Deficiency of either cyclooxygenase (COX)-1 or COX-2 alters epidermal differentiation and reduces mouse skin tumorigenesis

Nonsteroidal anti-inflammatory drugs are widely reported to inhibit carcinogenesis in humans and in rodents. These drugs are believed to act by inhibiting one or both of the known isoforms of cyclooxygenase (COX). However, COX-2, and not COX-1, is the isoform most frequently reported to have a key role in tumor development. Here we report that homozygous deficiency of either COX-1 or COX-2 reduces skin tumorigenesis by 75% in a multistage mouse skin model. Reduced tumorigenesis was observed even though the levels of stable 7,12-dimethylbenz(a)anthracene-DNA adducts were increased about 2-fold in the COX-deficient mice compared with wild-type mice. The premature onset of keratinocyte terminal differentiation appeared to be the cellular event leading to the reduced tumorigenesis because keratin 1 and keratin 10, two keratins that indicate the commitment of keratinocytes to differentiate, were expressed 8-13-fold and 10-20-fold more frequently in epidermal basal cells of the COX-1-deficient and COX-2-deficient mice, respectively, than in wild-type mice. Papillomas on the COX-deficient mice also displayed the premature onset of keratinocyte terminal differentiation. However, loricrin, a late marker of epidermal differentiation, was not significantly altered, suggesting that it was the early stages of keratinocyte differentiation that were primarily affected by COX deficiency. Because keratin 5, a keratin associated with basal cells, was detected differently in papillomas of COX-1-deficient as compared with COX-2-deficient mice, it appears that the isoforms do not have identical roles in papilloma development. Interestingly, apoptosis, a cellular process associated with nonsteroidal anti-inflammatory drug-induced inhibition of tumorigenesis, was not significantly altered in the epidermis or in papillomas of the COX-deficient mice. Thus, both COX-1 and COX-2 have roles in keratinocyte differentiation, and we propose that the absence of either isoform causes premature terminal differentiation of initiated keratinocytes and reduced tumor formation.     

Body composition of children aged 1 to 12 years with biliary atresia or Alagille syndrome

BACKGROUND: Growth and body composition have not been well described in older children with biliary atresia or Alagille syndrome living with their native liver. To optimize nutritional management of these conditions it is essential to understand the normal growth characteristics. OBJECTIVES: The purpose of this study was to evaluate and compare the growth and body composition of children, particularly school-age children, with biliary atresia and Alagille syndrome. METHODS: A single observer measured height, weight, arm anthropometry and skin fold thickness in subjects aged 1 to 12 years with biliary atresia or Alagille syndrome who had not undergone liver transplantation. RESULTS: Forty-six subjects (10 biliary atresia/36 Alagille syndrome) were assessed. Biliary atresia subjects were below average in height for age with normal weight and elevated body mass index. Mean fat stores were mildly depressed. The z-scores for body mass index and weight for age were inversely correlated with age. Alagille subjects were stunted and had low body weight and reduced fat and muscle stores. Body mass index z-score was inversely correlated with age despite improved cholestasis. CONCLUSIONS: Children with Alagille syndrome had significant growth deficits as measured by weight, height and upper arm anthropometry at all ages studied. In contrast, subjects with biliary atresia had normal weights and heights. However, body mass index and weight for age z-scores were lower in the older biliary atresia subjects. Few studies of anthropometry in biliary atresia or Alagille syndrome have included the school-aged child. This study addresses this gap in knowledge and provides baseline data for nutritional interventions in these patients.     

Financial management and job social skills training components in a summer business institute: a controlled evaluation in high achieving predominantly ethnic minority youth

Ninety-two adolescents, predominantly ethnic minority high school students, participated in a structured Summer Business Institute (SBI). Participating youth were randomly assigned to receive either job social skills or financial management skills training components. Students who additionally received the job social skills training component were more likely to recommend their employment agency to others than were youth who received the financial management component, rated their overall on-the-job work experience more favorably, and demonstrated higher scores in areas that were relevant to the skills that were taught in the job social skills workshops. The financial management component also appeared to be relatively effective, as youth who received this intervention improved their knowledge of financial management issues more than youth who received job social skills, and rated their workshops as more helpful in financial management, as well as insurance management. Future directions are discussed in light of these results.     

PKCtheta signals activation versus tolerance in vivo

Understanding the pathways that signal T cell tolerance versus activation is key to regulating immunity. Previous studies have linked CD28 and protein kinase C-theta (PKCtheta) as a potential signaling pathway that influences T cell activation. Therefore, we have compared the responses of T cells deficient for CD28 and PKCtheta in vivo and in vitro. Here, we demonstrate that the absence of PKCtheta leads to the induction of T cell anergy, with a phenotype that is comparable to the absence of CD28. Further experiments examined whether PKCtheta triggered other CD28-dependent responses. Our data show that CD4 T cell-B cell cooperation is dependent on CD28 but not PKCtheta, whereas CD28 costimulatory signals that augment proliferation can be uncoupled from signals that regulate anergy. Therefore, PKCtheta relays a defined subset of CD28 signals during T cell activation and is critical for the induction of activation versus tolerance in vivo.     

