Summary Background The health benefits of leisure-time physical activity are well known, but whether less exercise than the recommended 150 min a week can have life expectancy benefits is unclear. We ...assessed the health benefits of a range of volumes of physical activity in a Taiwanese population. Methods In this prospective cohort study, 416 175 individuals (199 265 men and 216 910 women) participated in a standard medical screening programme in Taiwan between 1996 and 2008, with an average follow-up of 8·05 years (SD 4·21). On the basis of the amount of weekly exercise indicated in a self-administered questionnaire, participants were placed into one of five categories of exercise volumes: inactive, or low, medium, high, or very high activity. We calculated hazard ratios (HR) for mortality risks for every group compared with the inactive group, and calculated life expectancy for every group. Findings Compared with individuals in the inactive group, those in the low-volume activity group, who exercised for an average of 92 min per week (95% CI 71–112) or 15 min a day (SD 1·8), had a 14% reduced risk of all-cause mortality (0·86, 0·81–0·91), and had a 3 year longer life expectancy. Every additional 15 min of daily exercise beyond the minimum amount of 15 min a day further reduced all-cause mortality by 4% (95% CI 2·5–7·0) and all-cancer mortality by 1% (0·3–4·5). These benefits were applicable to all age groups and both sexes, and to those with cardiovascular disease risks. Individuals who were inactive had a 17% (HR 1·17, 95% CI 1·10–1·24) increased risk of mortality compared with individuals in the low-volume group. Interpretation 15 min a day or 90 min a week of moderate-intensity exercise might be of benefit, even for individuals at risk of cardiovascular disease. Funding Taiwan Department of Health Clinical Trial and Research Center of Excellence and National Health Research Institutes.
Summary Background Both end-stage renal disease and chronic kidney disease are increasing worldwide; however, the full effect of chronic kidney disease is unknown because mortality risks for all five ...stages are unavailable. We assessed prevalence and mortality risks for all stages of chronic kidney disease and quantified its attributable mortality in Taiwan. Methods The cohort consisted of 462 293 individuals aged older than 20 years who participated in a standard medical screening programme since 1994. As of Dec 31, 2006, we identified 14 436 deaths. Chronic kidney disease was determined by glomerular filtration rate and urinary protein. We estimated national prevalence in Taiwan from the cohort by adjusting age and educational levels. Hazard ratios (HRs) were calculated with Cox proportionate hazards model. We calculated mortality attributable to chronic kidney disease for national population and for low socioeconomic status. Findings The national prevalence of chronic kidney disease was 11·93% (95% CI 11·66–12·28), but only 3·54% (3·37–3·68) of participants in the cohort were aware of their disorder. Prevalence was substantially higher in the group with low socioeconomic status than in the high status group (19·87% 19·84–19·91 vs 7·33% 7·31–7·35). 56 977 (12%) of cohort participants had chronic kidney disease; those with disease had 83% higher mortality for all cause (HR 1·83 1·73–1·93) and 100% higher for cardiovascular diseases (2·00 1·78–2·25), in a cohort that was observed for 13 years with median follow-up of 7·5 years (IQR 4·0–10·1). 10·3% (95% CI 9·57–11·03) of deaths in the entire population were attributable to chronic kidney disease, but 17·5% (16·27–18·67) of deaths in the low socioeconomic status population. 2350 (39%) deaths occurred before 65 years of age in those with chronic kidney disease. Regular users of Chinese herbal medicines had a 20% (odds ratio 1·20 1·16–1·24) increased risk of developing chronic kidney disease. Interpretation The high prevalence of chronic kidney disease and its associated all-cause mortality, especially in people with low socioeconomic status, make reduction of this disorder a public-health priority. Promotion of its recognition through the general public knowing their glomerular filtration rate and testing their urine is crucial to reduce premature deaths from all causes and to attenuate this global epidemic. Funding None.
Summary
Background
Ustekinumab, an interleukin (IL)‐12 and IL‐23 blocker, has emerged as a new therapeutic option for patients with psoriasis. It is generally well tolerated but safety data on the ...use of ustekinumab in patients with viral hepatitis are limited.
Objective
To assess the safety profile of ustekinumab in the treatment of patients with psoriasis who have concomitant hepatitis B or hepatitis C.
