Sex differences in visuospatial abilities persist during induced hypogonadism.

BACKGROUND: Despite well-established sex differences in the performance on tests of several cognitive domains (e.g., visuospatial ability), few studies in humans have evaluated if these sex differences are evident both in the presence of circulating sex hormones and during sex steroid hormonal suppression. Sex differences identified in the relative absence of circulating levels of estradiol and testosterone suggest that differences in brain structure or function exist independent of current hormonal environment and are more likely a reflection of differing developmental exposures and/or genetic substrates. OBJECTIVE: To evaluate cognitive performance in healthy eugonadal men and women before and again during GnRH agonist-induced hypogonadism. METHODS: Men (n=16) and women (n=15) without medical or psychiatric illness were matched for IQ. Cognitive tests were performed at baseline (when eugonadal) and after 6-8 weeks of GnRH agonist-induced gonadal suppression. The test batteries included measures of verbal and spatial memory, spatial ability, verbal fluency, motor speed/dexterity, and attention/concentration. Data were analyzed using repeated-measures models. RESULTS: During both eugonadism and hypogonadism, men performed significantly better than women on several measures of visuospatial performance including mental rotation, line orientation, Money Road Map, Porteus maze, and complex figure drawing. Although some test performances showed an effect of hormone treatment, the majority of these differences reflected an improved performance during hypogonadism compared with baseline (and probably reflected practice effects). CONCLUSION: The well-documented male advantage in visuospatial performance, which we observed during eugonadal conditions, was maintained in the context of short-term suppression of gonadal function in both men and women. These findings suggest that, in humans, sex differences in visuospatial performance are not merely dependent on differences in the current circulating sex steroid environment. Thus sex differences in visuospatial performance in adulthood could reflect early developmental effects of sex steroid exposure or other environmental exposures differing across the sexes as our data confirm that these differences are independent of circulating estradiol or testosterone levels in men and women.

Preparation of Mica and Silicon Substrates for DNA Origami Analysis and Experimentation.

The designed nature and controlled, one-pot synthesis of DNA origami provides exciting opportunities in many fields, particularly nanoelectronics. Many of these applications require interaction with and adhesion of DNA nanostructures to a substrate. Due to its atomically flat and easily cleaned nature, mica has been the substrate of choice for DNA origami experiments. However, the practical applications of mica are relatively limited compared to those of semiconductor substrates. For this reason, a straightforward, stable, and repeatable process for DNA origami adhesion on derivatized silicon oxide is presented here. To promote the adhesion of DNA nanostructures to silicon oxide surface, a self-assembled monolayer of 3-aminopropyltriethoxysilane (APTES) is deposited from an aqueous solution that is compatible with many photoresists. The substrate must be cleaned of all organic and metal contaminants using Radio Corporation of America (RCA) cleaning processes and the native oxide layer must be etched to ensure a flat, functionalizable surface. Cleanrooms are equipped with facilities for silicon cleaning, however many components of DNA origami buffers and solutions are often not allowed in them due to contamination concerns. This manuscript describes the set-up and protocol for in-lab, small-scale silicon cleaning for researchers who do not have access to a cleanroom or would like to incorporate processes that could cause contamination of a cleanroom CMOS clean bench. Additionally, variables for regulating coverage are discussed and how to recognize and avoid common sample preparation problems is described.

Oxyanions in perovskites: from superconductors to solid oxide fuel cells.

In this article we review work on oxyanion (carbonate, borate, nitrate, phosphate, sulphate, silicate) doping in perovskite materials beginning with early work on doping studies in superconducting cuprates, and extending to more recent work on doping into perovskite-type solid oxide fuel cell materials. In this doping strategy, the central atom of the oxyanion group occupies the perovskite B cation site, with the associated oxide ions filling 3 (carbonate, nitrate, borate) or 4 (phosphate, sulphate, silicate) of the available 6 anion sites around this site, albeit displaced so as to achieve the required geometry for the oxyanion. We highlight the potential of this doping strategy to prepare new systems, stabilize phases that cannot be prepared under ambient pressure conditions, and lead to modifications to the electronic and ionic conductivity. We also highlight the need for further work in this area, in particular to evaluate the carbonate content of perovskite phases in general.

Understanding nutrient biogeochemistry in agricultural catchments: the challenge of appropriate monitoring frequencies.

