46,XY disorders of sex development (DSD)

The term disorders of sex development (DSD) includes congenital conditions in which development of chromosomal, gonadal or anatomical sex is atypical. Mutations in genes present in X, Y or autosomal chromosomes can cause abnormalities of testis determination or disorders of sex differentiation leading to 46,XY DSD. Detailed clinical phenotypes allow the identification of new factors that can alter the expression or function of mutated proteins helping to understand new undisclosed biochemical pathways. In this review we present an update on 46,XY DSD aetiology, diagnosis and treatment based on extensive review of the literature and our three decades of experience with these patients.

The prevalence and significance of periodic leg movements during sleep in patients with congestive heart failure

The aim of this study was to evaluate (1) the prevalence of periodic leg movements during sleep (PLMs) in a consecutive sample of congestive heart failure (CHF) outpatients; (2) the presence of correlation between PLMs, subjective daytime sleepiness, and sleep architecture; and (3) the heart rate response to PLMs in CHF. Seventy-nine [50 men, age 59 +/- 11 years, body mass index (BMI) 26 +/- 5 kg/m(2)] consecutive adult stable outpatients with CHF [left ventricular ejection fraction (LVEF) 36 +/- 6%] were prospectively evaluated. The patients underwent assessment of echocardiography, sleepiness (Epworth Scale), and overnight in-lab polysomnography. Fifteen patients (19%) had PLM index > 5. These subjects were similar in sex distribution, BMI, subjective somnolence, LVEF, and apnea-hypopnea index (AHI), but were significantly older than subjects without PLMs. Sleep architecture was similar in subjects with and without PLMs. There was a small but significant elevation of heart rate after PLMs (80.1 +/- 9.4 vs. 81.5 +/- 9.2; p < 0.001). The cardiac acceleration was also present in absence of electroencephalogram activation. The prevalence of PLMs in consecutive sample of adult CHF outpatients was 19%. There were no differences in subjective daytime sleepiness, sleep architecture, AHI, and severity of CHF in subjects with and without PLMs. PLMs caused a small but statistically significant cardiac acceleration.

Effects of Perilipin (PLIN) Gene Variation on Metabolic Syndrome Risk and Weight Loss in Obese Children and Adolescents

Context: Genetic polymorphisms at the perilipin (PLIN) locus have been investigated for their potential utility as markers for obesity and metabolic syndrome (MS). We examined in obese children and adolescents (OCA) aged 7-14 yr the association of single-nucleotide polymorphisms (SNP) at the PLIN locus with anthropometric, metabolic traits, and weight loss after 20-wk multi-disciplinary behavioral and nutritional treatment without medication. Design: A total of 234 OCA [body mass index (BMI = 30.4 +/- 4.4 kg/m(2); BMI Z-score = 2.31 +/- 0.4) were evaluated at baseline and after intervention. We genotyped four SNPs (PLIN1 6209T -> C, PLIN4 11482G -> A, PLIN5 13041A -> G, and PLIN6 14995A -> T). Results: Allele frequencies were similar to other populations, PLIN1 and PLIN4 were in linkage disequilibrium (D` = 0.999; P < 0.001). At baseline, no anthropometric differences were observed, but minor allele A at PLIN4 was associated with higher triglycerides (111 +/- 49 vs. 94 +/- 42 mg/dl; P = 0.003), lower high-density lipoprotein cholesterol (40 +/- 9 vs. 44 +/- 10 mg/dl; P = 0.003) and higher homeostasis model assessment for insulin resistance (4.0 +/- 2.3 vs. 3.5 +/- 2.1; P +/- 0.015). Minor allele A at PLIN4 was associated with MS risk (age and sex adjusted) hazard ratio 2.4 (95% confidence interval = 1.1-4.9) for genotype GA and 3.5 (95% confidence interval = 1.2-9.9) for AA. After intervention, subjects carrying minor allele T at PLIN6 had increased weight loss (3.3 +/- 3.7 vs. 1.9 +/- 3.4 kg; P = 0.002) and increased loss of the BMI Z-score (0.23 +/- 0.18 vs. 0.18 +/- 0.15; P +/- 0.003). Due to group size, risk of by-chance findings cannot be excluded. Conclusion: The minor A allele at PLIN4 was associated with higher risk of MS at baseline, whereas the PLIN6 SNP was associated with better weight loss, suggesting that these polymorphisms may predict outcome strategies based on multidisciplinary treatment for OCA. (J Clin Endocrinol Metab 93: 4933-4940, 2008)

