Polyomavirus Nephropathy in Pediatric Kidney Transplant Recipients

Given the limited information regarding BK virus-associated nephropathy (BKVN) in pediatric kidney transplant recipients, we assessed the incidence, risk factors, clinical and virologic features of BKVN in pediatric renal transplant recipients at a single transplant center by means of a retrospective cohort study. Histologically confirmed BKVN developed in 6 of 173 (3.5%) kidney transplant recipients at a median of 15 months post-transplant (range: 4-47 months). At a median follow-up of 28 months (range: 5-32), all patients had functioning grafts with mean creatinine and GFR of 1.9 mg/dL and 58 mL/min/1.73 m2, respectively. At the time of diagnosis, all cases had viruria (median 6.1 x 10(6) copies/mL, range: 10(5) to 3.9 x 10(8) copies/mL) and viremia (median 21,000 copies/mL, range: 10,000-40,000 copies/mL). Recipient seronegativity for BKV was significantly associated with the development of BKVN (p = 0.01). BKVN is an important cause of late allograft dysfunction and is strongly associated with recipient seronegativity in pediatric kidney transplant recipients. Further studies to confirm this finding and to define the clinical utility of routine pre-transplant BKV serologic testing are warranted.     

Environmental allergens and asthma in urban elementary schools.

BACKGROUND: Asthma in school children is rising, and indoor allergens are very common triggers of asthma attacks; however, the risk of the school environment on asthma has not been well studied. OBJECTIVE: To determine the presence and the levels of common aeroallergens in schools, where asthma prevalence rates are high. METHODS: Settled dust samples were collected from 12 Baltimore City public elementary schools, and they were analyzed for the following allergens: cockroaches (Bla g 1/2), dust mites (Der f 1/p 1), dog (Can f 1), cat (Fel d 1), and mouse (Mus m 1). School asthma prevalence rates were correlated with allergen levels, and association between allergen levels and other risk factors present in the schools' environment was examined. RESULTS: The mean and range levels were 1.49 U/g (0 to 8) for Bla g 1/2; 0.38 microg/g (0 to 11.9) for the Der f 1/p 1; 1.44 microg/g (0.1 to 9.6) for Can f 1; 1.66 microg/g (0.2 to 12) for Fel d 1; and 6.24 microg/g (0.3 to 118.3) for Mus m 1. Dust mite, cat and dog allergens were significantly in rooms with carpet and/or area rugs, compared to rooms with bare floors (P < 0.05). Asthma prevalence rates varied from 11.8 to 20.8% between schools and positively correlation with the mean levels of Bla g 1/2 in the schools (P = 0.001). CONCLUSIONS: Common allergens that are known to trigger asthma were detected in all school environments, where asthma prevalence rates were high. However, the overall allergen levels were low, indicating that other factors, including exposures in the homes of asthmatic patients, may have more relevance to sensitization and symptoms than school exposures.     

A case series of LMWH use in pregnancy: Should trough anti-Xa levels guide dosing?

Introduction

Pregnancy is a thrombogenic state, increasing the risk for venous thromboembolism (VTE), and the risk of valve thrombosis amongst women with mechanical heart valves (MHV). While low molecular weight heparins (LMWH) are generally dosed based on weight (i.e., enoxaparin 1 mg/kg every 12 hours), data in pregnant women have shown that weight-based dosing does not consistently achieve target anti-Xa levels. In women with MHV, our practice includes titrating LMWH doses to target both trough and peak anti-Xa levels, while for those with VTE peak anti-Xa levels guide dosing.

Materials/Methods

This retrospective case series included pregnant women requiring LMWH treatment doses with at least 3 peak (+/− trough) anti-Xa levels. Our primary objective was to describe the actual LMWH dose required to achieve targeted anti-Xa levels relative to weight-based dosing in patients with MHV. Secondarily, we compared the same for VTE patients; compared actual dosing between those with MHV and VTE; and examined maternal and fetal outcomes.

Results/Conclusion

Women with MHV (N = 4) required greater than weight-based dosing of enoxaparin (1.35 mg/kg Q12H) to achieve targeted anti-Xa levels. Importantly, achieving target peak anti-Xa levels did not always ensure maintenance of minimum trough levels. VTE patients (N = 12) did not require more enoxaparin (0.96 mg/kg Q12H) than weight based dosing. MHV patients received more enoxaparin compared to VTE patients (P < 0.001). No bleeding or clotting complications were associated with LMWH administration. In pregnant women with MHV at high risk of thromboembolism, LMWH dosing guided by trough and peak anti-Xa levels should be considered.     

