Quantifying Gut Microbial Short-Chain Fatty Acids and Their Isotopomers in Mechanistic Studies Using a Rapid, Readily Expandable LC-MS Platform.

Short-chain fatty acids (SCFAs) comprise the largest group of gut microbial fermentation products. While absorption of most nutrients occurs in the small intestine, indigestible dietary components, such as fiber, reach the colon and are processed by the gut microbiome to produce a wide array of metabolites that influence host physiology. Numerous studies have implicated SCFAs as key modulators of host health, such as in regulating irritable bowel syndrome (IBS). However, robust methods are still required for their detection and quantitation to meet the demands of biological studies probing the complex interplay of the gut-host-health paradigm. In this study, a sensitive, rapid-throughput, and readily expandible UHPLC-QqQ-MS platform using 2-PA derivatization was developed for the quantitation of gut-microbially derived SCFAs, related metabolites, and isotopically labeled homologues. The utility of this platform was then demonstrated by investigating the production of SCFAs in cecal contents from mice feeding studies, human fecal bioreactors, and fecal/bacterial fermentations of isotopically labeled dietary carbohydrates. Overall, the workflow proposed in this study serves as an invaluable tool for the rapidly expanding gut-microbiome and precision nutrition research field.

Dietary fiber monosaccharide content alters gut microbiome composition and fermentation.

Members of the mammalian gut microbiota metabolize diverse complex carbohydrates that are not digested by the host, which are collectively labeled "dietary fiber." While the enzymes and transporters that each strain uses to establish a nutrient niche in the gut are often exquisitely specific, the relationship between carbohydrate structure and microbial ecology is imperfectly understood. The present study takes advantage of recent advances in complex carbohydrate structure determination to test the effects of fiber monosaccharide composition on microbial fermentation. Fifty-five fibers with varied monosaccharide composition were fermented by a pooled feline fecal inoculum in a modified MiniBioReactor array system over a period of 72 hours. The content of the monosaccharides glucose and xylose was significantly associated with the reduction of pH during fermentation, which was also predictable from the concentrations of the short-chain fatty acids lactic acid, propionic acid, and the signaling molecule indole-3-acetic acid. Microbiome diversity and composition were also predictable from monosaccharide content and SCFA concentration. In particular, the concentrations of lactic acid and propionic acid correlated with final alpha diversity and were significantly associated with the relative abundance of several of the genera, including Lactobacillus and Dubosiella. Our results suggest that monosaccharide composition offers a generalizable method to compare any dietary fiber of interest and uncover links between diet, gut microbiota, and metabolite production. IMPORTANCE: The survival of a microbial species in the gut depends on the availability of the nutrients necessary for that species to survive. Carbohydrates in the form of non-host digestible fiber are of particular importance, and the set of genes possessed by each species for carbohydrate consumption can vary considerably. Here, differences in the monosaccharides that are the building blocks of fiber are considered for their impact on both the survival of different species of microbes and on the levels of microbial fermentation products produced. This work demonstrates that foods with similar monosaccharide content will have consistent effects on the survival of microbial species and on the production of microbial fermentation products.

Using Machine Learning to Predict the Antibacterial Activity of Ruthenium Complexes.

Rising antimicrobial resistance (AMR) and lack of innovation in the antibiotic pipeline necessitate novel approaches to discovering new drugs. Metal complexes have proven to be promising antimicrobial compounds, but the number of studied compounds is still low compared to the millions of organic molecules investigated so far. Lately, machine learning (ML) has emerged as a valuable tool for guiding the design of small organic molecules, potentially even in low-data scenarios. For the first time, we extend the application of ML to the discovery of metal-based medicines. Utilising 288 modularly synthesized ruthenium arene Schiff-base complexes and their antibacterial properties, a series of ML models were trained. The models perform well and are used to predict the activity of 54 new compounds. These displayed a 5.7x higher hit-rate (53.7 %) against methicillin-resistant Staphylococcus aureus (MRSA) compared to the original library (9.4 %), demonstrating that ML can be applied to improve the success-rates in the search of new metalloantibiotics. This work paves the way for more ambitious applications of ML in the field of metal-based drug discovery.

