The role of environmental exposure to non-cigarette smoke in lung disease

Chronic exposure to household indoor smoke and outdoor air pollution is a major contributor to global morbidity and mortality. The majority of these deaths occur in low and middle-income countries. Children, women, the elderly and people with underlying chronic conditions are most affected. In addition to reduced lung function, children exposed to biomass smoke have an increased risk of developing lower respiratory tract infections and asthma-related symptoms. In adults, chronic exposure to biomass smoke, ambient air pollution, and opportunistic exposure to fumes and dust are associated with an increased risk of developing chronic bronchitis, chronic obstructive pulmonary disease (COPD), lung cancer and respiratory infections, including tuberculosis. Here, we review the evidence of prevalence of COPD in people exposed to non-cigarette smoke. We highlight mechanisms that are likely involved in biomass-smoke exposure-related COPD and other lung diseases. Finally, we summarize the potential preventive and therapeutic strategies for management of COPD induced by non-cigarette smoke exposure

Burden of chronic kidney disease in the general population and high-risk groups in South Asia: A systematic review and meta-analysis

BACKGROUND: Chronic kidney disease (CKD) is an emerging public health issue globally. The prevalence estimates on CKD in South Asia are however limited. This study aimed to examine the prevalence of CKD among the general and high-risk population in South Asia. METHODS: We conducted a systematic review and meta-analysis of population-level prevalence studies in South Asia (Afghanistan, Bangladesh, Bhutan, Maldives, Nepal, India, Pakistan, and Sri Lanka). Three databases namely PubMed, Scopus and Web of Science were systematically searched for published reports of kidney disease in South Asia up to 28 October 2020. A random-effect model for computing the pooled prevalence was used. RESULTS: Of the 8749 identified studies, a total of 24 studies were included in the review. The pooled prevalence of CKD among the general population was 14% (95% CI 11-18%), and 15% (95% CI 11-20%) among adult males and 13% (95% CI 10-17%) in adult females. The prevalence of CKD was 27% (95% CI 20-35%) in adults with hypertension, 31% (95% CI 22-41%) in adults with diabetes and 14% (95% CI 10-19%) in adults who were overweight/obese. We found substantial heterogeneity across the included studies in the pooled estimates for CKD prevalence in both general and high-risk populations. The prevalence of CKD of unknown origin in the endemic population was 8% (95% CI 3-16%). CONCLUSION: Our study reaffirms the previous reports that CKD represents a serious public health challenge in South Asia, with the disease prevalent among 1 in 7 adults in South Asian countries

On The Phase Structure and Thermodynamic Geometry of R-Charged Black Holes

We study the phase structure and equilibrium state space geometry of R-charged black holes in $D = 5$, 4 and 7 and the corresponding rotating $D3$, $M2$ and $M5$ branes. For various charge configurations of the compact black holes in the canonical ensemble we demonstrate new liquid-gas like phase coexistence behaviour culminating in second order critical points. The critical exponents turn out to be the same as that of four dimensional asymptotically AdS black holes in Einstein Maxwell theory. We further establish that the regions of stability for R-charged black holes are, in some cases, more constrained than is currently believed, due to properties of some of the response coefficients. The equilibrium state space scalar curvature is calculated for various charge configurations, both for the case of compact as well as flat horizons and its asymptotic behaviour with temperature is established.Comment: 1 + 33 pages, LaTeX, 25 figures. References adde

Gregory-Laflamme as the confinement/deconfinement transition in holographic QCD

We discuss the phase structure of N D4 branes wrapped on a temporal (Euclidean) and a spatial circle, in terms of the near-horizon AdS geometries. This system has been studied previously to understand four dimensional pure SU(N) Yang-Mills theory (YM4) through holography. In the usual treatment of the subject, the phase transition between the AdS soliton and the black D4 brane is interpreted as the strong coupling continuation of the confinement/deconfinement transition in YM4. We show that this interpretation is not valid, since the black D4 brane and the deconfinement phase of YM4 have different realizations of the Z_N centre symmetry and cannot be identified. We propose an alternative gravity dual of the confinement/deconfinement transition in terms of a Gregory-Laflamme transition of the AdS soliton in the IIB frame, where the strong coupling continuation of the deconfinement phase of YM4 is a localized D3 soliton. Our proposal offers a new explanation of several aspects of the thermodynamics of holographic QCD. As an example, we show a new mechanism of chiral symmetry restoration in the Sakai-Sugimoto model. The issues discussed in this paper pertain to gravity duals of non-supersymmetric gauge theories in general.Comment: 45 pages, 10 figures; v2: details of the analysis and new phase diagram in Sakai-Sugimoto model are added. version appeared in JHEP; v3: minor corrections. references are added; v4: minor correction

