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.

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.

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.

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.

Menstrual phase-independent retrieval deficit in women with PMS.

Memory and attention were evaluated in 19 women with prospectively documented premenstrual syndrome (PMS) and 17 women without PMS. Testing occurred during the late luteal and follicular phases of the menstrual cycle. Estrogen, progesterone, and FSH levels were obtained on testing days for 23 of the women, while mood measures were obtained for all of the women. Repeated measures analysis of variance yielded significant group differences on recall measures, with no differences noted on recognition indices. No significant session or interaction effects were observed. This pattern of results suggests impaired retrieval of learned information coincident with intact encoding. No significant effects were noted for any of the nonverbal memory, attention, or other neurocognitive variables. The obtained data support previous findings of a mild, phase-independent memory impairment in women with PMS and also contribute to a better understanding of the component memory processes involved.

Successful migraine prophylaxis with naproxen sodium.

Naproxen sodium, a potent inhibitor of prostaglandin biosynthesis and platelet aggregation, was studied for efficacy in migraine prophylaxis in a randomized, double-blind, placebo-controlled, crossover trial. On naproxen treatment, 52% of the patients had no severe headaches, whereas 19% had no severe headaches during placebo. Naproxen sodium was much better than placebo when patients' diaries were reviewed for severity of attacks, nausea, vomiting, activity reduction, duration of headache, and decreased use of therapeutic medication. The degree of platelet inhibition did not correlate with efficacy in preventing headache. Naproxen sodium can be recommended as a drug of first choice for migraine prevention.

The effect on memory of chronic prednisone treatment in patients with systemic disease.

There have been no systematic investigations of the effects of glucocorticoid treatment on memory in a clinical population despite experimental and clinical evidence that such treatment could cause memory disturbance. We conducted both cross-sectional and longitudinal studies. In Study 1, we administered tests of both hippocampal-dependent explicit memory and hippocampal-independent implicit memory to twenty-five prednisone-treated patients with systemic disease without CNS involvement and 25 matched clinical controls. All treated patients were taking doses of 5 to 40 mg of prednisone daily for at least 1 year. The glucocorticoid-treated group performed worse than the controls on tests of explicit memory, but the groups did not differ on the implicit memory task. Multiple regression analyses suggested that elderly patients are more susceptible to memory impairment with less protracted treatment. The results of Study 2, a prospective, longitudinal study of the effects of prednisone on memory across 3 months of therapy, suggest that even acute treatment can adversely affect memory. The observed alteration in memory was not secondary to inattention, affective disturbance, generalized global cognitive decline, or severity of disease. Results reported here, combined with previous clinical and experimental reports, indicate that the risk of memory impairment should be carefully considered before initiating treatment with glucocorticoids. Conversely, use of glucocorticoids should be considered in the differential diagnosis of memory loss. Finally, the potential benefit of anti-inflammatory treatment in Alzheimer's disease might be counterbalanced by possible iatrogenic memory impairment, at least when synthetic glucocorticoids are considered.

Visuoperceptual-spatial ability and visual memory in vascular dementia and dementia of the Alzheimer type.

This study investigated the relationship between visuoperceptual ability and visual memory in dementia. Twenty individuals with probable dementia of the Alzheimer type, 24 individuals with probable vascular dementia, and 20 healthy, elderly adults underwent neuropsychological evaluation. Hierarchical multiple regression analyses suggested that perceptual organization skills contributed to a significant amount of the variance in novel, but not famous, face recognition. This finding was most robust in the clinical groups. Causality cannot be attributed from this regression model. Results suggest, however, that visual processing deficits are more strongly related to the memory process at the time of encoding rather than during recognition of remote information.

Psychological aspects of premenstrual syndrome. II: Utility of standardized measures.

Depressed mood is a salient feature of Premenstrual Syndrome (PMS). Fourteen women with prospectively documented PMS and ten without PMS completed the short form of the Beck Depression Inventory (BDI) and the Zung Self-Rating Scale for Depression (Zung-D) during the follicular and late luteal phases of two consecutive menstrual cycles. The short form of the BDI assesses the more cognitive symptoms of depression, while the Zung-D identifies primarily vegetative symptoms. The short form of the BDI was sensitive to cyclic changes in the PMS women, while the Zung-D was not. The BDI items uniquely endorsed by the PMS women during the late luteal phase were pessimism, sense of failure, dissatisfaction, guilt, self-dislike, and indecision. The premenstrual dysphoria experienced by PMS women thus appears to be more cognitive than vegetative in nature. Finally, differential utility of standardized mood measures to detect premenstrual depression is suggested. The BDI proved to be the more sensitive measure.

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.

Psychological aspects of premenstrual syndrome. I: Cognition and memory.