Targeting Pathogenic Formate-Dependent Bacteria with a Bioinspired Metallo-Nitroreductase Complex.

Nitroreductases (NTRs) constitute an important class of oxidoreductase enzymes that have evolved to metabolize nitro-containing compounds. Their unique characteristics have spurred an array of potential uses in medicinal chemistry, chemical biology, and bioengineering toward harnessing nitro caging groups and constructing NTR variants for niche applications. Inspired by how they carry out enzymatic reduction via a cascade of hydride transfer reactions, we sought to develop a synthetic small-molecule NTR system based on transfer hydrogenation mediated by transition metal complexes harnessing native cofactors. We report the first water-stable Ru-arene complex capable of selectively and fully reducing nitroaromatics into anilines in a biocompatible buffered aqueous environment using formate as the hydride source. We further demonstrated its application to activate nitro-caged sulfanilamide prodrug in formate-abundant bacteria, specifically pathogenic methicillin-resistant Staphylococcus aureus. This proof of concept paves the way for a new targeted antibacterial chemotherapeutic approach leveraging on redox-active metal complexes for prodrug activation via bioinspired nitroreduction.

Feature-based deep neural network approach for predicting mortality risk in patients with COVID-19.

In this study, we integrate deep neural network (DNN) with hybrid approaches (feature selection and instance clustering) to build prediction models for predicting mortality risk in patients with COVID-19. Besides, we use cross-validation methods to evaluate the performance of these prediction models, including feature based DNN, cluster-based DNN, DNN, and neural network (multi-layer perceptron). The COVID-19 dataset with 12,020 instances and 10 cross-validation methods are used to evaluate the prediction models. The experimental results showed that the proposed feature based DNN model, holding Recall (98.62%), F1-score (91.99%), Accuracy (91.41%), and False Negative Rate (1.38%), outperforms than original prediction model (neural network) in the prediction performance. Furthermore, the proposed approach uses the Top 5 features to build a DNN prediction model with high prediction performance, exhibiting the well prediction as the model built by all features (57 features). The novelty of this study is that we integrate feature selection, instance clustering, and DNN techniques to improve prediction performance. Moreover, the proposed approach which is built with fewer features performs much better than the original prediction models in many metrics and can still remain high prediction performance.

Harnessing Transition Metal Scaffolds for Targeted Antibacterial Therapy.

Antimicrobial resistance, caused by persistent adaptation and growing resistance of pathogenic bacteria to overprescribed antibiotics, poses one of the most serious and urgent threats to global public health. The limited pipeline of experimental antibiotics in development further exacerbates this looming crisis and new drugs with alternative modes of action are needed to tackle evolving pathogenic adaptation. Transition metal complexes can replenish this diminishing stockpile of drug candidates by providing compounds with unique properties that are not easily accessible using pure organic scaffolds. We spotlight four emerging strategies to harness these unique properties to develop new targeted antibacterial agents.

Cryptic Plasmodium inui and Plasmodium fieldi Infections Among Symptomatic Malaria Patients in Thailand.

BACKGROUND: Some nonhuman primate Plasmodium species including P. knowlesi and P. cynomolgi can cross-transmit from macaque natural hosts to humans under natural infection. This study aims to retrospectively explore other simian Plasmodium species in the blood samples of symptomatic malaria patients in Thailand. METHODS: A total of 5271 blood samples from acute febrile patients from 5 malaria endemic provinces and 1015 blood samples from long-tailed and pig-tailed macaques from 3 locations were examined for Plasmodium species by microscopy and species-specific polymerase chain reaction. The Plasmodium mitochondrial cytochrome oxidase 1 (COX1) gene was analyzed by amplicon deep sequencing as well as Sanger sequencing from recombinant plasmid clones to reaffirm and characterize P. inui and P. fieldi. RESULTS: Besides human malaria, P. knowlesi, P. cynomolgi, P. inui and P. fieldi infections were diagnosed in 15, 21, 19, and 3 patients, respectively. Most P. inui and all P. fieldi infected patients had simultaneous infections with other Plasmodium species, and seemed to be responsive to chloroquine or artemisinin-mefloquine. P. inui was the most prevalent species among macaque populations. Phylogenetic analysis of the COX1 sequences from human and macaque isolates reveals the genetic diversity of P. inui and suggests that multiple parasite strains have been incriminated in human infections. CONCLUSIONS: Both P. inui and P. fieldi could establish infection in humans under natural transmission. Despite occurring at a low prevalence and mostly co-existing with other Plasmodium species, P. inui infections in humans have a wide distribution in Thailand.

