The increasing burden of heart failure (HF) and emerging knowledge regarding chloride as a prognostic marker in HF have increased the interest in the pathophysiology and interactions of chloride ...abnormalities with HF-related factors and treatments. Chloride is among the major electrolytes that play a unique role in fluid homeostasis and is associated with cardiorenal and neurohormonal systems. This review elucidates the role of chloride in the pathophysiology of HF, evaluates the effects of treatment on chloride (eg, diuretic agents cause higher urinary chloride excretion and consequently serum hypochloremia), and discusses recent evidence for the association between chloride levels and mortality.
ABSTRACT
We studied 17,576 members of 166 MLH1 and 224 MSH2 mutation‐carrying families from the Colon Cancer Family Registry. Average cumulative risks of colorectal cancer (CRC), endometrial cancer ...(EC), and other cancers for carriers were estimated using modified segregation analysis conditioned on ascertainment criteria. Heterogeneity in risks was investigated using a polygenic risk modifier. Average CRC cumulative risks at the age of 70 years (95% confidence intervals) for MLH1 and MSH2 mutation carriers, respectively, were estimated to be 34% (25%–50%) and 47% (36%–60%) for male carriers and 36% (25%–51%) and 37% (27%–50%) for female carriers. Corresponding EC risks were 18% (9.1%–34%) and 30% (18%–45%). A high level of CRC risk heterogeneity was observed (P < 0.001), with cumulative risks at the age of 70 years estimated to follow U‐shaped distributions. For example, 17% of male MSH2 mutation carriers have estimated lifetime risks of 0%–10% and 18% have risks of 90%–100%. Therefore, average risks are similar for the two genes but there is so much individual variation about the average that large proportions of carriers have either very low or very high lifetime cancer risks. Our estimates of CRC and EC cumulative risks for MLH1 and MSH2 mutation carriers are the most precise currently available.
Our estimates of colorectal and endometrial cancer risks for MLH1 and MSH2 mutation carriers are the most precise currently available. Average risks are similar for the two genes but there is so much individual variation about the average that a sizeable proportion of carries are almost certain to develop cancer whereas another sizeable proportion only have population‐level risks.
Ablative fractional laser treatment is considered the gold standard for skin rejuvenation. In order to understand how fractional laser works to rejuvenate skin, we performed microarray profiling on ...skin biopsies to identify temporal and dose-response changes in gene expression following fractional laser treatment. The backs of 14 women were treated with ablative fractional laser (Fraxel®) and 4 mm punch biopsies were collected from an untreated site and at the treated sites 1, 3, 7, 14, 21 and 28 days after the single treatment. In addition, in order to understand the effect that multiple fractional laser treatments have on skin rejuvenation, several sites were treated sequentially with either 1, 2, 3, or 4 treatments (with 28 days between treatments) followed by the collection of 4 mm punch biopsies. RNA was extracted from the biopsies, analyzed using Affymetrix U219 chips and gene expression was compared between untreated and treated sites. We observed dramatic changes in gene expression as early as 1 day after fractional laser treatment with changes remaining elevated even after 1 month. Analysis of individual genes demonstrated significant and time related changes in inflammatory, epidermal, and dermal genes, with dermal genes linked to extracellular matrix formation changing at later time points following fractional laser treatment. When comparing the age-related changes in skin gene expression to those induced by fractional laser, it was observed that fractional laser treatment reverses many of the changes in the aging gene expression. Finally, multiple fractional laser treatments, which cover different regions of a treatment area, resulted in a sustained or increased dermal remodeling response, with many genes either differentially regulated or continuously upregulated, supporting previous observations that maximal skin rejuvenation requires multiple fractional laser treatments. In conclusion, fractional laser treatment of human skin activates a number of biological processes involved in wound healing and tissue regeneration.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
It is important to distinguish between apprehensions that lead to vaccine rejection and those that do not. In this study, we (1) identifed latent classes of individuals by vaccination attitudes, and ...(2) compared classes of individuals by sociodemographic characteristics COVID-19 vaccination, and risk reduction behaviors. The COVID-19 Coping Study is a longitudinal cohort of US adults aged ≥ 55 years (n = 2358). We categorized individuals into three classes based on the adult Vaccine Hesitancy Scale using latent class analysis (LCA). The associations between class membership and sociodemographic characteristics, COVID-19 vaccination, and other behaviors were assessed using chi-square tests. In total, 88.9% were Vaccine Acceptors, 8.6% were Vaccine Ambivalent, and 2.5% Vaccine Rejectors. At the end, 90.7% of Acceptors, 62.4% of the Ambivalent, and 30.7% of the Rejectors had been vaccinated. The Ambivalent were more likely to be Black or Hispanic, and adopted social distancing and mask wearing behaviors intermediate to that of the Acceptors and Rejectors. Targeting the Vaccine Ambivalent may be an efficient way of increasing vaccination coverage. Controlling the spread of disease during a pandemic requires tailoring vaccine messaging to their concerns, e.g., through working with trusted community leaders, while promoting other risk reduction behaviors.
