Thiazide-associated hyponatremia increases the risk of major adverse cardiovascular events among elderly Taiwanese patients.

BACKGROUND: Thiazide-associated hyponatremia (TAH) has been supposed to increase the risk of major adverse cardiovascular events (MACE) in the elderly. Therefore, this study aimed to evaluate the association of TAH with the risk of MACE in elderly Taiwanese patients. METHODS: Data from the longitudinal generation tracking database (LGTD 2010) of the Health and Welfare Data Science Center (HWDC) were retrospectively assessed. The TAH study group was defined as using > 30 cumulative daily defined doses (CDDDs) thiazide diuretics within one year before diagnosis of hyponatremia. The control group (1:3 propensity score matching) had no diagnosis of hyponatremia but had used > 30 CDDDs thiazide diuretics within one year. Data on MACE were extracted using International Classification of Diseases codes. Outcomes were assessed using a multivariable Cox proportional hazard model and Kaplan-Meier analysis. RESULTS: A total of 1155 and 3465 individuals were enrolled in the TAH and the control groups, respectively. The rates of MACE (11.1% vs. 7.3%) and death (22.8% vs.12.2%) were significantly higher in the TAH group than the control group. In the TAH group, the adjusted HRs were 1.29 (CI 1.01 ‒ 1.65) for MACE, 1.39 (CI 1.19 ‒ 1.63) for all-cause death, and 1.61 (CI 0.90 ‒ 2.92) for stroke. CONCLUSION: TAH in patients above 65-years-old is associated with a 29% higher risk of MACE, 39% higher risk of all-cause death, and 61% higher risk of stroke. This work suggests that thiazides prescription in elderly patients should be more careful. However, further research is required to confirm our findings.

Sensor Fusion for Simultaneous Estimation of In-Plane Permeability and Porosity of Fiber Reinforcement in Resin Transfer Molding.

To meet the expectation of the industry, resin transfer molding (RTM) has become one of the most promising polymer processing methods to manufacture fiber-reinforced plastics (FRPs) with light weight, high strength, and multifunctional features. The permeability and porosity of fiber reinforcements are two of the primary properties that control the flow of resin in fibers and are critical to numerical simulations of RTM. In the past, various permeability measurement methods have been developed in the literature. However, limitations still exist. Furthermore, porosity is often measured independently of permeability. As a result, the two measurements do not necessarily relate to the same entity, which may increase the time and labor costs associated with experiments and affect result interpretation. In this work, a measurement system was developed by fusing the signals from capacitive sensing and flow visualization, based on which a novel algorithm was developed. Without complicated sensor design or expensive instrumentation, both in-plane permeability and porosity can be simultaneously estimated. The feasibility of the proposed method was illustrated by experiments and verified with numerical simulations.

Stomatal clustering in Begonia improves water use efficiency by modulating stomatal movement and leaf structure.

Stomata are a pivotal adaptation of land plants and control gas exchange. While most plants present solitary stomata, some plant species experiencing chronic water deficiency display clustered stomata on their epidermis; for instance, limestone-grown begonias. Moreover, the membrane receptor TOO MANY MOUTHS (TMM) plays a major role in spacing stomata on the epidermis in Arabidopsis, but the function of its Begonia orthologs is unknown. We used two Asian begonias, Begonia formosana (single stomata) and B. hernandioides (clustered stomata), to explore the physiological function of stomatal clustering. We also introduced the Begonia TMMs into Arabidopsis tmm mutants to study the function of Begonia TMMs. B. hernandioides showed higher water use efficiency under high light intensity, smaller stomata, and faster pore opening than B. formosana. The short distance between stomata in a cluster may facilitate cell-to-cell interactions to achieve synchronicity in stomatal movement. Begonia TMMs function similarly to Arabidopsis TMM to inhibit stomatal formation, although complementation by TMM from the clustered species was only partial. Stomatal clustering in begonias may represent a developmental strategy to build small and closer stomata to achieve fast responses to light which provides tight support between stomatal development and environmental adaption.

Six new species of Begonia from Guangxi, China.