Prognostic value of circulating tumor cells and its association with the expression of cancer stem cells in nasopharyngeal carcinoma patients.

The release of circulating tumor cells (CTCs) into vasculature is an early event in the metastatic process and the detection of CTCs has been widely used clinically. In addition, cancer stem cells (CSCs) are the source of distant metastasis. However, the relationship between CTCs and CSCs in nasopharyngeal carcinoma (NPC) patients was largely unknown. A total of 93 NPC patients were enrolled in this study. The CTCs in the peripheral blood were detected. The expression of ALDH1A1 in the tumor tissues of the corresponding patients was detected using immunohistochemistry (IHC). The prognostic value of CTCs level and the correlation with the expression of ALDH1A1 was evaluated. Data showed that the detection of CTCs was positively correlated with metastasis (p<0.001). The positive detection of CTCs was also associated with poor overall survival (p=0.025). CTCs ≥2 demonstrated good specificity and sensitivity in predicting distant metastasis, while CTCs ≥8 demonstrated better specificity and sensitivity in predicting prognosis than CTCs ≥2. Furthermore, we found that there was a positive relationship between the detection of CTCs and the expression of ALDH1A1 (p=0.001). The prognosis analysis also demonstrated that high ALDH1A1 expression was correlated with poor overall survival (p=0.006). Our study demonstrated a positive correlation between the CTCs and the expression of CSCs, both were positively correlated with metastasis and poor prognosis. These results indicated that the CTCs might indirectly reflect the expression of CSCs.

Consideration factors of older adults seeking medical treatment at outpatient services in Taiwan.

BACKGROUND: Taiwan will become a super-aged society by 2025, leading to the more frequent use of outpatient services by older adults for medical treatment compared with other age groups. Understanding the outpatient service consideration factors of older adults seeking medical treatment can improve health care quality. This study explored the selection factors and crucial considerations of older adults for outpatient services. METHODS: Qualitative study was conducted. Purposive sampling was used to recruit 16 older adults over 65 years of age with chronic disease who were patients of an internal medicine department and regularly returned for checkups. Data including reasons for receiving medical treatment, factors affecting their choice of hospitals, and health care and environmental considerations were collected through structured interviews. RESULTS: The older adults identified four factors. (1) The care of doctors: The doctors possessed professional skill, allocate sufficient consultation time, and undertake effective communication. (2) The care of other medical professionals: Other medical professionals provided services in a cordial manner. (3) The accessibility and convenience of outpatient services: Convenient transportation and registration as well as short consultation wait time. (4) Environment and equipment: The hospital had the novel facilities and satisfactory barrier-free equipment. CONCLUSIONS: The older adults cared most about the adequacy of diagnosis and treatment by doctors and other medical professionals. In addition, they reported having higher satisfaction with hospitals that provide comprehensive medical facilities, fast and convenient medical procedures, and short wait times.

Rapid Quantification of Gut Microbial Short-Chain Fatty Acids by pDART-MS.

