The Interfacial Interactions of Glycine and Short Glycine Peptides in Model Membrane Systems.

The interactions of amino acids and peptides at model membrane interfaces have considerable implications for biological functions, with the ability to act as chemical messengers, hormones, neurotransmitters, and even as antibiotics and anticancer agents. In this study, glycine and the short glycine peptides diglycine, triglycine, and tetraglycine are studied with regards to their interactions at the model membrane interface of Aerosol-OT (AOT) reverse micelles via 1H NMR spectroscopy, dynamic light scattering (DLS), and Langmuir trough measurements. It was found that with the exception of monomeric glycine, the peptides prefer to associate between the interface and bulk water pool of the reverse micelle. Monomeric glycine, however, resides with the N-terminus in the ordered interstitial water (stern layer) and the C-terminus located in the bulk water pool of the reverse micelle.

Patient-reported outcomes in multiple sclerosis: a systematic comparison of available measures.

Multiple patient-reported outcomes (PROs) are currently being used in multiple sclerosis (MS) but their application is inconsistent and guidance on the appropriateness of each tool is lacking. The objective of our study was to identify MS-specific PROs and systematically to assess the development process and the reliability and validity of various instruments. A systematic literature search was conducted on multiple data sources, including MEDLINE, Embase (using the Ovid platform) and Google Scholar, from 1996 to March 2015. Search terms included combinations of MS, PROs and quality of life. Randomized controlled trials or observational studies conducted on patients with MS and published in English were included. In addition, the PROQOLID database was explored. The MS-specific PROs were systematically assessed using the Evaluating the Measurement of Patient-Reported Outcomes tool. In total, 8094 articles were screened and 405 PROs were identified from 1102 relevant articles. PROs were classified into MS-specific (n = 82) and non-MS-specific (n = 323). The results for the eight PROs that are most commonly used in MS clinical trials are presented here. For these eight PROs, the overall summary scores ranged between 50.1 and 68.7. The Multiple Sclerosis Impact Scale-29 had the best overall mean score (68.7), followed by the Leeds Multiple Sclerosis Quality of Life (67.0). This is the first study to provide a standardized assessment of all PROs for MS. There is a lack of data on content validity for PROs used in MS research, which indicates the need for a robust instrument in MS developed according to the US Food and Drug Administration guidelines.

Maternal exposure to metals--concentrations and predictors of exposure.

A variety of metals are important for biological function but have also been shown to impact health at elevated concentrations, whereas others have no known biological function. Pregnant women are a vulnerable population and measures to reduce exposure in this group are important. We undertook a study of maternal exposure to the metals, aluminium, arsenic, copper, cobalt, chromium, lithium, manganese, nickel, selenium, tin, uranium and zinc in 173 participants across Western Australia. Each participant provided a whole blood and urine sample, as well as drinking water, residential soil and dust samples and completed a questionnaire. In general the concentrations of metals in all samples were low with the notable exception of uranium (blood U mean 0.07 µg/L, range <0.01-0.25 µg/L; urinary U mean 0.018 µg/g creatinine, range <0.01-0.199 µg/g creatinine). Factors that influenced biological concentrations were consumption of fish which increased urinary arsenic concentrations, hobbies (including mechanics and welding) which increased blood manganese concentrations and iron/folic acid supplement use which was associated with decreased concentrations of aluminium and nickel in urine and manganese in blood. Environmental concentrations of aluminium, copper and lithium were found to influence biological concentrations, but this was not the case for other environmental metals concentrations. Further work is underway to explore the influence of diet on biological metals concentrations in more detail. The high concentrations of uranium require further investigation.

Cadmium, lead and mercury exposure in non smoking pregnant women.

