Time-Efficient Inspiratory Muscle Strength Training Lowers Blood Pressure and Improves Endothelial Function, NO Bioavailability, and Oxidative Stress in Midlife/Older Adults With Above-Normal Blood Pressure

Background High‐resistance inspiratory muscle strength training (IMST) is a novel, time‐efficient physical training modality. &nbsp; Methods and Results We performed a double‐blind, randomized, sham‐controlled trial to investigate whether 6&nbsp;weeks of IMST (30&nbsp;breaths/day, 6&nbsp;days/week) improves blood pressure, endothelial function, and arterial stiffness in midlife/older adults (aged 50&ndash;79&nbsp;years) with systolic blood pressure &ge;120&nbsp;mm&nbsp;Hg, while also investigating potential mechanisms and long‐lasting effects. Thirty‐six participants completed high‐resistance IMST (75% maximal inspiratory pressure, n=18) or low‐resistance sham training (15% maximal inspiratory pressure, n=18). IMST was safe, well tolerated, and had excellent adherence (&asymp;95% of training sessions completed). Casual systolic blood pressure decreased from 135&plusmn;2&nbsp;mm&nbsp;Hg to 126&plusmn;3&nbsp;mm&nbsp;Hg (P&lt;0.01) with IMST, which was &asymp;75% sustained 6&nbsp;weeks after IMST (P&lt;0.01), whereas IMST modestly decreased casual diastolic blood pressure (79&plusmn;2&nbsp;mm&nbsp;Hg to 77&plusmn;2&nbsp;mm&nbsp;Hg, P=0.03); blood pressure was unaffected by sham training (all P&gt;0.05). Twenty‐four hour systolic blood pressure was lower after IMST versus sham training (P=0.01). Brachial artery flow‐mediated dilation improved &asymp;45% with IMST (P&lt;0.01) but was unchanged with sham training (P=0.73). Human umbilical vein endothelial cells cultured with subject serum sampled after versus before IMST exhibited increased NO bioavailability, greater endothelial NO synthase activation, and lower reactive oxygen species bioactivity (P&lt;0.05). IMST decreased C‐reactive protein (P=0.05) and altered select circulating metabolites (targeted plasma metabolomics) associated with cardiovascular function. Neither IMST nor sham training influenced arterial stiffness (P&gt;0.05). &nbsp; Conclusions High‐resistance IMST is a safe, highly adherable lifestyle intervention for improving blood pressure and endothelial function in midlife/older adults with above‐normal initial systolic blood pressure. &nbsp; Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT03266510. &nbsp;</p

Exercise decreases lipogenic gene expression in adipose tissue and alters adipocyte cellularity during weight regain after weight loss.

Exercise is a potent strategy to facilitate long-term weight maintenance. In addition to increasing energy expenditure and reducing appetite, exercise also favors the oxidation of dietary fat, which likely helps prevent weight re-gain. It is unclear whether this exercise-induced metabolic shift is due to changes in energy balance, or whether exercise imparts additional adaptations in the periphery that limit the storage and favor the oxidation of dietary fat. To answer this question, adipose tissue lipid metabolism and related gene expression were studied in obese rats following weight loss and during the first day of relapse to obesity. Mature, obese rats were weight-reduced for 2 weeks with or without daily treadmill exercise (EX). Rats were weight maintained for 6 weeks, followed by relapse on: a) ad libitum low fat diet (LFD), b) ad libitum LFD plus EX, or c) a provision of LFD to match the positive energy imbalance of exercised, relapsing animals. 24h retention of dietary- and de novo-derived fat were assessed directly using 14C palmitate/oleate and 3H20, respectively. Exercise decreased the size, but increased the number of adipocytes in both retroperitoneal (RP) and subcutaneous (SC) adipose depots, and prevented the relapse-induced increase in adipocyte size. Further, exercise decreased the expression of genes involved in lipid uptake (CD36 & LPL), de novo lipogenesis (FAS, ACC1), and triacylglycerol synthesis (MGAT & DGAT) in RP adipose during relapse following weight loss. This was consistent with the metabolic data, whereby exercise reduced retention of de novo-derived fat even when controlling for the positive energy imbalance. The decreased trafficking of dietary fat to adipose tissue with exercise was explained by reduced energy intake which attenuated energy imbalance during refeeding. Despite having decreased expression of lipogenic genes, the net retention of de novo-derived lipid was higher in both the RP and SC adipose of exercising animals compared to their energy gap-matched controls. Our interpretation of this data is that much of this lipid is being made by the liver and subsequently trafficked to adipose tissue storage. Together, these concerted effects may explain the beneficial effects of exercise on preventing weight regain following weight loss