Influence of gender on the clinical and laboratory spectra of patients with primary antiphospholipid syndrome

The objectives of this cross-sectional study were to evaluate the differences between males and females in the clinical and biochemical manifestations of primary antiphospholipid antibody syndrome (PAPS). The method involved 49 patients (38 premenopausal females and 11 males) diagnosed with PAPS (according to the Sapporo criteria) and their demographic data, clinical data, medications used and antiphospholipid antibodies were analyzed. The results of this study are as follows. Both the groups of patients were statistically similar regarding age, race, weight and body mass index. However, males were significantly taller than females (172 +/- A 8.9 vs. 159.2 +/- A 6.2 cm, p < 0.0001). The duration of disease was similar for females and males. The prevalence of pulmonary thromboembolism was higher in females than in males (34.2 vs. 0.0%, p = 0.024). Regarding other PAPS manifestations (arterial events, venous events, deep venous thrombosis, thrombocytopenia, acute myocardial infarction, angina, cerebrovascular accidents and Sneddon syndrome), comorbidities (arterial hypertension and dyslipidemia), lifestyle (physical activity, previous smoking and current smoking) and the use of medications (current and previous use of corticosteroids, as well as the use of statins or chloroquine), both groups were statistically similar (p > 0.05). More females than males tested positive for IgM anticardiolipin antibodies (76.3 vs. 36.4%, p = 0.025) or for at least one of the antiphospholipid antibodies tested (either IgM anticardiolipin or IgG anticardiolipin 84.2 vs. 45.5%, p = 0.016). However, both groups were similar regarding the frequency of positivity for lupus anticoagulant and isolated IgG anticardiolipin, as well as regarding mean levels of IgG and IgM anticardiolipin (p > 0.05). We concluded that, among PAPS patients, the frequency of pulmonary thromboembolism and of positivity for IgM anticardiolipin is higher in females than in males. Our findings show that there are gender differences in PAPS, differences that might be related to alterations in sex hormones.

Gender differences in work satisfaction

This paper explores differences between men and women in levels of work satisfaction, employing data from the Australian component of the International Project on Class Structure and Class Consciousness. While moment tend to be concentrated in low-status, low-paid positions, that is the secondary labour market, the data suggest that, in general, they are more satisfied with paid employment than men. Employment constraints are found to be a key factor in the observed differences in levels of work satisfaction. For both groups, however, it is clear that work satisfaction derives primarily from work-related factors.

Neutrophil depletion increases susceptibility to systemic and vaginal candidiasis in mice, and reveals differences between brain and kidney in mechanisms of host resistance

Infections caused by the yeast Candida albicans represent an increasing threat to debilitated and immunosuppressed patients, and neutropenia is an important risk factor. Monoclonal antibody depletion of neutrophils in mice was used to study the role of these cells in host resistance. Ablation of neutrophils increased susceptibility to both systemic and vaginal challenge. The fungal burden in the kidney increased threefold on day 1, and 100-fold on day 4, and infection was associated with extensive tissue destruction. However, a striking feature of the disseminated disease in neutrophil-depleted animals was the altered pattern of organ involvement. The brain, which is one of the primary target organs in normal mice, was little affected. There was a threefold increase in the number of organisms recovered from the brains of neutrophil-depleted mice on day 4 after infection, but detectable abscesses were rare. In contrast, the heart, which in normal mice shows only minor lesions, developed severe tissue damage following neutrophil depletion. Mice deficient in C5 demonstrated both qualitative and quantitative increases in the severity of infection after neutrophil depletion when compared with C5-sufficient strains. The results are interpreted as reflecting organ-specific differences in the mechanisms of host resistance.