BACKGROUND: With currently 1980 described species, the mega-diverse Begonia is now perhaps the 5th largest flowering plant genus, expanding rapidly from ca. 900 species in 1997 to its current size in merely two decades. In continuation of our studies of Asian Begonia, we report six additional new species from Guangxi, the region/province harboring the second richest Begonia flora of China. RESULTS: Based on morphological and molecular data, the new species B. aurora belongs to Begonia sect. Platycentrum, while the other five new species (viz. B. larvata, B. longiornithophylla, B. lui, B. scabrifolia, and B. zhuoyuniae) are members of Sect. Coelocentrum. Somatic chromosome numbers of B. longiornithophylla and B. zhuoyuniae at metaphase were counted as 2n = 30, consistent with previously reports for Sect. Coelocentrum. CONCLUSIONS: With the addition of the six new species, the total number of Begonia species in Guangxi increases from 86 to 92. Detailed description, line drawings, and color plates are provided to aid in identification.

H-Ras Transformation of Mammary Epithelial Cells Induces ERK-Mediated Spreading on Low Stiffness Matrix.

Oncogenic transformation of mammary epithelial cells (MECs) is a critical step in epithelial-to-mesenchymal transition (EMT), but evidence also shows that MECs undergo EMT with increasing matrix stiffness; the interplay of genetic and environmental effects on EMT is not clear. To understand their combinatorial effects on EMT, premalignant MCF10A and isogenic Ras-transformed MCF10AT are cultured on polyacrylamide gels ranging from normal mammary stiffness, ≈150 Pa, to tumor stiffness, ≈5700 Pa. Though cells spread on stiff hydrogels independent of transformation, only 10AT cells exhibit heterogeneous spreading behavior on soft hydrogels. Within this mixed population, spread cells exhibit an elongated, mesenchymal-like morphology, disrupted localization of the basement membrane, and nuclear localization of the EMT transcription factor TWIST1. MCF10AT spreading is not driven by typical mechanosensitive pathways including YAP and TGF-ß or by myosin contraction. Rather, ERK activation induces spreading of MCF10AT cells on soft hydrogels and requires dynamic microtubules. These findings indicate the importance of oncogenic signals, and their hierarchy with substrate mechanics, in regulating MEC EMT.

Rapid mechanochemical encapsulation of biocatalysts into robust metal-organic frameworks.

Metal-organic frameworks (MOFs) have recently garnered consideration as an attractive solid substrate because the highly tunable MOF framework can not only serve as an inert host but also enhance the selectivity, stability, and/or activity of the enzymes. Herein, we demonstrate the advantages of using a mechanochemical strategy to encapsulate enzymes into robust MOFs. A range of enzymes, namely ß-glucosidase, invertase, ß-galactosidase, and catalase, are encapsulated in ZIF-8, UiO-66-NH2, or Zn-MOF-74 via a ball milling process. The solid-state mechanochemical strategy is rapid and minimizes the use of organic solvents and strong acids during synthesis, allowing the encapsulation of enzymes into three prototypical robust MOFs while maintaining enzymatic biological activity. The activity of encapsulated enzyme is demonstrated and shows increased resistance to proteases, even under acidic conditions. This work represents a step toward the creation of a suite of biomolecule-in-MOF composites for application in a variety of industrial processes.

Phylogeography of Begonia luzhaiensis suggests both natural and anthropogenic causes for the marked population genetic structure.

