Stromal Rigidity Stress Accelerates Pancreatic Intraepithelial Neoplasia Progression and Chromosomal Instability via Nuclear Protein Tyrosine Kinase 2 Localization.

Because the mechanotransduction by stromal stiffness stimulates the rupture and repair of the nuclear envelope in pancreatic progenitor cells, accumulated genomic aberrations are under selection in the tumor microenvironment. Analysis of cell growth, micronuclei, and γH2AX foci links to mechanotransduction pressure in vivo during serial orthotopic passages of mouse KrasLSL-G12D/+;Trp53flox/flox;Pdx1-Cre (KPC) cancer cells in the tumor and in migrating through the size-restricted 3-µm micropores. To search for pancreatic cancer cell of origin, analysis of single-cell data sets revealed that the extracellular matrix shapes an alternate route of acinar-ductal transdifferentiation of acinar cells into a central hub of elegantly restrained topoisomerase II α (TOP2A)-overexpressing cancer cells that spread out as unique cancer clusters with copy number amplifications in MYC-PTK2 (protein tyrosine kinase 2) locus and PIK3CA. High-PTK2 expression is associated with 171 differentially methylated CpG loci, 319 differentially expressed genes, and poor overall survival in patients with The Cancer Genome Atlas-PAAD. Abolished RGD-integrin signaling by disintegrin KG blocked the PTK2 phosphorylation, increased cancer apoptosis, decreased VAV1 expression, and prolonged overall survival in the KPC mice. Decreases of α-smooth muscle actin deposition in the CD248 knockout KPC mice remodel the tissue stroma and down-regulated TOP2A expression in the epithelium. In summary, stromal stiffness induces the onset of cells of origin of cancer by ectopic TOP2A expression, and the genomic amplification of MYC-PTK2 locus via alternative transdifferentiation of pancreatic progenitor cells is the vulnerability useful for disintegrin KG treatment against cells-of-origin cancer.

Loss of fragile WWOX gene leads to senescence escape and genome instability.

Induction of DNA damage response (DDR) to ensure accurate duplication of genetic information is crucial for maintaining genome integrity during DNA replication. Cellular senescence is a DDR mechanism that prevents the proliferation of cells with damaged DNA to avoid mitotic anomalies and inheritance of the damage over cell generations. Human WWOX gene resides within a common fragile site FRA16D that is preferentially prone to form breaks on metaphase chromosome upon replication stress. We report here that primary Wwox knockout (Wwox-/-) mouse embryonic fibroblasts (MEFs) and WWOX-knockdown human dermal fibroblasts failed to undergo replication-induced cellular senescence after multiple passages in vitro. Strikingly, by greater than 20 passages, accelerated cell cycle progression and increased apoptosis occurred in these late-passage Wwox-/- MEFs. These cells exhibited γH2AX upregulation and microsatellite instability, indicating massive accumulation of nuclear DNA lesions. Ultraviolet radiation-induced premature senescence was also blocked by WWOX knockdown in human HEK293T cells. Mechanistically, overproduction of cytosolic reactive oxygen species caused p16Ink4a promoter hypermethylation, aberrant p53/p21Cip1/Waf1 signaling axis and accelerated p27Kip1 protein degradation, thereby leading to the failure of senescence induction in Wwox-deficient cells after serial passage in culture. We determined that significantly reduced protein stability or loss-of-function A135P/V213G mutations in the DNA-binding domain of p53 caused defective induction of p21Cip1/Waf1 in late-passage Wwox-/- MEFs. Treatment of N-acetyl-L-cysteine prevented downregulation of cyclin-dependent kinase inhibitors and induced senescence in Wwox-/- MEFs. Our findings support an important role for fragile WWOX gene in inducing cellular senescence for maintaining genome integrity during DDR through alleviating oxidative stress.

Enrichment of mRNA and Bisulfite-mRNA Library Preparation for Next-Generation Sequencing.