Methods
This study included 18 patients with concurrent psoriasis and hepatitis B virus (HBV) infection (14 patients) or hepatitis C virus (HCV) infection (four patients) who were treated with at least two ustekinumab injections. Viral loads were measured at baseline and each time before the administration of ustekinumab. Relevant clinical data were recorded.
Results
Among 11 patients positive for hepatitis B surface antigen (HBsAg), two out of the seven (29%) patients who did not receive antiviral prophylaxis exhibited HBV reactivation during ustekinumab treatment. No viral reactivation was observed in the three occult HBV‐infected patients (HBsAg‐negative/hepatitis B core antibody‐positive patients). One patient with HCV, liver cirrhosis and treated hepatocellular carcinoma (HCC) experienced HCV reactivation and recurrent HCC during the ustekinumab treatment. No significant increase in aminotransferase levels was observed in any patient.
Conclusions
Antiviral prophylaxis appears to minimize the risk of viral reactivation in patients with concurrent psoriasis and HBV infection. Without effective anti‐viral prophylaxis, the risk/benefit of ustekinumab treatment should be carefully assessed in patients with psoriasis and HBV or HCV infection and/or HCC. Close monitoring for HBV and HCV viral load is recommended, particularly for patients with high‐risk factors. Serum aminotransferase determination may not be useful for early detection of viral reactivation.
What's already known about this topic?
Interleukin (IL)‐12 plays a central role in mounting an immune response directed towards the elimination of pathogens.
Ustekinumab, an IL‐12/23 blocker may theoretically carry the risk of hepatitis B (HBV) and hepatitis C virus (HCV) reactivation with its use.
What does this study add?
Ustekinumab appears to be well tolerated in patients with concurrent psoriasis and HBV infection under antiviral prophylaxis.
The risk of HCV reactivation during ustekinumab treatment does exist and appropriate vigilance should be exercised, especially in specific high‐risk patient groups.
Context:
In postmenopausal osteoporosis, combining denosumab and teriparatide increases hip and spine bone mineral density more than either monotherapy.
Objective:
The objective of the study was to ...determine the effects of 2 years of combination therapy on bone microarchitecture and estimated strength.
Design:
This was an open-label, randomized controlled trial.
Participants and Methods:
We performed high-resolution peripheral quantitative computed tomography at the distal tibia and radius in 94 postmenopausal osteoporotic women randomized to 2 years of teriparatide 20 μg sc daily, denosumab 60 mg sc every 6 months, or both.
Results:
Total volumetric bone mineral density (vBMD) at the radius and tibia, trabecular vBMD at the radius, and cortical vBMD at the tibia all increased more in the combination group than both monotherapy groups (P < .002 for all comparisons with combination). Cortical thickness at the tibia also increased more in the combination group (8.1% ± 4.3%) than both other groups (P < .001). Cortical porosity at both the radius and tibia increased progressively over the 24-month treatment period in the teriparatide group but was stable in both other groups (P < .001 teriparatide vs both other groups). Trabecular vBMD at the tibia increased similarly in all groups, whereas radius trabecular vBMD increased more in the combination group than the other groups (P < .01 for both comparisons). Finite element analysis-estimated strength improved or was maintained by all treatments at both the radius and tibia.
Conclusions:
Two years of combined teriparatide and denosumab improves bone microarchitecture and estimated strength more than the individual treatments, particularly in cortical bone. These findings suggest that this regimen may be beneficial in postmenopausal osteoporosis.
As assessed by HR-pQCT, two years of combined teriparatide and denosumab improves bone microarchitecture and estimated strength more than the individual treatments, particularly in cortical bone.
BACKGROUND: The aim of this study was to isolate mesenchymal stem cells (MSCs) from amniotic fluid obtained by second‐trimester amniocentesis. METHODS: A novel two‐stage culture protocol for ...culturing MSCs was developed. Flow cytometry, RT–PCR and immunocytochemistry were used to analyse the phenotypic characteristics of the cultured MSCs. Von Kossa, Oil Red O and TuJ‐1 stainings were used to assess the differentiation potentials of MSCs. RESULTS: Amniotic fluid‐derived MSCs (AFMSCs) were successfully isolated, cultured and enriched without interfering with the routine process of fetal karyotyping. Flow cytometry analyses showed that they were positive for SH2, SH3, SH4, CD29, CD44 and HLA‐ABC (MHC class I), low positive for CD90 and CD105, but negative for CD10, CD11b, CD14, CD34, CD117, HLA‐DR, DP, DQ (MHC class II) and EMA. Importantly, a subpopulation of Oct‐4‐positive cells was detectable in our cultured AFMSCs. Under specific culture conditions, AFMSCs could be induced to differentiate into adipocytes, osteocytes and neuronal cells. CONCLUSIONS: We demonstrate that human multipotent MSCs are present in second‐trimester amniotic fluid. Considering the great potential of cellular therapy using fetal stem cells and the feasibility of intrauterine fetal tissue engineering, amniotic fluid may provide an excellent alternative source for investigation of human MSCs.
