With the aim of gathering temporal trends on bacterial epidemiology and resistance from multiple laboratories in China, the CHINET surveillance system was organized in 2005. Antimicrobial ...susceptibility testing was carried out according to a unified protocol using the Kirby-Bauer method or automated systems. Results were analyzed according to Clinical and Laboratory Standards Institute (CLSI) 2014 definitions. Between 2005 and 2014, the number of bacterial isolates ranged between 22 774 and 84 572 annually. Rates of extended-spectrum β-lactamase production among Escherichia coli isolates were stable, between 51.7 and 55.8%. Resistance of E. coli and Klebsiella pneumoniae to amikacin, ciprofloxacin, piperacillin/tazobactam and cefoperazone/sulbactam decreased with time. Carbapenem resistance among K. pneumoniae isolates increased from 2.4 to 13.4%. Resistance of Pseudomonas aeruginosa strains against all of antimicrobial agents tested including imipenem and meropenem decreased with time. On the contrary, resistance of Acinetobacter baumannii strains to carbapenems increased from 31 to 66.7%. A marked decrease of methicillin resistance from 69% in 2005 to 44.6% in 2014 was observed for Staphylococcus aureus. Carbapenem resistance rates in K. pneumoniae and A. baumannii in China are high. Our results indicate the importance of bacterial surveillance studies.
Morbidity and mortality from tuberculosis (TB) are high in Taiwan. We conducted a nationwide population‐based matched cohort study using data retrieved from the Taiwan's National Health Insurance ...Research Database to determine the impact of TB after liver transplantation (LT). During 2000–2011, we identified 3202 liver transplant recipients and selected subjects from the general population matched for age, sex, and comorbidities on the same index date of recognition of LT with a 1:10 ratio. The data were analyzed using Cox proportional hazards models. Compared to the matched cohort, liver transplant patients had a higher risk for TB (adjusted HR 2.25, 95% CI 1.65–3.05, p < 0.001), and those with TB showed higher mortality (HR 2.27, 95% CI 1.30–3.97, p = 0.004). Old age (HR 2.64, 95% CI 1.25–5.54, p = 0.011) and mammalian target of rapamycin inhibitors (mTORis) (HR 3.09, 95% CI 1.68–5.69, p < 0.001) were significant risk factors for TB in LT; mTORis were also associated with mortality after adjusting for confounders (HR 2.13, 95% CI 1.73–2.62, p < 0.001). Therefore, regular surveillance of TB and treatment of latent TB infection in high‐risk patients after LT are important, especially in TB‐endemic areas.
The authors demonstrate the high risk of tuberculosis in liver transplant recipients and define old age and mammalian target of rapamycin inhibitors as risk factors for tuberculosis after liver transplantation, which provides a practical guide to selecting high‐risk liver transplant patients for regular surveillance and treatment of tuberculosis.
There are still no effective therapies for hyposalivation caused by irradiation. In our previous study, bone marrow stem cells can be transdifferentiated into acinar-like cells in vitro. Therefore, ...we hypothesized that transplantation with bone marrow stem cells or acinar-like cells may help functional regeneration of salivary glands. Bone marrow stem cells were labeled with nanoparticles and directly co-cultured with acinar cells to obtain labeled acinar-like cells. In total, 140 severely combined immune-deficiency mice were divided into 4 groups for cell therapy experiments: (1) normal mice, (2) mice receiving irradiation around their head-and-neck areas; (3) mice receiving irradiation and intra-gland transplantation with labeled stem cells; and (4) mice receiving irradiation and intra-gland transplantation with labeled acinar-like cells. Our results showed that salivary glands damaged due to irradiation can be rescued by cell therapy with either bone marrow stem cells or acinar-like cells for recovery of saliva production, body weight, and gland weight. Transdifferentiation of bone marrow stem cells into acinar-like cells in vivo was also noted. This study demonstrated that cell therapy with bone marrow stem cells or acinar-like cells can help functional regeneration of salivary glands, and that acinar-like cells showed better therapeutic potentials than those of bone marrow stem cells.
