Notes

Evidence-based specialized medical prioritization regarding embryos using variety final results: a deliberate assessment along with meta-analysis.
asures were associated with VO2peak early post-breast cancer therapy. A combination of these parameters had good discrimination to identify patients with compromised functional independence and potentially increased future CVD risk.
Cardiometabolic disease, including cardiovascular disease (CVD) and type 2 diabetes (T2D), can result in serious late effects in patients with cancer. Preventing long-term complications in this population is an increasingly important priority in public health and clinical practice.

The aim of this study was to investigate the role of a healthy lifestyle in the transition from a healthy status to the development of cancer and subsequent CVD and T2D.

The analysis was based on data from the UK Biobank and included 2 subsamples a cancer-free cohort of 397,136 individuals in the general population and a cancer-prevalent cohort of 35,564 patients with cancer. All participants were 40 to 70 years of age and were free of CVD and T2D at recruitment. A healthy lifestyle that included no current smoking, regular physical activity, a healthy diet, and moderate alcohol consumption and sleep duration were included in a healthy lifestyle index (HLI).

In the cancer-free cohort, during a maximum follow-up period of 15risk for CVD and T2D. This study highlights the practical benefits of adherence to a healthy lifestyle.Anthracyclines are associated with risk of significant dose-dependent cardiotoxicity. Conventional heart failure therapies have neither ameliorated declining cardiac function nor addressed the underlying cause. Gene therapy may confer long-term cardioprotection by rendering the heart resistant to anthracyclines after 1 treatment, although the optimal therapeutic target remains to be elucidated. Recombinant adeno-associated virus is now clinically approved for the treatment of lipoprotein lipase deficiency, spinal muscular atrophy, and hereditary transthyretin amyloidosis. High-throughput methods allow selection of recombinant adeno-associated virus capsids that facilitate efficient gene delivery to specific target cells. Vector safety is enhanced by incorporating cardiac-specific promoters into vector design and localizing delivery to reduce off-target risk. Any cardioprotective transgene may bear a degree of risk as they may play as yet unknown roles, which require careful assessment using clinically relevant models. The innovative technologies outlined here make gene therapy a promising proof of principle, with potential further application to nonanthracycline chemotherapeutics.Cancer patients and survivors have elevated cardiovascular risk when compared with noncancer patients. Cardio-oncology has emerged as a new subspecialty to comanage and address cardiovascular complications in cancer patients such as heart failure, atherosclerotic cardiovascular disease (ASCVD), valvular heart disease, pericardial disease, and arrhythmias. Cardiac computed tomography (CT) can be helpful in identifying both clinical and subclinical ASCVD in cancer patients and survivors. Radiation therapy treatment planning CT scans and cancer staging/re-staging imaging studies can quantify calcium scores which can identify pre-existing subclinical ASCVD. Cardiac CT can be helpful in the evaluation of cardiac tumors and pericardial diseases, especially in patients who cannot tolerate or have a contraindication to cardiac magnetic resonance. In this review, we describe the optimal utilization of cardiac CT in cancer patients, including risk assessment for ASCVD and identification of cancer treatment-related cardiovascular toxicity.Cardiovascular disease and cancer are the 2 leading causes of death worldwide. Emerging evidence suggests common mechanisms between cancer and cardiovascular disease, including atrial fibrillation and atherosclerosis. With advances in cancer therapies, screening, and diagnostics, cancer-specific survival and outcomes have improved. This increase in survival has led to the coincidence of cardiovascular disease, including atrial fibrillation and atherosclerosis, as patients with cancer live longer. Additionally, cancer and cardiovascular disease share several risk factors and underlying pathophysiologic mechanisms, including inflammation, cancer-related factors including treatment effects, and alterations in platelet function. Patients with cancer are at increased risk for bleeding and thrombosis compared with the general population. Although optimal antithrombotic therapy, including agent choice and duration, has been extensively studied in the general population, this area remains understudied in patients with cancer despite their altered thrombotic and bleeding risk. Future investigation, including incorporation of cancer-specific characteristics to traditional thrombotic and bleeding risk scores, clinical trials in the cancer population, and the development of novel antithrombotic and anti-inflammatory strategies on the basis of shared pathophysiologic mechanisms, is warranted to improve outcomes in this patient population.
Beta blockers prolong life in patients with cardiovascular diseases. Negative chronotropic and inotropic effects carry the potential to adversely effect peripheral skeletal and airway smooth muscle contributing to further fatigue, dyspnea and exercise intolerance.

Do beta-blockers reduce maximal power output (MPO), VO2 max, cardiorespiratory responses, increase the perceived effort required to cycle and breath during cardiopulmonary exercise tests (CPET) and limit the capacity to exercise?

Retrospective observational study of subjects performing CPET to capacity from 1988 to 2012. Subjects with and without beta-blockers were compared baseline physiological characteristics, MPO, VO
max, heart rate max, ventilation responses and perceived exertion required to cycle and breathe (modified Borg scale). Forward stepwise linear additive regression was performed with MPO as the dependent factor with height, age, gender, muscle strength, FEV1 and DLCO as independent contributors.