Short-chain fatty acids (SCFAs) are small molecules ubiquitous in nature. In mammalian guts, SCFAs are mostly produced by anaerobic intestinal microbiota through the fermentation of dietary fiber. Levels of microbe-derived SCFAs are closely relevant to human health status and indicative to gut microbiota dysbiosis. However, the quantification of SCFA using conventional chromatographic approaches is often time consuming, thus limiting high-throughput screening tests. Herein, we established a novel method to quantify SCFAs by coupling amidation derivatization of SCFAs with paper-loaded direct analysis in real time mass spectrometry (pDART-MS). Remarkably, SCFAs of a biological sample were quantitatively determined within a minute using the pDART-MS platform, which showed a limit of detection at the µM level. This platform was applied to quantify SCFAs in various biological samples, including feces from stressed rats, sera of patients with kidney disease, and fermentation products of metabolically engineered cyanobacteria. Significant differences in SCFA levels between different groups of biological practices were promptly revealed and evaluated. As there is a burgeoning demand for the analysis of SCFAs due to an increasing academic interest of gut microbiota and its metabolism, this newly developed platform will be of great potential in biological and clinical sciences as well as in industrial quality control.

Harnessing Endogenous Formate for Antibacterial Prodrug Activation by in cellulo Ruthenium-Mediated Transfer Hydrogenation Reaction.

The abundance and evolving pathogenic behavior of bacterial microorganisms give rise to antibiotic tolerance and resistance which pose a danger to global public health. New therapeutic strategies are needed to keep pace with this growing threat. We propose a novel approach for targeting bacteria by harnessing formate, a cell metabolite found only in particular bacterial species, to activate an antibacterial prodrug and selectively inhibit their growth. This strategy is premised on transfer hydrogenation reaction on a biorthogonal substrate utilizing native formate as the hydride source as a means of uncaging an antibacterial prodrug. Using coordination-directed 3-component assembly to prepare a library of 768 unique Ru-Arene Schiff-base complexes, we identified several candidates that efficiently reduced sulfonyl azide functional group in the presence of formate. This strategy paves the way for a new approach of targeted antibacterial therapy by exploiting unique bacterial metabolites.

Association of serum chromium levels with malnutrition in hemodialysis patients.

BACKGROUND: Chromium is an essential trace metal that reduces oxidative stress and inflammation. In patients undergoing maintenance hemodialysis (MHD), a correlation among chromium exposure, inflammation, and malnutrition remains unclear. This study examined the possible effects of serum chromium levels (SCLs) in MHD patients. METHODS: Initially, 732 MHD patients in dialysis centers were recruited. A total of 647 patients met the inclusion criteria and were stratified by SCL into four equal-sized groups: first quartile (< 0.29 µg/L), second quartile (0.29-0.56 µg/L), third quartile (0.57-1.06 µg/L), and fourth quartile (> 1.06 µg/L). Demographic, biochemical, and dialysis-related data were obtained for analyses. The analysis included nutritional and inflammatory markers. RESULTS: As compared with the highest quartile group, more subjects in the lowest quartile group were of an older age; had lower hemoglobin and creatinine levels; had a higher prevalence of DM and malnutrition (serum albumin level < 3.6 g/dL); and higher serum transferrin saturation and ferritin levels. A stepwise multiple linear regression analysis revealed a significant negative correlation between malnutrition and SCL (ß coefficient = - 0.129, p = 0.012) and negative associations among body mass index (ß coefficient = - 0.010, p = 0.041), ferritin (ß coefficient = - 0.107, p = 0.001) and SCL. A multivariate logistic regression analysis also demonstrated a negative correlation between malnutrition and SCL. With a 10-fold increase in SCL, the risk ratio of malnutrition was 0.49 (95% confidence interval: 0.25-0.96; p = 0.039). CONCLUSIONS: SCL is significantly associated with malnutrition in MHD patients. Further evaluation of the relationship between clinical outcomes (morbidity/mortality) and SCL is necessitated.

Acute kidney injury and the risk of mortality in patients with methanol intoxication.

