Macrophage Depletion in Hypertensive Rats Accelerates Development of Cardiomyopathy

Inflammation contributes to the process of ventricular remodeling after acute myocardial injury. To investigate the role of macrophages in the chronic process of cardiac remodeling, they were selectively depleted by intravenous administration of liposomal clodronate in heart failure-prone hypertensive Ren-2 rats from the age of 7 until 13 weeks. plain liposomes were used for comparison. Liposomal clodronate treatment reduced the number of blood monocytes and decreased the number of macrophages in the myocardium. Compared to plain liposomes, liposomal clodronate treatment rapidly worsened left ventricular ejection function in hypertensive rats. Liposomal clodronate-treated Ren-2 rat hearts showed areas of myocyte loss with abundant inflammatory cell infiltration, predominantly comprising CD4 positive T lymphocytes. The current-study showed that lack of macrophages vas associated with earlier development of myocardial dysfunction in hypertensive rats. Modulation of macrophage function may be of value in the evolution of cardiomyopath

Whole-Body versus Local DXA-Scan for the Diagnosis of Osteoporosis in COPD Patients

Background. Osteoporosis is an extrapulmonary effect of chronic obstructive pulmonary disease (COPD). Diagnosis of osteoporosis is based on BMD measured by DXA-scan. The best location for BMD measurement in COPD has not been determined. Aim of this study was to assess whole-body BMD and BMD of the hip and lumbar spine (local DXA) in COPD patients and compare the prevalence of osteoporosis at these locations. Methods. Whole body as well as local DXA-scan were made in 168 COPD patients entering pulmonary rehabilitation. Patient-relevant characteristics were assessed. Prevalence of osteoporosis was determined. Characteristics of patients without osteoporosis were compared to patients with osteoporosis on local DXA. Results. A higher prevalence of osteoporosis was found using local DXA compared to whole-body DXA (39% versus 21%). One quarter of patients without osteoporosis on whole body-DXA did have osteoporosis on local DXA. Significant differences in patient characteristics between patients without osteoporosis based on both DXA measurements and patients with osteoporosis based on local DXA only were found. Conclusions. DXA of the hip and lumbar spine should be made to assess bone mineral density in COPD patients. The lowest T-score of these locations should be used to diagnose osteoporosis

Socio-economic and partner relationship factors associated with antenatal depressive morbidity among pregnant women in

Depression during pregnancy may negatively influence social functioning, birth outcomes and postnatal mental health. A cross-sectional analysis of the baseline survey of a prospective study was undertaken with an objective of determining the prevalence and socio-demographic factors associated with depressive morbidity during pregnancy in a Tanzanian peri-urban setting. Seven hundred and eighty seven second to third trimester pregnant women were recruited at booking for antenatal care at two primary health care clinics. Prenatal structured interviews assessed socio-economic, quality of partner relationships and selected physical health measures. Depressive symptoms were measured at recruitment and three and eight months postpartum using the Kiswahili version of the Hopkins Symptom Checklist. Completed antenatal measures available for 76.2% participants, showed a 39.5% prevalence of depression. Having a previous depressive episode (OR 4.35,

Multiple minor mergers: formation of elliptical galaxies and constraints for the growth of spiral disks

Multiple, sequential mergers are unavoidable in the hierarchical build-up picture of galaxies, in particular for the minor mergers that are frequent and highly likely to have occured several times for most present-day galaxies. However, the effect of repeated minor mergers on galactic structure and evolution has not been studied systematically so far. We present a numerical study of multiple, subsequent, minor galaxy mergers, with various mass ratios ranging from 4:1 to 50:1. The N-body simulations include gas dynamics and star formation. We study the morphological and kinematical properties of the remnants, and show that several so-called "minor" mergers can lead to the formation of elliptical-like galaxies that have global morphological and kinematical properties similar to that observed in real elliptical galaxies. The properties of these systems are compared with those of elliptical galaxies produced by the standard scenario of one single major merger. We thus show that repeated minor mergers can theoretically form elliptical galaxies without major mergers, and can be more frequent than major mergers, in particular at moderate redshift. This process must then have formed some elliptical galaxies seen today, and could in particular explain the high boxiness of massive ellipticals, and some fundamental relations observed in ellipticals. In addition, because repeated minor mergers, even at high mass ratios, destroy disks into spheroids, these results indicate that spiral galaxies cannot have grown only by a succession of minor mergers.Comment: A&A in press, final version to be published with minor corrections and updated reference lis

Tudásmenedzsment és a felsőoktatási intézmény, mint vállalat = Knowledge Management and the University as a Company