Lobular neoplasia at percutaneous breast biopsy: Variables associated with carcinoma at surgical excision

OBJECTIVE. The purpose of our study was to better define the rate and variables associated with cancer underestimation when lobular neoplasia is found at minimally invasive breast biopsy. MATERIALS AND METHODS. The records of 32,420 patients who underwent imaging-guided needle biopsy of the breast for mammographic or sonographic abnormalities from 1988 to 2000 were retrospectively reviewed. The 278 cases in which lobular neoplasia was the highest-risk lesion at biopsy were included. Of the 278 cases, 164 proceeded to surgical excision, allowing calculation of rates of underestimation from minimally invasive biopsy. RESULTS. Of the 32,420 minimally invasive breast biopsies, lobular neoplasia was found in 278 (0.9%). One hundred sixty-four of the 278 (59%) continued to surgical excision, where cancer was pathologically confirmed in 38 (23%). No difference was seen in the underestimation rates for lesions diagnosed as lobular carcinoma in situ (25%, 17 of 67 lesions) versus atypical lobular hyperplasia (22%, 21 of 97 lesions). Statistically significant underestimation of carcinoma was found with biopsy of masses (with or without associated microcalcifications) rather than calcifications only, a higher BI-RADS category (p \u3c 0.0001), use of a core biopsy device rather than a vacuum device (p \u3c 0.01), and obtaining fewer specimens (p \u3c 0.0001). CONCLUSION. Significant sampling error occurs regardless of the type of core biopsy device, number of specimens obtained, histologic-radiographic concordance, mammographic appearance, and complete excision of the lesion as determined by imaging. For this reason, all patients with lobular neoplasia at core or vacuum-assisted biopsy should undergo surgical excision until further differentiating criteria can be determined. © American Roentgen Ray Society

Stereotactic Breast Biopsy of Nonpalpable Lesions: Determinants of Ductal Carcinoma in Situ Underestimation Rates

PURPOSE: To measure the effect of biopsy device, probe size, mammographic lesion type, lesion size, and number of samples obtained per lesion on the ductal carcinoma in situ (DCIS) underestimation rate. MATERIALS AND METHODS: Nonpalpable breast lesions at 16 institutions received a histologic diagnosis of DCIS after 14-gauge automated large-core biopsy in 373 lesions and after 14- or 11-gauge directional vacuum-assisted biopsy in 953 lesions. The presence of histopathologic invasive carcinoma was noted at subsequent surgical biopsy. RESULTS: By performing the X2 test, independent significant DCIS underestimation rates by biopsy device were 20.4% (76 of 373) of lesions diagnosed at large-core biopsy and 11.2% (107 of 953) of lesions diagnosed at vacuum-assisted biopsy (P \u3c .001); by lesion type, 24.3% (35 of 144) of masses and 12.5% (148 of 1,182) of microcalcifications (P \u3c .001); and by number of specimens per lesion, 17.5% (88 of 502) with 10 or fewer specimens and 11.5% (92 of 799) with greater than 10 (P \u3c .02). DCIS underestimations increased with lesion size. CONCLUSION: DCIS underestimations were 1.9 times more frequent with masses than with calcifications, 1.8 times more frequent with large-core biopsy than with vacuum-assisted biopsy, and 1.5 times more frequent with 10 or fewer specimens per lesion than with more than 10 specimens per lesion