BACKGROUND: Methanol poisoning is a serious public health issue in developing countries, but few data are available in the literature on acute kidney injury (AKI) after methanol intoxication. METHODS: This study examined the clinical features, spectrum and outcomes of AKI in patients with methanol intoxication and evaluated the predictors of mortality after methanol intoxication. A total of 50 patients with methanol intoxication were seen at Chang Gung Memorial Hospital between 2000 and 2013. Patients were grouped according to the status of renal damage as AKI (n = 33) or non-AKI (n = 19). Demographic, clinical, laboratory, and mortality data were obtained for analysis. RESULTS: Most patients were middle-aged (47.8 ± 14.9 years), predominantly male (74.0%), and habitual alcohol consumers (70.0%). Most incidents were oral exposures (96.0%) and unintentional (66.0%). Two (4.0%) patients attempted suicide by intravenous injection of methanol. Five (10.0%) patients suffered methanol intoxication after ingestion of methomyl pesticide that contained methanol as a solvent. Compared to non-AKI patients, the AKI patients were older (50.9 ± 13.7 versus 41.6 ± 15.6 years, P = 0.034), predominantly male (90.9% versus 42.8%, P = 0.000), more habitual alcohol users (84.8% versus 41.2%, P = 0.001) and had more unintentional exposures (82.8% versus 35.3%, P = 0.001). Furthermore, there was a higher incidence of respiratory failure (63.6% versus 29.4%, P = 0.022) in the AKI group than in the non-AKI group, respectively. The laboratory studies revealed that the AKI patients suffered from more severe metabolic acidosis than the non-AKI patients. By the end of this study, 13 (39.5%) AKI patients and 1 (5.9%) non-AKI patient had died. The overall in-hospital hospital mortality rate was 28%. In a multivariate binary logistic regression model, it was demonstrated that AKI (odds ratio 19.670, confidence interval 1.026-377.008, P = 0.048) and Glasgow coma scale score (odds ratio 1.370, confidence interval 1.079-1.739, P = 0.010) were significant factors associated with mortality. The Kaplan-Meier analysis disclosed that AKI patients suffered lower cumulative survival than non-AKI patients (log-rank test, chi-square = 5.115, P = 0.024). CONCLUSIONS: AKI was common (66.0%) after methanol intoxication and was predictive of in-hospital hospital mortality. The development of AKI was associated with a 19.670-fold higher risk of in-hospital mortality.

Identifying risk groups of infectious spondylitis in patients with end-stage renal disease under hemodialysis: a propensity score-matched case-control study.

BACKGROUND: Patients with end-stage renal disease (ESRD) under hemodialysis (HD) are at greater risks of infectious spondylitis (IS), but there is no reliable predictor that facilitate early detection of this relatively rare and insidious disease. METHODS: A retrospective review of the medical records from patients with ESRD under HD over a 12-year period was performed at a tertiary teaching hospital, and those with a first-time diagnosis of IS were identified. A 1:4 propensity score-matched case-control study was carried out, and baseline characteristics, underlying diseases, and laboratory data were compared between the study group and the control group, one month before the date of diagnosis or the index date respectively. RESULTS: A total of 16 patients with IS were compared with 64 controls. After adjustment, recent access operation (odds ratio [OR], 13.27; 95% confidence interval [CI], 3.53 to 49.91; p <  0.001), degenerative spinal disease (OR, 12.87; 95% CI, 1.89 to 87.41; p = 0.009), HD through a tunneled cuffed catheter (OR, 6.75; 95% CI, 1.74 to 26.14; p = 0.006), low serum levels of hemoglobin, albumin, as well as high levels of red blood cell volume distribution width (RDW), alkaline phosphatase (ALP), and high sensitivity C-reactive protein were significant predictors for a IS diagnosis one month later. Receiver operating characteristic curves for hemoglobin, RDW, ALP, and albumin all showed good discrimination. The further multivariate models identified both high serum ALP levels and low serum RDW levels following a recent access intervention in patients with relatively short HD vintages may be indicative of the development of IS. CONCLUSION: Patients under HD with relatively short HD vintages showing either elevated ALP levels or low RDW levels following a recent access intervention should prompt clinical awareness about IS for timely diagnosis.

Blood lead level: an overlooked risk of carpal tunnel syndrome in hemodialysis patients.

