Abstract
Aims
Hypertension (HTN) can lead to heart and kidney damage. The gut microbiota has been linked to HTN, although it is difficult to estimate its significance due to the variety of other ...features known to influence HTN. In the present study, we used germ-free (GF) and colonized (COL) littermate mice to quantify the impact of microbial colonization on organ damage in HTN.
Methods and results
4-week-old male GF C57BL/6J littermates were randomized to remain GF or receive microbial colonization. HTN was induced by subcutaneous infusion with angiotensin (Ang) II (1.44 mg/kg/day) and 1% NaCl in the drinking water; sham-treated mice served as control. Renal damage was exacerbated in GF mice, whereas cardiac damage was more comparable between COL and GF, suggesting that the kidney is more sensitive to microbial influence. Multivariate analysis revealed a larger effect of HTN in GF mice. Serum metabolomics demonstrated that the colonization status influences circulating metabolites relevant to HTN. Importantly, GF mice were deficient in anti-inflammatory faecal short-chain fatty acids (SCFA). Flow cytometry showed that the microbiome has an impact on the induction of anti-hypertensive myeloid-derived suppressor cells and pro-inflammatory Th17 cells in HTN. In vitro inducibility of Th17 cells was significantly higher for cells isolated from GF than conventionally raised mice.
Conclusion
The microbial colonization status of mice had potent effects on their phenotypic response to a hypertensive stimulus, and the kidney is a highly microbiota-susceptible target organ in HTN. The magnitude of the pathogenic response in GF mice underscores the role of the microbiome in mediating inflammation in HTN.
The development of metabolic syndrome (MetS) is influenced by environmental factors such as smoking and alcohol consumption. We determined the combined effects of smoking and alcohol on MetS and its ...individual components.
64,046 participants aged 18-80 years from the LifeLines Cohort study were categorized into three body mass index (BMI) classes (BMI<25, normal weight; BMI 25-30, overweight; BMI≥30 kg/m2, obese). MetS was defined according to the revised criteria of the National Cholesterol Education Program's Adult Treatment Panel III (NCEP ATP III). Within each BMI class and smoking subgroup (non-smoker, former smoker, <20 and ≥20 g tobacco/day), the cross-sectional association between alcohol and individual MetS components was tested using regression analysis.
Prevalence of MetS varied greatly between the different smoking-alcohol subgroups (1.7-71.1%). HDL cholesterol levels in all alcohol drinkers were higher than in non-drinkers (0.02 to 0.29 mmol/L, P values<0.001). HDL cholesterol levels were lower when they were also a former or current smoker (<20 and ≥20 g tobacco/day). Consumption of ≤1 drink/day indicated a trend towards lower triglyceride levels (non-significant). Concurrent use alcohol (>1 drink/day) and tobacco showed higher triglycerides levels. Up to 2 drinks/day was associated with a smaller waist circumference in overweight and obese individuals. Consumption of >2 drinks/day increased blood pressure, with the strongest associations found for heavy smokers. The overall metabolic profile of wine drinkers was better than that of non-drinkers or drinkers of beer or spirits/mixed drinks.
Light alcohol consumption may moderate the negative associations of smoking with MetS. Our results suggest that the lifestyle advice that emphasizes smoking cessation and the restriction of alcohol consumption to a maximum of 1 drink/day, is a good approach to reduce the prevalence of MetS.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
OBJECTIVES:PORTAS-3 was designed to compare the frequency of pneumothorax or haemothorax in a primary open versus closed strategy for port implantation.
BACKGROUND DATA:The implantation strategy for ...totally implantable venous access ports with the optimal benefit/risk ratio remains unclear.
METHODS:PORTAS-3 was a multicentre, randomized, controlled, parallel-group superiority trial. Adult patients with oncological disease scheduled for elective port implantation were randomized to a primary open or closed strategy. Primary endpoint was the rate of pneumothorax or haemothorax. Assuming a difference of 2.5% between the 2 groups, a sample size of 1154 patients was needed to prove superiority of the open group. A logistic regression model after the intention-to-treat principle was applied for analysis of the primary endpoint.
RESULTS:Between November 9, 2014 and September 5, 2016, 1205 patients were randomized. Of these, 1159 (open n = 583; closed n = 576) were finally analyzed. The rate of pneumothorax or haemothorax was significantly reduced with the open strategy odds ratio 0.27, 95% confidence interval (CI) 0.09–0.88; P = 0.029. Operation time was shorter for the closed strategy. Primary success rates, tolerability, morbidity, dose rate of radiation, and 30-day mortality did not differ significantly between the groups.