The Effect of Written Posted Instructions on Collection of Clean-Catch Urine Specimens in the Emergency Department

Background

Urinalysis testing is frequently ordered in the emergency department (ED), but contamination of urine specimens limits the interpretation of results. The mid-stream, clean-catch (MSCC) procedure for urine specimen collection is recommended to decrease contamination rates, but without instructions this procedure has poor compliance.

A systematic review and meta-analysis on the antibiotic resistance of Neisseria meningitidis in the last 20 years in the world

BackgroundNeisseria meningitidis is one of the most important causes of meningitis and pathogens-associated deaths in developing and developed countries. Effective anti-microbial agents are pivotal to treat and control N. meningitidis infections. The aim of the present study was to systematically review published studies on the antibiotic resistance of N. meningitidis in the last 20 years (2000–2020) in the world.MethodsPublished researches were identified through a literature search using reputable databases including PubMed, Scopus, and Web of Science. Finally, 24 studies were included for a random-effects model meta-analysis.ResultsThe overall resistance to most commonly used antibiotics such as ceftriaxone, cefotaxime, ciprofloxacin and rifampin was low, ranging from 1 to 3.4%. However, non-sensitivity to penicillin, as the first-line antibiotic against N. meningitidis, was higher (27.2%). Altogether, the resistance to the first-line antibiotics (except penicillin) is still low indicating these drugs are effective against meningococcal meningitis. We also found a significant gap between MIC and disk diffusion for evaluating resistance to antibiotics in which disk diffusion overestimate the resistance rate.ConclusionsTo properly management and prevent the spread of N. miningitidis isolates resistant antibiotics, it is necessary to monitor the pattern of antibiotic susceptibility regionally and globally using the MIC methods.     

Variation in Estimates of Limited Health Literacy by Assessment Instruments and Non-Response Bias

Objectives

This paper compares estimates of poor health literacy using two widely used assessment tools and assesses the effect of non-response on these estimates.

Study Design and Setting

A total of 4,868 veterans receiving care at four VA medical facilities between 2004 and 2005 were stratified by age and facility and randomly selected for recruitment. Interviewers collected demographic information and conducted assessments of health literacy (both REALM and S-TOFHLA) from 1,796 participants. Prevalence estimates for each assessment were computed. Non-respondents received a brief proxy questionnaire with demographic and self-report literacy questions to assess non-response bias. Available administrative data for non-participants were also used to assess non-response bias.

Results

Among the 1,796 patients assessed using the S-TOFHLA, 8% had inadequate and 7% had marginal skills. For the REALM, 4% were categorized with 6th grade skills and 17% with 7–8th grade skills. Adjusting for non-response bias increased the S-TOFHLA prevalence estimates for inadequate and marginal skills to 9.3% and 11.8%, respectively, and the REALM estimates for ≤6th and 7–8th grade skills to 5.4% and 33.8%, respectively.

Conclusions

Estimates of poor health literacy varied by the assessment used, especially after adjusting for non-response bias. Researchers and clinicians should consider the possible limitations of each assessment when considering the most suitable tool for their purposes.KEY WORDS: health literacy, veterans, prevalence, measurement, non-response bias, REALM, S-TOFHLA     

Two approaches to tailoring treatment for cultural minority adolescents

At this time, compared with mainstream (Caucasian) youth, cultural minority adolescents experience more severe substance-related consequences and are less likely to receive treatment. Although several empirically supported interventions (ESIs), such as motivational interviewing (MI), have been evaluated with mainstream adolescents, fewer published studies have investigated the fit and efficacy of these interventions with cultural minority adolescents. In addition, many empirical evaluations of ESIs have not explicitly attended to issues of culture, race, and socioeconomic background in their analyses. As a result, there is some question about the external validity of ESIs, particularly in disadvantaged cultural minority populations. This review seeks to take a step toward filling this gap, by addressing how to improve the fit and efficacy of ESIs like MI with cultural minority youth. Specifically, this review presents the existing literature on MI with cultural minority groups (adult and adolescent), proposes two approaches for evaluating and adapting this (or other) behavioral interventions, and elucidates the rationale, strengths, and potential liabilities of each tailoring approach.     

Late-life depression and alcoholism

The relationship between alcohol use and later-life depression is complex. At-risk and problem drinking elevates the risk of depressive symptoms. The co-occurrence of alcohol use disorders and depression increases the potential for poor mental and physical health outcomes in older adults. Many older adults who are experiencing problems related to alcohol use do not meet alcohol abuse/dependence criteria. Depressive symptoms among older adults often are overlooked or misdiagnosed. The role of at-risk and problem alcohol use in depressive symptoms and vice versa may be underestimated. After a review of the literature, clinical recommendations for addressing late-life alcohol misuse and depression are presented.