Recent literature suggests that exposure to low concentrations of heavy metals may affect both maternal and child health. This study aimed to determine the biological heavy metals concentrations of pregnant women as well as environmental and dietary factors that may influence exposure concentrations. One hundred and seventy three pregnant women were recruited from Western Australia, each providing a sample of blood, first morning void urine, residential soil, dust and drinking water samples. Participants also completed a questionnaire which included a food frequency component. All biological and environmental samples were analysed for heavy metals using ICP-MS. Biological and environmental concentrations of lead and mercury were generally low (Median Pb Drinking Water (DW) 0.04 µg/L; Pb soil <3.0 µg/g; Pb dust 16.5 µg/g; Pb blood 3.67 µg/L; Pb urine 0.55; µg/L Hg DW <0.03; Hg soil <1.0 µg/g; Hg dust <1.0 µg/g; Hg blood 0.46 µg/L; Hg urine <0.40 µg/L). Cadmium concentrations were low in environmental samples (Median CdDW 0.02 µg/L; Cdsoil <0.30 ug/g; Cddust <0.30) but elevated in urine samples (Median 0.55 µg/L, creatinine corrected 0.70 µg/g (range <0.2-7.06 µg/g creatinine) compared with other studies of pregnant women. Predictors of increased biological metals concentrations in regression models for blood cadmium were residing in the Great Southern region of Western Australia and not using iron/folic acid supplements and for urinary cadmium was having lower household annual income. However, these factors explained little of the variation in respective biological metals concentrations. The importance of establishing factors that influence low human exposure concentrations is becoming critical in efforts to reduce exposures and hence the potential for adverse health effects.

Maternal exposure to perfluoroalkyl acids measured in whole blood and birth outcomes in offspring.

Perfluoralkyl and polyfluoralkyl substances have been measured in plasma and serum of pregnant women as a measure of prenatal exposure. Increased concentrations of individual perfluoroalkyl acids (PFAAs), (typically perfluorooctanoic acid (PFOA) and perfluoroctane sulfonate (PFOS) have been reported to be associated with reductions in birth weight and other birth outcomes. We undertook a study of 14 PFAAs in whole blood (including PFOS, PFHxS, PFHpA, PFOA, PFNA, PFDA and PFUnDA) from 98 pregnant women in Western Australia from 2008 to 2011. Median concentrations (in µg/L) were: PFOS 1.99; PFHxS 0.33; PFOA 0.86; PFNA 0.30; PFDA 0.12 and PFUnDA 0.08. Infants born to women with the highest tertile of PFHxS exposure had an increased odds of being <95% of their optimal birth weight (OR 3.5, 95% CI 1.1-11.5). Conversely, maternal blood concentrations of PFUnDA were associated with non-significant increases in average birth weight (+102g, 95% CI -41, 245) and significant increases in proportion of optimal birth weight (+4.7%, 95% CI 0.7, 8.8) per ln-unit change. This study has reported a range of PFAAs in the whole blood of pregnant women and suggests that PFHxS and PFUnDA may influence foetal growth and warrant further attention. Additional studies are required to identify the sources of PFAA exposure with a view to prevention, in addition to further studies investigating the long term health effects of these ubiquitous chemicals.

Investigation of the relationship between low environmental exposure to metals and bone mineral density, bone resorption and renal function.

Environmental exposure to metals has been linked to adverse health outcomes. Exposure to cadmium has been associated with decreased bone density, an increased risk of osteoporotic fracture and possible renal dysfunction. Older women are a group at risk of renal and bone density impacts and exposure to metals may be an important risk factor for these health outcomes. This study was a cross sectional study of 77 women aged 50 years and above examining the relationship between metals exposure and renal and bone health. Urinary and blood metals concentrations, plasma creatinine, iron, ferritin and transferrin were measured in these subjects. Bone biomarkers assessed included the pyridinium crosslinks, pyridinoline and deoxypyridinoline measured by ELISA. Renal function was assessed using eGFR and KIM-1. Whole body, hip and lumbar spine bone mineral density was assessed using DEXA. Blood and urinary metals concentrations were generally low in the subjects, with a median urinary cadmium concentration of 0.26 µg/g creatinine (range <0.065-1.03 µg/g). Urinary cadmium was found to be a significant predictor of bone mineral density at whole body, lumber spine, total hip and femoral neck, with increasing urinary Cd concentrations associated with decreased bone density. Urinary cadmium and aluminium concentrations were positively correlated with bone resorption whilst blood zinc and mercury concentrations were negatively correlated. Urinary aluminium was positively correlated with KIM-1 concentrations, a marker of early kidney damage, however blood zinc concentrations were significantly negatively correlated with this biomarker. This study provides additional support for low cadmium exposure being of concern for the health of older women. Further investigation into the role of exposure to other metals on bone and renal health is warranted.

Maternal exposure to alkali, alkali earth, transition and other metals: Concentrations and predictors of exposure.

