Acute effects of vasoactive drug treatment on brachial artery reactivity

AbstractObjectivesThe goal of this study was to investigate whether concomitant therapy with vasoactive medications alters the results of noninvasive assessment of endothelial function.BackgroundUltrasound assessment of brachial artery flow-mediated dilation is emerging as a useful clinical tool. The current practice of withholding cardiac medications before ultrasound studies has unknown utility and would limit the clinical use of the methodology.MethodsTo determine whether a single dose of a vasoactive drug influences brachial reactivity, we examined flow-mediated dilation and nitroglycerin-mediated dilation in 73 healthy subjects (age 27 ± 6 years). Studies were completed at baseline and 3 h after randomized treatment with a single oral dose of placebo, felodipine (5 mg), metoprolol (50 mg), or enalapril (10 mg). To determine if holding vasoactive therapy for 24 h before study yields different results than continuation of clinically prescribed medications, we examined vascular function in 72 patients (age 57 ± 10 years) with coronary artery disease. Ultrasound studies were performed 24 h after the last dose and again 3 h after patients took their clinically prescribed medications.ResultsIn healthy subjects one dose of all three drugs lowered blood pressure, and metoprolol also lowered heart rate. However, there was no significant effect of treatment on brachial artery dilation. In patients with coronary artery disease on chronic treatment, taking prescribed medications reduced blood pressure and heart rate, but had no significant effect on brachial artery dilation.ConclusionsRecent administration of commonly used nonnitrate vasoactive drugs has no significant effect on brachial reactivity. These findings suggest that current practice of withholding cardiac medications before testing endothelial function may not be necessary, making this methodology more practical for clinical use

Absence of Germline BRCA1 c.68_69delAG and c.5266dupC Mutations among Hormone Receptor-negative Breast Cancer Patients: A First Impression at a Tertiary Cancer-care Facility in Tanzania

The germline BRCA1 c.68_69delAG (185delAG) and c.5266dupC (5382insC) mutations are associated with hormone receptor-negative breast cancer (BC).  Limited studies have examined their contribution to alarming BC incidence in Sub Saharan Africa (SSA). Our study aimed to examine the contribution of  germline BRCA1 c.68_69delAG and c.5266dupC mutations to BC incidence among hormone receptor-negative BC patients admitted to Ocean Road Cancer Institute in Tanzania. Face-to-face interviews were conducted to capture socio-demographic characteristics, anthropometric measurements, family history of cancer and reproductive information from each patient. Their  histopathological data were extracted from the hospital medical records. The germline BRCA1 founder mutations were analyzed on blood samples using Sanger sequencing technology. The patients mean age at diagnosis was 47.05 ± 12.82 years. A family history of cancer was observed in 13.6% of patients. The germline BRCA1 c.68_69delAG and c.5266dupC mutations were not detected in the study group. Our findings indicate that the germline BRCA1 c.68_69delAG and c.5266dupC mutations do not contribute to BC manifestation in hormone receptor-negative BC patients in Tanzania. Thus, screening BC patients for these mutations has no clinical relevance. Our data further suggest that the c.68_69delAG and the c.5266dupC mutations should not be considered when developing genetic testing guidelines in Tanzania. Keywords: Breast cancer, germline BRCA1 mutation, c.68_69delAG (185delAG), c.5266dupC (5382insC), Tanzani

Sense of place in the changing process of house form: Case studies from Ankara, Turkey

This paper aims to investigate the impact of typomorphological changes of residential environments on residents’ sense of place’. Seven housing developments representing different types introduced in Ankara, Turkey since the late 19th-century are selected as case studies. Their morphological characters at the building, street and neighbourhood scales are examined, and typological transformations among the cases in terms of the degrees of continuity are identified. The paper proposes a conceptual model consisting of ten indicators to assess sense of place at the building, street and neighbourhood scales of the residents of the seven cases. The scores of sense of place are generated through structured interviews with the residents and analysed in SPSS. The results show that sense of place is negatively affected by typomorphological changes over time, particularly when mutational changes occur. Continuity in typomorphological transformation helps to maintain sense of place at a desirable level. Furthermore, physical changes at the street and neighbourhood scales have larger impact on sense of place than that at the building scale. The research thus suggests that planning and design should be responsive to traditional types in residential development, particularly at the street and neighbourhood scales to maintain residents’ sense of place

ADAM10 and ADAM17 promote SARS‐CoV‐2 cell entry and spike protein‐mediated lung cell fusion

The severe‐acute‐respiratory‐syndrome‐coronavirus‐2 (SARS‐CoV‐2) is the causative agent of COVID‐19, but host cell factors contributing to COVID‐19 pathogenesis remain only partly understood. We identify the host metalloprotease ADAM17 as a facilitator of SARS‐CoV‐2 cell entry and the metalloprotease ADAM10 as a host factor required for lung cell syncytia formation, a hallmark of COVID‐19 pathology. ADAM10 and ADAM17, which are broadly expressed in the human lung, cleave the SARS‐CoV‐2 spike protein (S) in vitro, indicating that ADAM10 and ADAM17 contribute to the priming of S, an essential step for viral entry and cell fusion. ADAM protease‐targeted inhibitors severely impair lung cell infection by the SARS‐CoV‐2 variants of concern alpha, beta, delta, and omicron and also reduce SARS‐CoV‐2 infection of primary human lung cells in a TMPRSS2 protease‐independent manner. Our study establishes ADAM10 and ADAM17 as host cell factors for viral entry and syncytia formation and defines both proteases as potential targets for antiviral drug development