Fourteen women with PMS and ten without PMS were evaluated with a battery of neuropsychological tests during the follicular and late luteal phases of two consecutive menstrual cycles. Classification was determined with NIMH diagnostic criteria and prospective record keeping. The results indicated that (1) the PMS women had significant difficulty in learning new material and this problem was not phase-dependent, (2) both groups performed better on a test of frontal lobe function during the follicular phase, and (3) mood did not account for any of the differences in cognitive functioning.

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.

Successful treatment of microsporidial keratoconjunctivitis with topical fumagillin in a patient with AIDS.

There recently have been several reports of microsporidial keratoconjunctivitis caused by the organism Encephalitozoon hellem. However, treatment of this infection has been largely ineffective. We report a case of a 35-year-old Hispanic woman with AIDS and E. hellem keratoconjunctivitis confirmed with light, electron, and immunofluorescence microscopy that resolved promptly with topical fumagillin, a crystalline antibiotic with proven efficacy against Encephalitozoon species. No corneal or systemic toxicities were noted using the dosage and preparation employed (10 mg/ml suspension in balanced salt solution). An easily prepared, topical fumagillin suspension appears to be a safe, effective treatment for E. hellem keratoconjunctivitis.

Boston HAPPENS Program: a model of health care for HIV-positive, homeless, and at-risk youth. Human immunodeficiency virus (HIV) Adolescent Provider and Peer Education Network for Services.

The Boston HAPPENS [Human immunodeficiency virus (HIV) Adolescent Provider and Peer Education Network for Services] Program is a project supported by Special Projects of National Significance (SPNS) Program, HIV/AIDS Bureau, Health Resources and Services Administration, which provides a network of care for homeless, at-risk, and HIV-positive youth (ages 12-24 years), involving eight agencies. The program has provided services to 1301 youth, including 46 who are HIV-positive. Boston HAPPENS provides a citywide network of culturally and developmentally appropriate adolescent-specific care, including: (a) outreach and risk-reduction counseling through professional and adult-supervised peer staff, (b) access to appropriate HIV counseling and testing support services, (c) life management counseling (mental health intake and visits as part of health care and at times of crisis), (d) health status screening and services needs assessment, (e) client-focused, comprehensive, multidisciplinary care and support, (f) follow-up and outreach to ensure continuing care, and (g) integrated care and communication among providers in the metropolitan Boston area. This innovative network of youth-specific care offers a continuum from street outreach to referral and HIV specialty care that crosses institutional barriers.

Acupuncture heroin detoxification: a single-blind clinical trial.

The increasing prevalence of HIV infection among injection drug users mandates the development of innovative treatments. While extensive clinical experience suggests that acupuncture detoxification is both safe and acceptable to those in withdrawal, little research has been conducted to assess its efficacy as a treatment modality. In this first controlled study of acupuncture heroin detoxification, 100 addicted persons were randomly assigned, in a single-blind design, to the standard auricular acupuncture treatment used for addiction or to a "sham" treatment that used points that were geographically close to the standard points. Attrition was high for both groups, but subjects assigned to the standard treatment attended the acupuncture clinic more days and stayed in treatment longer than those assigned to the sham condition. Additionally, attendance varied inversely with self-reports of frequency of drug use, suggesting that those with lighter habits found the treatment modality more helpful. Limitations of the study are discussed.

Benefits of massage therapy and use of a doula during labor and childbirth.

This article reviews the most recent literature on touch support and one-to-one support during labor and childbirth. The positive and negative aspects of the traditional birth attendant are presented. Research in one-to-one care and touch support during labor is examined with respect to husband/partner, nurses, nurse-midwives, and doulas (trained labor attendants). According to recent studies, women supported by doulas or midwives benefit by experiencing shorter labors and lower rates of epidural anesthesia and cesarean section deliveries. Also, a smaller percentage of their newborns experience fetal distress and/or are admitted to neonatal intensive care units. Women whose husbands or partners massage them during labor experience shorter labors. Nursing one-to-one support results in no significant obstetric outcomes. Antenatal perineal massage was found to reduce the rates of tears, cesarean section, and instrumental deliveries. Research in perineal massage during labor has shown no benefit.

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.

Evaluation of a targeted HIV testing program for at-risk youth.

With the advent of new therapies for HIV, case identification through HIV counseling and testing (CTS) has become critically important. Young women, youth of color, and disenfranchised youth are at significant risk of acquiring HIV. This study describes clients who access CTS at a program of comprehensive care for high-risk youth (aged 12 to 24 years), and assessed, using logistic regression analyses, whether youth at highest risk utilized CTS. Most of the 531 youth were female (72 percent) and nonwhite (60 percent). Sixty-eight percent received CTS. Logistic regression modeling revealed that white race and receiving care at the teaching hospital were the only independent predictors of testing. Data indicate that, despite targeted, youth-specific, developmentally appropriate and culturally sensitive outreach and intervention efforts, youth of color and high-risk youth are poorly accessing CTS. A greater understanding of the barriers to and cultural norms regarding CTS is needed.