Journal of investigative medicine : the official publication of the American Federation for Clinical Research
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Recent evidence has linked certain mammographic characteristics, including breast calcifications (Bcs) and mammographic density (MD), with atherosclerotic cardiovascular disease risk factors in women, but data are limited and inconsistent. We aimed to evaluate the association of MD and/or Bcs with hypertension, diabetes, and hypercholesterolemia in women ≥40 years of age. Through hospital electronic records, we retrospectively identified mammograms of non-pregnant women aged ≥40 years and without breast cancer and retrieved reports and relevant data. ⋯ MD-A may represent a new obesity index independently associated with hypercholesterolemia and additive to hypertension risk. Bcs are independently associated with diabetes. Combining MD and Bcs did not improve the odds significantly, which may reflect mechanistic differences.
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Domperidone is an effective antiemetic used worldwide, but there have been reports of possible cardiotoxicity. Our goal was to explore the cardiac safety and clinical efficacy of long-term domperidone, titrated as high as 120 mg/day, in patients not responding or unable to tolerate other therapies for gastroparesis (GP). This retrospective cohort study was conducted at a single tertiary care academic center. ⋯ Palpitations or chest pain was reported in 19% of patients without ECG abnormalities or adverse cardiac events. The mean severity of vomiting and nausea was improved by 82% and 55%, respectively. Long-term treatment with high doses of domperidone (40-120 mg/day) improved GP symptoms in patients previously refractory to other medical therapies and with a satisfactory cardiovascular risk profile.
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The area under the expiratory flow-volume (AEX-FV) loop has been evaluated before as a spirometric tool for assessing respiratory functional impairment. We computed the AEX-FV curves in spirometry tests performed on 20,313 participants in the National Health and Nutrition Examination Survey (NHANES) study. We analyzed 108,939 spirometry tests performed between 2007 and 2012 (5964 children; 14,349 adults). ⋯ We characterized indices of central tendency and dispersion of the measurements (eg, means and fifth percentiles-lower limits of normal) by age group (children vs adults), gender, race or ethnicity group and effort grading. Simple regression equations using logarithmic transformations of the above areas and using age, gender and height as inputs provided good predictive ability for the variable AEX-FV. Regular, digital spirometry could and should make available to clinicians and researchers the area under the curves for flow versus volume graph, providing additional tools in our armamentarium to evaluate ventilatory impairments and patterns, and possibly respiratory disability.
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The aim of the study was to explore the role and molecular mechanism of dual-specificity phosphatase 8 (DUSP8) in the drug resistance of trastuzumab in breast cancer. Real-time PCR and western blot detected the difference in expression of DUSP8 between breast cancer tissue/cells and trastuzumab-resistant tissues/cells. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of DUSP8 in breast cancer. si-DUSP8 or dusp8 overexpression vector was transiently transfected, and the effects of si-DUSP8 on apoptosis, cell viability and cell migration of drug-resistant cell lines were investigated by flow cytometry, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) and Transwell assays, and its regulation mechanism finally explored. ⋯ DUSP8 knockdown promotes apoptosis and reduces trastuzumab resistance in BT474/TR and SKBR3/TR cells by inhibiting cell migration and cell viability. Knockdown of DUSP8 increased the expression of p-p38 and p-ERK, and the regulation of DUSP8 in chemotherapy resistance of breast cancer cells may be realized by mediating mitogen-activated protein kinase (MAPK)-related signaling pathways. In conclusion, knockdown of DUSP8 expression in trastuzumab-resistant cells can inhibit cell migration and proliferation, and leads to decreased drug resistance by activating MAPK signaling pathway in trastuzumab-resistant cells.
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Chronic pancreatitis (CP) is a pathological fibroinflammatory syndrome of the pancreas. Currently, there are no therapeutic agents available for treating CP-associated pancreatic fibrosis. Fraxinus rhynchophylla (FR) reportedly exhibits anti-inflammatory, antioxidative and antitumor activities. ⋯ Moreover, FR treatment inhibited the expression of fibrotic mediators, such as α-smooth muscle actin (α-SMA), collagen, fibronectin 1, and decreased pro-inflammatory cytokines in isolated PSCs stimulated with transforming growth factor (TGF)-β. Furthermore, FR treatment suppressed the phosphorylation of Smad 2/3 but not of Smad 1/5 in TGF-β-stimulated PSCs. Collectively, these results suggest that FR ameliorates pancreatic fibrosis by inhibiting PSC activation during CP.