Genomic characterization of two novel reptilian papillomaviruses, Chelonia mydas papillomavirus 1 and Caretta caretta papillomavirus 1

In this paper we describe the characterization of the genomes of two sea turtle papillomaviruses, Chelonia mydas PV (CmPV-1) and Caretta caretta PV (CcPV-1). The isolation and sequencing of the first non-avian reptilian PVs extend the evolutionary history of PVs to include all amniotes. PVs have now been described in mammals, birds and non-avian reptiles. The chelonian PVs form a distinct clade most closely related to the avian PVs. Unlike the avian PVs, both chelonian PVs have canonical E6 and E7 ORFs, indicating that these genes were present in the common ancestor to mammalian and non-mammalian amniote PVs. Rates of evolution among the non-mammalian PVs were generally slower than those estimated for mammalian PVs, perhaps due to lower metabolic rates among the ectothermic reptiles.     

Potentially inappropriate prescribing for the elderly: effects of geriatric care at the patient and health care system level

BACKGROUND: Many studies have identified patient characteristics associated with potentially inappropriate prescribing in the elderly (PIPE), however, little attention has been directed toward how health care system factors such as geriatric care may affect this patient safety issue. OBJECTIVE: This study examines the association between geriatric care and PIPE in a community dwelling elderly population. RESEARCH DESIGN: Cross-sectional retrospective database study. SUBJECTS: Veterans age > or =65 years who received health care in the VA system during Fiscal Years (FY99-00), and also received at medications from the Veterans Administration in FY00. MEASURES: PIPE was identified using the Zhan adaptation of the Beers criteria. Geriatric care penetration was calculated as the proportion of patients within a facility who received at least 1 geriatric outpatient clinic or inpatient visit. ANALYSES: Logistic regression models with generalized estimating equations were used to assess the relationship between geriatric care and PIPE after controlling for patient and health care system characteristics. RESULTS: Patients receiving geriatric care were less likely to have PIPE exposure (odds ratio, 0.64; 95% confidence interval, 0.59-0.73). There was also a weak effect for geriatric care penetration, with a trend for patients in low geriatric care penetration facilities having higher risk for PIPE regardless of individual geriatric care exposure (odds ratio, 1.14; 95% confidence interval, 0.99-1.30). CONCLUSIONS: Although geriatric care is associated with a lower risk of PIPE, additional research is needed to determine if heterogeneity in the organization and delivery of geriatric care resulted in the weak effect of geriatric care penetration, or whether this is a result of low power.     

Identification of an antagonist that selectively blocks the activity of prostamides (prostaglandin-ethanolamides) in the feline iris

BACKGROUND AND PURPOSE: The prostamides (prostaglandin-ethanolamides) and prostaglandin (PG) glyceryl esters are biosynthesized by COX-2 from the respective endocannabinoids anandamide and 2-arachidonyl glycerol. Agonist studies suggest that their pharmacologies are unique and unrelated to prostanoid receptors. This concept was further investigated using antagonists. EXPERIMENTAL APPROACH: The isolated feline iris was used as a key preparation, where prostanoid FP receptors and prostamide activity co-exist. Activity at human recombinant FP and other prostanoid receptors was determined using stable transfectants. KEY RESULTS: In the feline iris, AGN 204396 produced a rightward shift of the dose-response curves for prostamide F2alpha and the prostamide F2alpha analog bimatoprost but did not block the effects of PGF2alpha and synthetic FP receptor agonists. Studies on human recombinant prostanoid receptors confirmed that AGN 204396 did not behave as a prostanoid FP receptor antagonist. AGN 204396 exhibited no antagonism at DP and EP1-4, but was a highly effective TP receptor antagonist. Contrary to expectation, the FP receptor antagonist AL-8810 efficaciously contracted the cat iris. AGN 204396 did not affect AL-8810 induced contractions, demonstrating that AL-8810 and AGN 204396 are pharmacologically distinct. Unlike AL-8810, the ethylamide derivate of AL-8810 was not an agonist. Al-8810 did not block prostamide F2alpha activity. Finally, AGN 204396 did not block PGE2-glyceryl ester activity. CONCLUSIONS AND IMPLICATIONS:The ability of AGN 204396 to selectively block prostamide responses suggests the existence of prostamide sensitive receptors as entities distinct from receptors recognizing PGF2alpha and PGE2-glyceryl ester.     