Lung cancer is the leading cause of cancer death worldwide, with metastasis underlying majority of related deaths. Angiomotin (AMOT), a scaffold protein, has been shown to interact with oncogenic ...Yes-associated protein/transcriptional co-activator with a PDZ-binding motif (YAP/TAZ) proteins, suggesting a potential role in tumor progression. However, the functional role of AMOT in lung cancer remains unknown. This study aimed to identify the patho-physiological characteristics of AMOT in lung cancer progression. Results revealed that AMOT expression was significantly decreased in clinical lung cancer specimens. Knockdown of AMOT in a low metastatic CL1-0 lung cancer cell line initiated cancer proliferation, migration, invasion and epithelial-mesenchymal transition. The trigger of cancer progression caused by AMOT loss was transduced by decreased cytoplasmic sequestration and increased nuclear translocation of oncogenic co-activators YAP/TAZ, leading to increased expression of the growth factor, Cyr61. Tumor promotion by AMOT knockdown was reversed when YAP/TAZ or Cyr61 was absent. Further, AMOT knockdown increased the growth and spread of Lewis lung carcinoma in vivo. These findings suggest that AMOT is a crucial suppressor of lung cancer metastasis and highlight its critical role as a tumor suppressor and its potential as a prognostic biomarker and therapeutic target for lung cancer.
There is increasing recognition that, in addition to negative psychological consequences of trauma such as post-traumatic stress disorder (PTSD), some individuals may develop post-traumatic growth ...(PTG) following such experiences. To date, however, data regarding the prevalence, correlates and functional significance of PTG in population-based samples are lacking.
Data were analysed from the National Health and Resilience in Veterans Study, a contemporary, nationally representative survey of 3157 US veterans. Veterans completed a survey containing measures of sociodemographic, military, health and psychosocial characteristics, and the Posttraumatic Growth Inventory-Short Form.
We found that 50.1% of all veterans and 72.0% of veterans who screened positive for PTSD reported at least 'moderate' PTG in relation to their worst traumatic event. An inverted U-shaped relationship was found to best explain the relationship between PTSD symptoms and PTG. Among veterans with PTSD, those with PTSD reported better mental functioning and general health than those without PTG. Experiencing a life-threatening illness or injury and re-experiencing symptoms were most strongly associated with PTG. In multivariable analysis, greater social connectedness, intrinsic religiosity and purpose in life were independently associated with greater PTG.
PTG is prevalent among US veterans, particularly among those who screen positive for PTSD. These results suggest that there may be a 'positive legacy' of trauma that has functional significance for veterans. They further suggest that interventions geared toward helping trauma-exposed US veterans process their re-experiencing symptoms, and to develop greater social connections, sense of purpose and intrinsic religiosity may help promote PTG in this population.
We demonstrate synthetic azimuthal gauge potentials for Bose-Einstein condensates from engineering atom-light couplings. The gauge potential is created by adiabatically loading the condensate into ...the lowest energy Raman-dressed state, achieving a coreless vortex state. The azimuthal gauge potentials act as effective rotations and are tunable by the Raman coupling and detuning. We characterize the spin textures of the dressed states, in agreements with the theory. The lowest energy dressed state is stable with a 4.5-s half-atom-number-fraction lifetime. In addition, we exploit the azimuthal gauge potential to demonstrate the Hess-Fairbank effect, the analogue of Meissner effect in superconductors. The atoms in the absolute ground state has a zero quasiangular momentum and transits into a polar-core vortex when the synthetic magnetic flux is tuned to exceed a critical value. Our demonstration serves as a paradigm to create topological excitations by tailoring atom-light interactions where both types of SO(3) vortices in the |⟨Fover →⟩|=1 manifold, coreless vortices and polar-core vortices, are created in our experiment. The gauge field in the stationary Hamiltonian opens a path to investigating rotation properties of atomic superfluids under thermal equilibrium.