Introduction: Carpal tunnel syndrome (CTS) is a severe complication observed in long-term maintenance hemodialysis (MHD) patients. The most common cause of CTS is dialysis-related ß2-microglobulin amyloidosis, which is associated with inflammation and oxidative stress in dialysis patients. Patients on MHD have higher blood lead levels (BLLs) than the general population. Lead (Pb) exposure in chronic dialysis patients has been noted to induce oxidative stress and inflammation. Therefore, lead-related inflammation and oxidative stress might contribute to CTS. Methods: The medical records of 866 MHD patients were reviewed. Two hundred and thirty-four patients with symptoms of CTS were surveyed by senior neurologists via physical examinations and nerve conduction studies. Patients in this study were stratified into groups with low-normal (<10 µg/dL), high-normal (10 to 20 µg/dL), and abnormal (>20 µg/dL) BLLs. The associations between CTS and BLLs and the clinical data were analyzed. Results: Multivariate logistic regression analyses showed that Log BLL (OR: 54.810, 95% CI: 13.622-220.54, p < .001), high-normal BLLs (OR: 4.839, 95% CI: 2.262-10.351, p < .001) with low-normal BLL as a reference, high BLLs (OR: 12.952, 95% CI: 5.391-31.119, p < .001) with low-normal BLL as a reference, and a BLL >12.3 µg/dL (OR: 6.827, 95% CI: 3.737-12.472, p < .001) were positively associated with CTS according to three different analyses. Discussion: In conclusion, blood lead levels were positively associated with CTS in patients on MHD. Dialysis patients should pay more attention to their environmental exposure to Pb. Avoidance of environmental Pb may reduce the incidence of CTS in MHD patients. Future studies will address the role of Pb in the pathophysiology of CTS in this patient population.

Revision and validation of a short scale to assess home environment for elementary school children in transnational families in Taiwan.

PURPOSE: To develop and test a brief scale of the home environment of elementary school children in transnational families or vulnerable families. DESIGN AND METHODS: The scale development process took place in three phases. In the first phase, a 61-item scale was generated by an expert panel based upon related literature and Chinese Home Observation for Measurement of the Environment (C-HOME). In the second phase 15 individual transnational families with elementary school children were interviewed, and items were reduced from 61 to 55 due to understandability or other practical considerations. Phase three's item analysis with 200 such families, reduced items to 41. Factor analysis followed, further reducing items to 27. Finally, the resulting 27-item scale underwent a test-retest with 57 subsample participants. RESULTS: An iterative process of item and factor analyses identified a seven-dimensional, 27-item Home Environment Assessment Scale (HEAS), which accounted for 52.28% of the total variance. K-R 20 was 0.76. The test-retest reliability for the full sample total score was 0.97. CONCLUSIONS: The results provide evidence supporting the scale consistency, content validity, and construct validity, and offer a useful instrument for health care professionals, especially pediatric nurses, to identify home environment interventions for young children in vulnerable families. PRACTICE IMPLICATIONS: The findings of HEAS-27 can serve to guide pediatric health care professionals in promptly screening, evaluating, and teaching families so that children in a vulnerable population have adequate quality and quantity of support in the home environment.

Nurses' Views on the Potential Use of Robots in the Pediatric Unit.

PURPOSE: To describe nurses' views on the potential use of robots in the pediatric unit. DESIGN AND METHODS: A qualitative descriptive design was employed. Semi-structured interviews were conducted with 23 nursing staff who worked in the pediatric unit. The interviews were audiotaped, transcribed, and analyzed using qualitative content analysis. RESULTS: Three themes emerged related to the nurses' views on the potential use of robots in the pediatric unit (1) care impact - advantages, which included: (a) reducing healthcare providers' workload and (b) adequately meeting the needs of pediatric patients and their families; (2) care impact - shortcomings, which included: (a) deficiency of individualized care and (b) reduced employment opportunities for skilled nursing staff; and (3) attitude impact, including (a) lifelong learning and (b) integrating culture and technology to meet pediatric care needs. CONCLUSIONS: Robots' application may ameliorate the overall quality of pediatric care, allowing for better apportioning of nurses' time and energies to focus on direct patient care and reducing nurses' workloads. However, some possible disadvantages need attention, including robots' inability to provide genuine human touch, demonstrate human emotions associated with pediatric care, and exhibit cultural sensitivity. It is desirable to embed nursing practice needs in the advanced functions of robots and thereby ensure safe, reliable robotics suitable for pediatric care usage. PRACTICE IMPLICATIONS: The findings can be used as a reference for nurses encountering challenges in working with robots, and for lifelong learning needs for pediatric nurses.

