Morning chronotype has been associated with a reduced risk of prostate and breast cancer. However, few studies have examined whether chronotype is associated with digestive tract cancer risk. We ...conducted a Mendelian randomization (MR) study to assess the associations of chronotype with major digestive tract cancers. A total of 317 independent genetic variants associated with chronotype at the genome‐wide significance level (P < 5 × 10−8) were used as instrumental variables from a genome‐wide meta‐analysis of 449 734 individuals. Summary‐level data on overall and six digestive tract cancers, including esophageal, stomach, liver, biliary tract, pancreatic and colorectal cancers, were obtained from the UK Biobank (11 952 cases) and FinnGen (7638 cases) study. Genetic liability to morning chronotype was associated with reduced risk of overall digestive tract cancer and cancers of stomach, biliary tract and colorectum in UK Biobank. The associations for the overall digestive tract, stomach and colorectal cancers were directionally replicated in FinnGen. In the meta‐analysis of the two sources, genetic liability to morning chronotype was associated with a decreased risk of overall digestive tract cancer (odds ratio OR 0.94, 95% confidence interval CI: 0.90‐0.98), stomach cancer (OR 0.84, 95% CI: 0.73‐0.97) and colorectal cancer (OR 0.92, 95% CI: 0.87‐0.98), but not with the other studied cancers. The associations were consistent in multivariable MR analysis with adjustment for genetically predicted sleep duration, short sleep, insomnia and body mass index. The study provided MR evidence of inverse associations of morning chronotype with digestive tract cancer, particularly stomach and colorectal cancers.
What's new?
Cancers of the digestive tract are associated with various traditional risk factors, including smoking and obesity. A possible novel risk factor may be chronotype, an individual's natural tendency to sleep at a particular time. In our study, the authors assessed potential associations between digestive tract cancers and chronotype using Mendelian randomization analysis of UK Biobank and FinnGen study data. Overall risk of digestive tract cancer, stomach cancer and colorectal cancer was found to be inversely associated with genetic liability to morning chronotype. Analyses further indicate that the associations are independent of sleep duration, short sleep, insomnia and body mass index.
Impaired diabetic wound healing is associated with the persistence of chronic inflammation and excessive oxidative stress, which has become one of the most serious clinical challenges. Wound ...dressings with anti-inflammatory and reactive oxygen species (ROS)-scavenging properties are desirable for diabetic wound treatment. In this study, a shape-adaptable, biodegradable, biocompatible, antioxidant, and immunomodulatory interleukin-33 (IL-33)-cytogel is developed by encapsulating IL-33 into physically cross-linked DNA hydrogels and used as wound dressings to promote diabetic wound healing. The porous microstructures and biodegradable properties of the IL-33-cytogel ensure the local sustained-release of IL-33 in the wound area, where the sustained-release of IL-33 is maintained for at least 7 days. IL-33-cytogel can induce local accumulation of group 2 innate lymphoid cells (ILC2s) and regulatory T cells (Tregs), as well as M1-to-M2 transition at the wound sites. Additionally, the antioxidant and biocompatible characteristics of DNA hydrogels promote the scavenging of intracellular ROS without affecting cell viability. As a result, local inflammation in the diabetic wound area is resolved upon IL-33-cytogel treatment, which is accompanied by improved granulation tissue regeneration and accelerated wound closure. This study demonstrates a promising strategy in tissue engineering and regenerative medicine by incorporating DNA hydrogels and cytokine immunotherapy for promoting diabetic wound healing.
We have found no study conducted outside of the United States on the association between physician volume and patient outcomes after coronary artery bypass graft surgery. The aim of this study is to ...examine the association between surgeon-hospital coronary artery bypass graft volume and patient outcomes using three-year population-based data on Taiwan.
This study uses the Taiwan National Health Insurance Research Database covering the period 2000 to 2002, with the study sample comprising 9,895 first-time coronary artery bypass graft admissions, treated by 316 surgeons in 46 hospitals.
Of the sampled patients, 356 (3.6%) were discharged after death. Those patients treated by low-volume (1-50 cases) surgeons had significantly higher mortality rates than those treated by medium-volume (51-100 cases) surgeons (7.0% vs 3.8%), high-volume (101-150 cases) surgeons (7.0% vs 2.7%), or very-high-volume (> or = 151 cases) surgeons (7.0% vs 3.2%). However, hospital coronary artery bypass graft volume alone is an insufficient predictor of hospital in-patient deaths (p = 0.078). The adjusted odds ratio of hospital in-patient deaths declined with increasing surgeon volume, with the odds of in-patient death for those patients treated by low-volume surgeons being 1.52 times those of medium-volume surgeons, 1.89 times those of high-volume surgeons, and 2.04 times those of very-high-volume surgeons.
We conclude that for all coronary artery bypass graft surgeries taking place in Taiwan, the skill and experience of individual surgeons is a more critical factor for patient outcome than either hospital equipment or surgical teams.