Elevated Prevalence of Suicide Attempts among Victims of Police Violence in the USA

Recent evidence suggests that police victimization is widespread in the USA and psychologically impactful. We hypothesized that civilian-reported police victimization, particularly assaultive victimization (i.e., physical/sexual), would be associated with a greater prevalence of suicide attempts and suicidal ideation. Data were drawn from the Survey of Police-Public Encounters, a population-based survey of adults (N = 1615) residing in four US cities. Surveys assessed lifetime exposure to police victimization based on the World Health Organization domains of violence (i.e., physical, sexual, psychological, and neglect), using the Police Practices Inventory. Logistic regression models tested for associations between police victimization and (1) past 12-month suicide attempts and (2) past 12-month suicidal ideation, adjusted for demographic factors (i.e., gender, sexual orientation, race/ethnicity, income), crime involvement, past intimate partner and sexual victimization exposure, and lifetime mental illness. Police victimization was associated with suicide attempts but not suicidal ideation in adjusted analyses. Specifically, odds of attempts were greatly increased for respondents reporting assaultive forms of victimization, including physical victimization (odds ratio = 4.5), physical victimization with a weapon (odds ratio = 10.7), and sexual victimization (odds ratio = 10.2). Assessing for police victimization and other violence exposures may be a useful component of suicide risk screening in urban US settings. Further, community-based efforts should be made to reduce the prevalence of exposure to police victimization.     

Discovery and optimization of triazolopyridazines as potent and selective inhibitors of the c-Met kinase

Tumorigenesis is a multistep process in which oncogenes play a key role in tumor formation, growth, and maintenance. MET was discovered as an oncogene that is activated by its ligand, hepatocyte growth factor. Deregulated signaling in the c-Met pathway has been observed in multiple tumor types. Herein we report the discovery of potent and selective triazolopyridazine small molecules that inhibit c-Met activity.     

Subclinical hypothyroidism and pregnancy outcomes

BACKGROUND: Clinical thyroid dysfunction has been associated with pregnancy complications such as hypertension, preterm birth, low birth weight, placental abruption, and fetal death. The relationship between subclinical hypothyroidism and pregnancy outcomes has not been well studied. We undertook this prospective thyroid screening study to evaluate pregnancy outcomes in women with elevated thyrotropin (thyroid-stimulating hormone, TSH) and normal free thyroxine levels. METHODS: All women who presented to Parkland Hospital for prenatal care between November 1, 2000, and April 14, 2003, had thyroid screening using a chemiluminescent TSH assay. Women with TSH values at or above the 97.5th percentile for gestational age at screening and with free thyroxine more than 0.680 ng/dL were retrospectively identified with subclinical hypothyroidism. Pregnancy outcomes were compared with those in pregnant women with normal TSH values between the 5th and 95th percentiles. RESULTS: A total of 25,756 women underwent thyroid screening and were delivered of a singleton infant. There were 17,298 (67%) women enrolled for prenatal care at 20 weeks of gestation or less, and 404 (2.3%) of these were considered to have subclinical hypothyroidism. Pregnancies in women with subclinical hypothyroidism were 3 times more likely to be complicated by placental abruption (relative risk 3.0, 95% confidence interval 1.1-8.2). Preterm birth, defined as delivery at or before 34 weeks of gestation, was almost 2-fold higher in women with subclinical hypothyroidism (relative risk, 1.8, 95% confidence interval 1.1-2.9). CONCLUSION: We speculate that the previously reported reduction in intelligence quotient of offspring of women with subclinical hypothyroidism may be related to the effects of prematurity. LEVEL OF EVIDENCE: II-2.     

Mitochondrial control region sequences from a Vietnamese population sample

Entire mitochondrial control region data were generated for 187 individuals from Vietnam. These samples have been previously typed for 16 autosomal short-tandem repeats (STRs) [1]. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

A SYSTEMATIC REVIEW OF QUESTIONNAIRES MEASURING THE HEALTH OF RESETTLING REFUGEE WOMEN

Because many ethnically diverse refugee women resettle in industrialized countries, several biopsychosocial factors need to be considered in caring for them. This systematic review of studies conducted with female refugees, asylum-seekers, or “unspecified” immigrants based on six electronic databases was conducted to determine which questionnaires best measure relevant variables. Questionnaires were reviewed for measurement properties, application of translation theory, and quality of representation. Studies must have included ?1 measure of the following: general health; torture, abuse, sex-and-gender-based violence (SGBV); depression; stress; posttraumatic stress disorder (PTSD); anxiety; somatization; migration history; social support; socioeconomic status; discrimination; or mother–child interactions. Fifty-six studies using 47 questionnaires were identified; only five had strong evidence for use with resettling refugee women. Thus, few high-quality tools are available to measure concepts relevant to resettling refugee women's health.     

Calculation of Effective Penetration Depth in X-Ray Diffraction for Pharmaceutical Solids

The use of the glancing incidence X-ray diffraction configuration to depth profile surface phase transformations is of interest to pharmaceutical scientists. The Parratt equation has been used to depth profile phase changes in pharmaceutical compacts. However, it was derived to calculate 1/e penetration at glancing incident angles slightly below the critical angle of condensed matter and is, therefore, applicable to surface studies of materials such as single crystalline nanorods and metal thin films. When the depth of interest is 50–200 μm into the surface, which is typical for pharmaceutical solids, the 1/e penetration depth, or skin depth, can be directly calculated from an exponential absorption law without utilizing the Parratt equation. In this work, we developed a more relevant method to define X-ray penetration depth based on the signal detection limits of the X-ray diffractometer. Our definition of effective penetration depth was empirically verified using bilayer compacts of varying known thicknesses of mannitol and lactose. © 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:3807–3814, 2010