Willardrocha9412

Background Cardiac hypertrophy (CH) occurs with an increase in myocardium mass as an adaptive compensation to increased stress. Prolonged CH causes decompensated heart failure (HF). Enhanced angiogenesis by vascular endothelial growth factor (VEGF) is observed in hypertrophied hearts; impaired angiogenesis by angiotensin II (AngII) is observed in failing hearts. Angiogenesis is executed by vascular endothelial cells (ECs). Abnormal Ca2+ homeostasis is a hallmark feature of hypertrophied and failing hearts. Ca2+-activated chloride channel transmembrane protein 16A (TMEM16A) is expressed in cardiomyocytes and ECs but its role in heart under stress remains unknown. check details Methods Pressure-overload-induced CH and HF mouse models were established. Echocardiography was performed to evaluate cardiac parameters. Quantitative real-time PCR, traditional and simple western assays were used to quantify molecular expression. Whole-cell patch-clamp experiments were used to detect TMEM16A current (ITMEM16A) and action potential dused ECs. Conclusion TMEM16A contributes insignificantly in myocardium remodeling during pressure-overload. TMEM16A is a positive regulator of migration and angiogenesis under normal condition or simulated stress. TMEM16A may become a new target for upregulation of angiogenesis in ischemic disorders like ischemic heart disease.Background Both heart failure (HF) with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF) can present a wide variety of cardiac morphologies consequent to cardiac remodeling. We sought to study if geometric changes to the heart during such remodeling will adversely affect the ejection fraction (EF) parameter's ability to serve as an indicator of heart function, and to identify the mechanism for it. Methods and Results A numerical model that simulated the conversion of myocardial strain to stroke volume was developed from two porcine animal models of heart failure. Hypertrophic wall thickening was found to elevate EF, while left ventricle (LV) dilation was found to depress EF when myocardial strain was kept constant, causing EF to inaccurately represent the overall strain function. This was caused by EF being calculated using the endocardial boundary rather than the mid-wall layer. Radial displacement of the endocardial boundary resulted in endocardial strain deviating from the overall LV strain, and this deviation varied with LV geometric changes. This suggested that using the epi- or endo-boundaries to calculate functional parameters was not effective, and explained why EF could be adversely affected by geometric changes. Further, when EF was modified by calculating it at the mid-wall layer instead of at the endocardium, this shortcoming was resolved, and the mid-wall EF could differentiate between healthy and HFpEF subjects in our animal models, while the traditional EF could not. Conclusion We presented the mechanism to explain why EF can no longer effectively indicate cardiac function during cardiac geometric changes relevant to HF remodeling, losing the ability to distinguish between hypertrophic diseased hearts from healthy hearts. Measuring EF at the mid-wall location rather than endocardium can avoid the shortcoming and better represent the cardiac strain function.Cutaneous microcirculatory perfusion is commonly measured using laser Doppler flowmetry (LDF) probes, which provide a continuous, non-invasive quantification of skin blood flow (SkBF). However, inhomogeneities in the skin's microvasculature density contribute to a decrease in reproducibility whenever an LDF probe is removed and replaced, as is the case during pre- and post-intervention or between-day measurements. Therefore, this study aimed to determine whether increasing the total number of individual LDF probes in a localized area improves the reproducibility of the measurement. Seven laser Doppler probes were secured in a custom-made acrylic holder designed to attach to the skin's surface easily. SkBF, local skin temperature (Tsk), and blood pressure (BP) were assessed in 11 participants (6 M, 5 F, 42 ± 15 years). SkBF and Tsk were measured from the dorsal forearm (arm trial) for 5 min. Next, the multi-laser device was moved to the lateral side of the calf (leg trial), and measurements were obtained for 5s within the same participant. Therefore, this application could provide more reproducible assessments between repeated measurements (e.g., before and after exercise or clinical procedures) where the LDF probes must be removed and replaced within the same location.Spontaneous day-time periodic breathing (sPB) constitutes a common phenomenon in systolic heart failure (HF). However, it is unclear whether PB during wakefulness could be easily induced and what are the physiological and clinical correlates of patients with HF in whom PB induction is possible. Fifty male HF patients (age 60.8 ± 9.8 years, left ventricle ejection fraction 28.0 ± 7.4%) were prospectively screened and 46 enrolled. After exclusion of patients with sPB the remaining underwent trial of PB induction using mild hypoxia (stepwise addition of nitrogen gas to breathing mixture) which resulted in identification of inducible (iPB) in 51%. All patients underwent assessment of hypoxic ventilatory response (HVR) using transient hypoxia and of hypercapnic ventilatory response (HCVR) employing Read's rebreathing method. The induction trial did not result in any adverse events and minimal SpO2 during nitrogen administration was ∼85%. The iPB group (vs. non-inducible PB group, nPB) was characterized by greater HVR (0.90 ± 0.47 vs. 0.50 ± 0.26 L/min/%; p less then 0.05) but comparable HCVR (0.88 ± 0.54 vs. 0.67 ± 0.68 L/min/mmHg; p = NS) and by worse clinical and neurohormonal profile. Mean SpO2 which induced first cycle of PB was 88.9 ± 3.7%, while in sPB mean SpO2 preceding first spontaneous cycle of PB was 96.0 ± 2.5%. There was a reverse relationship between HVR and the relative variation of SpO2 during induced PB (r = -0.49, p = 0.04). In summary, PB induction is feasible and safe in HF population using simple and standardized protocol employing incremental, mild hypoxia. Pathophysiology of iPB differs from sPB, as it relies mostly on overactive peripheral chemoreceptors. At the same time enhanced HVR might play a protective role against profound hypoxia during iPB.Chemerin is an adipokine involved in inflammation, adipogenesis, angiogenesis and energy metabolism, and has been hypothesized as a link between obesity and type II diabetes. In humans affected by obesity, chemerin gene expression in peripheral tissues and circulating levels are elevated. In mice, plasma levels of chemerin are upregulated by high-fat feeding and gain and loss of function studies show an association of chemerin with body weight, food intake and glucose homeostasis. Therefore, chemerin is an important blood-borne mediator that, amongst its other functions, controls appetite and body weight. Almost all studies of chemerin to date have focused on its release from adipose tissue and its effects on peripheral tissues with the central effects largely overlooked. To demonstrate a central role of chemerin, we manipulated chemerin signaling in the hypothalamus, a brain region associated with appetite regulation, using pharmacological and genetic manipulation approaches. Firstly, the selective chemerin its receptors and markers of adipogenesis, lipogenesis and brown adipocyte activation remained unchanged confirming that the effects are driven by the brain. Our behavioral analyses suggest that knockdown of CMKLR1 had an impact on object recognition. Our data demonstrate that CMKLR1 is functionally important for the central effects of chemerin on body weight regulation and neuroinflammation.In teleost fishes, ionocytes in the gills are important osmoregulatory sites in maintaining ionic balance. During the embryonic stages before the formation of the gills, ionocytes are located in the yolk-sac membrane and body skin. In Mozambique tilapia embryos, quintuple-color immunofluorescence staining allowed us to classify ionocytes into four types type I, showing only basolateral Na+/K+-ATPase (NKA) staining; type II, basolateral NKA and apical Na+, Cl- cotransporter 2; type III, basolateral NKA, basolateral Na+, K+, 2Cl- cotransporter 1a (NKCC1a) and apical Na+/H+ exchanger 3; and type IV, basolateral NKA, basolateral NKCC1a and apical cystic fibrosis transmembrane conductance regulator Cl- channel. The ionocyte population consisted mostly of type I, type II and type III in freshwater, while type I and IV dominated in seawater. In adult tilapia, dual observations of whole-mount immunocytochemistry and scanning electron microscopy showed morphofunctional alterations in ionocytes. After transfer from freshwater to seawater, while type-II ionocytes closed their apical openings to suspend ion absorption, type-III ionocytes with a concave surface were transformed into type IV with a pit via a transitory surface. The proposed model of functional classification of ionocytes can account not only for ion uptake in freshwater and ion secretion in seawater, but also for plasticity in ion-transporting functions of ionocytes in tilapia.