This work investigates atmospheric visibility by employing two statistical processes for high-frequency extraction: Sobel operator and fast Fourier transform (FFT). In replacing the traditional ...measurement methods for atmospheric visibility, the new approaches can provide accurate digital data urban visibility by establishing the numerical indices. The procedure is illustrated as follows. Digital images of urban areas in Kaohsiung, a city at the south of Taiwan, are analyzed according to brightness. High-frequency components of the image are extracted to calculate the index values by employing the Sobel operator and FFT. Finally, the correlation between each index and the visual range estimated by trained investigators are evaluated. A good correlation between two indices and the values obtained by visual investigation is affirmed by correlation coefficients (
R
2
), 0.8139 and 0.7797, respectively. Furthermore, both indices are highly correlated with each other (
R
2
=
0.9173
). Convenient transmission and the exchangeability of digital images of the real-time landscape facilitate the publication of results on the world wide web (WWW).
Tobacco smoking is an important risk factor for peripheral artery disease (PAD), but it remains unknown whether smokeless tobacco, such as Swedish snuff (snus), is also associated with this disease. ...We used data from the Cohort of Swedish Men including 24,085 men. Individuals were grouped into never, past, and current snus dippers as well as never, past quitting ≥ 10 years, past, quitting < 10 years, and current smokers. Incident PAD cases were defined by linkage of the cohort with the Swedish National Patient Register. Cox proportional hazards regression was used to analyze the data. Over a mean follow-up period of 9.1 years (from July 1, 2009 to December 31, 2019), 655 incident PAD cases were ascertained. Cigarette smoking but not Swedish snus dipping was associated with an increased risk of PAD. Compared with never snus dippers, the hazard ratio of PAD was 0.95 (95% confidence interval CI 0.73-1.24) for past snus dippers and 0.88 (95% CI 0.66-1.17) for current snus dippers. Compared to never smokers, the hazard ratio of PAD was 1.38 (95% CI 1.14-1.68) for past smoker who stopped smoking for ≥ 10 years, 2.61 (95% CI 1.89-3.61) for past smoker who stopped smoking for < 10 years, and 4.01 (95% CI 3.17, 5.08) for current smoker. In conclusion, cigarette smoking but not Swedish snus dipping increases the risk of PAD.
The aim of this study was to assess the effect of molecular weight (MW) on the transdermal delivery of macromolecules by erbium:yttrium–aluminum–garnet (Er:YAG) laser treatment. Fluorescein ...isothiocyanate (FITC)-labeled dextran (FD) of increasing MWs (4.4, 19.4, 38, and 77 kDa) was used as the model macromolecules to investigate the skin permeation in vitro. Fluorescence microscopy and scanning electron microscopic (SEM) images were utilized to examine the transport mechanisms of the macromolecules via the skin after laser treatment. The results indicate a significant increase in the permeation of FITC and FD across skin treated by the laser. The MWs of macromolecules and laser fluences were found to play important roles in controlling macromolecular absorption. Transdermal delivery of FD with a MW of at least 77 kDa could be achieved with laser treatment. Follicular routes were significant for FITC permeation, whereas intercellular pathways played important roles on the delivery of FD. Ablation of the stratum corneum (SC) layer, photomechanical stress on intercellular regions, and alterations of the morphology and arrangement of corneocytes are possible mechanisms of how the Er:YAG laser promotes macromolecular delivery. No alteration of viable skin morphology was observed after laser treatment and the partly ablation of the SC may be reversible. Hexameric insulin showed higher skin permeation than did FD with similar MWs (38 kDa) with laser enhancement. From the study presented herein, it is concluded that the Er:YAG laser can be effective for transdermal delivery of macromolecules and hydrophilic permeants such as peptides and protein-based drugs.
Bevacizumab added to 5-fluorouracil-based chemotherapy can improve outcomes in patients with metastatic colorectal cancer. Bevacizumab had several notable adverse effects including bowel perforation ...but pneumothorax had never been reported in the available English literature. We reported a 45-year-old male with lung metastases from colorectal cancer who had spontaneous pneumothorax after the second cycle of bevacizumab-containing chemotherapy. His pneumothorax resolved after tube thoracostomy with a small caliber catheter. The mechanism of pneumothorax developed after bevacizumab therapy was not clear as bowel perforation but tumor necrosis with ruptured parietal pleura might be the cause. In patients who had chest discomfort after bevacizumab-containing therapy, pneumothorax should never be overlooked as one of the differential diagnoses.
