Exposure to polybrominated diphenyl ethers (PBDEs): changes in thyroid, vitamin A, glutathione homeostasis, and oxidative stress in American kestrels (Falco sparverius).

Polybrominated diphenyl ethers (PBDEs), a class of additive flame retardants, are temporally increasing in wildlife tissues and capable of disrupting normal endocrine function. We determined whether in ovo and post-hatch exposure of captive American kestrels (Falco sparverius) to environmentally relevant PBDEs alter thyroid, retinol, and oxidative stress measures. Control eggs were injected with safflower oil and subsequent nestlings fed the same vehicle; dosed eggs received PBDE congeners (BDE-47, -99, -100, -153), which mainly comprise the Penta-BDE commercial mixture, dissolved in safflower oil at concentrations (1500 ng/g total [Sigma] PBDEs) approximating those in Great Lakes gull eggs. Nestlings hatching from dosed eggs were orally exposed for 29 days to variable SigmaPBDE concentrations that are similar to levels reported in tissues of Great Lakes trout (100 ng/g). Treatment kestrels had lower plasma thyroxine (T(4)), plasma retinol, and hepatic retinol and retinyl palmitate concentrations, but unaltered triiodothyronine (T(3)) concentrations and thyroid glandular structure. BDE-47, -100, and -99 were negatively associated with plasma T(4), plasma retinol (BDE-100, -99) and hepatic retinol (BDE-47). Despite an antioxidant-rich diet, PBDE exposure induced hepatic oxidative stress, particularly in females, with an increased hepatic GSSG:GSH ratio, a marginal increase in lipid peroxidation, and increased oxidized glutathione. Positive associations were found between concentrations of BDE-183 and thiols and, in males, between BDE-99 and reduced GSH, but a negative association occurred between BDE-99 and TBARS. Subsequently, concentrations of PBDE congeners in wild birds may alter thyroid hormone and vitamin A concentrations, glutathione metabolism and oxidative stress.     

A preliminary study comparing the endometrial expression of inhibin, activin and follistatin in women with a history of implantation failure after IVF treatment and a control group

The aim of this study was to evaluate the expression of activin: beta A and beta B subunit and follistatin in endometrium of women with implantation failure ( n = 10) and compare it with a fertile control group ( n = 7). Immunohistochemical staining intensity for follistatin in the endometrial glandular epithelium from women with implantation failure were significantly lower than that in control women ( P = 0.03). The decreased expression of follistatin in epithelial cells in the endometrium of women with implantation failure after in vitro fertilisation (IVF) may suggest that follistatin may play a role in the implantation process.     

Identification of phosphorylated 422(aP2) protein as pp15, the 15-kilodalton target of the insulin receptor tyrosine kinase in 3T3-L1 adipocytes.

[32P]pp15, the [32P]phosphorylated form of a specific cytosolic substrate of the insulin receptor tyrosine kinase, was purified to homogeneity from mouse 3T3-L1 adipocytes incubated with 32Pi. Evidence presented here and previously indicates that pp15 contains a single phosphotyrosine residue. Alkylated [32P]pp15 was subjected to limited digestion with trypsin, after which three incompletely digested tryptic [32P]phosphopeptides were purified for analysis. Amino acid and radiochemical sequence analysis of the [32P]phosphopeptides revealed that pp15 is the phosphorylation product of 422(aP2) protein, a 15-kDa adipocyte protein previously sequenced in this laboratory from the corresponding cDNA.     

Impaired Delay Eyeblink Conditioning in Amnesic Korsakoff s Patients and Recovered Alcoholics

The performance of amnesic Korsakoff patients in delay eyeblink classical conditioning was compared with that of recovered chronic alcoholic subjects and healthy normal control subjects. Normal control subjects exhibited acquisition of conditioned responses (CRs) to a previously neutral, conditioned tone stimulus (CS) following repeated pairings with an unconditioned air-puff stimulus, and demonstrated extinction of CRs when the CS was subsequently presented alone. Both amnesic Korsakoff patients and recovered chronic alcoholic subjects demonstrated an impairment in their ability to acquire CRs. These results indicate that the preservation of delay eyeblink conditioning in amnesia must depend on the underlying neuropathology of the amnesic syndrome. It is known that patients with amnesia caused by medial temporal lobe pathology have preserved conditioning. We have now demonstrated that patients with anmesia caused by Korsakoff's syndrome, as well as recovered chronic alcoholic subjects, have impaired conditioning. This impairment is most likely caused by cerebellar deterioration resulting from years of alcohol abuse.     