RNA post-transcriptional modifications in various types of RNA transcripts are associated with diverse RNA regulation in eukaryotic cells. Aberrant RNA 5-methylcytosine modifications and the dysregulated expression of RNA methyltransferases have been shown to be associated with various diseases, including cancers. Transcriptome-wide bisulfite-sequencing was developed to characterize the positions and the quantitative cytosine methylation levels in the bisulfite-converted RNA at the base-pair resolution. Herein, this protocol presents the procedures of two rounds of poly(A) RNA purification, three cycles of bisulfite reaction, and library preparation in detail to allow the transcriptome-wide mapping of mRNA 5-methylcytosine modification sites. The assessment of RNA quantity and quality after the main reaction is essential to monitor RNA integrity and is a critical step for ensuring high-quality sequencing libraries. Ideally, the procedures can be completed within three days. With this protocol, using high-quality total RNA as the input can practically build up robust bisulfite-mRNA libraries for next-generation sequencing from the sample of interest.

Characteristics of rectal chlamydia among men who have sex with men in southern Taiwan, 2020-2022: An emerging threat of rectal lymphogranuloma venereum L2b.

BACKGROUND: The prevalence of rectal chlamydia among men who have sex with men (MSM) without human deficiency virus infection (non-HIV) remains uncertain in Taiwan, and rectal lymphogranuloma venereum (LGV) among MSM has never been reported in the Far East. MATERIAL AND METHODS: From January 2020 to April 2022, MSM coming for anonymous voluntary counseling and testing, for pre-exposure prophylaxis, and for antiretroviral therapy were enrolled. All participants submitted his fecal samples and completed a QR-code questionnaire. Medical records of those who took regular medical visits for HIV were recorded. Multiplex polymerase chain reaction (PCR) was performed for all fecal samples, and ompA gene sequencing was therefore performed for each Chlamydia-positive fecal sample. RESULTS: Among 341 MSM during 2020-2022 in southern Taiwan, 21 (6.2%) had rectal chlamydia infection. Risk factors of rectal chlamydia included co-infection with rectal gonorrhea (adjusted odds ratio [AOR] 6.78, 95% confidence interval [CI] 1.44-31.91, P = 0.015) and multiple sexual partners (AOR 1.373, 95% CI 1.002-1.882, P = 0.048). Further ompA gene sequencing from 19 Chlamydia-positive fecal samples revealed that the prevalent genotypes or genovariants were Da (26.3%) and L2b (26.3%), followed by B (21.1%), J (14.3%), and G (9.5%). All cases of rectal LGV genovariant L2b presented as acute proctitis with diarrhea, anal pain, or discharge and were treated successfully with prolonged treatment of doxycycline. CONCLUSIONS: Rectal gonorrhea and multiple sexual partners are risk factors for rectal chlamydia. Clinicians in Taiwan should be aware of the emerging threat of rectal LGV among MSM with acute proctitis.

The Risk Factors for Radiolucent Nephrolithiasis among Workers in High-Temperature Workplaces in the Steel Industry.

Workers in high-temperature workplaces with inadequate water supply may exhibit symptoms of chronic dehydration and have increased risk of nephrolithiasis. The aim of this study was to investigate the risk of radiolucent stone formation among workers in a high-temperature workplace and the related risk factors associated with the condition. We collected data from 1681 workers in a steel factory in Southern Taiwan who underwent regular health examinations. Radiolucent stones were defined as positive findings on ultrasound with negative radiographic images. The prevalences of nephrolithiasis and radiolucent stones in this study were 12.0% and 5.1%, respectively. Heat exposure and age were two major risk factors influencing the probability of radiolucent stones. We combined the age and heat exposure into four groups (over and under 35 years of age with and without heat exposure) in a logistic regression. For workers younger than 35 years, the odds ratio of radiolucent stones was 2.695 (95% confidence interval: 1.201-6.049) in workers with heat exposure compared to workers without. Our investigation further demonstrated that heat exposure was a main risk factor for radiolucent stone formation. In conclusion, our identification of heat exposure as an independent factor for radiolucent stone development in steel workers highlights the need for attention to be paid to those working in similar environments.

TGFß: Signaling Blockade for Cancer Immunotherapy.

Discovered over four decades ago, transforming growth factor ß (TGFß) is a potent pleiotropic cytokine that has context-dependent effects on most cell types. It acts as a tumor suppressor in some cancers and/or supports tumor progression and metastasis through its effects on the tumor stroma and immune microenvironment. In TGFß-responsive tumors it can promote invasion and metastasis through epithelial-mesenchymal transformation, the appearance of cancer stem cell features, and resistance to many drug classes, including checkpoint blockade immunotherapies. Here we consider the biological activities of TGFß action on different cells of relevance toward improving immunotherapy outcomes for patients, with a focus on the adaptive immune system. We discuss recent advances in the development of drugs that target the TGFß signaling pathway in a tumor-specific or cell type-specific manner to improve the therapeutic window between response rates and adverse effects.