We evaluate different frequencies of riverine nutrient concentration measurement to interpret diffuse pollution in agricultural catchments. We focus on three nutrient fractions, nitrate-nitrogen (NO3-N), total reactive phosphorus (TRP) and total phosphorus (TP) observed using conventional remote laboratory-based, low-frequency sampling and automated, in situ high-frequency monitoring. We demonstrate the value of low-frequency routine nutrient monitoring in providing long-term data on changes in surface water and groundwater nutrient concentrations. By contrast, automated high-frequency nutrient observations provide insight into the fine temporal structure of nutrient dynamics in response to a full spectrum of flow dynamics. We found good agreement between concurrent in situ and laboratory-based determinations for nitrate-nitrogen (Pearson's R = 0.93, p < 0.01). For phosphorus fractions: TP (R = 0.84, p < 0.01) and TRP (R = 0.79, p < 0.01) the relationships were poorer due to the underestimation of P fractions observed in situ and storage-related changes of grab samples. A detailed comparison between concurrent nutrient data obtained by the hourly in situ automated monitoring and weekly-to-fortnightly grab sampling reveals a significant information loss at the extreme range of nutrient concentration for low-frequency sampling.

Cognitive performance in healthy women during induced hypogonadism and ovarian steroid addback.

Gynecology clinic-based studies have consistently demonstrated that induced hypogonadism is accompanied by a decline in cognitive test performance. However, a recent study in healthy asymptomatic controls observed that neither induced hypogonadism nor estradiol replacement influenced cognitive performance. Thus, the effects of induced hypogonadism on cognition might not be uniformly experienced across individual women. Moreover, discrepancies in the effects of hypogonadism on cognition also could suggest the existence of specific risk phenotypes that predict a woman's symptomatic experience during menopause. In this study, we examined the effects of induced hypogonadism and ovarian steroid replacement on cognitive performance in healthy premenopausal women. Ovarian suppression was induced with a GnRH agonist (Lupron) and then physiologic levels of estradiol and progesterone were reintroduced in 23 women. Cognitive tests were administered during each hormone condition. To evaluate possible practice effects arising during repeated testing, an identical battery of tests was administered at the same time intervals in 11 untreated women. With the exception of an improved performance on mental rotation during estradiol, we observed no significant effects of estradiol or progesterone on measures of attention, concentration, or memory compared with hypogonadism. In contrast to studies in which a decline in cognitive performance was observed in women receiving ovarian suppression therapy for an underlying gynecologic condition, we confirm a prior report demonstrating that short-term changes in gonadal steroids have a limited effect on cognition in young, healthy women. Differences in the clinical characteristics of the women receiving GnRH agonists could predict a risk for ovarian steroid-related changes in cognitive performance during induced, and possibly, natural menopause.

Heading for a fall? Management of head injury in infants.

Head injury is one of the commonest reasons for infants (< 1 year) to attend the Emergency Department (ED). Clinical management varies considerably and concern about non accidental injury results in a high admission rate in some hospitals. Information was obtained on 103 children under one year of age presenting to the ED with head injury in a prospective study. The average age was 6.7 months and 57% of patients were male. Twenty eight babies had skull x rays with 1 skull fracture diagnosed. None required CT brain scan. Ninety eight (94%) were discharged home from the ED. There were no unplanned returns, readmissions or adverse events. The incidence of traumatic brain injury in children under one year of age presenting with head injury is low and the majority can be safely discharged home.

Medical, social and societal issues in infants with abusive head trauma.