In the general population, increased adiposity is a significant risk factor for colorectal cancer (CRC), but whether obesity has similar effects in those with hereditary CRC is uncertain. This ...prospective study investigated the association between body mass index and cancer risk in patients with Lynch syndrome (LS).
Participants with LS were recruited to the CAPP2 study, in which they were randomly assigned to receive aspirin 600 mg per day or aspirin placebo, plus resistant starch 30 g per day or starch placebo (2 × 2 factorial design). Mean intervention period was 25.0 months, and mean follow-up was 55.7 months.
During follow-up, 55 of 937 participants developed CRC. For obese participants, CRC risk was 2.41× (95% CI, 1.22 to 4.85) greater than for underweight and normal-weight participants (reference group), and CRC risk increased by 7% for each 1-kg/m(2) increase in body mass index. The risk of all LS-related cancers in obese people was 1.77× (95% CI, 1.06 to 2.96; P = .03) greater than for the reference group. In subgroup analysis, obesity was associated with 3.72× (95% CI, 1.41 to 9.81) greater CRC risk in patients with LS with MLH1 mutation, but no excess risk was observed in those with MSH2 or MSH6 mutation (P = .5). The obesity-related excess CRC risk was confined to those randomly assigned to the aspirin placebo group (adjusted hazard ratio, 2.75; 95% CI, 1.12 to 6.79; P = .03).
Obesity is associated with substantially increased CRC risk in patients with LS, but this risk is abrogated in those taking aspirin. Such patients are likely to benefit from obesity prevention and/or regular aspirin.
Reflecting a complex set of interactions with its host,
Salmonella spp. require multiple genes for full virulence. Many of these genes are found in `pathogenicity islands' in the chromosome.
...Salmonella typhimurium possesses at least five such pathogenicity islands (SPI), which confer specific virulence traits and may have been acquired by horizontal transfer from other organisms. We highlight recent progress in characterizing these SPIs and the function of some of their genes. The role of virulence genes found on a highly conserved plasmid is also discussed. Collectively, these packages of virulence cassettes are essential for
Salmonella pathogenesis.
The steep rise in childhood obesity has emerged as a worldwide public health problem. The first 4 years of life are a critical window where long-term developmental patterns of body mass index (BMI) ...are established and a critical period for microbiota maturation. Understanding how the early-life microbiota relate to preschool growth may be useful for identifying preventive interventions for childhood obesity. We aim to investigate whether longitudinal shifts within the bacterial community between 3 months and 1 year of life are associated with preschool BMI z-score trajectories.
BMI trajectories from birth to 5 years of age were identified using group-based trajectory modeling in 3059 children. Their association with familial and environmental factors were analyzed. Infant gut microbiota at 3 months and 1 year was defined by 16S RNA sequencing and changes in diversity and composition within each BMIz trajectory were analyzed.