Three to 22% of youth undergoing surgery develop chronic postsurgical pain (CPSP). Negative biases in pain memories (i.e., recalling higher levels of pain as compared to initial reports) are a risk factor for CPSP development. Children's memories for pain are modifiable. Existing memory-reframing interventions reduced negatively biased memories associated with procedural pain and pain after minor surgery. However, not one study has tested the feasibility and acceptability of the memory-reframing intervention in youth undergoing major surgery.

The current pilot randomized clinical trial (RCT; NCT03110367; clinicaltrials.gov) examined the feasibility and acceptability of, as well as adherence to, a memory reframing intervention.

Youth undergoing a major surgery reported their baseline and postsurgery pain levels. Four weeks postsurgery, youth and one of their parents were randomized to receive control or memory-reframing instructions. Following the instructions, parents and youth reminisced about the surgery either as they normally would (control) or using the memory-reframing strategies (intervention). Six weeks postsurgery, youth completed a pain memory interview; parents reported intervention acceptability. Four months postsurgery, youth reported their pain.

Seventeen youth (76% girls,

=14.1years) completed the study. The intervention was feasible and acceptable. Parents, but not youth, adhered to the intervention principles. The effect sizes of the intervention on youth pain memories (



=0.22) and pain outcomes (



=0.23) were used to inform a larger RCT sample size.

Memory reframing is a promising avenue in pediatric pain research. Larger RCTs are needed to determine intervention efficacy to improve pain outcomes.

Memory reframing is a promising avenue in pediatric pain research. Larger RCTs are needed to determine intervention efficacy to improve pain outcomes.A growing number of studies have identified high rates of pediatric chronic postsurgical pain (CPSP) after major surgery. Pediatric CPSP is associated with pain-related distress and comorbid mental health outcomes, such as anxiety and depression. From a biopsychosocial perspective, youth factors, such as genetics, epigenetics, sex, presurgical pain, sleep, anxiety, and pain catastrophizing, as well as parent factors, such as cognitive appraisals of their child's pain expression and pain catastrophizing, converge and lead to chronic pain disability. A comprehensive and testable psychosocial model of the transition from acute to chronic pediatric postsurgical pain has not been developed. This narrative review begins by evaluating the epidemiology and trajectories of pediatric CPSP and moves on to examine the more influential psychosocial models that have been proposed to understand the development of pediatric CPSP. Much of the literature to date has been conducted on adolescents undergoing spinal fusion. To conceptualize the transition from acute to chronic pain in youth, a combined diathesis-stress and interpersonal fear avoidance model is presented.