Notes

Hif-1α is not needed for the development of cardiovascular adrenergic manage inside zebrafish (Danio rerio).
This study aimed to investigate the association of pulse pressure (PP) with the cardio-cerebrovascular disease (CCVD) risk and all-cause mortality according to blood pressure level using Korean national cohort data.

This study was retrospectively designed and based on the Korean National Health Insurance Service-National Health Screening Cohort. Participants aged 40-69 years at baseline were categorized into normal, elevated, stage 1, and stage 2 groups according to blood pressure. Each group was further classified into 5 groups separated by 10-mm Hg increments in PP. The primary composite outcome was defined as CCVDs and all-cause mortality. Cox proportional hazards regression models were adopted after stepwise adjustment for confounders to investigate the composite outcome.

During the follow-up period (median follow-up period, 12.0 years), the primary composite outcome occurred in 18,444 (15.0%) of 122,783 men and 10,096 (11.4%) of 88,550 women. After complete adjustment for confounders, in the stage 1 hypertensive men, the hazard ratio (95% confidence intervals [CIs]) of the 31-40, 41-50, 51-60, and >60 mm Hg PP groups was 1.112 (1.013-1.221), 1.035 (0.942-1.137), 1.009 (0.907-1.123), and 1.324 (1.130-1.551) in comparison with the ≤30 mm Hg PP group. In the stage 2 hypertensive men, the HRs (95% CIs) were 1.069 (0.949-1.204), 1.059 (0.940-1.192), 1.123 (0.999-1.263), and 1.202 (1.061-1.358) compared to the ≤30 mm Hg PP group. However, these associations were not significant in women.

Hypertensive men with an increased PP have an increased risk of CCVDs and all-cause mortality.
Hypertensive men with an increased PP have an increased risk of CCVDs and all-cause mortality.Bone fragility can progress with aging, but biomarkers to detect emerging osteopenia have not been fully elucidated. Growth/differentiation factor 15 (GDF-15) has pleiotropic roles in a broad range of age-related conditions, but its association with osteopenia is unknown. We examined the relationship between plasma GDF-15 levels and rate of change in bone parameters over 9 years of follow-up in 596 adults in the InCHIANTI study (baseline age, 65-94 years; women, 52.4%; mean follow-up, 7.0 ± 3.0 years). Plasma GDF-15 concentrations were measured using the 1.3k HTS SOMAscan assay. Eight bone parameters were measured in the right tibia by peripheral quantitative computed tomography; total bone density, trabecular bone density, medullary plus trabecular bone density, cortical bone density, total bone area, cortical bone area, medullary bone area, and minimum moment of inertia (mMOI). We ran sex-specific linear mixed-effect models with random intercepts and slopes adjusted for age, age-squared, education, body mass index, the rate of change in weight, smoking, sedentary behavior, cross-sectional areas of calf muscles and fat, 25-hydroxyvitamin D, parathyroid hormone, calcium, diabetes mellitus, and follow-up time. We found a significant association of "baseline GDF-15 × time" in models predicting cortical bone density and the mMOI in women, suggesting that the rates of decline in these bone parameters increased with higher GDF-15 (false discovery rate less then 0.05). Higher plasma levels GDF-15 predicted an accelerated decline in bone parameters in women, but was less associated in men. Furthermore studies are needed to understand the mechanisms underlying these sex differences.Sex determination is a critical element of successful vertebrate development, suggesting that sex chromosome systems might be evolutionarily stable across lineages. Tofacitinib For example, mammals and birds have maintained conserved sex chromosome systems over long evolutionary time periods. Other vertebrates, in contrast, have undergone frequent sex chromosome transitions, which is even more amazing considering we still know comparatively little across large swaths of their respective phylogenies. One reptile group in particular, the gecko lizards (infraorder Gekkota), shows an exceptional lability with regard to sex chromosome transitions and may possess the majority of transitions within squamates (lizards and snakes). However, detailed genomic and cytogenetic information about sex chromosomes is lacking for most gecko species, leaving large gaps in our understanding of the evolutionary processes at play. To address this, we assembled a chromosome-level genome for a gecko (Sphaerodactylidae Sphaerodactylus) and used this assembly to search for sex chromosomes among six closely related species using a variety of genomic data, including whole-genome re-sequencing, RADseq, and RNAseq. Previous work has identified XY systems in two species of Sphaerodactylus geckos. We expand upon that work to identify between two and four sex chromosome cis-transitions (XY to a new XY) within the genus. Interestingly, we confirmed two different linkage groups as XY sex chromosome systems that were previously unknown to act as sex chromosomes in tetrapods (syntenic with Gallus chromosome 3 and Gallus chromosomes 18/30/33), further highlighting a unique and fascinating trend that most linkage groups have the potential to act as sex chromosomes in squamates.
Primary hyperparathyroidism (PHPT) is associated with an increased risk of kidney stones. Few studies account for PHPT severity or stone risk when comparing stone events after parathyroidectomy vs nonoperative management.

Compare the incidence of kidney stone events in PHPT patients treated with parathyroidectomy vs nonoperative management.

Longitudinal cohort study with propensity score inverse probability weighting and multivariable Cox proportional hazards regression.

Veterans Health Administration integrated health care system.

A total of 44 978 patients with > 2 years follow-up after PHPT diagnosis (2000-2018); 5244 patients (11.7%) were treated with parathyroidectomy.

