Hepatocyte proliferation is the possible mechanism for the transient decrease in liver injury during steatosis stage of alcoholic liver disease

Steatosis is a frequent pathologic stage in alcoholic liver disease (ALD). Although the mechanisms for increased susceptibility of steatotic liver to injury have been postulated, the ability of these hepatocytes to proliferate and withstand injury is unknown. There are conflicting reports on the status of hepatocyte regeneration following chronic alcohol ingestion. Hence, the objective of this study was to investigate the temporal dynamics between the pattern of liver injury and hepatocyte proliferation during the steatosis stage of ALD. Alcoholic steatosis was induced in male Sprague-Dawley rats by feeding an ethanol (EtOH)-containing Lieber-DeCarli liquid diet for a period of 5 weeks. Microvesicular steatosis was evident in H&E sections by three weeks in the EtOH-treated rats, which further developed into panlobular macrovesicular steatosis by 5 weeks. Plasma transaminase activities indicated progressive increase in liver injury peaking at 3 weeks with significant but mild decrease at 4 and 5 weeks. CYP2E1 protein and activity was significantly increased in EtOH-fed rats as measured by Western blot and pNP hydroxylation assay. PCNA analysis of liver sections indicated that EtOH-treated rats had a significantly higher number of cells in S phase of cell division at weeks 1 (3.20 +/- 0.19), 2 (7.03 +/- 0.92), and 3 (4.23 +/- 1.41) when compared to controls (1.5 +/- 0.22). NF-kappaB DNA binding and Cyclin D1 proteins increased significantly in the EtOH-treated rats corresponding with enhanced hepatic proliferation. These data suggest the transient decline in liver injury during alcoholic steatosis is due to enhanced NF-kappaB-dependent hepatocyte proliferation.     

The effect of an educational program upon hospital antibiotic use

The effect of an educational program on the use of antibiotics was studied in a university-affiliated Veterans Administration Hospital. Following an initial survey of antibiotic usage, educational presentations of the collected data were made to the hospital staff which included specific prescribing errors and alternative recommendations. Then, another survey was conducted. Measurable changes following the educational presentations were limited to decreasing costs of unjustified antibiotic use. An effect was noted in decreasing unjustified use of antibiotics in prophylactic situations, but this remained the most common misuse. Thus, an educational program directed at specific prescribing errors produced little noticeable effect on the use of antibiotics in a university-affiliated hospital. The study indicates that more direct measures, such as control of use of particular antibiotics, may be required to produce a meaningful change in prescribing practices.     

How much will it hurt? HPV vaccine side effects and influence on completion of the three-dose regimen

We examined the prevalence of reported pain following human papillomavirus (HPV) vaccination and whether it differed from that for other adolescent vaccines or affected completion of the HPV vaccine regimen. In 2008, we conducted cross-sectional surveys with parents of adolescent girls aged 11–20 living in areas of North Carolina with elevated cervical cancer rates who had received at least one dose of HPV vaccine. Pain from HPV vaccination, while commonly reported by parents, was less frequent compared to other adolescent vaccines and did not appear to affect vaccine regimen completion. These findings may be important to increase HPV vaccination coverage.     

Longitudinal Predictors of Human Papillomavirus Vaccination Among a National Sample of Adolescent Males