Abusive head trauma (AHT) is the leading cause of death from traumatic brain injury in under 2 year olds. AHT presents with acute encephalopathy, subdural hemorrhages and retinal hemorrhages occurring in the context of an inappropriate or inconsistent history. We retrospectively analyzed, over a 10 year period, admissions and transfers to our hospital with suspected AHT to assess patterns of presentation, presenting symptoms, investigations, subsequent confirmation, social work input and both neurological and social outcomes. We analyzed all suspected AHT infants and children looking for the time of presentation, presenting symptoms, caregivers concerns prior to presentation, a family profile including stressors, investigations (in particular neuroradiology and ophthalmology assessments), treatment in hospital, length of stay in hospital, social work involvement, subsequent discharge, neurological outcome and subsequent social work follow up. Data was collected from the hospital HIPE system, RIS (radiology reports system) and records from the social work department from a period October 1998 to January 2009 inclusive. Of 22 patients with confirmed AHT, ages seizures and irritability followed by vomiting, poor feeding, a bulging fontanelle and lethargy. The father was the sole minder in 5 cases. There was a delayed history in 4 cases. One had multiple visits to his GP. All cases had subdural hemorrhages proven by either CT or MRI scans and retinal hemorrhages diagnosed by ophthalmology. One infant presented with a torn frenulum. Four had suspicious bruising. All had normal coagulation profiles, skeletal surveys and extensive metabolic tests. Hospital stays ranged from 1 to 124 days (the median was 28 days and mean 33 days). Ten (45%) infants required ventilatory support. Sixteen infants had social work involvement within 4 days of admission (7 of these were interviewed immediately). Outcomes after case conferences were that 6 returned home with parents, 9 were placed in foster care. Four parents (18%) admitted to shakng their infants. There was 1 death. Thirteen (60%) were normal on follow up. Two had ADHD. Two had language delay. Two had motor delay. One criminal prosecution has ensued as yet Children with suspected AHT should undergo appropriate investigations which should include brain imaging, ophthalmic examination, skeletal survey and blood investigations. Early social work assessment is a priority as part of the multidisciplinary approach. A prospective national study of AHT is required.

An analysis of results from 305 compounds tested with the yeast RAD54-GFP genotoxicity assay (GreenScreen GC)-including relative predictivity of regulatory tests and rodent carcinogenesis and performance with autofluorescent and coloured compounds.

Data from 305 non-proprietary compounds tested using the yeast RAD54-GFP (Green Fluorescent Protein) assay, GreenScreen GC, are presented, together with a detailed comparison with results from in vitro and in vivo genotoxicity tests and rodent carcinogenesis. In addition, observations on reproducibility and the performance of the test with autofluorescent and coloured compounds are described. Like the Ames test, the GreenScreen assay is shown to exhibit high specificity (82%), meaning that compounds with positive results are very likely to be genotoxic carcinogens. This is in contrast to mammalian cell tests established for use in regulatory testing that provide disappointingly low specificity and the inevitable generation of confounding false positive data. The analysis confirmed the observations of earlier studies, showing that a combination of an Ames test (or surrogate) with the yeast test provides high specificity as well as high sensitivity in the identification of rodent carcinogens.

Predictors of well-being among significant others of persons with multiple sclerosis.

OBJECTIVE: To examine patient and significant other characteristics as predictors of significant other well-being. METHODS: A total of 74 persons with multiple sclerosis (MS) and their significant others participated. Executive functioning was measured using neuropsychological tests. Awareness of cognitive deficit was measured as the discrepancy between the patient's reports of their abilities and objective test results. Awareness of functional deficit was measured as the discrepancy between the patient's and significant other's reports of the patient's functional abilities. Patient neurobehavioral disturbance was measured using a significant-other rated questionnaire. Significant other perceived social support and well-being (ie, psychological distress, life satisfaction, and general health status) were assessed using questionnaires filled out by the significant other. RESULTS: Executive dysfunction, neurobehavioral disturbance, and lack of awareness of functional deficits in patients were associated with poor well-being outcomes; whereas, lack of awareness of cognitive deficits was only weakly related to well-being. Social support was associated with positive well-being outcomes. CONCLUSIONS: Diminished insight regarding functional limitations may increase significant others' supervisory burden as patients attempt activities independently, whereas lack of awareness of cognitive deficits may not be directly associated with behavior-relevant impairments that significant others find distressing. Social support appears to be a powerful aid in diffusing the distress among significant others of MS patients.

Genetic modification and variations in solvent increase the sensitivity of the yeast RAD54-GFP genotoxicity assay.

The yeast (Saccharomyces cerevisiae) RAD54-GFP DNA repair reporter assay (GreenScreen assay, GSA) can be used for early genotoxicity screening in drug discovery. During the initial validation of this preregulatory assay, a subset of known genotoxic compounds that did not give reproducibly clear positive GSA results was identified. Cell permeability, inherent drug resistance mechanisms, metabolic activation and compound solubility were identified as possible barriers to the detection of specific compounds. In this study three types of modification to the existing assay protocol were explored in order to address these possibilities: (i) modification of the reporter host strain by deletion of genes involved in cell wall integrity or with products functioning as efflux pumps (PDR5, ERG6, SNQ2, YOR1); (ii) expression in the host yeast of human phase I metabolic activation genes and (iii) variation in the test solvent system for compounds with poor aqueous solubility. The modifications described and the assay results presented show how the assay may be tailored to suit specific classes of test compound in a more analytical mode. Improvements in assay sensitivity were seen in the detection of some genotoxins using yeast cell wall mutants and those expressing human cytochrome P450 genes.