Exposure to ambient air pollutants with kidney function decline in chronic kidney disease patients.

Chronic kidney disease (CKD) has been a global public health problem with many adverse outcomes, but data are lacking regarding the relationship between air pollutants and risk of renal progression in patients with CKD. This study was to investigate whether 1-year average exposure to ambient air pollutants -CO, NO, NO2, SO2, O3, PM2.5, and PM10-is related to renal function deterioration among patients with CKD. A total of 5301 CKD patients were included in this study between October 2008 and February 2016. To estimate each patient's exposure to ambient air pollution, we used the 24-h ambient air pollution concentration monitoring data collected one year prior to renal progression or their last renal function assessment. Renal progression was considered when estimated glomerular filtration rate (eGFR) decreased more than 25% from the baseline eGFR. Cox proportional hazard regression was performed to calculate hazard ratios (HRs). Among 5301 patients with CKD, 1813 (34.20%) developed renal progression during the 30.48 ± 14.99-month follow-up. Patients with the highest quartile exposure to CO [HR = 1.53 (95% CI: 1.24, 1.88)], NO [HR = 1.38 (95% CI: 1.11, 1.71)], NO2 [HR = 1.63 (95% CI: 1.36, 1.97)], SO2 [HR = 2.27 (95% CI: 1.83, 2.82)], PM2.5 [HR = 7.58 (95% CI: 5.97, 9.62)], and PM10 [HR = 3.68 (95% CI: 2.84, 4.78)] had a significantly higher risk of renal progression than those with the lowest quartile exposure. In the multipollutant model, the analyses yielded to similar results. These results reinforce the importance of measures to mitigate air pollution and strategies to prevent worsening of kidney function in patients with CKD. One-year high exposure to ambient CO, NO, NO2, SO2, PM2.5, and PM10 is significantly associated with deteriorated kidney function in patients with CKD among Taiwanese adults.

Renal replacement therapy and concurrent fluconazole therapy increase linezolid-related thrombocytopenia among adult patients.

Linezolid has been reported to be associated with thrombocytopenia. However, limited information is available on susceptibility to thrombocytopenia after linezolid usage. We aimed to investigate the risk factors for linezolid-associated thrombocytopenia (LAT). We conducted a retrospective cohort study of patients aged ≥ 18 years who received linezolid for ≥ 5 d during hospitalization in 2019. Information was extracted from electronic medical records. Thrombocytopenia was defined as a platelet count of < 100 × 109/L or a reduction from baseline ≥ 25%. Binary logistic regression and survival analyses were used to evaluate the risk factors for LAT. A total of 98 patients were enrolled. Thrombocytopenia occurred in 53.1% patients, with a median of 9 d after initiation of linezolid. There was no significant difference in the mortality or proportion of platelet transfusions between patients with and without thrombocytopenia. A higher risk of LAT was found in patients who received renal replacement therapy (RRT) (OR 4.8 [1.4-16.4]), or concurrent fluconazole (OR 3.5 [1.2-9.8]). Patients who received RRT (8 vs. 15 d) or concurrent fluconazole (11 vs. 15 d) had a shorter median time to develop thrombocytopenia. Those who simultaneously received RRT and fluconazole had the shortest median of time (6.5 d) and the highest risk of developing thrombocytopenia (87.5%).

Urban Air Pollution and Subclinical Atherosclerosis in Adolescents and Young Adults.

PURPOSE: The contribution of air pollution to subclinical atherosclerosis in a young population remains limited. This study aimed to assess whether long-term exposure to urban air pollutants increases carotid intima-media thickness (CIMT) in adolescents and young adults. METHODS: This study included 789 subjects between the ages of 12 and 30 years who lived in the Taipei metropolis from a cohort of young Taiwanese individuals. Residential addresses were geocoded, and annual average concentrations of particulate matter (PM) of different diameters, e.g., PM10, PM2.5-10, PM2.5, and nitrogen oxides (NOX), were assessed using land use regression models. The generalized least squares strategy with error term to consider the cluster effect of living addresses between individuals was used to examine the associations between urban air pollution and CIMTs. RESULTS: After adjusting for potential confounders, we found that interquartile range increases in PM2.5 (8.2 µg/m3) and NOX (17.5 µg/m3) were associated with 0.46% (95% CI: 0.02-0.90) and 1.00% (95% CI: 0.10-1.91) higher CIMTs, respectively. Stratified analyses showed that the relationships between CIMT and PM2.5 and NOX were more evident in subjects who were 18 years or older, female, nonsmoking, nonhypertensive, and nonhyperglycemic than in their respective counterparts. DISCUSSION: Long-term exposure to PM2.5 and NOX is associated with subclinical atherosclerosis in a young population. Age, sex, and health status may influence the vulnerability of air pollution-associated subclinical atherosclerosis.