Nicotine Promotes Tumor Growth and Metastasis in Mouse Models of Lung Cancer

Nicotine is the major addictive component of tobacco smoke. Although nicotine is generally thought to have limited ability to initiate cancer, it can induce cell proliferation and angiogenesis in a variety of systems. These properties might enable nicotine to facilitate the growth of tumors already initiated. Here we show that nicotine significantly promotes the progression and metastasis of tumors in mouse models of lung cancer. This effect was observed when nicotine was administered through intraperitoneal injections, or through over-the-counter transdermal patches.In the present study, Line1 mouse adenocarcinoma cells were implanted subcutaneously into syngenic BALB/c mice. Nicotine administration either by intraperitoneal (i.p.) injection or transdermal patches caused a remarkable increase in the size of implanted Line1 tumors. Once the tumors were surgically removed, nicotine treated mice had a markedly higher tumor recurrence (59.7%) as compared to the vehicle treated mice (19.5%). Nicotine also increased metastasis of dorsally implanted Line1 tumors to the lungs by 9 folds. These studies on transplanted tumors were extended to a mouse model where the tumors were induced by the tobacco carcinogen, NNK. Lung tumors were initiated in A/J mice by i.p. injection of NNK; administration of 1 mg/kg nicotine three times a week led to an increase in the size and the number of tumors formed in the lungs. In addition, nicotine significantly reduced the expression of epithelial markers, E-Cadherin and beta-Catenin as well as the tight junction protein ZO-1; these tumors also showed an increased expression of the alpha(7) nAChR subunit. We believe that exposure to nicotine either by tobacco smoke or nicotine supplements might facilitate increased tumor growth and metastasis.Our earlier results indicated that nicotine could induce invasion and epithelial-mesenchymal transition (EMT) in cultured lung, breast and pancreatic cancer cells. This study demonstrates for the first time that administration of nicotine either by i.p. injection or through over-the-counter dermal patches can promote tumor growth and metastasis in immunocompetent mice. These results suggest that while nicotine has only limited capacity to initiate tumor formation, it can facilitate the progression and metastasis of tumors pre-initiated by tobacco carcinogens

Evaluation of Greenbug and Yellow Sugarcane Aphid Feeding Behavior on Resistant and Susceptible Switchgrass Cultivars

Switchgrass (Panicum virgatum L.) is an emerging biofuel crop that serves as host for aphids. To discern the effects of plant age and possible resistance mechanisms, the feeding behavior of greenbugs (Schizaphis graminum Rondani.) and the yellow sugarcane aphid (Sipha flava Forbes.) was monitored on three diverse switchgrasses by the electrical penetration graph (EPG) technique. Callose deposition and genes associated with callose metabolism were also analyzed to discern their association with plant resistance. There was a strong host effect on greenbugs feeding on lowland cultivar Kanlow at the V3 stage of development, as compared to the greenbug-susceptible upland cultivar Summer and plants derived from Kanlow (♂) × Summer (♀) (K×S) crosses. These data confirmed that Kanlow at the V3 stage had antibiosis to greenbugs, which was absent in the Summer and K×S plants. In contrast, similar effects were not observed for yellow sugarcane aphids, excluding significant differences in the time to first probe on Kanlow plants at the V1 stage and reduction in time spent on pathway processes on Kanlow plants at the V3 stage. These data demonstrated that Kanlow plants may have multiple sources of resistance to the two aphids, and possibly some were phloem based. Microscopy of leaf sections stained with aniline blue for callose was suggestive of increased callose deposition in the sieve elements in Kanlow plants relative to Summer and K×S plants. RT-qPCR analysis of several genes associated with callose metabolism in infested plants was equivocal. Overall, these studies suggest the presence of multiple defense mechanisms against aphids in Kanlow plants, relative to Summer and K×S plants

Exploring the functional role of the CHRM2 gene in human cognition: results from a dense genotyping and brain expression study

