Developmental Lead Exposure and Prenatal Stress Result in Sex-Specific Reprograming of Adult Stress Physiology and Epigenetic Profiles in Brain.

Developmental exposure to lead (Pb) and prenatal stress (PS) both impair cognition, which could derive from their joint targeting of the hypothalamic-pituitary-adrenal axis and the brain mesocorticolimbic (MESO) system, including frontal cortex (FC) and hippocampus (HIPP). Glucocorticoids modulate both FC and HIPP function and associated mediation of cognitive and other behavioral functions. This study sought to determine whether developmental Pb ± PS exposures altered glucocorticoid-related epigenetic profiles in brain MESO regions in offspring of female mice exposed to 0 or 100 ppm Pb acetate drinking water from 2 mos prior to breeding until weaning, with half further exposed to prenatal restraint stress from gestational day 11-18. Overall, changes in females occured in response to Pb exposure. In males, however, Pb-induced neurotoxicity was modulated by PS. Changes in serum corticosterone levels were seen in males, while glucocorticoid receptor changes were seen in both sexes. In contrast, both Pb and PS broadly impacted brain DNA methyltransferases and binding proteins, particularly DNMT1, DNMT3a and methyl-CpG-binding protein 2, with patterns that differed by sex and brain regions. Specifically, in males, effects on FC epigenetic modifiers were primarily influenced by Pb, whereas extensive changes in HIPP were produced by PS. In females, Pb exposure and not PS primarily altered epigenetic modifiers in both FC and HIPP. Collectively, these findings indicate that epigenetic mechanisms may underlie associated neurotoxicity of Pb and of PS, particularly associated cognitive deficits. However, mechanisms by which this may occur will be different in males versus females.

Change in Lactate Levels After Hemodialysis in Patients With End-Stage Renal Disease.

STUDY OBJECTIVE: Patients with end-stage renal disease commonly visit the emergency department (ED). The purpose of this investigation is to examine the prevalence of baseline abnormal lactate levels and to evaluate the effects of hemodialysis on serum lactate levels. METHODS: This was a prospective observational cohort study performed at an outpatient dialysis facility at an urban tertiary care hospital. The study consisted of 226 patients with end-stage renal disease who were receiving long-term hemodialysis and were enrolled during a 2-day period at the beginning of December 2015. Blood drawn for lactate levels was immediately analyzed before and after hemodialysis sessions. All patients completed their hemodialysis sessions. RESULTS: The prevalence of an abnormal lactate level (greater than 1.8 mmol/L) before hemodialysis was 17.7% (n=40). Overall, lactate levels decreased by 27% (SD 35%) after hemodialysis, with a decrease of 37% (SD 31%) for subgroups with a lactate level of 1.9 to 2.4 mmol/L, and 62% (SD 14%) with a lactate of 2.5 to 3.9 mmol/L. CONCLUSION: The data presented help providers understand the prevalence of abnormal lactate values in an outpatient end-stage renal disease population. After hemodialysis, lactate levels decreased significantly. This information may help medical providers interpret lactate values when patients with end-stage renal disease present to the ED.

The Behavioural Outcomes of Anxiety scale (BOA): a preliminary validation in stroke survivors.

OBJECTIVES: To determine the psychometric properties of an observational scale of anxiety. DESIGN: A cross-sectional and longitudinal survey with stroke survivor-carer dyads. METHODS: Eighty-nine dyads recruited in community stroke groups completed: a demographic questionnaire; the Behavioural Outcomes of Anxiety scale (BOA), survivor-rated (survivor BOA) and carer-rated (carer BOA) versions; the anxiety scale of the Hospital Anxiety and Depression Scales (HADS-A), also in carer and survivor versions. Twenty-seven survivors and carers repeated the BOA after 1 week. RESULTS: Correlations between the carer BOA and the survivor HADS-A (r = .55, p < .001) and the survivor BOA (r = .73, p < .001) demonstrated construct validity. Cronbach's alpha for the carer BOA was .81; item statistics did not identify any items for exclusion. The test-retest coefficient at 1 week was 0.83. Receiver operating characteristic analysis against the survivor HADS-A and BOA produced areas under the curve of 0.75 and 0.88, respectively. At a cut-off score of 13/14 sensitivity and specificity against the HADS-A were 0.77 and 0.58, respectively, and 0.86 and 0.68 against the survivor BOA. The impact of stroke on memory was associated with elevated anxiety. Scores for both BOA versions were independent of demographic variables. CONCLUSIONS: The carer BOA has acceptable psychometric properties and is independent of survivor demographic variables such as age. It identifies self-reported cases with acceptable sensitivity and specificity. It has potential for use with persons unable to self-report anxiety. Further validation is recommended, but its continuing use is supported.