Abstract Induced pluripotent stem cells (iPSCs) hold great promise as a cell source for regenerative medicine yet its culture, maintenance of pluripotency and induction of differentiation remain ...challenging. Conversely, graphene (G) and graphene oxide (GO) have captured tremendous interests in the fields of materials science, physics, chemistry and nanotechnology. Here we report on that G and GO can support the mouse iPSCs culture and allow for spontaneous differentiation. Intriguingly, G and GO surfaces led to distinct cell proliferation and differentiation characteristics. In comparison with the glass surface, iPSCs cultured on the G surface exhibited similar degrees of cell adhesion and proliferation while iPSCs on the GO surface adhered and proliferated at a faster rate. Moreover, G favorably maintained the iPSCs in the undifferentiated state while GO expedited the differentiation. The iPSCs cultured on both G and GO surfaces spontaneously differentiated into ectodermal and mesodermal lineages without significant disparity, but G suppressed the iPSCs differentiation towards the endodermal lineage whereas GO augmented the endodermal differentiation. These data collectively demonstrated that the different surface properties of G and GO governed the iPSCs behavior and implicate the potentials of graphene-based materials as a platform for iPSCs culture and diverse applications.
Abstract
Background
The role of Helicobacter pylori (H. pylori) infection in the development of colorectal neoplasia has been a matter of scientific debate with controversial findings.
Aims
This ...study examined the association between H. pylori infection and colorectal cancer (CRC) in a nationwide population-based Chinese cohort study.
Methods
A total of approximately 3936 individuals with newly diagnosed H. pylori infection (the H. pylori-infected cohort) and 15 744 age- and sex-matched patients with diagnoses absence of H. pylori infection (the comparison cohort) from 2000 to 2005 were identified from Taiwan’s National Health Insurance Research Database. The Kaplan–Meier method was used for measuring the cumulative incidence of CRC in each cohort. Cox proportional hazards models were used to compute hazard ratios (HRs) and accompanying 95% confidence intervals (CIs) for the estimation of the association between H. pylori infection and CRC.
Results
The cumulative incidence of CRC was higher in H. pylori-infected cohort than that in the comparison cohort (log-rank test, P < 0.001). After adjustment for potential confounders, H. pylori infection was associated with a significantly increased risk of CRC (adjusted HR 1.87; 95% CI 1.37–2.57). In addition, the HR of CRC appeared to increase with increasing frequency of clinical visits for H. pylori infection.
Conclusions
Our study demonstrated that H. pylori infection was associated with an increased risk of CRC, which warrants confirmation and exploration of the underlying biologic mechanisms by future studies.
The material class of rare earth nickelates with high Ni3+ oxidation state is generating continued interest due to the occurrence of a metal-insulator transition with charge order and the appearance ...of non-collinear magnetic phases within this insulating regime. The recent theoretical prediction for superconductivity in LaNiO3 thin films has also triggered intensive research efforts. LaNiO3 seems to be the only rare earth nickelate that stays metallic and paramagnetic down to lowest temperatures. So far, centimeter-sized impurity-free single crystal growth has not been reported for the rare earth nickelates material class since elevated oxygen pressures are required for their synthesis. Here, we report on the successful growth of centimeter-sized LaNiO3 single crystals by the floating zone technique at oxygen pressures of up to 150 bar. Our crystals are essentially free from Ni2+ impurities and exhibit metallic properties together with an unexpected but clear antiferromagnetic transition.
Summary
Background HLA‐Cw*06 has a strong influence on the clinical features and the susceptibility to psoriasis in different ethnicities. It is also used as a biomarker to predict the therapeutic ...efficacy of biologics, with inconsistent results. Additionally, most Asian patients with psoriasis do not carry HLA‐Cw*06.
Objectives To determine additional HLA alleles which confer susceptibility or affect the severity of psoriasis in Chinese Han individuals. In addition, the potential of using HLA to predict treatment outcomes was also investigated.
Methods We conducted a case–control association study in 199 Chinese patients with psoriasis and 200 unrelated healthy controls. HLA‐B and HLA‐C genotyping was performed and correlated with the therapeutic efficacy of the biologics, including alefacept, efalizumab, etanercept and ustekinumab. Patients with psoriasis were divided into group A (high‐need patients with moderate to severe psoriasis) and B (general patients with psoriasis).
Results The frequencies of HLA‐B*60, HLA‐B*75, HLA‐Cw*06 and HLA‐Cw*10 were significantly increased in patients with psoriasis compared with the healthy controls. However, the prevalence of HLA‐Cw*06 was lower in group A compared with group B (6% vs. 17%, Pc = 0·04). HLA‐B*46 was found to be strongly associated with group A but not with group B patients with psoriasis. HLA‐Cw*01/HLA‐B*46 was also identified as a risk haplotype for Chinese patients with psoriasis, compatible with the results in Thais. Significant differences in response to biologics were observed between HLA‐Cw*01+ and HLA‐Cw*01− individuals in the alefacept treatment group, and between HLA‐B*37+ and HLA‐B*37−, and HLA‐B*58+ and HLA‐B*58− individuals in the efalizumab treatment group.
