Cognitive dysfunction and white matter hyperintensities in Fabry disease.

Fabry disease (FD) is an X-linked lysosomal storage disorder with multi-system involvement including cerebrovascular disease. Patients with FD also have a high risk of ischaemic stroke and TIA. White matter hyperintensities are common, but their clinical impact on cognition remains uncertain. Previous studies have examined the neuropsychological profile of FD, but have been inconclusive in part due to methodological limitations including small sample sizes. We sought to address these limitations in a case-control study of 26 patients with Fabry disease with mild to moderate disease symptoms matched with 18 healthy controls for age and premorbid intellectual level. We obtained detailed neuropsychological data and MRI neuroimaging data on the severity of white matter changes. Mood was accounted for as a possible confounder. Our results showed significant compromise of executive functions and information processing speed for the FD group. Error analyses suggested that the compromise of executive functions could not be entirely accounted for by slowed information processing speed. We demonstrated significant correlations between cognitive decline and the overall volume of white matter hyperintensities in the FD group. Our results point to significant compromise of cognition in FD even without stroke or mood difficulties. This suggests that neuropsychological assessment and rehabilitation should be routinely offered to patients with FD.

White matter integrity correlates with cognition and disease severity in Fabry disease.

Cerebral white matter pathology is a common CNS manifestation of Fabry disease, visualized as white matter hyperintensities on MRI in 42-81% of patients. Diffusion tensor imaging (DTI) MRI is a sensitive technique to quantify microstructural damage within the white matter with potential value as a disease biomarker. We evaluated the pattern of DTI abnormalities in Fabry disease, and their correlations with cognitive impairment, mood, anxiety, disease severity and plasma lyso-Gb3 levels in 31 patients with genetically proven Fabry disease and 19 age-matched healthy control subjects. We obtained average values of fractional anisotropy and mean diffusivity within the white matter and performed voxelwise analysis with tract-based spatial statistics. Using a standardized neuropsychological test battery, we assessed processing speed, executive function, anxiety, depression and disease severity. The mean age (% male) was 44.1 (45%) for patients with Fabry disease and 37.4 (53%) for the healthy control group. In patients with Fabry disease, compared to healthy controls the mean average white matter fractional anisotropy was lower in [0.423 (standard deviation, SD 0.023) versus 0.446 (SD 0.016), P = 0.002] while mean average white matter mean diffusivity was higher (749 × 10-6 mm2/s (SD 32 × 10-6) versus 720 × 10-6 mm2/s (SD 21 × 10-6), P = 0.004]. Voxelwise statistics showed that the diffusion abnormalities for both fractional anisotropy and mean diffusivity were anatomically widespread. A lesion probability map showed that white matter hyperintensities also had a wide anatomical distribution with a predilection for the posterior centrum semiovale. However, diffusion abnormalities in Fabry disease were not restricted to lesional tissue; compared to healthy controls, the normal appearing white matter in patients with Fabry disease had reduced fractional anisotropy [0.422 (SD 0.022) versus 0.443 (SD 0.017) P = 0.003] and increased mean diffusivity [747 × 10-6 mm2/s (SD 26 × 10-6) versus 723 × 10-6 mm2/s (SD 22 × 10-6), P = 0.008]. Within patients, average white matter fractional anisotropy and white matter lesion volume showed statistically significant correlations with Digit Symbol Coding Test score (r = 0.558, P = 0.001; and r = -0.633, P ≤ 0.001, respectively). Average white matter fractional anisotropy correlated with the overall Mainz Severity Score Index (r = -0.661, P ≤ 0.001), while average white matter mean diffusivity showed a strong correlation with plasma lyso-Gb3 levels (r = 0.559, P = 0.001). Our findings using DTI confirm widespread areas of microstructural white matter disruption in Fabry disease, extending beyond white matter hyperintensities seen on conventional MRI. Moreover, diffusion measures show strong correlations with cognition (processing speed), clinical disease severity and a putative plasma biomarker of disease activity, making them promising quantitative biomarkers for monitoring Fabry disease severity and progression.

