Dispositional, demographic, and social predictors of trajectories of intimate partner aggression in early adulthood.

OBJECTIVE: From a developmental systems perspective, the origins of maladjusted behavior are multifaceted, interdependent, and may differ at different points in development. Personality traits influence developmental outcomes, as do socialization environments, but the influence of personality depends on the socialization environment, and the influence of the socialization environment varies according to personality. The present study takes a developmental systems approach to investigate pathways through which dispositional traits in childhood might act in concert with peer and parental socialization contexts to predict trajectories of intimate partner aggression (IPA) during emerging adulthood. METHOD: The study included 466 participants (49% male, 81% European American, 15% African American) from a longitudinal study of social development. Measures of demographics, temperament, personality, parent-child relations, romantic relationships, peer relationships, and IPA were administered between 5 and 23 years of age. The study used latent growth curve analysis to predict variations in trajectories of IPA during early adulthood. RESULTS: Numerous variables predicted risk for the perpetration of IPA, but different factors were associated at the end of adolescence (e.g., psychopathic traits) than with changes across early adulthood (e.g., friend antisociality). Males and individuals with a history of resistance to control temperament showed enhanced susceptibility to social risk factors, such as exposure to antisocial peers and poor parent-adolescent relations. CONCLUSIONS: Consistent with a developmental systems perspective, multiple factors, including personality traits in early childhood and aspects of the social environment in adolescence, predict trajectories of IPA during early adulthood through additive, mediated, and moderated pathways. Knowledge of these risk factors and for whom they are most influential could help inform efforts to prevent the emergence and persistence of IPA. (PsycINFO Database Record

Maternal Therapy with Ad.VEGF-A165 Increases Fetal Weight at Term in a Guinea-Pig Model of Fetal Growth Restriction.

In a model of growth-restricted sheep pregnancy, it was previously demonstrated that transient uterine artery VEGF overexpression can improve fetal growth. This approach was tested in guinea-pig pregnancies, where placental physiology is more similar to humans. Fetal growth restriction (FGR) was attained through peri-conceptual nutrient restriction in virgin guinea pigs. Ad.VEGF-A165 or Ad.LacZ (1 × 1010vp) was applied at mid-gestation via laparotomy, delivered externally to the uterine circulation with thermosensitive gel. At short-term (3-8 days post surgery) or at term gestation, pups were weighed, and tissues were sampled for vector spread analysis, VEGF expression, and its downstream effects. Fetal weight at term was increased (88.01 ± 13.36 g; n = 26) in Ad.VEGF-A165-treated animals compared with Ad.LacZ-treated animals (85.52 ± 13.00 g; n = 19; p = 0.028). The brain, liver, and lung weight and crown rump length were significantly larger in short-term analyses, as well as VEGF expression in transduced tissues. At term, molecular analyses confirmed the presence of VEGF transgene in target tissues but not in fetal samples. Tissue histology analysis and blood biochemistry/hematological examination were comparable with controls. Uterine artery relaxation in Ad.VEGF-A165-treated dams was higher compared with Ad.LacZ-treated dams. Maternal uterine artery Ad.VEGF-A165 increases fetal growth velocity and term fetal weight in growth-restricted guinea-pig pregnancy.

Gene Targeting to the Uteroplacental Circulation of Pregnant Guinea Pigs.

Our study aimed to target adenoviral gene therapy to the uteroplacental circulation of pregnant guinea pigs in order to develop a novel therapy for fetal growth restriction. Four methods of delivery of an adenovirus encoding ß-galactosidase (Ad.LacZ) were evaluated: intravascular injection using phosphate-buffered saline (PBS) into (1) uterine artery (UtA) or (2) internal iliac artery or external administration in (3) PBS or (4) pluronic F-127 gel (Sigma Aldrich). Postmortem examination was performed 4 to 7 days after gene transfer. Tissue transduction was assessed by X-gal histochemistry and enzyme-linked immunosorbent assay. External vascular application of the adenovirus vector in combination with pluronic gel had 91.7% success rate in terms of administration (85% maternal survival) and gave the best results for maternal/fetal survival and local transduction efficiency without any spread to maternal or fetal tissues. This study suggests an optimal method of gene delivery to the UtAs of a small rodent for preclinical studies.

