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We found that US has the ability to inhibit tonic spiking activity through a predominately thermal mechanism. US-evoked effects persisted after blocking synaptic inputs, indicating that its actions were direct. Experiments also revealed that US-comparable heating blocked the axonal conduction of spontaneous action potentials. Finally, we found no evidence that US had significant mechanical effects on the neurons tested, a finding counter to prevailing views. We conclude that a non-sensory neuron can be directly inhibited via a thermal mechanism, a finding that holds promise for clinical neuromodulatory applications.
Serum DDTs during or just after pregnancy were associated with breast cancer in mothers (F0), and with breast cancer, mammographic density, and obesity in adult daughters (F1) in the Child Health and Development Studies multi-generational cohort in prior publications. Here, we investigate F0 perinatal serum DDT associations with granddaughters'(F2) measured obesity at a median age of 26 and self-reported age at menarche.
F2 weight, height and waist circumference were measured by trained examiners.
-DDT,
-DDT and
DDE were measured in archived F0 perinatal serum. F0 DDT associations with F2 outcomes, accounting for F1 characteristics, were estimated in log-linear models adjusted for F0 and F1 body mass index (BMI), race, and menarche timing (
= 258 triads for obesity;
= 235 triads for early menarche). Interactions between F0 BMI and DDTs were estimated.
F0
-DDT was associated with F2 obesity [Odds ratio (OR), 2.6; 95% confidence interval (CI), 1.3-6.7; tertile 3 vs. 1), among normal weight F0 (70%), but not among overweight and obese F0 (
= 0.03), independent of other DDTs. F0
-DDT was also associated with F2 early menarche (OR, 2.1; 95% CI, 1.1-3.9, tertile 3 vs. 1) and this association was not modified by F0 BMI.
Ancestral exposure to environmental chemicals, banned decades ago, may influence the development of earlier menarche and obesity, which are established risk factors for breast cancer and cardiometabolic diseases.
Discovery of actionable biomarkers of response to ancestral environmental exposures in young women may provide opportunities for breast cancer prevention.
Discovery of actionable biomarkers of response to ancestral environmental exposures in young women may provide opportunities for breast cancer prevention.Women with past gestational diabetes mellitus (GDM) are at risk of subsequent type 2 diabetes and adverse cardiovascular events. PD0166285 purchase Digital and telemedicine interventions targeting weight loss and reductions in body mass index (BMI) may help reduce risk for women with GDM. The aim was to compare the effectiveness of digital or telemedicine intervention with usual care. Randomized controlled trials (RCTs) were identified in Embase, Medline, CINAHL, PsycINFO and the Cochrane Library. Included trials recruited women with prior GDM but without pre-existing diabetes, and tested a digital or telemedicine intervention with or without an in-person component. Data extraction was carried out independently by two authors. The search yielded 898 citations. Eighteen articles reporting 15 trials were included, of which 8 tested digital interventions. Reported outcomes included weight, BMI, fasting plasma glucose and waist circumference. None of the included trials reported type 2 diabetes incidence or cardiovascular risk. Data were pooled using a random-effects model. The point estimate favored the intervention but was non-significant for both BMI (-0.90 kg/m2, 95% CI -1.89 to 0.09; p=0.08) and weight (-1.83 kg, 95% CI -4.08 to 0.42, p=0.11). Trials evaluating digital and telemedicine interventions identified clinically relevant, but non-significant improvements in BMI and weight compared with control. No trials assessed type 2 diabetes occurrence as an outcome. More well-designed RCTs with adequate power and long-term follow-up are needed to identify the impact of these interventions on type 2 diabetes occurrence.
Exercise training has been shown to be the most effective strategy to combat obesity and non-alcoholic fatty liver disease. However, exercise promotes loss of adipose tissue mass and improves obesity-related hepatic steatosis through mechanisms that remain obscure.
To study the role of interleukin-6 (IL-6) in high-fat diet (HFD)-induced adiposity and hepatic steatosis during treadmill running, IL-6 knockout (IL-6 KO) mice and wild-type (WT) mice were randomly divided into lean, obese (fed a HFD) and trained obese groups (fed a HFD and exercise trained).
After 20 weeks of HFD feeding and 8 weeks of treadmill running, we found that exercise obviously reduced HFD-induced body weight gain, inhibited visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) expansion and almost completely reversed obesity-related intrahepatic fat accumulation in WT mice. However, IL-6 knockout (IL-6 KO) mice are refractory to the benefits of treadmill training on body weight, VAT and SAT mass elevation, and hepaticese antiobesity effects may be associated with enhanced lipolysis and thermogenesis in white adipose tissue. The improvement in hepatic steatosis by exercise training may benefit from the marked inhibition of PPAR-γ expression by IL-6.Recently, multiple single-cell assays were developed for detecting histone marks at the single-cell level. These techniques are either limited by the low cell throughput or sparse reads which limit their applications. To address these problems, we introduce indexing single-cell immunocleavage sequencing (iscChIC-seq), a multiplex indexing method based on TdT terminal transferase and T4 DNA ligase-mediated barcoding strategy and single-cell ChIC-seq, which is capable of readily analyzing histone modifications across tens of thousands of single cells in one experiment. Application of iscChIC-seq to profiling H3K4me3 and H3K27me3 in human white blood cells (WBCs) enabled successful detection of more than 10,000 single cells for each histone modification with 11 K and 45 K nonredundant reads per cell, respectively. Cluster analysis of these data allowed identification of monocytes, T cells, B cells, and NK cells from WBCs. The cell types annotated from H3K4me3 single-cell data are specifically correlated with the cell types annotated from H3K27me3 single-cell data.