To reach the WHO target of hepatitis C virus (HCV) elimination by 2025, Taiwan started to implement free-of-charge direct-acting antiviral (DAA) treatment programme in 2017. Evaluating the progress ...of HCV microelimination among people living with HIV (PLWH) is a critical step to identify the barriers to HCV elimination. PLWH seeking care at a major hospital designated for HIV care in Taiwan between January 2011 and December 2021 were retrospectively included. For PLWH with HCV-seropositive or HCV seroconversion during the study period, serial HCV RNA testing was performed using archived samples to confirm the presence of HCV viremia and estimate the prevalence and incidence of HCV viremia. Overall, 4199 PLWH contributed to a total of 27,258.75 person-years of follow-up (PYFU). With the reimbursement of DAAs and improvement of access to treatments, the prevalence of HCV viremia has declined from its peak of 6.21% (95% CI, 5.39-7.12%) in 2018 to 2.09% (95% CI, 1.60-2.77%) in 2021 (decline by 66.4% 95% CI, 55.4-74.7%); the incidence has declined from 25.94 per 1000 PYFU (95% CI, 20.44-32.47) in 2019 to 12.15% per 1000 PYFU (95% CI, 8.14-17.44) (decline by 53.2% 95% CI, 27.3-70.6%). However, the proportion of HCV reinfections continued to increase and accounted for 82.8% of incident HCV infections in 2021. We observed significant declines of HCV viremia among PLWH with the expansion of the DAA treatment programme in Taiwan. Further improvement of the access to DAA retreatments is warranted to achieve the goal of HCV microelimination.
Inadequate hospital cleaning may contribute to cross-transmission of pathogens. It is important to implement effective cleaning for the safe hospital environment. We conducted a three-phase study ...using human factors engineering (HFE) approach to enhance environmental cleanliness.
This study was conducted using a prospective interventional trial, and 28 (33.3%) of 84 wards in a medical center were sampled. The three-phases included pre-intervention analysis (Phase 1), implementing interventions by HFE principles (Phase 2), and programmatic analysis (Phase 3). The evaluations of terminal cleaning and disinfection were performed using the fluorescent marker, the adenosine triphosphate bioluminescence assay, and the aerobic colony count method simultaneously in all phases. Effective terminal cleaning and disinfection was qualified with the aggregate outcome of the same 10 high-touch surfaces per room. A score for each high-touch surface was recorded, with 0 denoting a fail and 10 denoting a pass by the benchmark of the evaluation method, and the total terminal cleaning and disinfection score (TCD score) was a score out of 100.
In each phase, 840 high-touch surfaces were collected from 84 rooms after terminal cleaning and disinfection. After the interventions, the TCD score by the three evaluation methods all showed significant improved. The carriage incidence of multidrug-resistant organism (MDRO) decreased significantly from 4.1 per 1000 patient-days to 3.6 per 1000 patient-days (
= .03).
The HFE approach can improve the thoroughness and the effectiveness of terminal cleaning and disinfection, and resulted in a reduction of patient carriage of MDRO at hospitals. Larger studies are necessary to establish whether such efforts of cleanliness can reduce the incidence of healthcare-associated infection.
Abstract We have comprehensively studied the multiscale physical properties of the massive infrared dark cloud G28.34 (the Dragon cloud) with dust polarization and molecular line data from Planck, ...FCRAO-14 m, James Clerk Maxwell Telescope, and Atacama Large Millimeter/submillimeter Array. We find that the averaged magnetic fields of clumps tend to be either parallel with or perpendicular to the cloud-scale magnetic fields, while the cores in clump MM4 tend to have magnetic fields aligned with the clump fields. Implementing the relative orientation analysis (for magnetic fields, column density gradients, and local gravity), velocity gradient technique, and modified Davis–Chandrasekhar–Fermi analysis, we find that G28.34 is located in a trans-to-sub-Alfvénic environment; the magnetic field is effectively resisting gravitational collapse in large-scale diffuse gas, but is distorted by gravity within the cloud and affected by star formation activities in high-density regions, and the normalized mass-to-flux ratio tends to increase with increasing density and decreasing radius. Considering the thermal, magnetic, and turbulent supports, we find that the environmental gas of G28.34 is in a supervirial (supported) state, the infrared dark clumps may be in a near-equilibrium state, and core MM4-core4 is in a subvirial (gravity-dominant) state. In summary, we suggest that magnetic fields dominate gravity and turbulence in the cloud environment at large scales, resulting in relatively slow cloud formation and evolution processes. Within the cloud, gravity could overwhelm both magnetic fields and turbulence, allowing local dynamical star formation to happen.
