Virginia Commonwealth University

About: Virginia Commonwealth University is a education organization based out in Richmond, Virginia, United States. It is known for research contribution in the topics: Population & Poison control. The organization has 23822 authors who have published 49587 publications receiving 1787046 citations. The organization is also known as: VCU.

Risk Factors and Opportunities for Prevention of Early-onset Neonatal Sepsis: A Multicenter Case-Control Study

Abstract: Background. Early-onset group B streptococcal (GBS) prevention efforts are based on targeted use of intrapartum antibiotic prophylaxis (IAP); applicability of these prevention efforts to infections caused by other organisms is not clear. Methods. Multicenter surveillance during 1995 to 1996 for culture-confirmed, early-onset sepsis in an aggregate of 52 406 births; matched case-control study of risk factors for GBS and other sepsis. Results. Early-onset disease occurred in 188 infants (3.5 cases per 1000 live births). GBS (1.4 cases per 1000 births) andEscherichia coli (0.6 cases per 1000 births) caused most infections. GBS sepsis less often occurred in preterm deliveries compared with other sepsis. Compared with gestation-matched controls without documented sepsis, GBS disease was associated with intrapartum fever (matched OR, 4.1; CI, 1.2–13.4) and frequent vaginal exams (matched OR, 2.9; CI, 1.1–8.0). An obstetric risk factor—preterm delivery, intrapartum fever, or membrane rupture ≥18 hours—was found in 49% of GBS cases and 79% of other sepsis. IAP had an adjusted efficacy of 68.2% against any early-onset sepsis. Ampicillin resistance was evident in 69% of E coliinfections. No deaths occurred among susceptible E coliinfections, whereas 41% of ampicillin-resistant E coliinfections were fatal. Ninety-one percent of infants who developed ampicillin-resistant E coli infections were preterm, and 59% of these infants were born to mothers who had received IAP. Conclusions. Either prenatal GBS screening or a risk-based strategy could potentially prevent a substantial portion of GBS cases. Sepsis caused by other organisms is more often a disease of prematurity. IAP seemed efficacious against early-onset sepsis. However, the severity of ampicillin-resistant E colisepsis and its occurrence after maternal antibiotics suggest caution regarding use of ampicillin instead of penicillin for GBS prophylaxis.

A meta-analysis of six-month studies of antiplaque and antigingivitis agents

Abstract: Background and Methods The author conducted a systematic review of the literature to evaluate the efficacy of antigingivitis and antiplaque products in six-month trials. He searched electronic databases for six-month randomized clinical studies that evaluated both antiplaque and antigingivitis properties of dentifrices or mouthrinses. In addition, the author solicited unpublished studies from manufacturers. Results Seventeen studies support the antiplaque, antigingivitis effects of dentifrices containing 0.30 percent triclosan, 2.0 percent Gantrez copolymer. There was no evidence of efficacy for triclosan products containing either soluble pyrophosphate or zinc citrate. Dentifrices with stannous fluoride had statistically significant, but marginally clinically significant, evidence of an antiplaque effect; however, there was both a statistically and clinically significant antigingivitis effect. The largest body of studies (21 studies) supported the efficacy of mouthrinses with essential oils. A smaller body of studies (seven) supported a strong antiplaque, antigingivitis effect of mouthrinses with 0.12 percent chlorhexidine. Results for mouthrinses with cetylpyridinium chloride varied and depended on the product's formula. Conclusions The studies in this systematic review provide strong evidence of the antiplaque, antigingivitis effects of multiple agents. These results support the use of these agents as part of a typical oral hygiene regimen.

Past, present and future perspectives in nonalcoholic fatty liver disease.

Abstract: Nonalcoholic fatty liver disease (NAFLD) was first described as a distinct clinical entity four decades ago. However, the condition has become the centre of attention within hepatology owing to its high prevalence and growing contribution to the burden of end-stage liver disease in the general population. This Perspective provides an overview on the development of knowledge related to NAFLD with a focus on landmark findings that have influenced current paradigms and key knowledge gaps that need to be filled to make progress. Specifically, a timeline of scientific discovery of both basic disease mechanisms (with a focus on human data) and the evolution of knowledge about the clinical course of the disease is provided and related to current approaches to treat and eventually prevent NAFLD.

Molecular mechanisms of lipotoxicity and glucotoxicity in nonalcoholic fatty liver disease

Abstract: The exposure of hepatocytes to high concentrations of lipids and carbohydrates and the ensuing hepatocellular injury are termed lipotoxicity and glucotoxicity, respectively. A common denominator is metabolic derangement, especially in regards to intracellular energy homeostasis, which is brought on by glucose intolerance and insulin resistance in tissues. In this review, we highlight the lipids and carbohydrates that provoke hepatocyte injury and the mechanisms involved in lipotoxicity and glucotoxicity, including endoplasmic reticulum stress, oxidative stress and mitochondrial impairment. Through upregulation of proteins involved in various pathways including PKR-like ER kinase (PERK), CCAAT/enhancer-binding homologous protein (CHOP), c-Jun NH2-terminal kinase-1 (JNK), Bcl-2 interacting mediator (BIM), p53 upregulated modulator of apoptosis (PUMA), and eventually caspases, hepatocytes in lipotoxic states ultimately undergo apoptosis. The protective role of certain lipids and possible targets for pharmacological therapy are explored. Finally, we discuss the role of high fructose and glucose diets in contributing to organelle impairment and poor glucose transport mechanisms, which perpetuate hyperglycemia and hyperlipidemia by shunting of excess carbohydrates into lipogenesis.

Reversible Inhibitors of Fatty Acid Amide Hydrolase That Promote Analgesia: Evidence for an Unprecedented Combination of Potency and Selectivity

Abstract: Fatty acid amide hydrolase (FAAH) is the primary catabolic regulator of several bioactive lipid amides in vivo, including the endogenous cannabinoid anandamide and the sleep-inducing substance oleamide. Inhibitors of FAAH are considered a potential therapeutic approach for the treatment of several nervous system disorders, including pain, anxiety, and insomnia. However, for FAAH inhibitors to achieve clinical utility, they must not only display efficacy in vivo but also selectivity for this enzyme relative to the numerous other serine hydrolases present in mammalian proteomes. Here, we report a general strategy for evaluating the pharmacological activity and target specificity of FAAH inhibitors and its implementation to develop the first class of selective reversible inhibitors of this enzyme that are highly efficacious in vivo. Using a series of functional proteomics, analytical chemistry, and behavioral pharmacology assays, we have identified a class of α-keto-heterocycles that show unprecedented selectivity for FAAH relative to other mammalian hydrolases, and, when administered to rodents, raise central nervous system levels of anandamide and promote cannabinoid receptor 1-dependent analgesia in several assays of pain sensation. These studies provide further evidence that FAAH may represent an attractive therapeutic target and describe a general route by which inhibitors of this enzyme can be optimized to achieve exceptional potency, selectivity, and efficacy in vivo.