ratio and histology. ALDH2*2 KI mice were susceptible to HS-induced ALI in vivo. Silencing ALDH2 induced 4-HNE and ROS accumulation in HUVECs subjected to heat stress. Alda-1 attenuated the heat stress-induced activation of inflammatory pathways, senescence and apoptosis in HUVECs. The lung homogenates of mice pretreated with Alda-1 exhibited significantly elevated ALDH2 activity and decreased ROS accumulation after WBH. Alda-1 significantly decreased the WBH-induced accumulation of 4-HNE and p65 and p38 activation. Here, we demonstrated the crucial roles of ALDH2 in protecting against heat stress-induced ROS production and vascular inflammation and preserving the viability of ECs. The activation of ALDH2 by Alda-1 attenuates WBH-induced ALI in vivo.

Association of Tumor Hydroxyindole O-Methyltransferase and Serum 5-Methoxytryptophan with Long-Term Survival of Hepatocellular Carcinoma.

5-methoxytryptophan (5-MTP) is a recently discovered tryptophan (Trp) metabolite with anti-inflammatory and tumor-suppressing actions. Its synthesis is catalyzed by hydroxyindole O-methyltransferase (HIOMT). HIOMT levels were reported to be decreased in some patients with colorectal, pancreatic and breast cancer. It is unclear whether tissue HIOMT levels is altered in hepatocellular carcinoma (HCC). It is also unclear whether serum 5-MTP concentration is influenced by HCC. In this study, 150 HCC and adjacent normal liver tissues and serum samples were obtained from the HCC biobank established by a prospective multicenter study. Serum samples from 47 healthy subjects were included as a reference. HIOMT mRNA was measured by real time PCR. Serum 5-MTP and selected Trp metabolites were analyzed by quantitative LC-MS. HCC tissue HIOMT mRNA levels adjusted for adjacent normal tissue HIOMT mRNA levels was associated with overall and relapse-free (RF) survival. Combined serum 5-MTP or tissue HIOMT mRNA and serum kynurenine (Kyn) analysis predicted prolonged overall and RF survival following liver resection. A high serum 5-MTP or tissue HIOMT mRNA and low serum Kyn is associated with long-term survival. In conclusion, tumor tissue HIOMT mRNA and serum 5-MTP are potential biomarkers of HCC, especially when analyzed in combination with serum Kyn.

Association of Serum Phosphate with Low Handgrip Strength in Patients with Advanced Chronic Kidney Disease.

Muscle wasting and hyperphosphatemia are becoming increasingly prevalent in patients who exhibit a progressive decline in kidney function. However, the association between serum phosphate (Pi) level and sarcopenia in advanced chronic kidney disease (CKD) patients remains unclear. We compared the serum Pi levels between advanced CKD patients with (n = 51) and those without sarcopenia indicators (n = 83). Low appendicular skeletal muscle mass index (ASMI), low handgrip strength, and low gait speed were defined per the standards of the Asian Working Group for Sarcopenia. Mean serum Pi level was significantly higher in advanced CKD patients with sarcopenia indicators than those without sarcopenia indicators (3.88 ± 0.86 vs. 3.54 ± 0.73 mg/dL; p = 0.016). Univariate analysis indicated that serum Pi was negatively correlated with ASMI, handgrip strength, and gait speed. Multivariable analysis revealed that serum Pi was significantly associated with handgrip strength (standardized ß = -0.168; p = 0.022) and this association persisted even after adjustments for potential confounders. The optimal serum Pi cutoff for predicting low handgrip strength was 3.65 mg/dL, with a sensitivity of 82.1% and specificity of 56.6%. In summary, low handgrip strength is common in advanced CKD patients and serum Pi level is negatively associated with handgrip strength.

Development and application of a chronic kidney disease-specific health literacy, knowledge and disease awareness assessment tool for patients with chronic kidney disease in Taiwan.

OBJECTIVES: This study aims to develop an assessment tool for health literacy and knowledge specific to chronic kidney disease (CKD) for use in examining the associations between health literacy, disease-specific knowledge and disease awareness among patients with CKD in Taiwan. DESIGN: An assessment tool in Mandarin and Taiwanese was developed based on patient input, panel discussions with experts and a literature review, and checked for validity and reliability in a pilot test. Formal data were collected through population-based sampling with a set quota according to region and hospital accreditation level. Cross-sectional data were collected to confirm the reliability and validity of the assessment tool. Levels of health literacy, disease knowledge, and disease awareness were then reported and analysed. SETTING: Sample hospitals included 10 medical centres, 18 regional hospitals and 15 local hospitals in Taiwan. Researchers were granted Internal Review Board approval and obtained agreement to collect data in all study settings. PARTICIPANTS: Patients at least 20 years old who had been diagnosed with CKD of any stage were eligible to participate. The formal assessment collected 1155 valid questionnaires, yielding an 87.3% response rate. The mean age of participants was 67.48 years (SD=12.87, range 22-98), while 484 (41.95%) were female and 78% were aware they had CKD. RESULTS: The self-devised instrument proved to have excellent reliability and validity. Use of the instrument in the main study showed that CKD-specific health literacy was significantly associated with age (ß=-0.33, p<0.00), educational attainment and disease awareness (ß=0.13, p<0.00). CKD-specific knowledge was also significantly associated with age (ß=-0.18, p<0.00), educational attainment and disease awareness (ß=0.19, p<0.00). CONCLUSIONS: This CKD-specific health literacy and knowledge assessment tool developed for Mandarin and Taiwanese-speaking patients is reliable and well validated. Patients with CKD who are aware of and understand their disease performed better in the assessment.

Effects of Intradialytic Exercise on Dialytic Parameters, Health-Related Quality of Life, and Depression Status in Hemodialysis Patients: A Randomized Controlled Trial.

Exercise is fundamentally important in managing chronic diseases and improving health-related quality of life (HRQL). However, whether intradialytic exercise is safe through assessment of changes in dialytic parameters and has a positive impact on HRQL and depression status of hemodialysis patients requires further research with diverse racial and cultural populations to identify. This study aimed to evaluate the effects of intradialytic exercise on dialytic parameters, HRQL, and depression status in hemodialysis patients. A randomized controlled trial was conducted at a medical center in Northern Taiwan. Sixty-four hemodialysis patients were recruited using stratified random sampling. Participants were randomized into an experimental group (EG, n = 32) or a control group (CG, n = 32). The EG received a 12-week intradialytic exercise program while the CG maintained their usual lifestyles. Dialytic parameters, HRQL, and depression status were collected at baseline and at 12 weeks. The results indicated no differences in the dialytic parameters from the baseline between both groups. However, the EG had increased HRQL (ß = 22.6, p < 0.001) and reduced depression status (ß = -7.5, p = 0.02) at 12 weeks compared to the CG. Therefore, a 12-week intradialytic exercise regime is safe and effective in improving HRQL and reducing depression status for hemodialysis patients.