Most studies of metals exposure focus on the heavy metals. There are many other metals (the transition, alkali and alkaline earth metals in particular) in common use in electronics, defense industries, emitted via combustion and which are naturally present in the environment, that have received limited attention in terms of human exposure. We analysed samples of whole blood (172), urine (173) and drinking water (172) for antimony, beryllium, bismuth, cesium, gallium, rubidium, silver, strontium, thallium, thorium and vanadium using ICPMS. In general most metals concentrations were low and below the analytical limit of detection with some high concentrations observed. Few factors examined in regression models were shown to influence biological metals concentrations and explained little of the variation. Further study is required to establish the source of metals exposures at the high end of the ranges of concentrations measured and the potential for any adverse health impacts in children.

Multimodal contribution to speech perception revealed by independent component analysis: a single-sweep EEG case study.

In this single-sweep electroencephalographic case study, independent component analysis (ICA) was used to investigate multimodal processes underlying the enhancement of speech intelligibility in noise (for monosyllabic English words) by visualizing facial motion concordant with the audio speech signal. Wavelet analysis of the single-sweep IC activation waveforms revealed increased high-frequency energy for two ICs underlying the visual enhancement effect. For one IC, current source density analysis localized activity mainly to the superior temporal gyrus, consistent with principles of multimodal integration. For the other IC, activity was distributed across multiple cortical areas perhaps reflecting global mappings underlying the visual enhancement effect.

Single-sweep EEG analysis of neural processes underlying perception and production of vowels.

This single-sweep electroencephalographic study using independent component analysis was conducted to determine the neural processes underlying both speech perception and production of vowels. The same neural processes located in auditory and motor areas of the brain that significantly distinguish between a speech production and a control mental rehearsal task were found for both auditory evoked responses and speech planning responses. Thus identifying common task dependent neural processes underlying speech production and perception.

The effects of benzodiazepines on hormones in women with idiopathic hirsutism.

A single blind study was planned to investigate whether benzodiapines would reduce androgens in women with idiopathic hirsutism. Placebo was given for the first month followed by four months of a benzodiazepine (chlorazepate 15 mg nocte or diazepam 10 mg nocte ). Plasma samples were collected during the follicular and luteal phases of each therapy month. Hair growth was assessed monthly. Eighteen women concluded the five months of the trial of whom ten received chlorazepate and eight diazepam. Comparison of follicular plasma samples during the placebo phase and fourth month of benzodiazepine found a significant increase in sex hormone binding globulin and a significant decrease in dehydroepiandrosterone sulphate with benzodiazepine therapy. No significant effects on hair growth were observed. A longer therapy time may be needed to demonstrate effects of benzodiapines on hirsutism. Further studies are needed to determine whether benzodiazepines affect hormonal parameters in normal men and women.

Schizophrenia in Afro-Caribbean immigrants.

Hospital admission rates for schizophrenia are higher in Afro-Caribbean immigrants to Britain than in the white British-born population. However, the reported differences in incidence and prevalence could be due to confounding variables: the diagnosis of schizophrenia might not carry the same prognostic implications in the two groups; and the differences in formal admission rates might not persist when demographic and diagnostic differences are allowed for. The case-notes of 50 Afro-Caribbean immigrants and 41 British-born white patients with a hospital diagnosis of schizophrenia were examined retrospectively, the average period covered being 12 years. There were no differences in the number of readmissions, but in the Afro-Caribbean group readmissions were shorter. Involuntary admissions were twice as common in Afro-Caribbeans and this excess was not explained by differences in age, sex, or type of illness. The reported excess of schizophrenia in Afro-Caribbean immigrants to Britain is real, but the illness seems to run a milder course than in the white British-born population.

Patient satisfaction: ethnic origin or explanatory model?

Despite concern over their psychiatric treatment, little is known about black and ethnic minority patient satisfaction with psychiatric services and whether perceived 'ethnicity' or discrepant understanding of illness experience is most relevant. Twenty-one white British and 63 ethnic minority patients were interviewed for their opinions on psychiatric in-patient care, their treatment preferences and their explanatory models of their illness. The most significant association with satisfaction was not ethnic origin but the patient's explanatory model of their illness which showed little association with ethnicity whether patients were voluntary or involuntary. Satisfaction is most likely when there is concordance between the patient's and psychiatrist's explanatory model.

Polychlorinated biphenyl (PCB) and dioxin concentrations in residential dust of pregnant women.