42,771 subjects were included 7,787 were receiving beta-blocker [mean age 61yrs, BMI 28.40kg/m
, 9% airflow obstruction (FEV1/FVC<0.7)] and 34,984 were not [mean age 51yrs, BMI 27.40kg/m
, 11% airflow obstruction]. Heart rate was lower by 18.2% (95% C.I. 18.15-18.38) (p<0.0001) while Oxygen pulse (VO
/HR) was higher by 19.5% (95% C.I. 19.3-19.7) in those receiving beta blockers. Maximum power output (MPO) was 3.3% lower in those taking beta-blockers. The perceived effort required to cycle and breathe (mBorg) was 8% lower in those taking beta-blockers.

Increases in oxygen pulse minimize the reduction in exercise intolerance and symptom handicap associated with beta-blockers.
Increases in oxygen pulse minimize the reduction in exercise intolerance and symptom handicap associated with beta-blockers.Progressive sodium retention and cumulative plasma volume expansion occur to support the developing fetus during pregnancy. Sodium retention is regulated by individual tubular transporters and channels. An increase or decrease in any single transporter could cause a change in sodium balance. selleck inhibitor Understanding the time-course for changes in each sodium transporter during pregnancy will enable us to understand progressive sodium retention seen in pregnancy. Here, we examined the activity of the major apical sodium transporters found in the nephron using natriuretic response tests in virgin, early pregnant, mid-pregnant, and late pregnant rats. We also measured renal and serum aldosterone levels. We found that furosemide sensitive sodium transport (NKCC2) is only increased during late pregnancy, thiazide sensitive sodium transport (NDCBE/pendrin) is increased in all stages of pregnancy, and that benzamil sensitive sodium transport (ENaC) is increased beginning in mid-pregnancy. We also found that serum aldosterone levels progressively increased throughout gestation and kidney tissue aldosterone levels increased only during late pregnancy. Here we have shown progressive turning on of specific sodium transport mechanisms to help support progressive sodium retention through the course of gestation. These mechanisms contribute to the renal sodium retention and plasma volume expansion required for an optimal pregnancy.The Musashi RNA-binding proteins (RBPs) regulate translation of target mRNAs and maintenance of cell stemness and tumorigenesis. Musashi-1 (MSI1), long considered as an intestinal and neural stem cell marker, has been more recently found to be over expressed in many cancers. It has served as an important drug target for treating acute myeloid leukemia and solid tumors such as ovarian, colorectal and bladder cancer. One of the reported binding targets of MSI1 is Numb, a negative regulator of the Notch signaling. However, the dynamic mechanism of Numb RNA binding to MSI1 remains unknown, largely hindering effective drug design targeting this critical interaction. Here, we have performed extensive all-atom microsecond-timescale simulations using a robust Gaussian accelerated molecular dynamics (GaMD) method, which successfully captured multiple times of spontaneous and highly accurate binding of the Numb RNA from bulk solvent to the MSI1 protein target site. GaMD simulations revealed that Numb RNA binding to MSI1 involved largely induced fit in both the RNA and protein. The simulations also identified important low-energy intermediate conformational states during RNA binding, in which Numb interacted mainly with the β2-β3 loop and C terminus of MSI1. The mechanistic understanding of RNA binding obtained from our GaMD simulations is expected to facilitate rational structure-based drug design targeting MSI1 and other RBPs.[This corrects the article DOI 10.1016/j.crfs.2019.11.007.].[This corrects the article DOI 10.1016/j.crfs.2020.09.001.].Thin vertical nanowires based on III-V compound semiconductors are viable candidates as channel material in metal oxide semiconductor field effect transistors (MOSFETs) due to attractive carrier transport properties. However, for improved performance in terms of current density as well as contact resistance, adequate characterization techniques for resolving doping distribution within thin vertical nanowires are required. We present a novel method of axially probing the doping profile by systematically changing the gate position, at a constant gate length L g of 50 nm and a channel diameter of 12 nm, along a vertical nanowire MOSFET and utilizing the variations in threshold voltage V T shift (∼100 mV). The method is further validated using the well-established technique of electron holography to verify the presence of the doping profile. Combined, device and material characterizations allow us to in-depth study the origin of the threshold voltage variability typically present for metal organic chemical vapor deposition (MOCVD)-grown III-V nanowire devices.
The best approach to provide comprehensive care for individuals with co-occurring disorders (CODs) related to substance use and mental health is to address both disorders through an integrated treatment approach. However, only 25% of behavioral health agencies offer integrated care and less than 7% of individuals who need integrated treatment receive it. A project used a cluster-randomized waitlist control group design to evaluate the effectiveness of Network for the Improvement of Addiction Treatment (NIATx) implementation strategies to improve access to addiction and psychotropic medications.

This study represents a secondary analysis of data from the NIATx project. Forty-nine agencies were randomized to Cohort1 (active implementation group, receiving the NIATx strategy [n=25]) or Cohort2 (waitlist control group [n=24]). Data were collected at three time points (Baseline, Year1 and Year2). A two-level (patient within agency) multinomial logistic regression model investigated the effects of implementation strategy condition on one of four medication outcomes both medication types, only psychotropic medication, only addiction medication, or neither medication type.
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