Conclusions In addition to HLA‐Cw*06, the HLA‐Cw*01/HLA‐B*46 haplotype was also increased in Chinese patients with psoriasis. High‐need patients with psoriasis had a lower frequency of HLA‐Cw*06 but a higher prevalence of HLA‐B*46 compared with general patients with psoriasis in our population.
SB1518 is an innovative pyrimidine-based macrocycle that shows a unique kinase profile with selective inhibition of Janus Kinase-2 (JAK2; IC50=23 and 19 nM for JAK2(WT) and JAK2(V617F), respectively) ...within the JAK family (IC50=1280, 520 and 50 nM for JAK1, JK3 and TYK2, respectively) and fms-like tyrosine kinase-3 (FLT3; IC50=22 nM). SB1518 shows potent effects on cellular JAK/STAT pathways, inhibiting tyrosine phosphorylation on JAK2 (Y221) and downstream STATs. As a consequence SB1518 has potent anti-proliferative effects on myeloid and lymphoid cell lines driven by mutant or wild-type JAK2 or FLT3, resulting from cell cycle arrest and induction of apoptosis. SB1518 has favorable pharmacokinetic properties after oral dosing in mice, is well tolerated and significantly reduces splenomegaly and hepatomegaly in a JAK2(V617F)-driven disease model. SB1518 dose-dependently inhibits intra-tumor JAK2/STAT5 signaling, leading to tumor growth inhibition in a subcutaneous model generated with SET-2 cells derived from a JAK2(V617F) patient with megakaryoblastic leukemia. Moreover, SB1518 is active against primary erythroid progenitor cells sampled from patients with myeloproliferative disease. In summary, SB1518 has a unique profile and is efficacious and well tolerated in JAK2-dependent models. These favorable properties are now being confirmed in clinical studies in patients with myelofibrosis and lymphoma.
Background and purpose
To assess the efficacy of various antiepileptic drugs (AEDs) for controlling post‐stroke epilepsy.
Methods
This nationwide cohort study was conducted by using data from 2004 to ...2008 on new occurrence of post‐stroke epilepsy obtained from the National Health Insurance Research Database of Taiwan. The examined AEDs were phenytoin (PHT), valproic acid (VPA), carbamazepine (CBZ) and new AEDs. Recurrent seizures requiring either emergency room (ER) visits or hospitalization were used to measure the efficacy of seizure control. The Kaplan−Meier failure curve and Cox proportional hazard regression analyses were used to compare the risk of seizure recurrence in patients taking various AEDs.
Results
In all, 3622 late‐onset post‐stroke epilepsy patients were selected. Overall, 1.05 and 0.70 recurrent seizure incidences occurred per 100 person‐months based on ER visits 95% confidence interval (CI) 0.95–1.15 and hospitalizations (95% CI 0.62–0.78), respectively. The incidences of ER visits for patients using different AEDs were 1.26, 0.70, 0.43 and 0.38 per 100 person‐months for PHT, VPA, CBZ and new AEDs, respectively. Compared with patients using PHT, the adjusted hazard ratios for ER visits were 0.56 (95% CI 0.42–0.74; P < 0.001), 0.37 (95% CI 0.18–0.75; P = 0.006) and 0.28 (95% CI 0.15–0.52; P < 0.001) for patients using VPA, CBZ and new AEDs, respectively. The adjusted hazard ratios of hospitalizations for seizure recurrence yielded similar results.
Conclusions
This large nationwide, population‐based study demonstrated that late‐onset post‐stroke epilepsy patients using VPA and new AEDs have better seizure control than those using PHT as demonstrated by lower risks of ER visits and hospitalization.
We report results on the searches of weakly interacting massive particles (WIMPs) with sub-GeV masses (mχ) via WIMP-nucleus spin-independent scattering with Migdal effect incorporated. Analysis on ...time-integrated (TI) and annual modulation (AM) effects on CDEX-1B data are performed, with 737.1 kg day exposure and 160 eVee threshold for TI analysis, and 1107.5 kg day exposure and 250 eVee threshold for AM analysis. The sensitive windows in mχ are expanded by an order of magnitude to lower DM masses with Migdal effect incorporated. New limits on σχNSI at 90% confidence level are derived as 2×10−32∼7×10−35 cm2 for TI analysis at mχ∼50–180 MeV/c2, and 3×10−32∼9×10−38 cm2 for AM analysis at mχ∼75 MeV/c2–3.0 GeV/c2.
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