Clinically significant kidney stone event.

The cohort had a mean age of 66.0 years, was 87.8% male, and 66.4% White. Patients treated with parathyroidectomy had higher mean serum calcium (11.2 vs 10.8mg/dL) and were more likely to have a history of kidney stone events. Among patients with baseline history of kidney stones,d risk of stone events declined with time, suggesting a benefit to surgical treatment.
Observational studies have shown that elevated uric acid (UA) is associated with chronic kidney disease (CKD). However, whether the relationship is causal remains unclear.

To determine the association of plasma UA and incident CKD and the causal relationship between plasma UA and rapid decline in kidney function (RDKF) in patients with type 2 diabetes (T2D).

Multivariable Cox regression was conducted to evaluate the hazard ratio (HR) between plasma UA and incident CKD among 1300 normoalbuminuric patients in 2 T2D study cohorts (DN, n = 402; SMART2D, n = 898). A weighted genetic risk score (wGRS) was calculated based on 10 single nucleotide polymorphism (SNPs) identified in genome-wide association studies of UA in East Asians. Mendelian randomization (MR) analysis was performed among 1146 Chinese T2D patients without CKD (estimated glomerular filtration rate [eGFR] > 60 mL/min/1.73m2) at baseline (DN, 478; SMART2D, 668). The wGRS and individual SNPs were used as genetic instruments and RDKF was defined as eGFR decline of 5 mL/min/1.73m2/year or greater.

During mean follow-up of 5.2 and 5.4 years, 81 (9%) and 46 (11%) participants in SMART2D and DN developed CKD, respectively. A 1-SD increment in plasma UA conferred higher risk of incident CKD (DN, adjusted-HR = 1.40 [95% CI, 1.02-1.91], P = 0.036; SMART2D, adjusted-HR = 1.31 [95% CI, 1.04-1.64], P = 0.018). Higher wGRS was associated with increased odds for RDKF (meta-adjusted odds ratio = 1.12 [95% CI, 1.01-1.24], P = 0.030, Phet = 0.606).

Elevated plasma UA is an independent risk factor for incident CKD. Furthermore, plasma UA potentially has a causal role in early eGFR loss in T2D patients.
Elevated plasma UA is an independent risk factor for incident CKD. Furthermore, plasma UA potentially has a causal role in early eGFR loss in T2D patients.Intestinal metaplasia (IM) is a risk factor for gastric cancer following infection with Helicobacter pylori. To explore the susceptibility of pure gastric IM to cancer development, we investigated genetic alterations in single IM gastric glands. We isolated 50 single IM or non-IM glands from the inflamed gastric mucosa of 11 patients with intramucosal gastric carcinoma (IGC) and 4 patients without IGC; 19 single glands in the noninflamed gastric mucosa of 11 individuals from our cohort and previous dataset were also included as controls. Whole-exome sequencing of single glands revealed significantly higher accumulation of somatic mutations in various genes within IM glands compared with non-IM glands. Clonal ordering analysis showed that IM glands expanded to form clusters with shared mutations. In addition, targeted-capture deep sequencing and copy number (CN) analyses were performed in 96 clustered IM or non-IM gastric glands from 26 patients with IGC. CN analyses were also performed on 41 IGC samples and Ts and somatic mutations.Insects have a large ratio of surface area to volume because of their small size; thus, they face the potential for desiccation in the terrestrial environment. Nonetheless, they constitute over half of identified species and their success on land can be attributed, in part, to adaptations that limit water loss and allow for effective gains of water from food, fluids or atmospheric water vapour. Reduction of water loss from the gut involves sophisticated mechanisms of ion recycling and water recovery by epithelia of the Malpighian tubules and hindgut. Water loss across the body surface is greatly reduced by the evolution of very thin but highly impermeable lipid-rich layers in the epicuticle. Respiratory water loss can be reduced through effective spiracular control mechanisms and by mechanisms for convective rather than diffusive gas exchange. In addition to extracting water from food sources, some insects are capable of absorption of atmospheric water vapour through processes that have evolved independently in multiple groups.The venom glands of reptiles, particularly those of front-fanged advanced snakes, must satisfy conflicting biological demands rapid synthesis of potentially labile and highly toxic proteins, storage in the gland lumen for long periods, stabilization of the stored secretions, immediate activation of toxins upon deployment and protection of the animal from the toxic effects of its own venom. This dynamic system could serve as a model for the study of a variety of different phenomena involving exocrine gland activation, protein synthesis, stabilization of protein products and secretory mechanisms. However, these studies have been hampered by a lack of a long-term model that can be propagated in the lab (as opposed to whole-animal studies). Numerous attempts have been made to extend the lifetime of venom gland secretory cells, but only recently has an organoid model been shown to have the requisite qualities of recapitulation of the native system, self-propagation and long-term viability (>1 year). A tractable model is now available for myriad cell- and molecular-level studies of venom glands, protein synthesis and secretion. However, venom glands of reptiles are not identical, and many differ very extensively in overall architecture, microanatomy and protein products produced. This Review summarizes the similarities among and differences between venom glands of helodermatid lizards and of rear-fanged and front-fanged snakes, highlighting those areas that are well understood and identifying areas where future studies can fill in significant gaps in knowledge of these ancient, yet fascinating systems.
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