Polyurethanes are widely used as blood-contacting biomaterials, due to their good biocompatibility and mechanical properties. Nevertheless, their blood compatibility is still not adequate for more ...demanding
applications. Surface modification is an effective way to improve the hemocompatibility for biomaterials. The purpose of the present study was to synthesize a novel nonthrombogenic biomaterial by modifying
the surface of polyurethane. Ozonization was used to introduce active peroxide groups onto the segmented poly(ether-urethane) (SPEU) film surface and graft polymerization of N,N′-dimethyl (methacryloyloxyethyl)
ammonium propanesulfonate (DMAPS), a sulfobetaine structure, onto the ozone-activated SPEU surface was conducted. The SPEU-g-PDMAPS film was characterized by ATR-FTIR, XPS, and contact angle measurements.
ATR-FTIR and XPS confirmed the graft polymerization. The grafted film possessed a relatively hydrophilic surface, as revealed by contact angle measurement. The blood compatibility of the grafted films was
evaluated by a platelet-rich plasma (PRP) adhesion study and scanning electron microscopy, using SPEU film as the reference. No platelet adhesion was observed for the grafted films incubated with PRP at
37°C for 60 and 180 min. This new sulfobetaine structure grafted biomaterial might have potential for biomedical applications.
Comparable global data on health and nutrition of school-aged children and adolescents are scarce. We aimed to estimate age trajectories and time trends in mean height and mean body-mass index (BMI), ...which measures weight gain beyond what is expected from height gain, for school-aged children and adolescents.
For this pooled analysis, we used a database of cardiometabolic risk factors collated by the Non-Communicable Disease Risk Factor Collaboration. We applied a Bayesian hierarchical model to estimate trends from 1985 to 2019 in mean height and mean BMI in 1-year age groups for ages 5–19 years. The model allowed for non-linear changes over time in mean height and mean BMI and for non-linear changes with age of children and adolescents, including periods of rapid growth during adolescence.
We pooled data from 2181 population-based studies, with measurements of height and weight in 65 million participants in 200 countries and territories. In 2019, we estimated a difference of 20 cm or higher in mean height of 19-year-old adolescents between countries with the tallest populations (the Netherlands, Montenegro, Estonia, and Bosnia and Herzegovina for boys; and the Netherlands, Montenegro, Denmark, and Iceland for girls) and those with the shortest populations (Timor-Leste, Laos, Solomon Islands, and Papua New Guinea for boys; and Guatemala, Bangladesh, Nepal, and Timor-Leste for girls). In the same year, the difference between the highest mean BMI (in Pacific island countries, Kuwait, Bahrain, The Bahamas, Chile, the USA, and New Zealand for both boys and girls and in South Africa for girls) and lowest mean BMI (in India, Bangladesh, Timor-Leste, Ethiopia, and Chad for boys and girls; and in Japan and Romania for girls) was approximately 9–10 kg/m2. In some countries, children aged 5 years started with healthier height or BMI than the global median and, in some cases, as healthy as the best performing countries, but they became progressively less healthy compared with their comparators as they grew older by not growing as tall (eg, boys in Austria and Barbados, and girls in Belgium and Puerto Rico) or gaining too much weight for their height (eg, girls and boys in Kuwait, Bahrain, Fiji, Jamaica, and Mexico; and girls in South Africa and New Zealand). In other countries, growing children overtook the height of their comparators (eg, Latvia, Czech Republic, Morocco, and Iran) or curbed their weight gain (eg, Italy, France, and Croatia) in late childhood and adolescence. When changes in both height and BMI were considered, girls in South Korea, Vietnam, Saudi Arabia, Turkey, and some central Asian countries (eg, Armenia and Azerbaijan), and boys in central and western Europe (eg, Portugal, Denmark, Poland, and Montenegro) had the healthiest changes in anthropometric status over the past 3·5 decades because, compared with children and adolescents in other countries, they had a much larger gain in height than they did in BMI. The unhealthiest changes—gaining too little height, too much weight for their height compared with children in other countries, or both—occurred in many countries in sub-Saharan Africa, New Zealand, and the USA for boys and girls; in Malaysia and some Pacific island nations for boys; and in Mexico for girls.
The height and BMI trajectories over age and time of school-aged children and adolescents are highly variable across countries, which indicates heterogeneous nutritional quality and lifelong health advantages and risks.
Wellcome Trust, AstraZeneca Young Health Programme, EU.
Summary Despite significant progress in treating chronic lymphocytic leukaemia (CLL), resistance to therapy remains challenging. NOTCH1 activation, common in CLL, confers adverse prognosis. This ...study explores the impact of NOTCH1 signalling on venetoclax sensitivity in vitro. Although NOTCH1 activation minimally impaired the susceptibility of CLL cells to venetoclax, ex vivo cell competition studies reveal that cells with constitutive NOTCH1 activation outgrew their wild‐type counterparts in the presence of ongoing venetoclax exposure. Our findings suggest that while NOTCH1 activation is insufficient to confer venetoclax refractoriness, there is enhanced potential for cells with NOTCH1 activation to escape and thus become fully resistant to venetoclax.
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