CONCLUSION:A primary open strategy by cut-down of the cephalic vein, if necessary enhanced by a modified Seldinger technique, reduces the frequency of pneumothorax or haemothorax after central venous port implantation significantly compared with a closed strategy by primary puncture of the subclavian vein without routine sonographic guidance. Therefore, open surgical cut-down should be the reference standard for port implantation in comparable cohorts.
TRIAL REGISTRATION:German Clinical Trials Register DRKS 00004900.
The development of cost-effective molecular devices that efficiently capture and convert sunlight into other useful forms of energy is a promising approach to meet the world’s increasing energy ...demands. These devices are designed through a successful combination of materials and molecules that work synergistically to promote light-driven chemical reactions. Light absorption by a surface-bound chromophore triggers a sequence of interfacial electron transfer processes. The efficiencies of the devices are governed by the dynamic balance between the electron transfer reactions that promote energy conversion and undesirable side reactions. Therefore, it is necessary to understand and control these processes to optimize the design of the components of the devices and to achieve higher energy conversion efficiencies. In this context, this review discusses general aspects of interfacial electron transfer reactions in dye-sensitized TiO2 molecular devices for solar energy conversion. A theoretical background on the Marcus-Gerischer theory for interfacial electron transfer and theoretical models for electron transport within TiO2 films are provided. An overview of dye-sensitized solar cells (DSSCs) and dye-sensitized photoelectrosynthesis cells (DSPECs) is presented, and the electron transfer and transport processes that occur in both classes of devices are emphasized and detailed. Finally, the main spectroscopic, electrochemical and photoelectrochemical experimental techniques that are employed to elucidate the kinetics of the electron transfer reactions discussed in this review are presented.
Primary open-angle glaucoma (POAG), the most common optic neuropathy, is a heritable disease. Siblings of POAG cases have a ten-fold increased risk of developing the disease. Intraocular pressure ...(IOP) and optic nerve head characteristics are used clinically to predict POAG risk. We conducted a genome-wide association meta-analysis of IOP and optic disc parameters and validated our findings in multiple sets of POAG cases and controls. Using imputation to the 1000 genomes (1000G) reference set, we identified 9 new genomic regions associated with vertical cup-disc ratio (VCDR) and 1 new region associated with IOP. Additionally, we found 5 novel loci for optic nerve cup area and 6 for disc area. Previously it was assumed that genetic variation influenced POAG either through IOP or via changes to the optic nerve head; here we present evidence that some genomic regions affect both IOP and the disc parameters. We characterized the effect of the novel loci through pathway analysis and found that pathways involved are not entirely distinct as assumed so far. Further, we identified a novel association between CDKN1A and POAG. Using a zebrafish model we show that six6b (associated with POAG and optic nerve head variation) alters the expression of cdkn1a. In summary, we have identified several novel genes influencing the major clinical risk predictors of POAG and showed that genetic variation in CDKN1A is important in POAG risk.
Arctic air masses undergo intense transformations when moving southward from closed sea ice to warmer open waters in marine cold-air outbreaks (CAOs). Due to the lack of measurements of diabatic ...heating and moisture uptake rates along CAO flows, studies often depend on atmospheric reanalysis output. However, the uncertainties connected to those datasets remain unclear. Here, we present height-resolved airborne observations of diabatic heating, moisture uptake, and cloud evolution measured in a quasi-Lagrangian manner. The investigated CAO was observed on 1 April 2022 during the HALO-(AC)3 campaign. Shortly after passing the sea-ice edge, maximum diabatic heating rates over 6 K h−1 and moisture uptake over 0.3 gkg-1h-1 were measured near the surface. Clouds started forming and vertical mixing within the deepening boundary layer intensified. The quasi-Lagrangian observations are compared with the fifth-generation global reanalysis (ERA5) and the Copernicus Arctic Regional Reanalysis (CARRA). Compared to these observations, the mean absolute errors of ERA5 versus CARRA data are 14 % higher for air temperature over sea ice (1.14 K versus 1.00 K) and 62 % higher for specific humidity over ice-free ocean (0.112 g kg−1 versus 0.069 g kg−1). We relate these differences to issues with the representation of the marginal ice zone and corresponding surface fluxes in ERA5, as well as the cloud scheme producing excess liquid-bearing, precipitating clouds, which causes a too-dry marine boundary layer. CARRA's high spatial resolution and demonstrated higher fidelity towards observations make it a promising candidate for further studies on Arctic air mass transformations.
