In this Phase 2b study, 331 low‐to‐moderate risk de novo kidney transplant patients (approximately 60% deceased donors) were randomized to a more intensive (MI) or less intensive (LI) regimen of ...tofacitinib (CP‐690, 550), an oral Janus kinase inhibitor or cyclosporine (CsA). All patients received basiliximab induction, mycophenolic acid and corticosteroids. Primary endpoints were: incidence of biopsy‐proven acute rejection (BPAR) with a serum creatinine increase of ≥0.3 mg/dL and ≥20% (clinical BPAR) at Month 6 and measured GFR at Month 12. Similar 6‐month incidences of clinical BPAR (11%, 7% and 9%) were observed for MI, LI and CsA. Measured GFRs were higher (p < 0.01) at Month 12 for MI and LI versus CsA (65 mL/min, 65 mL/min vs. 54 mL/min). Fewer (p < 0.05) patients in MI or LI developed chronic allograft nephropathy at Month 12 compared with CsA (25%, 24% vs. 48%). Serious infections developed in 45%, 37% and 25% of patients in MI, LI and CsA, respectively. Anemia, neutropenia and posttransplant lymphoproliferative disorder occurred more frequently in MI and LI compared with CsA. Tofacitinib was equivalent to CsA in preventing acute rejection, was associated with improved renal function and less chronic allograft histological injury, but had side‐effects at the doses evaluated.
The authors present the results of a phase 2b trial of tofacitinib in renal transplantation.
Epidemiological studies indicate that traffic noise increases the incidence of coronary artery disease, hypertension and stroke. The underlying mechanisms remain largely unknown. Field studies with ...nighttime noise exposure demonstrate that aircraft noise leads to vascular dysfunction, which is markedly improved by vitamin C, suggesting a key role of oxidative stress in causing this phenomenon.
We developed a novel animal model to study the vascular consequences of aircraft noise exposure. Peak sound levels of 85 and mean sound level of 72 dBA applied by loudspeakers for 4 days caused an increase in systolic blood pressure, plasma noradrenaline and angiotensin II levels and induced endothelial dysfunction. Noise increased eNOS expression but reduced vascular NO levels because of eNOS uncoupling. Noise increased circulating levels of nitrotyrosine, interleukine-6 and vascular expression of the NADPH oxidase subunit Nox2, nitrotyrosine-positive proteins and of endothelin-1. FACS analysis demonstrated an increase in infiltrated natural killer-cells and neutrophils into the vasculature. Equal mean sound pressure levels of white noise for 4 days did not induce these changes. Comparative Illumina sequencing of transcriptomes of aortic tissues from aircraft noise-treated animals displayed significant changes of genes in part responsible for the regulation of vascular function, vascular remodelling, and cell death.
We established a novel and unique aircraft noise stress model with increased blood pressure and vascular dysfunction associated with oxidative stress. This animal model enables future studies of molecular mechanisms, mitigation strategies, and pharmacological interventions to protect from noise-induced vascular damage.
Summary
Guidelines for doctors managing osteoporosis in the Asia-Pacific region vary widely. We compared 18 guidelines for similarities and differences in five key areas. We then used a structured ...consensus process to develop clinical standards of care for the diagnosis and management of osteoporosis and for improving the quality of care.
Purpose
Minimum clinical standards for assessment and management of osteoporosis are needed in the Asia-Pacific (AP) region to inform clinical practice guidelines (CPGs) and to improve osteoporosis care. We present the framework of these clinical standards and describe its development.
Methods
We conducted a structured comparative analysis of existing CPGs in the AP region using a “5IQ” model (identification, investigation, information, intervention, integration, and quality). One-hundred data elements were extracted from each guideline. We then employed a four-round Delphi consensus process to structure the framework, identify key components of guidance, and develop clinical care standards.
Results
Eighteen guidelines were included. The 5IQ analysis demonstrated marked heterogeneity, notably in guidance on risk factors, the use of biochemical markers, self-care information for patients, indications for osteoporosis treatment, use of fracture risk assessment tools, and protocols for monitoring treatment. There was minimal guidance on long-term management plans or on strategies and systems for clinical quality improvement. Twenty-nine APCO members participated in the Delphi process, resulting in consensus on 16 clinical standards, with levels of attainment defined for those on identification and investigation of fragility fractures, vertebral fracture assessment, and inclusion of quality metrics in guidelines.