RNA bisulfite sequencing reveals NSUN2-mediated suppression of epithelial differentiation in pancreatic cancer.

Posttranscriptional modifications in RNA have been considered to contribute to disease pathogenesis and tumor progression. NOL1/NOP2/Sun domain family member 2 (NSUN2) is an RNA methyltransferase that promotes tumor progression in several cancers. Pancreatic cancer relapse inevitably occurs even in cases where primary tumors have been successfully treated. Associations of cancer progression due to reprogramming of the cancer methyl-metabolome and the cancer genome have been noted, but the effect of base modifications, namely 5-methylcytosine (m5C), in the transcriptome remains unclear. Aberrant regulation of 5-methylcytosine turnover in cancer may affect posttranscriptional modifications in coding and noncoding RNAs in disease pathogenesis. Mutations in NSUN2 have been reported as drivers of neurodevelopmental disorders in mice, and upregulated expression of NSUN2 in tumors of the breast, bladder, and pancreas has been reported. In this study, we conducted mRNA whole transcriptomic bisulfite sequencing to categorize NSUN2 target sites in the mRNA of human pancreatic cancer cells. We identified a total of 2829 frequent m5C sites in mRNA from pancreatic cancer cells. A total of 90.9% (2572/2829) of these m5C sites were mapped to annotated genes in autosomes and sex chromosomes X and Y. Immunohistochemistry staining confirmed that the NSUN2 expression was significantly upregulated in cancer lesions in the LSL-KrasG12D/+;Trp53fl/fl;Pdx1-Cre (KPC) spontaneous pancreatic cancer mouse model induced by Pdx1-driven Cre/lox system expressing mutant KrasG12D and p53 deletion. The in vitro phenotypic analysis of NSUN2 knockdown showed mild effects on pancreatic cancer cell 2D/3D growth, morphology and gemcitabine sensitivity in the early phase of tumorigenesis, but cumulative changes after multiple cell doubling passages over time were required for these mutations to accumulate. Syngeneic transplantation of NSUN2-knockdown KPC cells via subcutaneous injection showed decreased stromal fibrosis and restored differentiation of ductal epithelium in vivo. SIGNIFICANCE: Transcriptome-wide mRNA bisulfite sequencing identified candidate m5C sites of mRNAs in human pancreatic cancer cells. NSUN2-mediated m5C mRNA metabolism was observed in a mouse model of pancreatic cancer. NSUN2 regulates cancer progression and epithelial differentiation via mRNA methylation.

Urban Fine Particulate Matter and Elements Associated with Subclinical Atherosclerosis in Adolescents and Young Adults.

The relationships between the elemental constituents of PM2.5 and atherosclerosis remain limited, especially in young populations. This study included 755 subjects aged 12-30 years in the Taipei metropolis. A land use regression model was used to estimate residential annual mean concentrations of PM2.5 and eight elemental constituents. We evaluated the percent differences in carotid intima-media thickness (CIMT) with PM2.5 and elemental constituent exposures by linear regressions. Interquartile range increments for PM2.5 (4.5 µg/m3), sulfur (108.6 ng/m3), manganese (2.0 ng/m3), iron (34.5 ng/m3), copper (3.6 ng/m3), and zinc (20.7 ng/m3) were found to associate with 0.92% (95% confidence interval (CI): 0.17-1.66), 0.51% (0.02-1.00), 0.36% (0.05-0.67), 0.98% (0.15-1.82), 0.74% (0.01-1.48), and 1.20% (0.33-2.08) higher CIMTs, respectively. Factor analysis identified four air pollution source-related factors, and the factors interpreted as traffic and industry sources were associated with higher CIMTs. Stratified analyses showed the estimates were more evident in subjects who were ≥18 years old, females, or who had lower household income. Our study results provide new insight into the impacts of source-specific air pollution, and future research on source-specific air pollution effects in young populations, especially in vulnerable subpopulations, is warranted.