VEGF Gene Transfer to the Utero-Placental Circulation of Pregnant Guinea Pigs to Enhance Fetal Growth.

In this chapter, we describe a novel method of adenoviral gene transfer to the uterine and radial arteries of pregnant guinea pigs to improve fetal growth. Adenoviruses encoding VEGF-A165 or a reporter gene ß-galactosidase were reconstituted in pluronic gel and applied topically to the exposed uterine and radial arteries following laparotomy. Pluronic gel is a thermosensitive gel that is liquid at 4 °C, but becomes solid as soon as it comes in contact with body temperature. It thereby acts as a slow-release vehicle for viral vectors to the target tissue and also facilitates closer contact of the viruses with the host tissue. Our studies have shown that adenoviral gene delivery using pluronic gel resulted in the highest transduction efficiency compared to intra-arterial administration or external administration in PBS as a vehicle, when measured by X-gal staining, immunohistochemistry, or Western blotting.

Hypoxic tumors and their effect on immune cells and cancer therapy.

The abnormal decrease or the lack of oxygen supply to cells and tissues is called hypoxia. This condition is commonly seen in various diseases such as rheumatoid arthritis and atherosclerosis, also in solid cancers. Pre-clinical and clinical studies have shown that hypoxic cancers are extremely aggressive, resistant to standard therapies (chemotherapy and radiotherapy), and thus very difficult to eradicate. Hypoxia affects both the tumor and the immune cells via various pathways. This review summarizes the most common effects of hypoxia on immune cells that play a key role in the anti-tumor response, the limitation of current therapies, and the potential solutions that were developed for hypoxic malignancies.

Statin-related adverse events: a meta-analysis.

BACKGROUND: The absolute frequencies of adverse events (AEs) between statins and placebo are very low in clinical trials, making clinical interpretation and application difficult. OBJECTIVES: This meta-analysis was intended to synthesize the collective AE data observed in prospective randomized clinical trials to facilitate clinical interpretation. METHODS: Using the search terms atorvastatin, simvastatin,pravastatin, rosuvastatin, fluvastatin, lovastatin, prospective trial, and randomized trial, the MEDLINE/EMBASE and the Cochrane Collaboration databases were reviewed for prospective randomized primary and secondary prevention trials of statin monotherapy. Nonrandomized uncontrolled studies and those missing AE data were excluded. The Mantel-Haenszel test for fixed and random effects was used to calculate odds ratios (ORs) and log ORs. RESULTS: Eighteen trials including 71,108 persons, and 301,374 person-years of follow-up were represented in this analysis. There were 36,062 persons receiving a statin and 35,046 receiving a placebo. Statin therapy increased the risk of any AE by 39% (OR = 1.4; 95% CI, 1.09-1.80; P = 0.008; NNH [number needed to harm] = 197) compared with placebo. Statins were associated with a 26% reduction in the risk of a clinical cardiovascular event (OR = 0.74; 95% CI, 0.69-0.80; P < 0.001; number needed to treat = 27). Treating 1000 patients with a statin would prevent 37 cardiovascular events, and 5 AEs would be observed. Serious events (creatine phosphokinase >10 times the upper limit of normal or rhabdomyolysis) are infrequent (NNH = 3400) and rhabdomyolysis, although serious, is rare (NNH = 7428). Atorvastatin was associated with the greatest risk of AEs and fluvastatin with the least risk. Simvastatin, pravastatin, and lovastatin had similar odds of AEs. Nonurgent AEs such as myalgia and liver function elevations were responsible for approximately two thirds of AEs reported in trials. CONCLUSIONS: Statin therapy was associated with greater odds of AEs compared with placebo but with substantial clinical benefit. Similar rates of serious AEs were observed between statin and placebo.