BACKGROUND: Sino-Vietnamese limestone karsts (SVLK) are a biodiversity hotspot rich in endemic plant species associated with caves and cave-like microhabitats. Based on phylogenetic studies of Begonia sect. Coelocentrum, a species-rich and characteristic SVLK clade, geographic isolation caused by extensive and continuous karstification was proposed as the major driving force triggering population diversification and geographic speciation. To test this proposition, population genetics and phylogeography of Begonia luzhaiensis were investigated using EST-SSR markers and the chloroplast trnC-ycf6 intergenic spacer. RESULTS: F statistics, Bayesian clustering analysis, AMOVA, and PCoA of both data sets all indicated substantial population differentiation and significant isolation by distance. Nested clade phylogeographic analyses inferred that historical fragmentations have been prominent, congruent with Guangxi's geohistory of karstification as well as suggesting a mountain chain in northeastern Guangxi could have also acted as a major geographic barrier. A Bayesian skyline plot (BSP) indicated a slight decline in effective population size at 75,000 years ago (75 Kya), coinciding with the last glacial period during which the increased aridity in East Asia had retarded karstification, negatively affecting the populations of B. luzhaiensis. However, BSP detected a continuous and further population decline until the present time even though summer monsoons have resumed since the end of the last glacial maximum. CONCLUSIONS: The microevolution patterns of B. luzhaiensis support that limited gene flow would have greatly enhanced the effects of random genetic drift and has been a major factor promoting diversification in Begonia, highly congruent with previous proposition. Based our study, we further propose that the arrival of Paleolithic Homo sapiens whose activities centered around limestone caves could have had further impacts on the populations of B. luzhaiensis, resulting in additional population decline. Further habitat destruction could have resulted from the transition from hunter gathering to food-producing societies ca. 20-10 Kya and the development of agriculture ca. 10 Kya in South China. Implications of the current study for SVLK plant conservation are also discussed.

Comparing the Effect of Folic Acid and Pentoxifylline on Delaying Dialysis Initiation in Patients with Advanced Chronic Kidney Disease.

BACKGROUND: We hypothesized that the nutrient loss and chronic inflammation status may stimulate progression in advanced chronic kidney disease. Therefore, we aimed to generate a study to state the influence of combined nutritional and anti-inflammatory interventions. METHODS: The registry from the National Health Insurance Research Database in Taiwan was searched for 20-90 years individuals who had certified end-stage renal disease. From January 2005 through December 2010, the diagnosis code ICD-9 585 (chronic kidney disease, CKD) plus erythropoiesis-stimulating agent (ESA) use was defined as entering advanced chronic kidney disease. The ESA starting date was defined as the first index date, whereas the initiation day of maintenance dialysis was defined as the second index date. The duration between the index dates was analyzed in different medical treatments. RESULTS: There were 10,954 patients analyzed. The combination therapy resulted in the longest duration (n = 2184, median 145 days, p < 0.001) before the dialysis initiation compared with folic acid (n = 5073, median 111 days), pentoxifylline (n = 1119, median 102 days, p = 0.654), and no drug group (control, n = 2578, median 89 days, p < 0.001). Lacking eGFR data and the retrospective nature are important limitations. CONCLUSIONS: In patients with advanced CKD on the ESA treatment, the combination of folic acid and pentoxifylline was associated with delayed initiation of hemodialysis.

Mechanical activation of noncoding-RNA-mediated regulation of disease-associated phenotypes in human cardiomyocytes.

How common polymorphisms in noncoding genome regions can regulate cellular function remains largely unknown. Here we show that cardiac fibrosis, mimicked using a hydrogel with controllable stiffness, affects the regulation of the phenotypes of human cardiomyocytes by a portion of the long noncoding RNA ANRIL, the gene of which is located in the disease-associated 9p21 locus. In a physiological environment, cultured cardiomyocytes derived from induced pluripotent stem cells obtained from patients who are homozygous for cardiovascular-risk alleles (R/R cardiomyocytes) or from healthy individuals who are homozygous for nonrisk alleles contracted synchronously, independently of genotype. After hydrogel stiffening to mimic fibrosis, only the R/R cardiomyocytes exhibited asynchronous contractions. These effects were associated with increased expression of the short ANRIL isoform in R/R cardiomyocytes, which induced a c-Jun N-terminal kinase (JNK) phosphorylation-based mechanism that impaired gap junctions (particularly, loss of connexin-43 expression) following stiffening. Deletion of the risk locus or treatment with a JNK antagonist was sufficient to maintain gap junctions and prevent asynchronous contraction of cardiomyocytes. Our findings suggest that mechanical changes in the microenvironment of cardiomyocytes can activate the regulation of their function by noncoding loci.

Proton pump inhibitors use and risk of chronic kidney disease in diabetic patients.

