Visuospatial Processing Deficits Linked to Posterior Brain Regions in Premanifest and Early Stage Huntington's Disease.

OBJECTIVES: Visuospatial processing deficits have been reported in Huntington's disease (HD). To date, no study has examined associations between visuospatial cognition and posterior brain findings in HD. METHODS: We compared 119 premanifest (55> and 64<10.8 years to expected disease onset) and 104 early symptomatic (59 stage-1 and 45 stage-2) gene carriers, with 110 controls on visual search and mental rotation performance at baseline and 12 months. In the disease groups, we also examined associations between task performance and disease severity, functional capacity and structural brain measures. RESULTS: Cross-sectionally, there were strong differences between all disease groups and controls on visual search, and between diagnosed groups and controls on mental rotation accuracy. Only the premanifest participants close to onset took longer than controls to respond correctly to mental rotation. Visual search negatively correlated with disease burden and motor symptoms in diagnosed individuals, and positively correlated with functional capacity. Mental rotation ("same") was negatively correlated with motor symptoms in stage-2 individuals, and positively correlated with functional capacity. Visual search and mental rotation were associated with parieto-occipital (pre-/cuneus, calcarine, lingual) and temporal (posterior fusiform) volume and cortical thickness. Longitudinally, visual search deteriorated over 12 months in stage-2 individuals, with no evidence of declines in mental rotation. CONCLUSIONS: Our findings provide evidence linking early visuospatial deficits to functioning and posterior cortical dysfunction in HD. The findings are important since large research efforts have focused on fronto-striatal mediated cognitive changes, with little attention given to aspects of cognition outside of these areas. (JINS, 2016, 22, 595-608)

AIDS prevention in South Africa

No abstract available

New hyperekplexia mutations provide insight into glycine receptor assembly, trafficking, and activation mechanisms

Background: Hyperekplexia mutations have provided much information about glycine receptor structure and function. Results: Weidentified and characterized nine new mutations. Dominant mutations resulted in spontaneous activation, whereas recessive mutations precluded surface expression. Conclusion: These data provide insight into glycine receptor activation mechanisms and surface expression determinants. Significance: The results enhance our understanding of hyperekplexia pathology and glycine receptor structure-function. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc. Published in the U.S.A

Guidelines to support HIV-affected individuals and couples to achieve pregnancy safely: Update 2018

No abstract available

The Meso-Structured Magnetic Atmosphere -- A Stochastic Polarized Radiative Transfer Approach

We present a general radiative transfer model which allows the Zeeman diagnostics of complex and unresolved solar magnetic fields. Present modeling techniques still rely to a large extent on a-priori assumptions about the geometry of the underlying magnetic field. In an effort to obtain a more flexible and unbiased approach we pursue a rigorous statistical description of the underlying atmosphere. Based on a Markov random field model the atmospheric structures are characterized in terms of probability densities and spatial correlations. This approach allows us to derive a stochastic transport equation for polarized light valid in a regime with an arbitrary fluctuating magnetic field on finite scales. One of the key ingredients of the derived stochastic transfer equation is the correlation length which provides an additional degree of freedom to the transport equation and can be used as a diagnostic parameter to estimate the characteristic length scale of the underlying magnetic field. It is shown that the stochastic transfer equation represents a natural extension of the (polarized) line formation under the micro- and macroturbulent assumption and contains both approaches as limiting cases. In particular, we show how in an inhomogeneous atmosphere asymmetric Stokes profiles develop and that the correlation length directly controls the degree of asymmetry and net circular polarization (NCP). In a number of simple numerical model calculations we demonstrate the importance of a finite correlation length for the polarized line formation and its impact on the resulting Stokes line profiles

A comparison of nutritional intake and daily physical activity of girls aged 8-11 years old in Makkah, Saudi Arabia according to weight status

Abstract Background Obesity rates in Saudi Arabia are amongst the highest in the world. It is known that teenage girls are less active than teenage boys, but less is known about the diet and activity patterns in younger girls. Therefore this study sought to investigate dietary intake and daily physical activity in girls aged 8-11 years old in Saudi Arabia. Methods This was a cross- sectional observational study conducted in seven schools across the city of Makkah. A total of 266 girls had anthropometric measurements taken including height, weight, waist circumference and body fat estimations. Dietary assessment using a 4 day unweighed diet diary was undertaken in 136 of these participants, and 134 agreed to monitor their physical activity for the 4 days using an accelerometer. After exclusion for under-reporting, 109 remained in the dietary analysis and 78 in the physical activity analyses. Differences in means between BMI groups were determined using one-way ANOVA with post hoc Tukey test. Multivariable linear regression analysis was performed to look at the effect of multiple variables on body weight. Results A total of 30% of participants were classified obese or overweight. There was a significant difference in the mean daily energy intake between the BMI groups with the obese group having the highest energy, fat, carbohydrate and protein intake (obese group: 2677 ± 804 kcal/d; healthy weight group: 1806 ± 403 kcal/d, p < 0.001), but the percentage contribution of the macronutrients to energy intake remained the same across the BMI groups. There were no differences in number of steps taken per day or time spent in moderate to vigorous intensity exercise according to BMI category. Most of the girls did not meet daily physical activity guidelines (5969 to 6773 steps per day and 18.5 - 22.5 mins per day of moderate to vigorous activity). Multiple linear regression showed that energy intake positively predicted body weight (Beta = 0.279, p =0 .001), whereas, total energy expenditure per kg of body weight and family income had a significant negative influence on body weight (Beta = −0.661, p < 0.001; −0.131, p = 0.028 respectively). Conclusions The results of this cross sectional analysis suggest that obesity in girls aged 8-11 years is linked to excessive energy intake from all macronutrients and the majority of girls in all weight categories are inactive. Research should be conducted to further investigate causal relationships in longitudinal studies and develop interventions to promote dietary change and activity that is culturally acceptable for girls in Saudi Arabia