Objectives. We conducted a longitudinal study to examine human papillomavirus (HPV) vaccine uptake among male adolescents and to identify vaccination predictors.Methods. In fall 2010 and 2011, a national sample of parents with sons aged 11 to 17 years (n = 327) and their sons (n = 228) completed online surveys. We used logistic regression to identify predictors of HPV vaccination that occurred between baseline and follow-up.Results. Only 2% of sons had received any doses of HPV vaccine at baseline, with an increase to 8% by follow-up. About 55% of parents who had ever received a doctor’s recommendation to get their sons HPV vaccine did vaccinate between baseline and follow-up, compared with only 1% of parents without a recommendation. Fathers (odds ratio = 0.29; 95% confidence interval = 0.09, 0.80) and non-Hispanic White parents (odds ratio = 0.29; 95% confidence interval = 0.11, 0.76) were less likely to have vaccinated sons. Willingness to get sons HPV vaccine decreased from baseline to follow-up among parents (P < .001) and sons (P = .003).Conclusions. Vaccination against HPV remained low in our study and willingness to vaccinate may be decreasing. Physician recommendation and education about HPV vaccine for males may be key strategies for improving vaccination.Quadrivalent human papillomavirus (HPV) vaccine against types 6, 11, 16, and 18 is approved to protect against genital warts (caused mostly by HPV types 6 and 111) and anal cancer (caused mostly by HPV types 16 and 182) in males.3 About 4% of men in the United States report a previous diagnosis of genital warts,4 and about 2250 new cases of anal cancer occur annually among males in the United States.5 Given the high levels of HPV concordance among sexual partners,6 vaccinating males may also have indirect health benefits for their partners.7 United States guidelines began including HPV vaccine for males in October 2009.8 The Advisory Committee on Immunization Practices first provided a permissive recommendation, recommending the 3-dose quadrivalent vaccine series for males aged 9 to 26 years but not making it part of their routine vaccination schedule.8 In October 2011, the Advisory Committee on Immunization Practices updated its stance on HPV vaccine for males and recommended routine vaccination of boys aged 11 to 12 years with catch-up vaccination for males aged 13 to 21 years.9 The updated recommendation continues to allow HPV vaccine to be given to males aged as young as 9 years and up to 26 years.9Although numerous studies have examined HPV vaccine uptake among females,10 data on HPV vaccine uptake among males are sparse. Despite mostly encouraging early levels of parental acceptability of the vaccine for males,11–13 initial estimates found that only about 2% of male adolescents in the United States had received any doses of HPV vaccine by the end of 2010.14,15 Recent data suggest that this increased to about 8% by the end of 2011.16 We are not aware of any studies that have examined predictors of vaccine uptake among males.Our study addresses several important gaps in the existing literature. We provide the first longitudinal examination of HPV vaccination among males and identify predictors of vaccine uptake. In doing so, we used data from both parents and their adolescent sons because many adolescents are involved in vaccination decisions.17 We also examined longitudinal changes in vaccine acceptability among parents and sons and parents’ reasons for not getting their sons HPV vaccine, because these data may provide valuable insight about future HPV vaccine uptake among males.     

Mother–Daughter Communication About HPV Vaccine

PurposeParent–child conversations about human papillomavirus (HPV) vaccine may provide parents with the opportunity to talk with their daughters about sexual health. We sought to characterize mothers' communication with their adolescent daughters about HPV vaccine.MethodsWe surveyed 609 mothers of girls aged between 11 and 20 years living in North Carolina in Fall 2008. We used logistic regression to identify the correlates of mother–daughter communication.ResultsMost mothers (81%) reported having discussed HPV vaccine with their daughters. For almost half of these families (47%), discussion of HPV vaccine led to a conversation about sex. This was more common among mothers who believed that their daughters may be sexually active (odds ratio [OR]: 1.88; 95% confidence interval [CI]: 1.25–2.83), had greater knowledge of HPV vaccine (OR: 2.46; 95% CI: 1.07–5.64), lived in urban areas (OR: 1.75; 95% CI: 1.21–2.54), or reported being born-again Christians (OR: 1.74; 95% CI: 1.17–2.58). Most mothers who talked with their daughters about HPV vaccine reported having discussed the reasons for and against getting vaccinated (86%). Mothers most commonly reported having discussed the potential HPV vaccine benefits, usually protection against cervical cancer (56%), and less frequently reported having discussed the perceived disadvantages of HPV vaccine.ConclusionsHPV vaccine conversations may provide opportunities for sexual health promotion and sexually transmitted infection (STI) prevention.     

Crystal structures that suggest late development of genetic code components for differentiating aromatic side chains

Early forms of the genetic code likely generated "statistical" proteins, with similar side chains occupying the same sequence positions at different ratios. In this scenario, groups of related side chains were treated by aminoacyl-tRNA synthetases as a single molecular species until a discrimination mechanism developed that could separate them. The aromatic amino acids tryptophan, tyrosine, and phenylalanine likely constituted one of these groups. A crystal structure of human tryptophanyl-tRNA synthetase was solved at 2.1 A with a tryptophanyl-adenylate bound at the active site. A cocrystal structure of an active fragment of human tyrosyl-tRNA synthetase with its cognate amino acid analog was also solved at 1.6 A. The two structures enabled active site identifications and provided the information for structure-based sequence alignments of approximately 45 orthologs of each enzyme. Two critical positions shared by all tyrosyl-tRNA synthetases and tryptophanyl-tRNA synthetases for amino acid discrimination were identified. The variations at these two positions and phylogenetic analyses based on the structural information suggest that, in contrast to many other amino acids, discrimination of tyrosine from tryptophan occurred late in the development of the genetic code.