The cumulative number of cases of acquired immunodeficiency syndrome (AIDS) in the United States has grown as the cube of time rather than exponentially. We explain this by interactions involving partner choice and sexual frequency in a risk-behavior model with biased mixing. This leads to a saturation wave of infection moving from high-to low-risk groups. If this description is correct, then the decreasing growth rate of AIDS cases is not due to behavior changes; rather it is due to the intrinsic epidemiology of the disease.Understanding the growth of human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) is complex because infection depends on behaviors that are considered private and because individuals with HIV vary in their infectivity and progression to AIDS. Previous mathematical models predict an initial exponential growth of infection ultimately progressing to saturation of the population. In this article, we develop a model explaining the observed cubic growth of AIDS and apply it to the homosexual population.The risk-based model builds on the fact that the amount of "risky" behavior (sexual behavior that puts one at risk for contracting HIV) is not distributed equally among the population. It also assumes that people with similar risk behavior tend to interact primarily among themselves (biased mixing) rather than equally with others (homogeneous mixing). Finally, the model incorporates epidemiologic data on the progression from initial HIV infection to AIDS.The total number ofAIDS cases reported to the Centers for Disease Control (CDC) in the United States has grown as the cube of time (1-3). A reasonable best fit function for the cumulative AIDS cases (pre-1987.5 definition) is A = 174.6(ty -1981.2)3 + 340 + 2%, [1] where the error is relative to total cases and ty is the date in years (see Fig. 1). This fit is accurate between ty = 1982.5 and the change in AIDS case definition in 1987. Nearly cubic growth is evident in different geographic regions, sexual preference groups, intravenous drug users, age groups (except children and elderly), and racial groups. Eq. 1 is surprising, since a cubic sum for all AIDS cases of the form in Eq. 1 requires that the cubics for each major infected group be synchronized in time to less than 6 months. Because there are no large populations in the United States without infected persons (1, 4, 5), this synchronization applies to standard metropolitan statistical areas as well.To demonstrate why this cubic growth is unexpected, we note that the initial growth rate of any infection in a homogeneous population (where behavior remains constant in time) will be constant with time. In contrast, cubic growth of and 4, unknown. The dotted lines are an extrapolation of the cubic slope, indicating that the various sexual preference groups were seeded within a 6-month window. This implies that at least one individual in each of the four sexual preference groups was a member of the original high-risk group (td : 6 months). Four racial...
Routine early feeding of subjects undergoing cesarean delivery can be implemented without an increase in gastrointestinal symptoms or paralytic ileus.
BackgroundChronic obstructive pulmonary disease (COPD) is characterized by an irreversible airflow limitation in response to inhalation of noxious stimuli, such as cigarette smoke. However, only 15–20 % smokers manifest COPD, suggesting a role for genetic predisposition. Although genome-wide association studies have identified common genetic variants that are associated with susceptibility to COPD, effect sizes of the identified variants are modest, as is the total heritability accounted for by these variants. In this study, an extreme phenotype exome sequencing study was combined with in vitro modeling to identify COPD candidate genes.ResultsWe performed whole exome sequencing of 62 highly susceptible smokers and 30 exceptionally resistant smokers to identify rare variants that may contribute to disease risk or resistance to COPD. This was a cross-sectional case-control study without therapeutic intervention or longitudinal follow-up information. We identified candidate genes based on rare variant analyses and evaluated exonic variants to pinpoint individual genes whose function was computationally established to be significantly different between susceptible and resistant smokers. Top scoring candidate genes from these analyses were further filtered by requiring that each gene be expressed in human bronchial epithelial cells (HBECs). A total of 81 candidate genes were thus selected for in vitro functional testing in cigarette smoke extract (CSE)-exposed HBECs. Using small interfering RNA (siRNA)-mediated gene silencing experiments, we showed that silencing of several candidate genes augmented CSE-induced cytotoxicity in vitro.ConclusionsOur integrative analysis through both genetic and functional approaches identified two candidate genes (TACC2 and MYO1E) that augment cigarette smoke (CS)-induced cytotoxicity and, potentially, COPD susceptibility.Electronic supplementary materialThe online version of this article (doi:10.1186/s40246-015-0058-7) contains supplementary material, which is available to authorized users.
MiR-106b is an oncomir and a potential target for anti-cancer therapy. We hypothesize that grape seed procyanidin extract (GSE) exerts antineoplastic effects on lung cancer through modulations of miR-106b and its downstream target. We found that GSE significantly down-regulated miR-106b in a variety of lung neoplastic cells and increased cyclin-dependent kinase inhibitor 1A (CDKN1A) mRNA and protein (p21) levels. Transfection of miR-106b mimics reversed the up-regulations of CDKN1A mRNA and p21, abrogated the GSE induced anti-proliferative and anti-invasive properties in lung cancer cells. Oral gavage of leucoselect phytosome (LP), a standardized GSE to athymic nude mice down-regulated MIR106B mRNA and miR-106b expressions, and increased CDKN1A mRNA expression in tumor xenografts, correlating to significant reduction of tumor growth. To assess bioavailability, GSE and metabolites in plasma levels, between 60–90 minutes after gavage of LP were measured by LC/MS at treatment week 4 and 8. A novel bioactivity assay was also developed using lung homogenates from treated mice co-cultured with human lung cancer cells. LP-treated mouse lung homogenates significantly reduced proliferations of various lung cancer cells. Our findings reveal novel antineoplastic mechanisms by GSE, further define the pharmacokinetics and pharmacodynamics of LP, and support the continued investigation of LP against lung cancer.
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