How Communities of Marine Stramenopiles Varied with Environmental and Biological Variables in the Subtropical Northwestern Pacific Ocean.

MArine STramenopiles (MASTs) have been recognized as parts of heterotrophic protists and contribute substantially to protist abundances in the ocean. However, little is known about their spatiotemporal variations with respect to environmental and biological factors. The objectives of this study are to use canonical correspondence analysis to investigate how MASTs communities are shaped by environmental variables, and co-occurrence networks to examine their potential interactions with prokaryotic communities. Our dataset came from the southern East China Sea (sECS) in the subtropical northwestern Pacific, and involved 14 cruises along a coastal-oceanic transect, each of which sampled surface water from 4 to 7 stations. MASTs communities were revealed by metabarcoding of 18S rDNA V4 region. Most notably, MAST-9 had a high representation in warm waters in terms of read number and diversity. Subclades of MAST-9C and -9D showed slightly different niches, with MAST-9D dominating in more coastal waters where concentrations of nitrite and Synechococcus were higher. MAST-1C was a common component of colder water during spring. Overall, canonical correspondence analysis showed that MASTs communities were significantly influenced by temperature, nitrite and Synechococcus concentrations. The co-occurrence networks showed that certain other minor prokaryotic taxa can influence MAST communities. This study provides insight into how MASTs communities varied with environmental and biological variables.

Integrin αvß8 on T cells suppresses anti-tumor immunity in multiple models and is a promising target for tumor immunotherapy.

αvß8 integrin, a key activator of transforming growth factor ß (TGF-ß), inhibits anti-tumor immunity. We show that a potent blocking monoclonal antibody against αvß8 (ADWA-11) causes growth suppression or complete regression in syngeneic models of squamous cell carcinoma, mammary cancer, colon cancer, and prostate cancer, especially when combined with other immunomodulators or radiotherapy. αvß8 is expressed at the highest levels in CD4+CD25+ T cells in tumors, and specific deletion of ß8 from T cells is as effective as ADWA-11 in suppressing tumor growth. ADWA-11 increases expression of a suite of genes in tumor-infiltrating CD8+ T cells normally inhibited by TGF-ß and involved in tumor cell killing, including granzyme B and interferon-γ. The in vitro cytotoxic effect of tumor CD8 T cells is inhibited by CD4+CD25+ cells, and this suppressive effect is blocked by ADWA-11. These findings solidify αvß8 integrin as a promising target for cancer immunotherapy.

The shape and dynamics of deformations of viscoelastic fluids by water droplets.

Many studies on the deformation of soft films by liquids confirmed the increase in the radius of the deformation and the decrease in the apparent contact angle. However, due to the thinness, the dynamics of the deformation could not be observed until the thermodynamic equilibrium. Thus, the dynamics on thick soft materials was studied until equilibrium to contrast the effect of different interfacial energy between different soft materials and water. Therefore, we prepared two different polymeric fluids with similar rheology by cross-linking monomers, yet with different contact angles with water. Sometime after water droplets were placed on these thick polymers, 3D profiles of the deformation were recorded. Though the effect of the surface tension was not verified, the same trend in the dynamics was observed as with thin films, except for the decrease in the radius after the initial increase. The three-phase boundaries (TPBs) were found not at the apex of the ridges formed during the transition to equilibrium. By calculating the surface tensions and angles of each interface at the equilibrium, we found that the temporary imbalance among surface tensions induced the slip of the TPBs toward the center of water droplets, thus dislocating the TPBs and decreasing the radius.

Urban Open Space Is Associated with Better Renal Function of Adult Residents in New Taipei City.

The purpose of this study is to explore the association between proximity to open space and adult renal function. This was a cross-sectional study. Adult residents of Taipei metropolis were recruited in the analysis. The proximity of each subject to open space was measured using the Geographic Information System. Residents were divided into two groups: with and without chronic kidney disease (CKD). We made univariable comparisons between the two groups. The logistic regression models were used to estimate the odds ratio of CKD. Forest plot was used to examine the effect of interaction between distance to open space and subgroup variable on CKD. A total number of 21,656 subjects with mean age 53.6 years were enrolled in the study. Of the subjects, 2226 (10.28%) had CKD. The mean and standard deviation of distance to open space were 117.23 m and 80.19 m, respectively. Every 100 m distance to open space was associated with an odds ratio of 1.071 for CKD. Subgroup analysis revealed that residents of female, without hypertension, or without impaired fasting glucose (IFG) living more than 200 m from open spaces have greater odds of CKD than those living less than 200 m. Conclusions: Proximity to open space was associated with a lower prevalence of CKD among adults in Taiwan. Such association was enhanced among females and healthy adults without hypertension or impaired fasting glucose (IFG).