Polychlorinated biphenyls (PCBs) and dioxins are well known for their persistence in the environment. PCBs can be found in the residential environment long after the use of these chemicals in domestic products and industrial processes has ceased. Dioxins have been assessed in Australia as being of very low concentrations. Despite concerns about residential dust as a source of human exposure to persistent chemicals, there has been limited testing of PCBs and dioxins in dust in Australia. As part of an assessment of maternal exposure to a variety of persistent toxic substances, we analysed 30 residential dust samples from a variety of geographical settings for their dioxin and PCB concentrations. PCBs were found in most samples, the median and range concentrations (pg g(-1)) of dominant congeners of PCB were as follows: PCB118 (315; <35.0-29 000), PCB105 (130; 14.0-16 000) and PCB156 (440; <5.00-2800). Dioxin concentrations were generally low with median concentrations for the total sum of dioxin-like polychlorinated dibenzodioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs) of 3.75 pg g(-1) each. There was a very high percentage of non-detects. Concentrations of both PCBs and dioxins were low compared with most studies reporting residential dust concentrations internationally. Age of dwelling was the only factor observed to influence both PCB congener concentrations and dioxin isomers in multivariate regression analyses. No other housing or sociodemographic variables, including proximity to industry, were important predictors in multivariate linear regression models.

Management of hirsutism.

PIP: This discussion of the management of hirsutism focuses on clinical assessment, investigations, evaluation of treatment methods, therapeutic regimens, medical therapy, cosmetic therapy, and supportive therapy for hirsute women. Initial clinical evaluation of the hirsute woman should consider the site, type, and extent or area of hair growth as well as age of onset and rate of appearance. In part what is normal is determined by societal attitudes and cultural norms, and it may be that a woman seeking treatment for hirsutism is simply over concerned by a normal growth pattern. A well defined coarse growth of hair on the chin and cheeks of sudden onset at any age suggests an underlying endocrine problem, whereas women with fine downy facial hair, even when this is extensive, are less likely to have an endocrine disturbance than those with a coarse growth. Data about family history, ethnic background, age of onset, and rate of appearance will help identify those cases needing more detailed investigation. Physical examination included pelvic examination to exclude ovarian enlargement and examination of genitals to exclude clitoral hypertrophy together with assessment of the overall severity of hirsutism will further define those patients who require further investigation. Urinary 24 hour 17 ketosteroid excretion and plasma androgens should be estimated as a baseline investigation to identify those patients whose hirsutism is due to androgen secreting tumors or adrenal hyperplasia. Testosterone production rate and testosterone metabolic clearance rate have been shown to be well increased in hirsute women and to correlate well with severity of hirsutism. In certain patients laboratory evidence may suggest either the ovaries or the adrenals as the major source of androgen excess. The ideal response to treatment is reduced growth rate and reversion of coarse, dark, terminal hair to a lighter, more downy growth. There is no uniformly reliable, simple, objective method of assessing response to therapy. The aim of medical therapy for idiopathic hirsutism is suppression or inhibition of androgen effect. Cosmetic therapy aims to minimize or remove the excess hair either temporarily or permanently. There are 2 types of medical therapy--suppressive therapy and antiandrogen therapy. In suppressive therapy, treatment regimens suppress abnormal plasma androgen levels. Antiandrogen therapy counteracts the effect of androgens at the hair follicles. Some form of cosmetic therapy is almost always needed in conjunction with the various forms of medical therapy. Cosmetic treatments include camouflage by bleaching and various mechanical means of removing the hair temporarily or permanently.^ieng

Institutionalizing social support through the church and into the community.

The positive influence of social support on such health related outcomes as patient adherence to medical regimens and stress reduction at the worksite has captured the attention of public health researchers and practitioners alike. Yet, the broader social outcome of building community competency to undertake and sustain health related solutions without constant intervention from professionals still remains elusive. The difficulty may lie with the need to uncover on each occasion the various roles and functions of social support structures that may or may not exist in a given community. The intent would then be to graft an intervention onto these existing roles and functions in order to mirror the naturally occurring social support structures. A conceptual framework that has been used to institutionalize health related activities through the role and function of the black Church, as a social unit of identity and solution for rural black communities in North Carolina, is put forth for consideration.

Female androgenetic alopecia: an update.

Androgenetic alopecia is an androgen dependent disorder occurring in genetically susceptible individuals. The pattern of hair loss in women differs from that of classical male pattern alopecia, being more diffuse and with retention of the frontal hair line in most cases. Characteristic histopathological changes occur but biopsy is rarely helpful in diagnosis. Although research has shown subtle alterations in the androgen status of women with androgenetic alopecia, most patients presenting with this disorder are normal endocrinologically. Anti-androgen therapy will result in some improvement in up to 50% of patients after 6 to 12 months of therapy, but in practice will usually only decrease the rate of hair loss and not result in new hair growth.