Detection of motor changes in huntington's disease using dynamic causal modeling

Deficits in motor functioning are one of the hallmarks of Huntington's disease (HD), a genetically caused neurodegenerative disorder. We applied functional magnetic resonance imaging (fMRI) and dynamic causal modeling (DCM) to assess changes that occur with disease progression in the neural circuitry of key areas associated with executive and cognitive aspects of motor control. Seventy-seven healthy controls, 62 pre-symptomatic HD gene carriers (preHD), and 16 patients with manifest HD symptoms (earlyHD) performed a motor finger-tapping fMRI task with systematically varying speed and complexity. DCM was used to assess the causal interactions among seven pre-defined regions of interest, comprising primary motor cortex, supplementary motor area (SMA), dorsal premotor cortex, and superior parietal cortex. To capture heterogeneity among HD gene carriers, DCM parameters were entered into a hierarchical cluster analysis using Ward's method and squared Euclidian distance as a measure of similarity. After applying Bonferroni correction for the number of tests, DCM analysis revealed a group difference that was not present in the conventional fMRI analysis. We found an inhibitory effect of complexity on the connection from parietal to premotor areas in preHD, which became excitatory in earlyHD and correlated with putamen atrophy. While speed of finger movements did not modulate the connection from caudal to pre-SMA in controls and preHD, this connection became strongly negative in earlyHD. This second effect did not survive correction for multiple comparisons. Hierarchical clustering separated the gene mutation carriers into three clusters that also differed significantly between these two connections and thereby confirmed their relevance. DCM proved useful in identifying group differences that would have remained undetected by standard analyses and may aid in the investigation of between-subject heterogeneity

T-cell regulation in Erythema Nodosum Leprosum.

Leprosy is a disease caused by Mycobacterium leprae where the clinical spectrum correlates with the patient immune response. Erythema Nodosum Leprosum (ENL) is an immune-mediated inflammatory complication, which causes significant morbidity in affected leprosy patients. The underlying cause of ENL is not conclusively known. However, immune-complexes and cell-mediated immunity have been suggested in the pathogenesis of ENL. The aim of this study was to investigate the regulatory T-cells in patients with ENL. Forty-six untreated patients with ENL and 31 non-reactional lepromatous leprosy (LL) patient controls visiting ALERT Hospital, Ethiopia were enrolled to the study. Blood samples were obtained before, during and after prednisolone treatment of ENL cases. Peripheral blood mononuclear cells (PBMCs) were isolated and used for immunophenotyping of regulatory T-cells by flow cytometry. Five markers: CD3, CD4 or CD8, CD25, CD27 and FoxP3 were used to define CD4+ and CD8+ regulatory T-cells. Clinical and histopathological data were obtained as supplementary information. All patients had been followed for 28 weeks. Patients with ENL reactions had a lower percentage of CD4+ regulatory T-cells (1.7%) than LL patient controls (3.8%) at diagnosis of ENL before treatment. After treatment, the percentage of CD4+regulatory T-cells was not significantly different between the two groups. The percentage of CD8+ regulatory T-cells was not significantly different in ENL and LL controls before and after treatment. Furthermore, patients with ENL had higher percentage of CD4+ T-ells and CD4+/CD8+ T-cells ratio than LL patient controls before treatment. The expression of CD25 on CD4+ and CD8+ T-cells was not significantly different in ENL and LL controls suggesting that CD25 expression is not associated with ENL reactions while FoxP3 expression on CD4+ T-cells was significantly lower in patients with ENL than in LL controls. We also found that prednisolone treatment of patients with ENL reactions suppresses CD4+ T-cell but not CD8+ T-cell frequencies. Hence, ENL is associated with lower levels of T regulatory cells and higher CD4+/CD8+ T-cell ratio. We suggest that this loss of regulation is one of the causes of ENL