How to Use the American Geriatrics Society 2015 Beers Criteria—A Guide for Patients,Clinicians, Health Systems,and Payors

The Beers Criteria are a valuable tool for clinical care and quality improvement but may be misinterpreted and implemented in ways that cause unintended harms. This article describes the intended role of the 2015 American Geriatrics Society (AGS) Beers Criteria and provides guidance on how patients, clinicians, health systems, and payors should use them. A key theme underlying these recommendations is to use common sense and clinical judgment in applying the 2015 AGS Beers Criteria and to remain mindful of nuances in the criteria. The criteria serve as a “warning light” to identify medications that have an unfavorable balance of benefits and harms in many older adults, particularly when compared with pharmacological and nonpharmacological alternatives. However, there are situations in which use of medications included in the criteria can be appropriate. As such, the 2015 AGS Beers Criteria work best not only when they identify potentially inappropriate medications, but also when they educate clinicians and patients about the reasons those medications are included and the situations in which their use may be more or less problematic. The criteria are designed to support, rather than supplant, good clinical judgment.     

Nutritional Status of Young Children with Inherited Blood Disorders in Western Kenya

To determine the association between a range of inherited blood disorders and indicators of poor nutrition, we analyzed data from a population-based, cross-sectional survey of 882 children 6–35 months of age in western Kenya. Of children with valid measurements, 71.7% were anemic (hemoglobin < 11 g/dL), 19.1% had ferritin levels < 12 μg/L, and 30.9% had retinol binding protein (RBP) levels < 0.7 μmol/L. Unadjusted analyses showed that compared with normal children, homozygous α⁺-thalassemia individuals had a higher prevalence of anemia (82.3% versus 66.8%, P = 0.001), but a lower prevalence of low RBP (20.5% versus 31.4%, P = 0.024). In multivariable analysis, homozygous α⁺-thalassemia remained associated with anemia (adjusted odds ratio [aOR] = 1.8, P = 0.004) but not with low RBP (aOR = 0.6, P = 0.065). Among young Kenyan children, α⁺-thalassemia is associated with anemia, whereas G6PD deficiency, haptoglobin 2-2, and HbS are not; none of these blood disorders are associated with iron deficiency, vitamin A deficiency, or poor growth.     

Soil-Transmitted Helminth Infection and Nutritional Status Among Urban Slum Children in Kenya

To evaluate the nutritional impact of soil-transmitted helminth (STH) infection, we conducted a cross-sectional survey of 205 pre-school (PSC) and 487 school-aged children (SAC) randomly selected from the surveillance registry of the Centers for Disease Control and Prevention of the Kibera slum in Kenya. Hemoglobin, iron deficiency (ID), vitamin A deficiency (VAD), inflammation, malaria, anthropometry, and STH ova were measured. Poisson regression models evaluated associations between STH and malnutrition outcomes and controlled for confounders. Approximately 40% of PSC and SAC had STH infection, primarily Ascaris and Trichuris; 2.9% of PSC and 1.1% of SAC had high-intensity infection. Malnutrition prevalence among PSC and SAC was anemia (38.3% and 14.0%, respectively), ID (23.0% and 5.0%, respectively), VAD (16.9% and 4.5%, respectively), and stunting (29.7% and 16.9%, respectively). In multivariate analysis, STH in PSC was associated with VAD (prevalence ratio [PR] = 2.2, 95% confidence interval = 1.1–4.6) and ID (PR = 3.3, 95% confidence interval = 1.6–6.6) but not anemia or stunting. No associations were significant in SAC. Integrated deworming and micronutrient supplementation strategies should be evaluated in this population.