Color rendering based on a plasmon fullerene cavity.

Fullerene in the plasmon fullerene cavity is utilized to propagate plasmon energy in order to break the confinement of the plasmonic coupling effect, which relies on the influential near-field optical region. It acts as a plasmonic inductor for coupling gold nano-islands to the gold film; the separation distances of the upper and lower layers are longer than conventional plasmonic cavities. This coupling effect causes the discrete and continuum states to cooperate together in a cavity and produces asymmetric curve lines in the spectra, producing a hybridized resonance. The effect brings about a bright and saturated displaying film with abundant visible colors. In addition, the reflection spectrum is nearly omnidirectional, shifting by only 5% even when the incident angle changes beyond ± 60°. These advantages allow plasmon fullerene cavities to be applied to reflectors, color filters, visible chromatic sensors, and large-area display.

Uremic Pruritus is Associated with Two-Year Cardiovascular Mortality in Long Term Hemodialysis Patients.

BACKGROUND/AIMS: Uremic pruritus (UP) is an unpleasant complication in patients undergoing maintenance dialysis. Cardiovascular and infection related deaths are the major causes of mortality in patients undergoing dialysis. Studies on the correlation between cardiovascular or infection related mortality and UP are limited. METHODS: We analyze 866 maintenance hemodialysis (MHD) patients in our hemodialysis centers. Clinical parameters and 24-month cardiovascular and infection-related mortality are recorded. RESULTS: The associations between all-cause, cardiovascular and infection related mortality with clinical data including UP are analyzed. Multivariate Cox regression demonstrated that UP is a significantly predictor for 24-month cardiovascular mortality in the MHD patients (Hazard ratio: 3.164; 95% confidence interval, 1.743-5.744; p < 0.001). CONCLUSION: Uremic pruritus is one of the predictor of 24-month cardiovascular mortality in MHD patients.

Family Aggregation and Heritability of ESRD in Taiwan: A Population-Based Study.

BACKGROUND: Aggregation of end-stage renal disease (ESRD) has been observed in families of European origin, as well as those of African origin. However, it is not well documented if this disease aggregates in Asian families. Furthermore, the contribution of genetic factors and shared environmental factors to family aggregation remains unclear. STUDY DESIGN: Population-based cross-sectional cohort study. SETTING & PARTICIPANTS: All 23,422,955 individuals registered in the Taiwan National Health Insurance Research Database in 2013. Among these, 47.45%, 57.45%, 47.29%, and 1.51% had a known parent, child, sibling, or twin, respectively. We identified 87,849 patients who had a diagnosis of ESRD. PREDICTOR: Family history of ESRD. OUTCOMES & MEASUREMENTS: ESRD and heritability defined as the proportion of phenotypic variance attributable to genetic factors. RESULTS: Having an affected first-degree relative with ESRD was associated with an adjusted relative risk of 2.46 (95% CI, 2.32-2.62). Relative risks were 96.38 (95% CI, 48.3-192.34) for twins of patients with ESRD, 2.15 (95% CI, 2.02-2.29) for parents, 2.78 (95% CI, 2.53-3.05) for offspring, 4.96 (95% CI, 4.19-5.88) for siblings, and 1.66 (95% CI, 1.54-1.78) for spouses without genetic similarities. Heritability in this study was 31.1% to 11.4% for shared environmental factors and 57.5% for nonshared environmental factors. LIMITATIONS: This was a registry database study and we did not have detailed information about clinical findings or the definite causes of ESRD. CONCLUSIONS: This whole population-based family study in Asia confirmed, in a Taiwanese population, that a family history of ESRD is a strong risk factor for this disease. Moderate heritability was noted and environmental factors were related to disease. Family history of ESRD is an important piece of clinical information.