Seven donor and acceptor 2,6‐disubstituted 4,4‐difluoro‐4‐bora‐3a,4a‐diaza‐s‐indacene (BODIPY) dyes have been synthesized and characterized. Including MPBTCA, which is a known compound, the seven ...BODIPY dyes have been characterized by varied physical methods, such as UV/Visible absorption spectroscopy, low energy photo‐electron spectroscopy (AC‐2), and HOMO‐LUMO DFT/TDDFT calculation. All seven BODIPY dyes have absorption λmax around 535–545 nm, which is significantly longer than 499 nm of 4,4‐difluoro‐1,3,5,7,8‐pentamethyl‐4‐bora‐3a,4a‐diaza‐s‐indacene (PM 546). Having structural variation on donor group, acceptor group, donor π‐spacer, acceptor π‐spacer, and the substituent on boron, some BODIPY dyes exhibit small extinction coefficients or spectral integrals in solution (MPCtBTCA, MPBT‐pyO, MPBTT‐pyO, MTBTCA), broadening absorption spectral profile (MTBTCA), weak intramolecular charge transfer characteristics (MPBT‐pyO, MPBTT‐pyO, MTBTCA), too low LUMO energy level (PPBTCA), or insufficient dye‐uptake by TiO2 FTO (MPBT‐pyO, MPBTT‐pyO, MTBTCA). Two of the seven BODIPY dyes, MPBTCA and MPBTTCA, do not show the adverse properties like other BODIPY dyes. With our improved TiO2 FTO (fluorine doped tin oxide) dyeing method, namely a solution dropping method, high performance dye‐sensitized solar cells (DSCs) have been realized by MPBTCA and MPBTTCA photosensitizers. Power conversion efficiencies of 6.3 and 6.4 % have been achieved by MPBTCA and MPBTTCA DSCs, respectively. To the best of our knowledge, MPBTCA and MPBTTCA are the most efficient dyes for the donor and acceptor 2,6‐disubstituted BODIPY DSCs so far.
Dyeing to meet you: A series of 2,6‐disubstituted BODIPY derivatives have been synthesized and characterized, and subsequently tested for use in dye‐sensitized solar cells. Theoretical calculations and spectroscopic data suggest reasons for the improved performance, including a power conversion efficiency as high as 6.4% for MPBTTCA.
Diabetic nephropathy is characterized as the progressive development of renal insufficiency in a setting of hyperglycemia. Previous studies indicate that reactive oxygen species (ROS) play an ...important role in high glucose-induced renal injury. Cilostazol was reported to lower the production of superoxide significantly in situ. We hypothesized that cilostazol administration in streptozotocin-induced diabetic rats exerts effects via improving oxidative stress. Male Sprague-Dawley rats were fed with cilostazol (5 mg/kg or 25 mg/kg) for 12 weeks after streptozotocin-induced diabetes mellitus. The results showed that cilostazol decreased reactive oxygen species activity significantly in the kidneys of diabetic rats and improved the urine albumin/creatinine ratio. Cilostazol can also improve the levels of serum cholesterol, triglyceride, and LDL-cholesterol. Additionally, diabetes-caused increased glomerular size, TGF-β, and NF-κB decreased under treatment with cilostazol in diabetic rats. Our results indicate that cilostazol has beneficial effects in early diabetic nephropathy.
Cantharidin (CTD) is a traditional Chinese medicine and an effective component isolated from blister beetle, and it has been demonstrated to have anticancer, antibiotic, antivirus activities and ...immune-regulated functions. It has been reported that CTD induces cell cycle arrest and apoptosis in many cancer cell types. However, there are no reports showing that CTD would induce cell cycle arrest and apoptosis in human colorectal cancer colo 205 cells. In this study, we studied colo 205 cells which were treated with CTD and demonstrated its molecular mechanisms in apoptosis. CTD induced growth inhibition, G2/M phase arrest and apoptosis in colo 205 cells. The IC50 is 20.53 µM in CTD-treated colo 205 cells. DAPI/TUNEL double staining and Annexin V assays were used to confirm the apoptotic cell death in colo 205 cells after CTD exposure. CTD caused G2/M arrest, down-regulated CDK1 activity, decreased Cyclin A, Cyclin B, CDK1 and increased CHK1 and p21 protein levels. Colorimetric assays also indicated that CTD triggered activities of casapse-8, -9 and -3 in colo 205 cells. Moreover, CTD increased ROS production and decreased the level of mitochondrial membrane potential (ΔΨm) in colo 205 cells. Consequently, CTD-induced growth inhibition was significantly attenuated by N-acetylcysteine (NAC, a scavenger). CTD stimulated the protein levels of Fas/CD95, the caspase-3 active form, cytochrome c and Bax, but suppressed the protein levels of pro-caspase-8, pro-caspase-9 and Bcl-2, determined by Western blot analysis. Based on our observations, we suggest that CTD is able to induce G2/M phase arrest and apoptosis in colo 205 cells through inhibition of CDK1 activity and caspase-dependent signaling pathways.