Acral peeling skin syndrome: a case of two brothers.

We report two brothers of Middle Eastern descent with consanguineous parents who present with numerous fragile, flaccid blisters on the hands and feet. In addition to spontaneous peeling, they can manually peel skin from acral areas without pain. The symptoms worsen with warm temperatures, excessive water exposure, and perspiration. Two biopsies from flaccid blisters on the feet were taken from the older brother, which revealed cleavage at the level of the stratum corneum. A diagnosis of acral peeling skin syndrome was made.

Frequency of use of suturing and repair techniques preferred by dermatologic surgeons.

BACKGROUND: There are many closure techniques and suture types available to cutaneous surgeons. Evidence-based data are not available regarding the frequency of use of these techniques by experienced practitioners. OBJECTIVE: To quantify, by anatomic site, the frequency of use of common closure techniques and suture types by cutaneous surgeons. METHOD: A prospective survey of the members of the Association of Academic Dermatologic Surgeons that used length-calibrated visual-analog scales to elicit the frequency of use of specific suture techniques. RESULTS: A response rate of 60% (61/101) indicated reliability of the received data. Epidermal layers were closed most often, in descending order, by simple interrupted sutures (38-50%), simple running sutures (37-42%), and vertical mattress sutures (3-8%), with subcuticular sutures used more often on the trunk and extremities (28%). The most commonly used superficial sutures were nylon (51%) and polypropylene (44%), and the most common absorbable suture was polyglactin 910 (73%). Bilayered closures, undermining, and electrocoagulation were used, on average, in 90% or more sutured repairs. The median diameters (defined as longest extent along any axis) of most final wound defects were 1.1 to 2.0 cm (56%) or 2.1 to 3.0 cm (37%). Fifty-four percent of wounds were repaired by primary closure, 20% with local flaps, and 10% with skin grafting, with the remaining 15% left to heal by second intent (10%) or referred for repair (5%). Experience-related differences were detected in defect size and closure technique: defects less than 2 cm in diameter were seen by less experienced surgeons, and defects greater than 2 cm by more experienced surgeons (Wilcoxon's rank-sum test: p=.02). But more experienced surgeons were less likely to use bilayered closures (r=-0.28, p=.036) and undermining (r=-0.28, p=.035). CONCLUSIONS: There is widespread consensus among cutaneous surgeons regarding optimal suture selection and closure technique by anatomic location. More experienced surgeons tend to repair larger defects but, possibly because of their increased confidence and skill, rely on less complicated repairs.

Techniques for cutaneous sutured closures: variants and indications.

Many different suture techniques are routinely used by cutaneous surgeons for the closure of surgical wounds. This paper reviews several common suture techniques and their associated subtypes. In particular, for each technique, we discuss the method for placement, generally accepted indications, controversies regarding utility, and objective evidence of efficacy.

Neural growth, neural damage and neurotrophins in the kindling model of epilepsy.

Do seizures change the brain? Studies on the kindling model--a widely used animal model of epilepsy--suggest that they do. Dr. Racine, one of the pioneers in the kindling field, describes the basic phenomena of kindling, and discusses the possible roles of cell growth and cell death in this model.

The cholinergic system modulates kindling and kindling-induced mossy fiber sprouting.

In a previous study, our laboratory demonstrated that the intraventricular infusion of nerve growth factor (NGF) accelerated kindling rates and enhanced mossy fiber sprouting in the absence of noticeable kindling-associated neuronal loss. The purpose of the present study was to investigate whether these NGF effects were mediated via the cholinergic system. This study evaluated the effects of the cholinergic agonist pilocarpine and the cholinergic antagonist scopolamine on kindling rates and kindling-induced mossy fiber sprouting in adult rats. The results showed that pilocarpine accelerated kindling rates and enhanced kindling-induced mossy fiber sprouting in the CA3 region of the hippocampus, whereas scopolamine retarded kindling rates and blocked kindling-induced mossy fiber sprouting in the CA3 and IML regions. These findings suggest that the cholinergic system may contribute to the long-term structural and functional alterations that are characteristic of the kindled state. Moreover, these data provide support for the hypothesis that NGF infusions may mediate kindling and kindling-induced mossy fiber sprouting via regulation of the cholinergic system.