AIMS: Chronic kidney disease consumes a huge amount of medical resources and proton pump inhibitors may be a potential factor for the increasing prevalence. This population-based cohort study investigates the risk of chronic kidney disease in a diabetic population using proton pump inhibitors in Taiwan. METHODS: This study is based on a specific diabetic database obtained from the National Health Insurance Research Database. Individuals with a new diagnosis of diabetes from 2002 to 2013 were enrolled. "Exposure" to proton pump inhibitors was defined as at least one prescription and dosage over 180 DDD (defined daily dose) in one year after the index date. A multivariable Cox proportional hazard model and competing-risk regression model were applied. RESULTS: There were 5994 patients in the final cohort of proton pump inhibitor users and 23,976 patients in the matched controlled cohort based on 1:4 propensity score matching. Compared with no exposure users, PPIs exposure group had more anemia prevalence, anti-hypertension medication and NSAIDs prescriptions. The multivariable Cox proportional hazard model showed that the adjusted hazard ratio of chronic kidney disease was 1.52 (95% CI 1.40-1.65) in diabetic individuals with PPIs exposure, compared with no exposure users. CONCLUSIONS: Proton pump inhibitors use is associated with 1.52-fold increased risk of chronic kidney disease in diabetic patients when the dosage is over 180 DDD in one year in Taiwan.

Exploitation of Thermoresponsive Switching Organic Field-Effect Transistors.

In this work, a novel thermoresponsive switching transistor is developed through the rational design of active materials based on the typical field-effect transistor (FET) device configuration, where the active material is composed of a blend of a thermal expansion polymer and a polymeric semiconductor. Herein, polyethylene (PE) is employed as the thermal expansion polymer because of its high volume expansion coefficient near its melting point (90-130 °C), which similarly corresponds to the overheating point that would cause damage or cause fire in the devices. It is revealed that owing to the thermistor property of PE, the FET characteristics of the derived device will be largely decreased at high temperatures (100-120 °C). It is because the high volume expansion of PE at such high temperature (near its T m) effectively increases the distance of the crystalline domains of poly(3-hexylthiophene-2,5-diyl) to result in a great inhibition of current. Besides, the performance of this device will recover back to its original value after cooling from 120 to 30 °C owing to the volume contraction of PE. The reversible FET characteristics with temperature manifest the good thermal sensitivity of the PE-based device. Our results demonstrate a facile and promising approach for the development of next-generation overheating shutdown switches for electrical circuits.

Development and characterization of EST-SSR markers for Begonia luzhaiensis (Begoniaceae).

PREMISE OF THE STUDY: Microsatellite primers were developed for Begonia luzhaiensis (Begoniaceae) to assess genetic diversity and population genetic structure. METHODS AND RESULTS: Based on the transcriptome data of B. luzhaiensis, 60 primer pairs were selected for initial validation, of which 16 yielded polymorphic microsatellite loci in 57 individuals. The number of alleles observed for these 16 loci ranged from one to nine. The observed and expected heterozygosity ranged from 0.000 to 1.000 and from 0.000 to 0.804 with averages of 0.370 and 0.404, respectively. Five loci could be successfully amplified in B. leprosa. CONCLUSIONS: The expressed sequence tag-simple sequence repeat markers are the first specifically developed for B. luzhaiensis and the first developed in Begonia sect. Coelocentrum. These markers will be useful for future studies of the genetic structure and phylogeography of B. luzhaiensis.

Prediction of Mortality in Incident Hemodialysis Patients: A Validation and Comparison of CHADS2, CHA2DS2, and CCI Scores.

BACKGROUND: The CHADS2 and CHA2DS2 scores are usually applied for stroke prediction in atrial fibrillation patients, and the Charlson comorbidity index (CCI) is a commonly used scale for assessing morbidity. The role in assessing mortality with score system in hemodialysis is not clear and comparisons are lacking. We aimed at evaluating CHADS2, CHA2DS2, and CCI scores to predict mortality in incident hemodialysis patients. METHODS: Using data from the Nation Health Insurance system of Taiwan (NHIRD) from 1 January 2005 to 31 December 2009, individuals ≧20 y/o who began hemodialysis identified by procedure code and receiving dialysis for > 3 months were included for our study. Renal transplantation patients after dialysis or PD patients were excluded. We calculated the CHADS2, CHA2DS2, and CCI score according to the ICD-9 code and categorized the patients into three groups in each system: 0-1, 2-3, over 4. A total of 3046 incident hemodialysis patients enrolled from NHIRD were examined for an association between the separate scoring systems (CHADS2, CHA2DS2, and CCI score) and mortality. RESULTS: CHADS2 and CHA2DS2 scores revealed good predictive value for total mortality (CHADS2 AUC = 0.805; CHA2DS2 AUC = 0.790). However, the CCI score did not reveal a similarly satisfying result (AUC = 0.576). CONCLUSIONS: Our results show that CHADS2 and CHA2DS2 scores can be applied for mortality prediction in incident hemodialysis patients.