The objective of this study was to develop a simultaneous analysis method of furan and its 10 derivatives in different food commodities. The results indicated that furan and its 10 derivatives could ...be separated within 9.5 min by using a HP-5MS column and gas chromatography-tandem mass spectrometry (GC-MS/MS) with multiple reaction monitoring mode for detection. Furthermore, this method could resolve several furan isomers, such as 2-methyl furan and 3-methyl furan, as well as 2,3-dimethyl furan and 2,5-dimethyl furan. The most optimal extraction conditions were: 5 g of the fruit or juice sample mixed with 5 mL of the saturated NaCl solution, separately, or 1 g of the canned oily fish sample mixed with 9 mL of the saturated NaCl solution, followed by the equilibration of each sample at 35 °C for 15 min, using a carboxen-polydimethylsiloxane SPME arrow to adsorb the analytes for 15 min at 35 °C for subsequent analysis by GC-MS/MS. For method validation of all the analytes in the different food matrices, the recovery was 76-117% and the limit of the quantitation was 0.003-0.675 ng/g, while the relative standard deviation (RSD%) of the intra-day variability range from 1-16%, and that of the inter-day variability was from 4-20%. The method validation data further demonstrated that a reliable method was established for the analysis of furan and its 10 derivatives in commercial foods.
We developed a new probe, Gd-DO3A-Am-PBA, for imaging tumors. Our results showed active targeting of Gd-DO3A-Am-PBA to sialic acid (SA) moieties, with increased cellular labeling in vitro and ...enhanced tumor accumulation and retention in vivo, compared to the commercial Gadovist. The effectiveness of our newly synthesized probe lies in its adequate retention phase, which is expected to provide a suitable time window for tumor diagnosis and a faster renal clearance, which will reduce toxicity risks when translated to clinics. Hence, this study can be extended to other tumor types that express SA on their surface. Targeting and MR imaging of any type of tumors can also be achieved by conjugating the newly synthesized contrast agent with specific antibodies. This study thus opens new avenues for drug delivery and tumor diagnosis via imaging.
We present prenatal diagnosis of a 15q11.2-q14 deletion of paternal origin associated with increased nuchal translucency (NT), mosaicism for de novo multiple unbalanced translocations involving ...15q11-q14, 5qter, 15qter, 17pter and 3qter, and Prader–Willi syndrome (PWS).
A 32-year-old, primigravid woman underwent amniocentesis at 18 weeks of gestation because of an increased NT thickness of 5.6 mm and abnormal maternal serum screening results in the first trimester. The pregnancy was conceived by in vitro fertilization and embryo transfer. Amniocentesis revealed a karyotype of 45,XX,der(5)t(5;15)(q35;q14),-15 16/45,XX,-15,der(17)t(15;17)(q14;p13)3/45,XX,der(15)t(15;15)(q35;q14),-152. The parental karyotypes were normal. Prenatal ultrasound findings were unremarkable. Array comparative genomic hybridization (aCGH) analysis on the DNA extracted from cultured amniocytes revealed the result of arr 15q11.2q14 (22,765,628–38,651,755) × 1.0 GRCh37 (hg19) with a 15.886-Mb 15q11.2-q14 deletion encompassing TUBGCP5, CYFIP1, NIPA2, NIPA1, SNRPN, SNURF, SNORD116-1, IPW, UBE3A, ACTC1 and MEIS2. The pregnancy was subsequently terminated, and a malformed fetus with facial dysmorphism was delivered. The cord blood had a karyotype of 45,XX,der(5)t(5;15)(q35;q14),-1546/45,XX,der(3)t(3;15) (q29;q14),-152/45,XX,-15,der(17)t(15;17)(q14;p13)2. The placenta had a karyotype of 45,XX,der(5) t(5;15)(q35;q14),-15. Polymorphic DNA marker analysis confirmed a paternal origin of the proximal 15q deletion.
Increased NT and abnormal maternal serum screening results may prenatally be associated with PWS. Chromosome 15 rearrangements in PWS include mosaicism for de novo multiple unbalanced translocations.
Cellular reprogramming of somatic cells to patient-specific induced pluripotent stem cells (iPSCs) enables in-vitro modeling of human cardiac disorders for pathogenic and therapeutic investigations. ...However, using iPSC-derived cardiomyocytes (iPSC-CMs) to model an adult-onset heart disease remains challenging because of the uncertainty regarding the ability of relatively immature iPSC-CMs to fully recapitulate adult disease phenotypes. Arrhythmogenic right ventricular dysplasia (ARVD) is an inherited cardiomyopathy characterized by pathological fibrofatty infiltration and cardiomyocyte (CM) loss predominantly in the right ventricle (RV), leading to heart failure and lethal arrhythmias. Over 50% of affected individuals have desmosome gene mutations, most commonly inPKP2encoding plakophilin-2. Using Yamanaka’s pluripotent factors, we generated iPSC lines from ARVD patients withPKP2mutations. We first developed a method to induce metabolic maturation of iPSC-CMs and showed that induction of adult-like metabolic energetics from an embryonic/glycolytic state is essential to model an adult-onset cardiac disease using patient-specific iPSCs. Furthermore, we showed that coactivation of normal peroxisome proliferator-activated receptor (PPAR)-α and abnormal PPARγ pathways in ARVD iPSC-CMs resulted in exaggerated CM lipogenesis, CM apoptosis, Na+channel downregulation and defective intracellular calcium handling, recapitulating the pathological signatures of ARVD. Using this model, we revealed novel pathogenic insights that metabolic derangement in an adult-like metabolic milieu underlies ARVD pathologies, enabling us to propose novel disease-modifying therapeutic strategies. (Circ J 2015; 79: 1402–1408)
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