Inhaled Corticosteroids and the Risk of Lung Cancer in Chronic Obstructive Pulmonary Disease Patients: A Systematic Review and Meta-Analysis

BACKGROUND: The global prevalence of chronic obstructive pulmonary disease (COPD) is increasing, and the risk of lung cancer in these patients is high. The use of inhaled corticosteroids (ICSs) in COPD patients could help to decrease potential lung cancer risk. We planned to conduct this systematic review and meta-analysis to determine the role of ICS in the risk of lung cancer among COPD patients. METHODS: A comprehensive search of PubMed, Science Direct, Google Scholar, and Cochrane library and a manual search of the list of references were conducted. Studies with cohort, case-control, and randomized clinical trial designs for any ICS use reporting the incidence/hazard ratio (HR) of lung cancer were included. The random-effects model was used to pool hazard ratios. Subgroup analysis and metaregression analysis were employed. Funnel plot and Egger regression test were used to assess publication bias. RESULTS: Combining the results of 14 observations, the pooled HR for cancer risk reduction was 0.69 (95% CI 0.59-0.79), p value ≤ 0.001. The use of ICS in COPD patients showed a 31% reduction in the risk of lung cancer. Subgroup meta-analysis showed a significant reduction in the risk of lung cancer as well. CONCLUSION: The use of ICS in COPD patients reduces the risk of lung cancer. The risk reduction was independent of smoking status and latency period. Future studies should focus on the optimum dose and controlling confounders like asthma

Optogenetic Manipulation of Cerebellar Purkinje Cell Activity In Vivo

Purkinje cells (PCs) are the sole output neurons of the cerebellar cortex. Although their anatomical connections and physiological response properties have been extensively studied, the causal role of their activity in behavioral, cognitive and autonomic functions is still unclear because PC activity cannot be selectively controlled. Here we developed a novel technique using optogenetics for selective and rapidly reversible manipulation of PC activity in vivo. We injected into rat cerebellar cortex lentiviruses expressing either the light-activated cationic channel channelrhodopsin-2 (ChR2) or light-driven chloride pump halorhodopsin (eNpHR) under the control of the PC-specific L7 promoter. Transgene expression was observed in most PCs (ChR2, 92.6%; eNpHR, 95.3%), as determined by immunohistochemical analysis. In vivo electrophysiological recordings showed that all light-responsive PCs in ChR2-transduced rats increased frequency of simple spike in response to blue laser illumination. Similarly, most light-responsive PCs (93.8%) in eNpHR-transduced rats decreased frequency of simple spike in response to orange laser illumination. We then applied these techniques to characterize the roles of rat cerebellar uvula, one of the cardiovascular regulatory regions in the cerebellum, in resting blood pressure (BP) regulation in anesthetized rats. ChR2-mediated photostimulation and eNpHR-mediated photoinhibition of the uvula had opposite effects on resting BP, inducing depressor and pressor responses, respectively. In contrast, manipulation of PC activity within the neighboring lobule VIII had no effect on BP. Blue and orange laser illumination onto PBS-injected lobule IX didn't affect BP, indicating the observed effects on BP were actually due to PC activation and inhibition. These results clearly demonstrate that the optogenetic method we developed here will provide a powerful way to elucidate a causal relationship between local PC activity and functions of the cerebellum

Malnutrition and iron deficiency anaemia in lactating women in urban slum communities from Addis Ababa, Ethiopia

Objective: To determine the status of iron deficiency anaemia (IDA) and malnutrition in lactating women. Design: A cross-sectional study. Setting: Six urban slum communities in Teklehaimanot district, Addis Ababa. Subjects: One thousand and seventeen lactating women were enrolled and assessed for their haemoglobin (Hgb), serum ferritin level and body mass index (BMI) during the month of March 2001. Iron deficiency anaemia was considered when Hgb and serum ferritin concentrations were less than 12gm/dl and 12 µg/l respectively, whereas, a BMI less than 18.5% kg/m2 was considered malnourished. Main outcome measures: Determinations of haemoglobin, serum ferritin and BMI measurements. Results: The overall prevalence of iron deficiency anaemia (IDA) and protein energy malnutrition in the slum communities was 22.3% and 27.1% respectively. The mean age of mothers (28.4±6.12 years) indicates that prevalence of malnutrition and iron deficiency anaemia was higher among younger mothers than among older mothers. The prevalence of malnutrition was positively correlated with the serum ferritin concentration status, of the mothers (r=0.12, p=0.2, RR=1.03). Conclusion: It is observed that malnutrition and IDA are major health problems and therefore, an appropriate nutrition intervention package to improve the nutrition situation of the communities is recommended (E Afr Med J:2003 80(4): 191-194

Gene flow and metacommunity arrangement affects coevolutionary dynamics at the mutualism–antagonism interface

Interspecific interactions are affected by community context and, as a consequence, show spatial variation in magnitude and sign. The selective forces imposed by interactions at the mutualism-antagonism interface are a consequence of the traits involved and their matching between species. If mutualistic and antagonistic communities are linked by gene flow, coevolution between a pair of interacting species is influenced by how selection varies in space. Here we investigate the effects of metacommunity arrangement, i.e. patterns of connection between communities and the number of communities, on the coevolutionary dynamics between two species for which the sign and magnitude of the interaction varies across the landscape. We quantify coevolutionary outcome as an index that can be decomposed into the contribution of intraspecific genetic diversity and interspecific interaction. We show that polymorphisms and mismatches are an expected outcome, which is influenced by spatial structure, interaction strength and the degree of gene flow. The index describes how variation is distributed within and between species, and provides information on the directionality of the mismatches and polymorphisms. Finally, we argue that depending on metacommunity arrangement, some communities have disproportionate roles in maintaining genetic diversity, with implications for the coevolution of interacting species in a fragmented landscape

Individual-based model

The code for run simulations based on the model presented in the paper

SM_Costa-SysBio_2017_SysBio_review

Supplementary Materia