Sex differences in a Murine Model of Complex Regional Pain Syndrome.

Complex Regional Pain Syndrome (CRPS) is a major cause of chronic pain after surgery or trauma to the limbs. Despite evidence showing that the prevalence and severity of many forms of chronic pain, including CRPS, differ between males and females, laboratory studies on sex-related differences in animal models of CRPS are not available, and the impact of sex on the transition from acute to chronic CRPS pain and disability are unexplored. Here we make use of a tibia fracture/cast mouse model that recapitulates the nociceptive, functional, vascular, trophic, inflammatory and immune aspects of CRPS. Our aim is to describe the chronic time course of nociceptive, motor and memory changes associated with fracture/cast in male and female mice, in addition to exploring their underlying spinal mechanisms. Our behavioral data shows that, compared to males, female mice display lower nociceptive thresholds following fracture in the absence of any differences in ongoing or spontaneous pain. Furthermore, female mice show exaggerated signs of motor dysfunction, deficits in fear memory, and latent sensitization that manifests long after the normalization of nociceptive thresholds. Our biochemical data show differences in the spinal cord levels of the glutamate receptor NR2b, suggesting sex differences in mechanisms of central sensitization that could account for differences in duration and severity of CRPS symptoms between the two groups.

Six new species of Begonia (Begoniaceae) from limestone areas in Northern Vietnam.

BACKGROUND: Species of Begonia are richly represented in limestone karst areas across the Sino-Vietnamese border. More than one hundred species were known, many of which were documented recently. RESULTS: In continuation of our systematic studies of Asian Begonia, we report six species of Begonia that are unknown to science, namely B. caobangensis [sect. Platycentrum], B. circularis, B. melanobullata, B. langsonensis, B.locii and B. montaniformis [sect. Coelocentrum] from Northern Vietnam. Diagnostic features that separate them from morphologically allied species are provided. Somatic chromosome numbers were determined, which supports their placement in the respective sections. Foliar SEM microphotographs were taken and described. CONCLUSION: A careful study of the literature, herbarium specimens and living plants, both in the wild and in cultivation in the experimental greenhouse, supports the recognition of the six new species, which are described and illustrated.

Three new species of Begonia endemic to the Puerto Princesa Subterranean River National Park, Palawan.

BACKGROUND: Begonia is a mega-diverse genus of flowering plants prone to generating micro-endemic species, especially on limestone habitats. During fieldwork in the Puerto Princesa Subterranean River National Park, Palawan (Philippines), three species were encountered which did not match any previously described from the region. RESULTS: Following morphological, anatomical, molecular phylogenetic and cytological investigation a hypothesis of three new species is supported. The three new species belong to a clade endemic to Palawan and Borneo. CONCLUSIONS: The limestone habitats in the Puerto Princesa Subterranean River National Park environs support a unique flora. The description of three new species from a small area within the park demonstrates how much remains to be discovered there, and the importance of its continued protection.

Begonia wuzhishanensis (sect. Diploclinium, Begoniaceae), a new species from Hainan Island, China.

BACKGROUND: Hainan is the largest island of the Indo-Burma Biodiversity Hotspot and has the best preserved and most extensive tropical forests in China. A recent study on distribution of endangered species in China identifies southern Hainan as one of eight hotspots for plant conservation in the country. In continuation of our studies of Asian Begonia, we report the discovery of an attractive undescribed species, B. wuzhishanensis C.-I Peng, X.H. Jin & S.M. Ku, from Hainan Island. RESULTS: Living plant of the new species, Begonia wuzhishanensis, was collected in 2009 and cultivated in the experimental greenhouse for morphological and cytological studies. It flowered consecutively in 2012 and 2013 in the experimental greenhouse, Academia Sinica. It was assigned to the large, heterogeneous sect. Diploclinium. The chromosome number of this new species was determined to be 2n = 26. CONCLUSIONS: A careful study of literature, herbarium specimens and living plants, both in the wild and in cultivation, support the recognition of the new species Begonia wuzhishanensis, which is described in this paper. Begonia wuzhishanensis is currently known only from Fanyang, Wuzhishan Mountain in the center of the island. A line drawing, color plate, and a distribution map are provided to aid in identification.