Results of a technology demonstration project to compare rapid aquatic toxicity screening tests in the analysis of industrial effluents.

The results of a 'BioWise' demonstration project to assess the comparative sensitivity and practicality of seven new assays for the direct assessment of ecotoxicity in industrial effluents are presented. In addition the aim of the project was to validate the results of the new assays against benchmark data generated from non-proprietary, rapid, microplate screening assays using the regulatory species; freshwater crustacean Daphnia magna and green algae Selenastrum capricornutum, chosen in view of their environmental relevance. The new commercial test assays were: Daphnia magna, Selenastrum capricornutum and Thamnocephalus platyurus Toxkits supplied by Vickers Laboratories Ltd, containing dormant, immobilised life stages of the test species; GreenScreen EM, a yeast based assay for genotoxicity and general acute toxicity supplied by Gentronix Ltd; and CellSense a mediated, amperometric whole cell biosensor based on immobilised activated sludge and E. coli. 38 effluent samples supplied by members of SOCSA (Specialised Organic Chemicals Sector Association) were examined over a period of 13 months, in the project co-ordinated by the AstraZeneca Brixham Environmental Laboratory, and part funded by BioWise via the UK Government Department of Trade and Industry.

The GreenScreen genotoxicity assay: a screening validation programme.

A yeast (Saccharomyces cerevisiae) DNA repair reporter assay termed the GreenScreen assay (GSA) is described. This is a novel, cost-effective genotoxicity screen, developed to provide a pre-regulatory screening assay for use by the pharmaceutical industry and in other applications where significant numbers of compounds need to be tested. It provides a higher throughput and a lower compound consumption than existing eukaryotic genotoxicity assays and is sensitive to a broad spectrum of mutagens and, importantly, clastogens. We describe a simple, robust assay protocol and a validation study. The end-point of the test reflects the typically eukaryotic chromosomes and DNA metabolizing enzymes of yeast. The capacity for metabolic activation (MA) in yeast is limited compared with the mammalian liver or its extracts, but the assay does detect a subset of compounds that would require MA in existing genotoxicity tests. The GSA detects a different spectrum of compounds to bacterial genotoxicity assays and thus, together with an in silico structure-activity relationship (SAR) screen, and possibly a high throughput bacterial screen, would provide an effective preview of the regulatory battery of genotoxicity tests.

Poisoning in a paediatric hospital.

BACKGROUND: Poisoning is a major cause of morbidity and mortality in children and adolescents. Pharmaceutical and household products are responsible for the majority of cases. AIM: To analyse poisoning cases presenting to a paediatric hospital. METHODS: A retrospective study of all poisoning cases presenting to the Accident and Emergency (A&E) department of one hospital over a nine-month period. Children from birth to 15 years of age were included. The cases were categorised into accidental or intentional with or without suicidal intention. Demographic features included age, gender, toxin, location of poisoning, need for admission and mortality. RESULTS: A total of 148 cases were recorded, 47% were male, 31% were hospitalised and there was no mortality. Of ingestions, 74% were between 1 and 4 years of age and 86% were accidental. Of the intentional, 33% were suicidal, all 12 years or older. CONCLUSIONS: Few unintentional ingestions in the paediatric group result in serious toxicity. Mortality is rare. There is increasing intentional poisoning and alcohol abuse in adolescents. Poison prevention should be part of all well child visits. Agencies catering for children should carry educational leaflets for parents on how to 'poison proof' a child's environment, as the majority of incidents occur at home.

Transition from pediatric to adult-oriented health care: a challenge for patients with chronic disease.

Pediatric providers can expect that 1 of every 10 patients they see will have a chronic, activity-limiting health condition. Thanks to earlier diagnosis and improved therapies, most of these children will live well into adulthood. This means that eventually they will require care that focuses on adult health issues. Providers in the United States and around the world are recognizing the need for coordinated processes to transition adolescents and young adults with chronic conditions to adult health care. These models rely on the participation and input of the adolescent, his or her family, and pediatric and adult health professionals. This paper distinguishes medical transition from medical transfer; discusses potential barriers to transition; examines new initiatives to develop and study transition models; and reviews federal legislation influencing health care transitions.

Prefrontal cortex as the site of estrogen's effect on cognition.