Psychosocial pathways to inconsistent condom use among male sex workers: personality, drug misuse and criminality

Background: This research compared street male sex workers in Santo Andre, Brazil, that reported consistent condom use with those that revealed inconsistent condom use with their clients, concerning personality aspects, impulsiveness, alcohol and drug consumption, depressive symptoms, sociodemographic data and criminal involvement. Methods: Eighty-six male sex workers were evaluated in face-to-face interviews at their place of work. A `snowball` sampling procedure was used to access this hard-to-reach population. Findings: Male sex workers with inconsistent condom use showed greater involvement with criminal activities, higher reward dependence level and more frequent self-report of being HIV-positive. Conclusions: Conceptualisation of male sex workers` psychological characteristics may be required where HIV risk is not only attributed to sex work per se, but to other aspects such as personality-related factors and negative identity.

The Role of SRY Mutations in the Etiology of Gonadal Dysgenesis in Patients with 45,X/46,XY Disorder of Sex Development and Variants

Background: The potential involvement of SRY in abnormal gonadal development in 45,X/46,X,der(Y) patients was proposed following the identification of SRY mutations in a few patients with Turner syndrome (TS). However, its exact etiological role in gonadal dysgenesis in patients with Y chromosome mosaicisms has not yet been clarified. Aims: It was the aim of this study to screen for allelic variation in SRY in a large cohort of patients with disorders of sex development due to chromosomal abnormalities with 45, X/46, X, der(Y) karyotype. Patients: Twenty-seven patients, 14 with TS and 13 with mixed gonadal dysgenesis (MGD), harboring 45, X/46, X, der(Y) karyotypes were selected. Methods: Genomic DNA was extracted from peripheral blood leukocytes of all patients and from gonadal tissue in 4 cases. The SRY coding region was PCR amplified and sequenced. Results: We identified only 1 polymorphism (c.561C -> T) in a 45,X/46,XY MGD patient, which was detected in blood and in gonadal tissue. Conclusion: Our results indicate that mutations in SRY are rare findings in patients with Y chromosome mosaicisms. Therefore, a significant role of mutated SRY in the etiology of gonadal dysgenesis in patients harboring 45, X/46, XY karyotype and variants seems very unlikely. Copyright (C) 2010 S. Karger AG, Basel

Response programming in dementia of the Alzheimer type: A kinematic analysis

Although planning is important for the functioning of patients with dementia of the Alzheimer Type (DAT), little is known about response programming in DAT. This study used a cueing paradigm coupled with quantitative kinematic analysis to document the preparation and execution of movements made by a group of 12 DAT patients and their age and sex matched controls. Participants connected a series of targets placed upon a WACOM SD420 graphics tablet, in response to the pattern of illumination of a set of light emitting diodes (LEDs). In one condition, participants could programme the upcoming movement, whilst in another they were forced to reprogramme this movement on-line (i.e. they were not provided with advance information about the location of the upcoming target). DAT patients were found to have programming deficits, taking longer to initiate movements; particularly in the absence of cues. While problems spontaneously programming a movement might cause a greater reliance upon on-line guidance, when both groups were required to guide the movement on-line, DAT patients continued to show slower and less efficient movements implying declining sensori-motor function; these differences were not simply due to strategy or medication status. (C) 1997 Elsevier Science Ltd.