Anti-PD-1 antibodies (anti-PD-1) have clinical activity in a number of malignancies. All clinical trials have excluded patients with significant preexisting autoimmune disorders (ADs) and only one ...has included patients with immune-related adverse events (irAEs) with ipilimumab. We sought to explore the safety and efficacy of anti-PD-1 in such patients.
Patients with advanced melanoma and preexisting ADs and/or major immune-related adverse events (irAEs) with ipilimumab (requiring systemic immunosuppression) that were treated with anti-PD-1 between 1 July 2012 and 30 September 2015 were retrospectively identified.
One hundred and nineteen patients from 13 academic tertiary referral centers were treated with anti-PD-1. In patients with preexisting AD (N=52), the response rate was 33%. 20 (38%) patients had a flare of AD requiring immunosuppression, including 7/13 with rheumatoid arthritis, 3/3 with polymyalgia rheumatica, 2/2 with Sjogren’s syndrome, 2/2 with immune thrombocytopaenic purpura and 3/8 with psoriasis. No patients with gastrointestinal (N=6) or neurological disorders (N=5) flared. Only 2 (4%) patients discontinued treatment due to flare, but 15 (29%) developed other irAEs and 4 (8%) discontinued treatment. In patients with prior ipilimumab irAEs requiring immunosuppression (N=67) the response rate was 40%. Two (3%) patients had a recurrence of the same ipilimumab irAEs, but 23 (34%) developed new irAEs (14, 21% grade 3–4) and 8 (12%) discontinued treatment. There were no treatment-related deaths.
In melanoma patients with preexisting ADs or major irAEs with ipilimumab, anti-PD-1 induced relatively frequent immune toxicities, but these were often mild, easily managed and did not necessitate discontinuation of therapy, and a significant proportion of patients achieved clinical responses. The results support that anti-PD-1 can be administered safely and can achieve clinical benefit in patients with preexisting ADs or prior major irAEs with ipilimumab.
We analyse emission spectra of WASP-12b from a partial phase curve observed over three epochs with the
Hubble
Space Telescope, covering eclipse, quadrature, and transit, respectively. As the 1.1-day ...period phase curve was only partially covered over three epochs, traditional methods to extract the planet flux and instrument systematic errors cannot recover the thermal emission away from the secondary eclipse. To analyse this partial phase curve, we introduce a new method, which corrects for the wavelength-independent component of the systematic errors. Our new method removes the achromatic instrument and stellar variability, and uses the measured stellar spectrum in eclipse to then retrieve a relative planetary spectrum in wavelength at each phase. We are able to extract the emission spectrum of an exoplanet at quadrature outside of a phase curve for the first time; we recover the quadrature spectrum of WASP-12b up to an additive constant. The dayside emission spectrum is extracted in a similar manner, and in both cases we are able to estimate the brightness temperature, albeit at a greatly reduced precision, because our method removes the absolute level of the spectra, and therefore relies on fitting the slope of the emission spectrum instead of its amplitude. We estimate the brightness temperature from the dayside (
T
day
= 3186 ± 677 K) and from the quadrature spectrum (
T
quad
= 2124 ± 417 K) and combine them to constrain the energy budget of the planet. We compare our extracted relative spectra to global circulation models of this planet, which are generally found to be a good match. However, we do see tentative evidence of a steeper spectral slope in the measured dayside spectrum compared to our models. We find that we cannot match this increased slope by increasing optical opacities in our models. We also find that this spectral slope is unlikely to be explained by a non-equilibrium water abundance, as water advected from the nightside is quickly dissociated on the dayside. We present our technique for analysing partial or full phase curves from HST/WFC3 using common mode methods. Importantly, and unlike previous phase curve analyses, this technique does not assume a functional form for the planet’s emission with phase and does not require a full-orbit phase curve. The success of this technique relies upon stable pointing of the telescope between visits, with less than 0.1 pixels drift for example. This technique becomes powerful in the study of new regimes in exoplanetary systems such as for longer period planets, and is ideally suited for future observations with JWST and ARIEL.
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