Conclusion
The 5IQ analysis confirmed previous anecdotal observations of marked heterogeneity of osteoporosis clinical guidelines in the AP region. The Framework provides practical, clear, and feasible recommendations for osteoporosis care and can be adapted for use in other such vastly diverse regions. Implementation of the standards is expected to significantly lessen the global burden of osteoporosis.
Summary
Azole‐resistant environmental Aspergillus fumigatus presents a threat to public health but the extent of this threat in Southeast Asia is poorly described. We conducted environmental ...surveillance in the Mekong Delta region of Vietnam, collecting air and ground samples across key land‐use types, and determined antifungal susceptibilities of Aspergillus section Fumigati (ASF) isolates and azole concentrations in soils. Of 119 ASF isolates, 55% were resistant (or non‐wild type) to itraconazole, 65% to posaconazole and 50% to voriconazole. Azole resistance was more frequent in A. fumigatus sensu stricto isolates (95%) than other ASF species (32%). Resistant isolates and agricultural azole residues were overrepresented in samples from cultivated land. cyp51A gene sequence analysis showed 38/56 resistant A. fumigatus sensu stricto isolates carried known resistance mutations, with TR34/L98H most frequent (34/38).
Public health insurance (PHI) has been implemented with different levels of participation in many countries, from voluntary to mandatory. In Vietnam, a law amendment made PHI compulsory nationwide in ...2015 with a tolerance phase allowing people a flexible time to enroll. This study aims to examine mechanisms under which the amendment affected the enrollment, healthcare utilization, and out-of-pocket (OOP) expenditures by middle- and low-income households in this transitioning process.Using the biennial Vietnam Household Living Standard Surveys, the study applied the doubly robust difference-in-differences approach to compare outcomes in the post-amendment period from the 2016 survey with those in the pre-amendment period from the 2014 survey. The approach inheriting advantages from its predecessors, i.e., the difference-in-differences and the augmented inverse-probability weighting methods, can mitigate possible biases in policy evaluations due to the changes within the group and between groups over time in the cross-section observational study.The results showed health insurance expansion with extensive subsidies in premiums and medical coverage for persons other than the full-time employed, young children or elderly members in the family, significantly increased enrollments in the middle- and low-income groups by 9% and 8%, respectively. The number of visits for PHI-eligible services also increased, approximately 0.5 more visit per person in the middle-income and 1 more visit per person in the low-income. The amendment, however, so far did not show any significant effect on reducing OOP payments, neither for the low nor the middle-income groups. To further expand PHI coverage and financial protections, policymakers should focus on improving public health facilities, contracting PHI to more accredited private health providers, and motivating the high-income group's enrollments.
The aim of this study was to explore the gut microbiota profiles of colorectal cancer (CRC) patients and to examine the relationship between gut microbiota and other key molecular factors involved in ...CRC tumorigenesis. In this study, a 16S rDNA sequencing platform was used to identify possible differences in the microbiota signature between CRC and adjacent normal mucosal tissue. Differences in the microbiota composition in different anatomical colorectal tumor sites and their potential association with KRAS mutation were also explored. In this study, the number of Firmicutes and Actinobacteria decreased, while the number of Fusobacteria increased in the gut of CRC patients. In addition, at the genus level,
Fusobacterium
was identified as the key contributor to CRC tumorigenesis. In addition, a different distribution of gut microbiota in ascending and descending colon cancer samples was observed. Lipopolysaccharide biosynthesis-associated microbial genes were enriched in tumor tissues. Our study suggests that specific mucosa-associated microbiota signature and function are significantly changed in the gut of CRC patients, which may provide insight into the progression of CRC. These findings could also be of value in the creation of new prevention and treatment strategies for this type of cancer.