A prospective pilot study of antibodies against human papillomaviruses and cutaneous squamous cell carcinoma nested in the Oxford component of the European Prospective Investigation into Cancer and Nutrition

In a prospective pilot study nested in the EPIC-Oxford cohort, we examined the seroprevalence of antibodies against the L1 antigen of 38 human papilloma virus (HPV) types among 39 cases of cutaneous squamous cell carcinoma (SCC) for whom plasma was collected prior to diagnosis (incident) and 80 controls. Fifteen cases having already developed SCC at blood collection (prevalent) were also tested. There were no statistically significant differences in the seroprevalence of antibodies against any of the HPV types examined between incident cases and controls, nor was there a difference in the seroprevalence of multiple infections. However, consistent with results from published case-control studies, the seroprevalence of many beta-HPV types was higher among prevalent cases than among either incident cases or controls. For example the seroprevalence of antibodies against HPV-8 was 20% (16/80) in controls, 23% (9/39) among incident cases and 40% (6/15) among prevalent cases. Among the incident cases only, the seroprevalence was 16% (5/32) among those for whom blood was collected 18+ months prior to diagnosis, but 57% (4/7) among those for whom diagnosis was within 18 months of blood collection, a pattern seen for many of the HPV types. This might suggest that if HPV is involved in the aetiology of SCC, the process occurs close to the time of diagnosis, or that the antibody response observed in people with SCC is a consequence of tumor formation. Further and larger prospective studies are needed to clarify the role of HPV in the aetiology of cutaneous SCC.     

Concurrent and Longitudinal Associations Between Diurnal Cortisol and Body Mass Index Across Adolescence

PurposeChildhood and adolescent obesity have reached epidemic levels; however, little is known about the psychobiological underpinnings of obesity in youth and whether these differ from the mechanisms identified in adults. The current study examines concurrent (i.e., measured at the same point in time) and longitudinal (i.e., using earlier cortisol measures to predict later body mass index [BMI]) associations between diurnal cortisol and BMI across adolescence.MethodsAdolescent diurnal cortisol was measured over 3 days at each 11, 13, and 15 years. Hierarchical linear modeling was used to extract average measures of predicted morning, afternoon, evening levels of cortisol and the diurnal slope at each assessment. Adolescent BMI (kg/m²) was measured at 11, 13, 15, and 18 years. Sex, family socioeconomic status, mother's BMI, pubertal status, and adolescent mental health were examined as possible confounding variables.ResultsLinear regressions revealed that blunted patterns of adolescent cortisol were associated with increased measures of BMI across adolescence both concurrently and longitudinally, particularly when examining measures of cortisol in early adolescence. Multinomial logistic regressions extended the linear regression findings beyond BMI scores to encompass categories of obesity.ConclusionsThe current study builds on previous research documenting diurnal cortisol–obesity findings in adults by demonstrating similar findings exist both concurrently and longitudinally in adolescents. Findings suggest the association between cortisol and BMI is developmentally influenced and that blunted diurnal cortisol patterns can be identified in overweight individuals at a younger age than previously thought.     

Recent advances in magnetic resonance imaging of the knee

The examination of the knee has rapidly become the most important non-neurologic application of MR imaging. The widespread availability of high signal-to-noise knee coils has made routine imaging with T2-weighted sequences in both coronal and sagittal planes possible in 30 minutes. The spin-echo sequence remains the most important imaging technique, although many newer sequences have also been applied to the knee, with varying degrees of success. Important pitfalls in diagnosis, such as high signal intensity in the posterior horn of the medial meniscus and the transverse meniscal ligament, displaced buckethandle meniscal tears, and discoid menisci, can be recognized with experience. Common clinical problems that are encountered include meniscal cysts, osteonecrosis, and bone bruises. Detection of subtle injuries of the medial collateral ligament, patellar tendon, and anterior cruciate ligament requires careful observation. Intra-articular loose bodies can be reliably detected with MR imaging, and it should be recognized that localized pigmented villonodular synovitis can sometimes simulate the appearance of a loose body. MR imaging is a valuable noninvasive procedure that is complementary to arthroscopy in the evaluation of diseases of the knee.     

Imaging of the distal radioulnar joint

The distal radioulnar joint can be evaluated by many different imaging techniques, including plain radiography, arthrography, tomography, nuclear medicine bone scanning, computed tomography, and magnetic resonance imaging. Each of these techniques has advantages and disadvantages that must be considered when determining the appropriate diagnostic evaluation for a particular patient.     

CIN2 is a much less reproducible and less valid diagnosis than CIN3: results from a histological review of population-based cervical samples.

We wished to compare the relative reproducibility and validity of cervical intraepithelial neoplasia (CIN) 2 and CIN3 diagnoses. In a population-based cohort study (1993-2001) of human papillomavirus (HPV) and cervical neoplasia in Costa Rica, we compared community pathologists' diagnoses with those of the 2 independent reviewers from the United States (total, n = 357). As measures of validity, we correlated primary and review diagnoses with HPV positivity and cytological interpretations. Two review pathologists agreed with 84% and 81%, respectively, of initial diagnoses of CIN3 compared with 13% and 31% of CIN2. The CIN3 diagnoses made by review pathologists were 94% oncogenic HPV positive, compared with 72% of CIN2 diagnoses. Eighty-one percent of CIN3 diagnoses versus 61% of CIN2 were correlated with high-grade cytological interpretations. The CIN3 is a substantially more reproducible diagnosis that can be validated more frequently with HPV tests and cytological interpretations than CIN2.