Time-Dependent Physicochemical Changes of Carbonate Surfaces from SmartWater (Diluted Seawater) Flooding Processes for Improved Oil Recovery.

Over the past few decades, field- and laboratory-scale studies have shown enhancements in oil recovery when reservoirs, which contain high-salinity formation water (FW), are waterflooded with modified-salinity salt water (widely referred to as the low-salinity, dilution, or SmartWater effect for improved oil recovery). In this study, we investigated the time dependence of the physicochemical processes that occur during diluted seawater (i.e., SmartWater) waterflooding processes of specific relevance to carbonate oil reservoirs. We measured the changes to oil/water/rock wettability, surface roughness, and surface chemical composition during SmartWater flooding using 10-fold-diluted seawater under mimicked oil reservoir conditions with calcite and carbonate reservoir rocks. Distinct effects due to SmartWater flooding were observed and found to occur on two different timescales: (1) a rapid (<15 min) increase in the colloidal electrostatic double-layer repulsion between the rock and oil across the SmartWater, leading to a decreased oil/water/rock adhesion energy and thus increased water wetness and (2) slower (>12 h to complete) physicochemical changes of the calcite and carbonate reservoir rock surfaces, including surface roughening via the dissolution of rock and the reprecipitation of dissolved carbonate species after exchanging key ions (Ca2+, Mg2+, CO32-, and SO42- in carbonates) with those in the flooding SmartWater. Our experiments using crude oil from a carbonate reservoir reveal that these reservoir rock surfaces are covered with organic-ionic preadsorbed films (ad-layers), which the SmartWater removes (detaches) as flakes. Removal of the organic-ionic ad-layers by SmartWater flooding enhances oil release from the surfaces, which was found to be critical to increasing the water wetness and significantly improving oil removal from carbonates. Additionally, the increase in water wetness is further enhanced by roughening of the rock surfaces, which decreases the effective contact (interaction) area between the oil and rock interfaces. Furthermore, we found that the rate of these slower physicochemical changes to the carbonate rock surfaces increases with increasing temperature (at least up to an experimental temperature of 75 °C). Our results suggest that the effectiveness of improved oil recovery from SmartWater flooding depends strongly on the formation of the organic-ionic ad-layers. In oil reservoirs where the ad-layer is fully developed and robust, injecting SmartWater would lead to significant removal of the ad-layer and improved oil recovery.

Rates of cavity filling by liquids.

Understanding the fundamental wetting behavior of liquids on surfaces with pores or cavities provides insights into the wetting phenomena associated with rough or patterned surfaces, such as skin and fabrics, as well as the development of everyday products such as ointments and paints, and industrial applications such as enhanced oil recovery and pitting during chemical mechanical polishing. We have studied, both experimentally and theoretically, the dynamics of the transitions from the unfilled/partially filled (Cassie-Baxter) wetting state to the fully filled (Wenzel) wetting state on intrinsically hydrophilic surfaces (intrinsic water contact angle <90°, where the Wenzel state is always the thermodynamically favorable state, while a temporary metastable Cassie-Baxter state can also exist) to determine the variables that control the rates of such transitions. We prepared silicon wafers with cylindrical cavities of different geometries and immersed them in bulk water. With bright-field and confocal fluorescence microscopy, we observed the details of, and the rates associated with, water penetration into the cavities from the bulk. We find that unconnected, reentrant cavities (i.e., cavities that open up below the surface) have the slowest cavity-filling rates, while connected or non-reentrant cavities undergo very rapid transitions. Using these unconnected, reentrant cavities, we identified the variables that affect cavity-filling rates: (i) the intrinsic contact angle, (ii) the concentration of dissolved air in the bulk water phase (i.e., aeration), (iii) the liquid volatility that determines the rate of capillary condensation inside the cavities, and (iv) the presence of surfactants.