Purpose: ALK rearrangement detection using FISH is the standard test to identify patients with non–small cell lung carcinoma (NSCLC) eligible for treatment with ALK inhibitors. Recently, ALK protein expression in resectable NSCLC showed predictive value. We evaluated tumor response rate and survival after crizotinib treatment of patients with advanced NSCLC with ALK activation using both dichotomous immunohistochemical (IHC) staining and FISH. Experimental Design: Patients with stage IV NSCLC treated with crizotinib were selected. Tumor response was assessed. ALK rearrangements were detected by FISH (Vysis ALK-break-apart FISH-Probe KIT) and IHC [Ventana ALK (D5F3) CDx assay]. Cohorts of patients with ALK-FISH–positive advanced NSCLC from four other hospitals were used for validation. Results: Twenty-nine consecutive patients with ALK-positive advanced NSCLC diagnosed by FISH and/or IHC on small biopsies or fine-needle aspirations (FNA) were treated with ALK inhibitors. All ALK-IHC–positive patients responded to crizotinib except three with primary resistance. No tumor response was observed in 13 ALK-FISH–positive but ALK-IHC–negative patients. This was confirmed in an external cohort of 16 patients. Receiver operator characteristic (ROC) curves for ALK-IHC and ALK-FISH compared with treatment outcome showed that dichotomous ALK-IHC outperforms ALK-FISH [tumor response area under the curve: (AUC), 0.86 vs. 0.64, P ¼ 0.03; progression-free survival (PFS): AUC 0.86 vs. 0.36, P ¼ 0.005; overall survival (OS): AUC, 0.78 vs. 0.41, P ¼ 0.01, respectively]. Conclusions: Dichotomous ALK-IHC is superior to ALK-FISH on small biopsies and FNA to predict tumor response and survival to crizotinib for patients with advanced NSCLC. Our data strongly suggest adapting the guidelines and using dichotomous ALK-IHC as standard companion diagnostic test to select patients with NSCLC who benefit from ALK-targeting therapy

Randomised controlled trial of first-line tyrosine-kinase inhibitor (TKI) versus intercalated TKI with chemotherapy for EGFR-mutated nonsmall cell lung cancer

Introduction Previous studies have shown interference between epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors and chemotherapy in the cell cycle, thus reducing efficacy. In this randomised controlled trial we investigated whether intercalated erlotinib with chemotherapy was superior compared to erlotinib alone in untreated advanced EGFR-mutated nonsmall cell lung cancer (NSCLC). Materials and methods Treatment-naïve patients with an activating EGFR mutation, ECOG performance score of 0–3 and adequate organ function were randomly assigned 1:1 to either four cycles of cisplatin-pemetrexed with intercalated erlotinib (day 2–16 out of 21 days per cycle) followed by pemetrexed and erlotinib maintenance (CPE) or erlotinib monotherapy. The primary end-point was progression-free survival (PFS). Secondary end-points were overall survival, objective response rate (ORR) and toxicity. Results Between April 2014 and September 2016, 22 patients were randomised equally into both arms; the study was stopped due to slow accrual. Median follow-up was 64 months. Median PFS was 13.7 months (95% CI 5.2–18.8) for CPE and 10.3 months (95% CI 7.1–15.5; hazard ratio (HR) 0.62, 95% CI 0.25–1.57) for erlotinib monotherapy; when compensating for number of days receiving erlotinib, PFS of the CPE arm was superior (HR 0.24, 95% CI 0.07–0.83; p=0.02). ORR was 64% for CPE versus 55% for erlotinib monotherapy. Median overall survival was 31.7 months (95% CI 21.8–61.9 months) for CPE compared to 17.2 months (95% CI 11.5–45.5 months) for erlotinib monotherapy (HR 0.58, 95% CI 0.22–1.41 months). Patients treated with CPE had higher rates of treatment-related fatigue, anorexia, weight loss and renal toxicity. Conclusion Intercalating erlotinib with cisplatin-pemetrexed provides a longer PFS compared to erlotinib alone in EGFR-mutated NSCLC at the expense of more toxicity

'It is like a tomato stall where someone can pick what he likes': structure and practices of female sex work in Kampala, Uganda.

BACKGROUND: Effective interventions among female sex workers require a thorough knowledge of the context of local sex industries. We explore the organisation of female sex work in a low socio-economic setting in Kampala, Uganda. METHODS: We conducted a qualitative study with 101 participants selected from an epidemiological cohort of 1027 women at high risk of HIV in Kampala. Repeat in-depth life history and work practice interviews were conducted from March 2010 to June 2011. Context specific factors of female sex workers' day-to-day lives were captured. Reported themes were identified and categorised inductively. RESULTS: Of the 101 women, 58 were active self-identified sex workers operating in different locations within the area of study and nine had quit sex work. This paper focuses on these 67 women who gave information about their involvement in sex work. The majority had not gone beyond primary level of education and all had at least one child. Thirty one voluntarily disclosed that they were HIV-positive. Common sex work locations were streets/roadsides, bars and night clubs. Typically sex occurred in lodges near bars/night clubs, dark alleyways or car parking lots. Overall, women experienced sex work-related challenges at their work locations but these were more apparent in outdoor settings. These settings exposed women to violence, visibility to police, a stigmatising public as well as competition for clients, while bars provided some protection from these challenges. Older sex workers tended to prefer bars while the younger ones were mostly based on the streets. Alcohol consumption was a feature in all locations and women said it gave them courage and helped them to withstand the night chill. Condom use was determined by clients' willingness, a woman's level of sobriety or price offered. CONCLUSIONS: Sex work operates across a variety of locations in the study area in Kampala, with each presenting different strategies and challenges for those operating there. Risky practices are present in all locations although they are higher on the streets compared to other locations. Location specific interventions are required to address the complex challenges in sex work environments