<p>Abstract</p> <p>Background</p> <p>The <it>CHRM2 </it>gene, located on the long arm of chromosome 7 (7q31-35), is involved in neuronal excitability, synaptic plasticity and feedback regulation of acetylcholine release, and has been implicated in higher cognitive processing. The aim of this study is the identification of functional (non)coding variants underlying cognitive phenotypic variation.</p> <p>Methods</p> <p>We previously reported an association between polymorphisms in the 5'UTR regions of the <it>CHRM2 </it>gene and intelligence.. However, no functional variants within this area have currently been identified. In order to identify the relevant functional variant(s), we conducted a denser coverage of SNPs, using two independent Dutch cohorts, consisting of a children's sample (N = 371 ss; mean age 12.4) and an adult sample (N= 391 ss; mean age 37.6). For all individuals standardized intelligence measures were available. Subsequently, we investigated genotype-dependent <it>CHRM2 </it>gene expression levels in the brain, to explore putative enhancer/inhibition activity exerted by variants within the muscarinic acetylcholinergic receptor.</p> <p>Results</p> <p>Using a test of within-family association two of the previously reported variants – rs2061174, and rs324650 – were again strongly associated with intelligence (<it>P </it>< 0.01). A new SNP (rs2350780) showed a trend towards significance. SNP rs324650, is located within a short interspersed repeat (SINE). Although the function of short interspersed repeats remains contentious, recent research revealed potential functionality of SINE repeats in a gene-regulatory context. Gene-expression levels in post-mortem brain material, however were not dependent on rs324650 genotype.</p> <p>Conclusion</p> <p>Using a denser coverage of SNPs in the <it>CHRM2 </it>gene, we confirmed the 5'UTR regions to be most interesting in the context of intelligence, and ruled out other regions of this gene. Although no correlation between genomic variants and gene expression was found, it would be interesting to examine allele-specific effects on CHRM2 transcripts expression in much more detail, for example in relation to transcripts specific halve-life and their relation to LTP and memory.</p

Role of Myosin Va in the Plasticity of the Vertebrate Neuromuscular Junction In Vivo

Background: Myosin Va is a motor protein involved in vesicular transport and its absence leads to movement disorders in humans (Griscelli and Elejalde syndromes) and rodents (e.g. dilute lethal phenotype in mice). We examined the role of myosin Va in the postsynaptic plasticity of the vertebrate neuromuscular junction (NMJ). Methodology/Principal Findings: Dilute lethal mice showed a good correlation between the propensity for seizures, and fragmentation and size reduction of NMJs. In an aneural C2C12 myoblast cell culture, expression of a dominant-negative fragment of myosin Va led to the accumulation of punctate structures containing the NMJ marker protein, rapsyn-GFP, in perinuclear clusters. In mouse hindlimb muscle, endogenous myosin Va co-precipitated with surface-exposed or internalised acetylcholine receptors and was markedly enriched in close proximity to the NMJ upon immunofluorescence. In vivo microscopy of exogenous full length myosin Va as well as a cargo-binding fragment of myosin Va showed localisation to the NMJ in wildtype mouse muscles. Furthermore, local interference with myosin Va function in live wildtype mouse muscles led to fragmentation and size reduction of NMJs, exclusion of rapsyn-GFP from NMJs, reduced persistence of acetylcholine receptors in NMJs and an increased amount of punctate structures bearing internalised NMJ proteins. Conclusions/Significance: In summary, our data show a crucial role of myosin Va for the plasticity of live vertebrate neuromuscular junctions and suggest its involvement in the recycling of internalised acetylcholine receptors back to th

Robust Reproducible Resting State Networks in the Awake Rodent Brain

Resting state networks (RSNs) have been studied extensively with functional MRI in humans in health and disease to reflect brain function in the un-stimulated state as well as reveal how the brain is altered with disease. Rodent models of disease have been used comprehensively to understand the biology of the disease as well as in the development of new therapies. RSN reported studies in rodents, however, are few, and most studies are performed with anesthetized rodents that might alter networks and differ from their non-anesthetized state. Acquiring RSN data in the awake rodent avoids the issues of anesthesia effects on brain function. Using high field fMRI we determined RSNs in awake rats using an independent component analysis (ICA) approach, however, ICA analysis can produce a large number of components, some with biological relevance (networks). We further have applied a novel method to determine networks that are robust and reproducible among all the components found with ICA. This analysis indicates that 7 networks are robust and reproducible in the rat and their putative role is discussed