Effects of joint lavage on knee synovitis in rheumatoid arthritis.

Ten patients with rheumatoid arthritis and persistent knee synovitis had synovial fluid aspirated through a 14 gauge wide-bore needle followed by joint lavage and intra-articular triamcinolone. This resulted in the removal of variable quantities of intra-articular debris including rice bodies. When compared to a control group of patients, the addition of joint lavage to the standard procedure of aspiration and injection of corticosteroid resulted in more sustained resolution of synovitis after 12 weeks as judged by knee tenderness and circumference, recurrence of effusion, and synovial fluid leucocyte count. This study suggests that knee joint lavage may be a useful adjunct to therapy in rheumatoid arthritis patients having persistent knee synovitis.

Serum C-19 steroid sulphates in females with clinical hyperandrogenism.

Serum sulphates of 5-androstene-3 beta, 17 beta-diol (5-ADIOL-S), 5 alpha-androstane-3 alpha,17 beta-diol (3 alpha-DIOL-S) and dehydroepiandrosterone (DHEA-S), as well as unconjugated androstenedione (AD), testosterone (T) and 17 alpha-hydroxyprogesterone (17OHP), sex hormone binding globulin (SHBG) and the free androgen index (FAI) were measured by specific radioimmunoassay in girls with premature adrenarche (n = 9-16), and in hirsute women with (1) late onset 21 hydroxylase deficiency (n = 14), (2) polycystic ovarian disease (n = 28) and (3) idiopathic hirsutism (n = 74). Levels were also determined in females with androgenic alopecia (n = 35-45), in normal prepubertal girls (n = 9-14) and in normal adult women (n = 50-73). Mean serum concentrations of 5-ADIOL-S, 3 alpha-DIOL-S, DHEA-S, AD, T, and FAI were elevated and SHBG depressed, in all patient groups compared with controls, except for DHEA-S and T in patients with alopecia. We conclude that in addition to DHEA-S, 5-ADIOL-S may have a role as a pro-hormone in the synthesis of more potent androgens (T, DHT) in peripheral tissues such as skin; in addition, 3 alpha-DIOL-S may be a marker of peripheral androgen metabolism.

Plasma C19 steroid sulphate levels and indices of androgen bioavailability in female pattern androgenic alopecia.

Female pattern androgenic alopecia (AA) is a relatively common endocrine abnormality in premenopausal women. However, unlike hirsutism, little is known about the androgen metabolism and plasma C19 steroid sulphate profiles in this disorder. We have therefore measured the plasma levels of dehydroepiandrosterone sulphate (DHEA-S), 5-androstene-3 beta,17 beta-diol sulphate (5-ADIOL-S), 5 alpha-androstane-3 alpha, 17 beta-diol sulphate (3 alpha-DIOL-S), androstenedione (AD), total testosterone (T), free testosterone (FT), sex hormone binding globulin (SHBG), non-SHBG bound T, luteinizing hormone (LH) and follicle stimulating hormone (FSH), and have calculated the free androgen index (FAI): 100 x T (nmol/l) divided by SHBG (nmol/l), in premenopausal women with AA (n = 25-45) and in normal premenopausal women (n = 17-73). While mean plasma concentrations of DHEA-S and T were not significantly different from controls, mean SHBG concentrations were significantly lower (47 +/- 3 vs 64 +/- 3 nmol/l) and the mean free androgen index (4.4 +/- 0.4 vs 2.4 +/- 0.2), and mean concentrations of free testosterone (45 +/- 5 vs 26 +/- 1.4 pmol/l), non-SHBG bound T (0.9 +/- 0.2 vs 0.6 +/- 0.1 nmol/l) and androstenedione (4.3 +/- 0.3 vs 3.4 +/- 0.2 nmol/l) were significantly elevated in women with AA. Furthermore, mean plasma concentrations of 5-ADIOL-S (512 +/- 42 nmol/l) and 3 alpha-DIOL-S (76 +/- 7 nmol/l) were significantly higher than levels found in normal women (272 +/- 12 nmol/l and 52 +/- 2 nmol/l respectively). The nature of the hyperandrogenism associated with AA may thus only be revealed by a comprehensive plasma androgen and androgen sulphate profile, which may explain apparently aberrant data for a given patient. In addition, 5-ADIOL-S and 3 alpha-DIOL-S may serve as excellent plasma markers of both the existence of the disorder and the efficacy of its treatment.