Begonia wui-senioris (sect. Platycentrum, Begoniaceae), a new species from Myanmar.

BACKGROUND: The flora of Myanmar is under-collected compared with all other tropical Asian countries. An unknown Begonia was grown from seeds collected from a limestone hill in Central Myanmar, and compared with potentially allied species. RESULTS: The unknown Begonia is rhizomatous, has peltate leaves, 2-locular ovaries, and is evergreen. It is clearly assignable to sect. Platycentrum. Only two other species of Begonia, B. josephii and B. subperfoliata, in Myanmar have peltate leaves, but they are deciduous tuberous plants with 3-locular ovaries and belong to sect. Diploclinium. CONCLUSIONS: Thorough studies of literature and herbarium materials support the recognition of a new species, Begonia wui-senioris, which is fully described and illustrated. Begonia wui-senioris has the lowest chromosome number (2n = 14) for the genus.

Two new species of Begonia sect. Coelocentrum, B. guixiensis and B. longa, from Sino-Vietnamese limestone karsts.

BACKGROUND: In our recent molecular phylogenetic study of Asian Begonia, two undescribed species, B. guixiensis sp. ined. (S. Guangxi, China) and B. longa sp. ined. (Vietnam), were sampled and placed within the strongly supported clade composed of Begonia sect. Coelocentrum and other co-distributed rhizomatous species in the Sino-Vietnamese limestone karsts. While Begonia sect. Coelocentrum has been recircumscribed based on the phylogenetic relationships, B. guixiensis sp. ined. and B. longa sp. ined. remain illegitimate names. In continuation of our studies in Asian Begonia, these two new species are described and illustrated. RESULTS: Begonia guixiensis resembles B. cylindrica in the peltate, subcoriaceous leaves, differing by the shape of ovary/fruit and the type of placentation. In aspect, B. longa bears a superficial resemblance to B. brevipedunculata in leaf shape in particular, differing by many other features such as the long internodes, shorter petioles and smaller leaves, longer peduncles and 3-locular ovary. The chromosome number of both new species is determined as 2n = 30. CONCLUSION: A careful study of the literature, herbarium specimens and living plants, both in the wild and in cultivation in the experimental greenhouse, support the recognition of the two new species, which are described and illustrated herein.

Novelties in Begonia sect. Coelocentrum: B. longgangensis and B. ferox from limestone areas in Guangxi, China.

BACKGROUND: The spectacular karst limestone landscape in Guangxi harbors high-level diversity and endemism of Begonia species, especially those of sect. Coelocentrum. In continuation of our studies in this area, we report the discovery of two attractive new species from southwestern Guangxi: Begonia longgangensis and B. ferox. RESULTS: Begonia longgangensis resembles B. liuyanii, also from Longgang Nature Reserve, in the broadly ovate to suborbicular leaf blade, differing by the much smaller leaves, subglabrous leaf surface, pink flowers, dichasial cymes and the remarkably long stolons sent out from rhizomes. Unexpectedly, both diploid (2n = 30) and triploid counts (2n = 45) were observed in plants collected from the type locality. Begonia ferox probably has the most prominent bullate leaves for the genus. In this aspect, it is similar to B. nahangensis reported from northern Vietnam recently, but is readily distinguishable by the ovate, chartaceous leaves with an acuminate apex; tomentose peduncle not exceeding petioles; and the much larger stature in vegetative parts. A diploid count of 2n = 30 was determined for this unique new species. CONCLUSIONS: All available data support the recognition of the two new species. Begonia longgangensis has remarkably long stolons and B. ferox is characterized by the prominent bullate leaves. Line drawings, color plates and comparisons are provided to aid in identification of the novelties.