Worse renal outcome of lupus nephritis in male patients: a case-control study

Background: Progression and long-term renal outcome of lupus nephritis (LN) in male patients is a controversial subject in the literature. The aim of this study was to evaluate the influence of male gender on the renal outcome of LN. Methods: All male (M) LN patients who fulfilled American College of Rheumatology lupus criteria and who were referred for a kidney biopsy from 1999 to 2009 were enrolled in the study. Subjects with end-stage renal disease at baseline, or follow-up time below 6 months, were excluded. Cases were randomly matched to female (F) patients according to the class of LN, baseline estimated glomerular filtration rate (eGFR, Modification of Diet in Renal Disease simplified formula) and follow-up time. Treatment was decided by the clinical staff based on usual literature protocols. The primary endpoint was doubling of serum creatinine and/or end-stage renal disease. The secondary endpoint was defined as a variation of glomerular filtration rate (GFR) per year (Delta GFR/y index), calculated as the difference between final and initial eGFR adjusted by follow-up time for each patient. Results: We included 93 patients (31 M : 62 F). At baseline, M and F patients were not statistically different regarding WHO LN class (II 9.7%, IV 71%, V 19.3%), eGFR (M 62.4 +/- 36.4 ml/min/1.73 m(2) versus F 59.9 +/- 32.7 ml/min/1.73 m(2)), follow-up time (M 44.2 +/- 27.3 months versus F 39.9 +/- 27.9 months), and 24-hour proteinuria (M 5.3 +/- 4.6 g/day versus F 5.2 +/- 3.0 g/day), as well as age, albumin, C3, antinuclear antibody, anti-DNA antibody and haematuria. There was no difference in the primary outcome (M 19% versus F 13%, log-rank p = 0.62). However, male gender was significantly associated with a worse renal function progression, as measured by Delta GFR/y index (beta coefficient for male gender -12.4, 95% confidence interval -22.8 to -2.1, p = 0.02). The multivariate linear regression model showed that male gender remained statistically associated with a worse renal outcome even after adjustment for eGFR, proteinuria, albumin and C3 complement at baseline. Conclusion: In our study, male gender presented a worse evolution of LN (measured by an under GFR recovering) when compared with female patients with similar baseline features and treatment. Factors that influence the progression of LN in men and sex-specific treatment protocols should be further addressed in new studies. Lupus (2011) 20, 561-567.

Increased tissue resistance in the nude mouse against Candida albicans without altering strain-dependent differences in susceptibility

Strain differences in tissue responses to infection with Candida albicans were examined in nude mice having susceptible (CBA/CaH) and resistant (BALB/c) parentage. Homozygous (nu/nu) mice of both strains were more resistant to systemic infection with C. albicans than heterozygous (nu/+) littermates as indicated by a reduction in both the severity of tissue damage and colony counts in the brain and kidney. However, the tissue lesions in nu/nu CBA/CaH mice were markedly more severe than those in nu/nu mice with the BALB/c background. This pattern was reflected in the greater fungal burden in the CBA/CaH strain. Analysis of cDNA from infected tissues using a competitive polymerase chain reaction excluded interferon-gamma (IFN-gamma), tumour necrosis factor-alpha (TNF-alpha), and interleukin 6 (IL-6) as mediators of the enhanced resistance of the nude mice. The results confirm that the different patterns of lesion severity in BALB/c and CBA/CaH mice do not involve T lymphocyte-mediated pathology, and are consistent with the hypothesis that strain-dependent tissue damage is not dependent on the effector function of macrophages or their precursors.

Cortical Thickness Reduction of Normal Appearing Cortex in Patients with Polymicrogyria

OBJECTIVE To examine cortical thickness and volumetric changes in the cortex of patients with polymicrogyria, using an automated image analysis algorithm. METHODS Cortical thickness of patients with polymicrogyria was measured using magnetic resonance imaging (MRI) cortical surface-based analysis and compared with age-and sex-matched healthy subjects. We studied 3 patients with disorder of cortical development (DCD), classified as polymicrogyria, and 15 controls. Two experienced neuroradiologists performed a conventional visual assessment of the MRIs. The same data were analyzed using an automated algorithm for tissue segmentation and classification. Group and individual average maps of cortical thickness differences were produced by cortical surface-based statistical analysis. RESULTS Patients with polymicrogyria showed increased thickness of the cortex in the same areas identified as abnormal by radiologists. We also identified a reduction in the volume and thickness of cortex within additional areas of apparently normal cortex relative to controls. CONCLUSIONS Our findings indicate that there may be regions of reduced cortical thickness, which appear normal from radiological analysis, in the cortex of patients with polymicrogyria. This finding suggests that alterations in neuronal migration may have an impact in the cortical formation of the cortical areas that are visually normal. These areas are associated or occur concurrently with polymicrogyria.