Performance of the CMS Cathode Strip Chambers with Cosmic Rays

The Cathode Strip Chambers (CSCs) constitute the primary muon tracking device in the CMS endcaps. Their performance has been evaluated using data taken during a cosmic ray run in fall 2008. Measured noise levels are low, with the number of noisy channels well below 1%. Coordinate resolution was measured for all types of chambers, and fall in the range 47 microns to 243 microns. The efficiencies for local charged track triggers, for hit and for segments reconstruction were measured, and are above 99%. The timing resolution per layer is approximately 5 ns

Factors determining the survival of nasopharyngeal carcinoma with lung metastasis alone: does combined modality treatment benefit?

<p>Abstract</p> <p>Background</p> <p>Nasopharyngeal carcinoma (NPC) with lung metastasis alone has been reported as a relatively favorable prognostic group, and combined modality treatment might be indicated for selected cases. However, the prognostic factors determining survival of this group and the indication of combined therapy have not been thoroughly studied.</p> <p>Methods</p> <p>We retrospectively reviewed 246 patients of NPC with lung metastasis(es) alone presented at diagnosis or as the first failure after primary treatment from 1993 to 2008 in an academic tertiary hospital. Univariate and multivariate survival analyses of post-metastasis survival (PMS) and overall survival (OS) were carried out to determine the prognostic factors.</p> <p>Results</p> <p>The 3-year, 5-year, and 10-year of PMS and OS for the whole cohort were 34.3%, 17.0%, 8.6% and 67.8%, 45.4%, 18.5%, respectively. The median PMS (45.6 months <it>vs</it>. 23.7 months) and OS (73.7 months <it>vs</it>. 46.2 months) of patients treated with combined therapy was significantly longer than that of those treated with chemotherapy alone (<it>P </it>< 0.001). Age, disease-free interval (DFI) and treatment modality were evaluated as independent prognostic factors of OS, while only age and treatment modality retain their independent significance in PMS analysis. In stratified survival analysis, compared to chemotherapy alone, combined therapy could benefit the patients with DFI > 1 year, but not those with DFI ≤ 1 year.</p> <p>Conclusions</p> <p>Age ≤ 45 years, DFI > 1 year, and the combined therapy were good prognostic factors for NPC patients with lung metastasis(es) alone. The combination of local therapy and the basic chemotherapy should be considered for these patients with DFI > 1 year.</p

Performance and Operation of the CMS Electromagnetic Calorimeter

The operation and general performance of the CMS electromagnetic calorimeter using cosmic-ray muons are described. These muons were recorded after the closure of the CMS detector in late 2008. The calorimeter is made of lead tungstate crystals and the overall status of the 75848 channels corresponding to the barrel and endcap detectors is reported. The stability of crucial operational parameters, such as high voltage, temperature and electronic noise, is summarised and the performance of the light monitoring system is presented

Endothelial Microparticles (EMP) for the Assessment of Endothelial Function: An In Vitro and In Vivo Study on Possible Interference of Plasma Lipids

BACKGROUND: Circulating endothelial microparticles (EMP) reflect the condition of the endothelium and are of increasing interest in cardiovascular and inflammatory diseases. Recently, increased numbers of EMP following oral fat intake, possibly due to acute endothelial injury, have been reported. On the other hand, the direct interference of lipids with the detection of EMP has been suggested. This study aimed to investigate the effect of lipid-rich solutions, commonly administered in clinical practice, on the detection, both in vitro and in vivo, of EMP. METHODS: For the in vitro assessment, several lipid-rich solutions were added to whole blood of healthy subjects (n = 8) and patients with coronary heart disease (n = 5). EMP (CD31+/CD42b-) were detected in platelet poor plasma by flow cytometry. For the in vivo study, healthy volunteers were evaluated on 3 different study-days: baseline evaluation, following lipid infusion and after a NaCl infusion. EMP quantification, lipid measurements and peripheral arterial tonometry were performed on each day. RESULTS: Both in vitro addition and in vivo administration of lipids significantly decreased EMP (from 198.6 to 53.0 and from 272.6 to 90.6/µl PPP, respectively, p = 0.001 and p = 0.012). The EMP number correlated inversely with the concentration of triglycerides, both in vitro and in vivo (r = -0.707 and -0.589, p<0.001 and p = 0.021, respectively). The validity of EMP as a marker of endothelial function is supported by their inverse relationship with the reactive hyperemia index (r = -0.758, p = 0.011). This inverse relation was confounded by the intravenous administration of lipids. CONCLUSION: The confounding effect of high circulating levels of lipids, commonly found in patients that receive intravenous lipid-based solutions, should be taken into account when flow cytometry is used to quantify EMP