Four BMIz trajectories were identified: low stable, normative, high stable, and rapid growth. Infants in the rapid growth trajectory were less likely to have been breastfed, and gained less microbiota diversity in the first year of life. Relative abundance of Akkermansia increased with age in children with stable growth, but decreased in those with rapid growth, abundance of Ruminococcus and Clostridium at 1 year were elevated in children with rapid growth. Children who were breastfed at 6 months had increased levels of Sutterella, and decreased levels of Ruminococcus and Clostridium.
This study provides new insights into the relationship between the gut microbiota in infancy and patterns of growth in a cohort of preschool Canadian children. We highlight that rapid growth since birth is associated with bacteria shown in animal models to have a causative role in weight gain. Our findings support a novel avenue of research targeted on tangible interventions to reduce childhood obesity.
Why it’s worthwhile training as a psychiatrist Looi, Jeffrey CL; Finlay, Angus JF
Australasian psychiatry : bulletin of the Royal Australian and New Zealand College of Psychiatrists,
12/2020, Letnik:
28, Številka:
6
Journal Article
Recenzirano
Objectives:
We provide experiential reflections upon the process of training and working as a psychiatrist, with the aim of sparking and maintaining interest in psychiatry as a medical career.
...Conclusions:
There are many benefits and worthwhile experiences from training and working in psychiatry, especially in the privilege of providing holistic care for persons suffering from mental illness.
In mouse peritoneal and other serous cavities, the transcription factor GATA6 drives the identity of the major cavity resident population of macrophages, with a smaller subset of cavity-resident ...macrophages dependent on the transcription factor IRF4. Here we showed that GATA6
macrophages in the human peritoneum were rare, regardless of age. Instead, more human peritoneal macrophages aligned with mouse CD206
LYVE1
cavity macrophages that represent a differentiation stage just preceding expression of GATA6. A low abundance of CD206
macrophages was retained in C57BL/6J mice fed a high-fat diet and in wild-captured mice, suggesting that differences between serous cavity-resident macrophages in humans and mice were not environmental. IRF4-dependent mouse serous cavity macrophages aligned closely with human CD1c
CD14
CD64
peritoneal cells, which, in turn, resembled human peritoneal CD1c
CD14
CD64
cDC2. Thus, major populations of serous cavity-resident mononuclear phagocytes in humans and mice shared common features, but the proportions of different macrophage differentiation stages greatly differ between the two species, and dendritic cell (DC2)-like cells were especially prominent in humans.
We report the concentrations and isotope ratios of light noble gases (He, Ne, Ar) in 10 small basalt fragments derived from lunar regolith soils at the Apollo 12 landing site. We use cosmic ray ...exposure (CRE) and shielding condition histories to consider their geological context. We have devised a method of using cosmogenic Ne isotopes to partition the CRE history of each sample into two stages: a duration of “deep” burial (shielding of 5–500 g cm−2) and a duration of near‐surface exposure (shielding of 0 g cm−2). Three samples show evidence of measurable exposure at the lunar surface (durations of between 6 ± 2 and 7 ± 2 Myr). The remaining seven samples show evidence of a surface residence duration of less than a few hundred thousand years prior to collection. One sample records a single‐stage CRE age range of between 516 ± 36 and 1139 ± 121 Myr, within 0–5 g cm−2 of the lunar surface. This is consistent with derivation from ballistic sedimentation (i.e., local regolith reworking) during the Copernicus crater formation impact at ~800 Myr. The remaining samples show CRE age clusters around 124 ± 11 Myr and 188 ± 15 Myr. We infer that local impacts, including Surveyor crater (180–240 Ma) and Head crater (144 Ma), may have brought these samples to depths where the cosmic ray flux was intense enough to produce measurable cosmogenic Ne isotopes. More recent small impacts that formed unnamed craters may have exhumed these samples from their deep shielding conditions to the surface (i.e., ~0–5 g cm−2) prior to collection from the lunar surface during the Apollo 12 mission.
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