Number of cholangitis episodes as a prognostic marker to predict timing of liver transplantation in biliary atresia patients after Kasai portoenterostomy.

BACKGROUND: Cholangitis may affect liver failure of biliary atresia (BA) patients after Kasai portoenterostomy (KP). We examined whether the number of cholangitis episodes could be a prognostic marker for liver transplant (LT) in children with BA after Kasai portoenterostomy (KP). METHODS: Data for BA patients born after 1998 and undergoing KP were obtained from National Health Insurance Research Database (NHIRD), Taiwan. Patients were followed up until the end of 2011. Incidence and the number of cholangitis episodes were recorded and compared between patients based on LT status. RESULTS: Ninety-six (26.8%) of the 366 BA patients underwent LT. More patients who underwent KP at < 60 days of age survived with their native liver (P = 0.007). The mean age at first cholangitis was 0.9 years and 0.8 years in the LT and non-LT groups, respectively (P = 0.868). The cumulative incidence of cholangitis within 2 years after KP did not differ between the groups (hazard ratio 1.2; 95% CI 0.9-1.6). However, the total number of cholangitis episodes was higher in the LT group within 2 years after KP (P < 0.001). CONCLUSIONS: Cholangitis occurrence was not related to LT in the first 2 years after KP in BA patients, but the number of cholangitis episodes could be a prognostic marker for future LT.

Cyclodextrin-assisted dispersive liquid-liquid microextraction for the preconcentration of carbamazepine and clobazam with subsequent sweeping micellar electrokinetic chromatography.

A new version of dispersive liquid-liquid microextraction, namely, cyclodextrin-assisted dispersive liquid-liquid microextraction, with subsequent sweeping micellar electrokinetic chromatography has been developed for the preconcentration and sensitive detection of carbamazepine and clobazam. α-Cyclodextrin and chloroform were used as the dispersive agent and extraction solvent, respectively. After the extraction, carbamazepine and clobazam were analyzed using micellar electrokinetic chromatography with ultraviolet detection. The detection sensitivity was further enhanced using the sweeping technique. Under optimal extraction and stacking conditions, the calibration curves of carbamazepine and clobazam were linear over a concentration range of 2.0-200.0 ng/mL. The method detection limits at a signal-to-noise ratio of 3 were 0.6 and 0.5 ng/mL with sensitivity enhancement factors of 3575 and 4675 for carbamazepine and clobazam, respectively. This developed method demonstrated high sensitivity enhancement factors and was successfully applied to the determination of carbamazepine and clobazam in human urine samples. The precision and accuracy for urine samples were less than 4.2 and 6.9%, respectively.

Traffic-related air pollution associated with chronic kidney disease among elderly residents in Taipei City.

The associations of air pollution with chronic kidney disease (CKD) have not yet been fully studied. We enrolled 8,497 Taipei City residents older than 65 years and calculated the estimated glomerular filtration rate (eGFR) using the Taiwanese Chronic Kidney Disease Epidemiology Collaboration equation. Proteinuria was assessed via dipstick on voided urine. CKD prevalence and risk of progression were defined according to the KDIGO 2012 guidelines. Land-use regression models were used to estimate the participants' one-year exposures to PM of different sizes and traffic-related exhaust, PM2.5 absorbance, nitrogen dioxide (NO2), and NOx. Generalized linear regressions and logistic regressions were used to examine the associations of one-year air pollution exposures with eGFR, proteinuria, CKD prevalence and risk of progression. The results showed that the interquartile range (IQR) increments of PM2.5 absorbance (0.4 × 10-5/m) and NO2 (7.0 µg/m3) were associated with a 1.07% [95% confidence interval (CI): 0.54-1.57] and 0.84% (95% CI: 0.37-1.32) lower eGFR, respectively; such relationships were magnified in subjects who had an eGFR >60 ml/min/1.73 m2 or who were non-diabetic. Similar associations were also observed for PM10 and PM2.5-10. Two-pollutant models showed that PM10 and PM2.5 absorbance were associated with a lower eGFR. The odd ratios (ORs) of CKD prevalence and risk of progression also increased with exposures to PM2.5 absorbance and NO2. In summary, one-year exposures to traffic-related air pollution were associated with lower eGFR, higher CKD prevalence, and increased risk of CKD progression among the elderly population. Air pollution-related impaired renal function was stronger in non-CKD and non-diabetic subjects.