The hippocampus has long been presumed the primary site of action of estrogens on cognition; and explicit memory is considered the cognitive function most vulnerable to menopausal loss of estrogen. We hypothesize instead that the prefrontal cortex and its neural circuitry are prime mediators of estrogen's role in cognition. We also propose that previously reported menopausal cognitive decline, presumed to be hippocampally mediated, may be secondary to executive dysfunction. We used a cross sectional design to compare the performance of nine menopausal women on hormone replacement therapy (HRT) and 10 menopausal women with no prior exposure to HRT on a battery of neuropsychological tests. The battery was comprised primarily of tests of memory and executive functioning. Executive functioning is mediated by the frontal lobes and encompasses working memory, directed attention, the inhibition of inappropriate responses, cognitive set switching, and behavioral monitoring. Unlike most previous studies, we used a memory measure that yields multiple scores reflecting various problem-solving strategies and error types, thus isolating spared and impaired cognitive processes. Results yielded both qualitative and quantitative evidence for disruption of cognitive processes subserved by the frontal lobes rather than the hippocampus: 1) despite intact free recall on a list-learning task (CVLT), untreated menopausal women were relatively impaired in correctly recognizing words previously learned and distinguishing them from items not on the list (discriminability), 2) untreated women also had difficulty inhibiting inappropriate responses in the form of perseverative errors, and 3) the non-HRT group consistently performed worse on the N-back test of working memory. The prefrontal cortex is critical for intact working memory and estrogen enhances performance on working memory tasks. In conclusion, this study provides preliminary evidence for executive dysfunction in untreated menopausal women as women with HRT outperformed women without HRT on tests requiring directed attention, inhibition of inappropriate responses, and cognitive set switching.

The prevalence of formal risk adjustment in health plan purchasing.

This paper describes the prevalence of formal risk adjustment of payments made to health plans by Medicare, Medicaid, state governments, and private payers. In this paper, 'formal risk adjustment" is defined as the adjustment of premiums paid to health plans based on individual-level diagnostic or demographic information. We find that formal risk adjustment is used for about one-fifth of all enrollees in capitated health plans. While the Medicare and Medicaid programs rely on formal risk adjustment for virtually all their health plan enrollees, the practice is used for only about 1% of privately insured health plan enrollees. Ourfindings raise the question of why regulators have adopted formal risk adjustment, but private purchasers for the most part have not.

Rapid hiv testing in urban outreach: a strategy for improving posttest counseling rates.

In 1998, 48% of persons who had HIV testing at publicly funded sites in the United States failed to return for test results and posttest counseling. Opportunities for timely HIV therapy were lost; valuable resources were wasted. This study tested the hypothesis that rapid HIV testing enables a high percentage of high-risk outreach clients to learn their serostatus. We did on-site counseling and rapid HIV testing at community-based organizations (e.g., chemical dependency programs, homeless shelters) in North Minneapolis. The project tested 735 persons. All but one (99.9%) learned their HIV serostatus. African Americans made up 79% of subjects. Rapid testing has a role to play in HIV outreach. It is useful in populations who are at high risk of HIV infection, who currently are not accessing HIV testing, and who have high failure to return rates. Future developments in rapid testing technology will make this testing option more convenient and cost-effective.

Youth perceptions of comprehensive adolescent health services through the Boston HAPPENS program.

INTRODUCTION: The Boston HAPPENS (HIV Adolescent Provider and Peer Education Network for Services) program is a collaborative network of care made up of 8 organizations that serve youth and provide coordinated care for human immunodeficiency virus (HIV)-positive, homeless, and at-risk youth aged 12 to 24 years. Learning youth perceptions about the program is essential to determine if the program is meeting their needs. METHODS: In this qualitative evaluation, 18 youth served by the network met in 4 focus groups to provide their view of the program. Services within 5 categories were assessed: (a) medical care, (b) mental health and substance abuse care, (c) HIV prevention and care, (d) case management, and (e) allocation of finances. RESULTS: Boston HAPPENS has achieved name recognition and provides many needed services for youth from a wide variety of backgrounds. The youth were comfortable receiving care and were appreciative of the comprehensive services available. They provided suggestions for how mental health services could be offered as one-on-one counseling as part of "wellness care." Young participants also requested more recreational and support opportunities for young people living with HIV. DISCUSSION: Qualitative evaluations such as this give a voice to youth to advocate for services they need. By including youth ideas and perspectives during program development and implementation, services can be more attractive to groups of at-risk youth who historically have been less likely to seek care.