Epigenetic therapy using histone deacetylase inhibitors (HDACi) has shown promise in clinical trials for the treatment of human malignancies. In addition to the immediate effects on the tumour cell ...growth, HDACi upregulates the expression of MHC class I-related chain molecules A and B (MICA and MICB), resulting in an enhanced susceptibility of tumour cells to natural killer cell-mediated lysis. The molecular mechanism underlying is still unclear.
The transcriptional regulation mechanism underlying suberoylanilide hydroxamic acid (SAHA)-mediated regulation of MICA and related miRNA expression was investigated using promoter acetylation assays, bioinformatics analysis and chromatin immunoprecipitation assay.
SAHA upregulates the transcription of MICA/B by promoting MICA-associated histone acetylation while suppressing the MICA/B-targeting miRNAs miR-20a, miR-93 and miR-106b. The mechanism by which SAHA repressed miRNAs transcription involved repression of their host genes (miR-17-92 cluster and MCM7). SAHA downregulated the miR-17-92 cluster by abolishing tyrosine phosphorylation of STAT3 and decreased MCM7 transcription through localised histone deacetylation.
The HDACi SAHA epigenetically upregulates MICA expression through regulating the expression of miR-17-92 cluster and MCM7 in hepatoma, thus enhancing the sensitivity of HCC to natural killer cell-mediated lysis. This novel mechanism of action provides promise for HDACi in therapy of HCC.
This paper describes a real-time online prototype driver-fatigue monitor. It uses remotely located charge-coupled-device cameras equipped with active infrared illuminators to acquire video images of ...the driver. Various visual cues that typically characterize the level of alertness of a person are extracted in real time and systematically combined to infer the fatigue level of the driver. The visual cues employed characterize eyelid movement, gaze movement, head movement, and facial expression. A probabilistic model is developed to model human fatigue and to predict fatigue based on the visual cues obtained. The simultaneous use of multiple visual cues and their systematic combination yields a much more robust and accurate fatigue characterization than using a single visual cue. This system was validated under real-life fatigue conditions with human subjects of different ethnic backgrounds, genders, and ages; with/without glasses; and under different illumination conditions. It was found to be reasonably robust, reliable, and accurate in fatigue characterization.
In the last decade, the development of clinical practice guidelines in China has grown rapidly. However, with regards to the guidelines that have been established in the past, few were of high ...quality and in line with international standards. The main reason for this was that many clinical experts were not familiar with the procedures and rules of clinical guidelines before established, which lowered the quality seriously. Clinical practice guidelines are based on a clinical problem that is distilled into populations, interventions, comparison and outcome (PICO). After comprehensive systematic review, recommendations are made through evidence grading and strength of recommendation system. In addition, other issues should be noted such as pros and cons of the recommendation for specific population, preferences and values of the population, cost-effectiveness, and the health care system. A high-quality guideline requires multidimensional thinking (from clinicians, patients and policy makers), the implementation
This paper details the study of La2O3 modifications and their effect on the stability of a NiO–CaO/Al2O3 sorption complex catalyst used in the ReSER (reactive sorption enhanced reforming) process of ...hydrogen production. The La2O3-modified NiO–CaO/Al2O3 sorption complex catalyst was prepared by isometric impregnation. The microstructure, morphology and reducibility of the La2O3-modified sorption complex catalyst were characterized by means of BET, TEM, XRD and TPR. The stability of the catalyst used in the ReSER process was evaluated on a laboratory-scale fixed-bed reactor. Our results showed that modifying the sorption complex catalyst with La2O3 improved its stability up to 30 cycles of the ReSER process for hydrogen production, while only seven cycles were obtained without La2O3 modification. We showed that the source of the stability improvement that the La2O3 in the catalyst not only functioned to restrain the decrease of the support surface area and reduce the sintering of nano-CaCO3, which could limit the decay of the sorption capacity and stability of the catalyst, but also increased the interaction between nickel oxide and the support, which improved the stability of the catalyst by increasing the dispersion of nickel grains and inhibited the growth of nickel grain size.
► The La2O3-modified complex catalyst improved the stability of catalytic activity. ► La2O3 enhanced the interaction of NiO and Al2O3 and inhibited NiAl2O4 formation. ► La2O3 increased the dispersion of NiO grain and inhibited the growth of NiO.
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