Atherosclerosis results in the narrowing of arterial blood vessels and this causes significant changes in the endogenous shear stress between healthy and constricted arteries. Nanocontainers that can ...release drugs locally with such rheological changes can be very useful. Here, we show that vesicles made from an artificial 1,3-diaminophospholipid are stable under static conditions but release their contents at elevated shear stress. These vesicles have a lenticular morphology, which potentially leads to instabilities along their equator. Using a model cardiovascular system based on polymer tubes and an external pump to represent shear stress in healthy and constricted vessels of the heart, we show that drugs preferentially release from the vesicles in constricted vessels that have high shear stress.
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IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The Canadian Network for Mood and Anxiety Treatments (CANMAT) last published clinical guidelines for the management of major depressive disorder (MDD) in 2016. Owing to advances in the field, an ...update was needed to incorporate new evidence and provide new and revised recommendations for the assessment and management of MDD in adults.
CANMAT convened a guidelines editorial group comprised of academic clinicians and patient partners. A systematic literature review was conducted, focusing on systematic reviews and meta-analyses published since the 2016 guidelines. Recommendations were organized by lines of treatment, which were informed by CANMAT-defined levels of evidence and supplemented by clinical support (consisting of expert consensus on safety, tolerability, and feasibility). Drafts were revised based on review by patient partners, expert peer review, and a defined expert consensus process.
The updated guidelines comprise eight primary topics, in a question-and-answer format, that map a patient care journey from assessment to selection of evidence-based treatments, prevention of recurrence, and strategies for inadequate response. The guidelines adopt a personalized care approach that emphasizes shared decision-making that reflects the values, preferences, and treatment history of the patient with MDD. Tables provide new and updated recommendations for psychological, pharmacological, lifestyle, complementary and alternative medicine, digital health, and neuromodulation treatments. Caveats and limitations of the evidence are highlighted.
The CANMAT 2023 updated guidelines provide evidence-informed recommendations for the management of MDD, in a clinician-friendly format. These updated guidelines emphasize a collaborative, personalized, and systematic management approach that will help optimize outcomes for adults with MDD.
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NUK, OILJ, SAZU, UKNU, UL, UM, UPUK
Alcohol use, abuse, and addiction, and resulting health hazards are highly sex-dependent with unknown mechanisms. Previously, strong links between the SMPD3 gene and its coded protein neutral ...sphingomyelinase 2 (NSM) and alcohol abuse, emotional behavior, and bone defects were discovered and multiple mechanisms were identified for females. Here we report strong sex-dimorphisms for central, but not for peripheral mechanisms of NSM action in mouse models. Reduced NSM activity resulted in enhanced alcohol consumption in males, but delayed conditioned rewarding effects. It enhanced the acute dopamine response to alcohol, but decreased monoaminergic systems adaptations to chronic alcohol. Reduced NSM activity increased depression- and anxiety-like behavior, but was not involved in alcohol use for the self-management of the emotional state. Constitutively reduced NSM activity impaired structural development in the brain and enhanced lipidomic sensitivity to chronic alcohol. While the central effects were mostly opposite to NSM function in females, similar roles in bone-mediated osteocalcin release and its effects on alcohol drinking and emotional behavior were observed. These findings support the view that the NSM and multiple downstream mechanism may be a source of the sex-differences in alcohol use and emotional behavior.
Functionalization of material systems is one of the key developments nowadays in the textile industry, where particles are frequently used to enhance the properties of fibers and to add new ...functionalities. This book focuses on innovative textile materials and is a perfect guide for professionals in the textile industry and scientists alike. An overview of particle technology is provided before addressing all topics relevant to particle-enhanced textiles, i.e. the properties and application of micro/nanoparticles in textiles, production techniques, safety, as well as regulatory and intellectual property aspects. The book covers the composition and applications of various types of textile fillers, finishings, and microfibers. gives an outlook on future trends and challenges in the research, development, and production of nano- and micro-enabled textiles. The authors of the book, who are leading experts in their fields, address many aspects relevant to the use of particle-enhanced textiles in industrial applications as well as in our daily life. A particular emphasis is put on practical examples of applications and products, safety and sustainability issues and the potential for further innovation. This book should bring inspiration for textile scientists in using particles for improving textiles and further expanding their possibilities of use.
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