Supplementation of Vitamin E, Vitamin C, and Zinc Attenuates Oxidative Stress in Burned Children: A Randomized, Double-Blind, Placebo-Controlled Pilot Study

The aim of this study was to investigate the effect of supplementation of vitamin E, vitamin C, and zinc on the oxidative stress in burned children. In a prospective double-blind placebo-controlled pilot study, 32 patients were randomized as no supplementation (n = 15) or antioxidant supplementation (n = 17) groups. Supplementation consisted of the antioxidant mixture of vitamin C (1.5 times upper intake level), vitamin E (1.35 times upper intake level), and zinc (2.0 times recommended dietary allowance) administered during 7 days starting on the second day of admittance into the hospital. Energy requirement was calculated by the Curreri equation, and protein input was 3.0 g/kg of ideal body mass index (percentile 50 degrees). Total antioxidant capacity of plasma and malondialdehyde were used to monitor oxidative stress. The time of wound healing was evaluated as the main clinical feature. Patients (age 54.2 +/- 48.9 months, 65.6% males), who exhibited 15.5 +/- 6.7% of total burn area, showed no differences in age and sex, when compared with controls. Intake of the administered antioxidants was obviously higher in treated subjects (P = .005), and serum differences were confirmed for vitamin E and C, but not for zinc (P = .180). There was a decrease in lipid peroxidation (malondialdehyde level) (P = .006) and an increase in vitamin E concentrations in the antioxidant supplementation group (P = .016). The time of wound healing was lower in the supplemented group (P < .001). The antioxidant supplementation through vitamin E and C and the mineral zinc apparently enhanced antioxidant protection against oxidative stress and allowed less time for wound healing. (J Burn Care Res 2009;30:859-866)

Antiretroviral Drug Resistance in a Respondent-Driven Sample of HIV-Infected Men Who Have Sex With Men in Brazil

Background: There are few studies on HIV subtypes and primary and secondary antiretroviral drug resistance (ADR) in community-recruited samples in Brazil. We analyzed HIV clade diversity and prevalence of mutations associated with ADR in men who have sex with men in all five regions of Brazil. Methods: Using respondent-driven sampling, we recruited 3515 men who have sex with men in nine cities: 299 (9.5%) were HIV-positive; 143 subjects had adequate genotyping and epidemiologic data. Forty-four (30.8%) subjects were antiretroviral therapy-experienced (AE) and 99 (69.2%) antiretroviral therapy-naive (AN). We sequenced the reverse transcriptase and protease regions of the virus and analyzed them for drug resistant mutations using World Health Organization guidelines. Results: The most common subtypes were B (81.8%), C (7.7%), and recombinant forms (6.9%). The overall prevalence of primary ADR resistance was 21.4% (i.e. among the AN) and secondary ADR was 35.8% (i.e. among the AE). The prevalence of resistance to protease inhibitors was 3.9% (AN) and 4.4% (AE); to nucleoside reverse transcriptase inhibitors 15.0% (AN) and 31.0% (AE) and to nonnucleoside reverse transcriptase inhibitors 5.5% (AN) and 13.2% (AE). The most common resistance mutation for nucleoside reverse transcriptase inhibitors was 184V (17 cases) and for nonnucleoside reverse transcriptase inhibitors 103N (16 cases). Conclusions: Our data suggest a high level of both primary and secondary ADR in men who have sex with men in Brazil. Additional studies are needed to identify the correlates and causes of antiretroviral therapy resistance to limit the development of resistance among those in care and the transmission of resistant strains in the wider epidemic.

Outbreak of vancomycin-resistant enterococci in a tertiary hospital: The lack of effect of measures directed mainly by surveillance cultures and differences in response between Enterococcus faecium and Enterococcus faecalis

To describe the effect of active surveillance to control vancomycin-resistant enterococci (VRE) after an outbreak, 549 surveillance rectal cultures were performed in 308 patients (35% positive). An educational intervention to prevent transmission was implemented. Infection and colonization by VR-Enterococcus faecalis decreased, but Enterococcus faecium persisted despite control measures. Infections by VR-E faecalis fell to zero in 2008. We observed difficulties in controlling colonization with measures directed mainly by surveillance cultures and differences between responses of E faecium and E faecalis.