Knowledge of consequences, academic performance and drug consumption among undergraduate students in one university in Jamaica / Conhecimento das consequências, desempenho acadêmico e consumo de drogas entre estudantes de graduação em uma universidade da Jamaica / Conocimiento de las consecuencias, desempeño académico y consumo de drogas entre estudiantes universitarios de grado en una universidad de Jamaica

ABSTRACT Objective: determine the prevalence of drug use and to investigate the relationship between knowledge of consequences and drug consumption as well as the relationship between academic performance and drug consumption among university undergraduate students in Jamaica. Method: the study uses a cross sectional design. A total of 250 undergraduate students were selected through a randomized cluster sampling process. A modified survey instrument consisting of over 70 items relating to socio-demographics, knowledge of consequences, drug consumption and academic performance measures was used to test the research question and hypothesis. Results: the findings revealed low levels of drug usage as well as problematic usage, however, there was a weak negative yet statistically significant correlation between the academic performance and alcohol use (r=-.139, p=.028) which suggested that an increase in alcohol usage is associated with reduction in academic performance. The independent T test also revealed a statistically significant difference between those who used alcohol and those who did not use alcohol in the past 12 months based on academic performance. Conclusion: the findings will inform policy decisions regarding drug use and the provision of intervention services. It is recommended that this research should be extended to other universities in Jamaica.

RESUMO Objetivo: determinar a prevalência do uso de drogas e investigar a relação entre o conhecimento das consequências e o consumo de drogas, bem como a relação entre o desempenho acadêmico e o consumo de drogas entre estudantes universitários da Jamaica. Método: o estudo usa um design transversal. Um total de 250 estudantes de graduação foram selecionados por meio de um processo de amostragem por conglomerado randomizado. Um instrumento de pesquisa modificado, composto por mais de 70 itens referentes a aspectos sociodemográficos, conhecimento de consequências, consumo de drogas e medidas de desempenho acadêmico, foi utilizado para testar a pergunta e a hipótese da pesquisa. Resultados: os resultados revelaram baixos níveis de uso de drogas, bem como uso problemático, no entanto, houve uma correlação negativa fraca, embora estatisticamente significativa entre o desempenho acadêmico e uso de álcool (r = -. 139, p = .028), o que sugeriu que um aumento no uso de álcool está associado à redução do desempenho acadêmico. O teste T independente também revelou uma diferença estatisticamente significativa entre aqueles que usaram álcool e aqueles que não usaram álcool nos últimos 12 meses com base no desempenho acadêmico. Conclusão: os resultados informarão as medidas sobre o uso de drogas e a prestação de serviços de intervenção. Recomenda-se que esta pesquisa seja estendida a outras universidades na Jamaica.

RESUMEN Objetivo: determinar la prevalencia del uso de drogas e investigar la relación entre el conocimiento de las consecuencias y el consumo de drogas, así como la relación entre el desempeño académico y el consumo de drogas entre estudiantes universitarios de Jamaica. Método: el estudio utilizó un diseño transversal. Se seleccionó un total de 250 estudiantes universitarios de grado a través de un proceso de muestreo por conglomerado aleatorizado. Se utilizó un instrumento de investigación modificado, compuesto por más de 70 ítems referentes a aspectos sociodemográficos, al conocimiento de las consecuencias, al consumo de drogas y a las medidas de desempeño académico, para comprobar la pregunta y la hipótesis de la investigación. Resultados: los resultados revelaron bajos niveles de uso de drogas, así como uso problemático. Sin embargo, hubo una correlación negativa débil, aunque estadísticamente significativa entre el desempeño académico y el uso de alcohol (r = - 0,139; p = 0,028), que sugiere que un aumento en el uso de alcohol está asociado a la reducción del desempeño académico. La prueba T independiente también indicó una diferencia estadísticamente significativa entre aquellos que consumieron alcohol y aquellos que no consumieron en los últimos 12 meses sobre la base del desempeño académico. Conclusión: los resultados informarán las medidas sobre el uso de drogas y la prestación de servicios de intervención. Se recomienda que esta investigación se extienda a otras universidades en Jamaica.

Phosphatidylinositol 3,5-bisphosphate and Fab1p/PIKfyve underPPIn endo-lysosome function.

PtdIns(3,5)P(2) is one of the seven regulatory PPIn (polyphosphoinositides) that are ubiquitous in eukaryotes. It controls membrane trafficking at multiple points in the endosomal/lysosomal system and consequently regulates the size, shape and acidity of at least one endo-lysosomal compartment. PtdIns(3,5)P(2) appears to exert this control via multiple effector proteins, with each effector specific for a subset of the various PtdIns(3,5)P(2)-dependent processes. Some putative PtdIns(3,5)P(2) effectors have been identified, including Atg18p-related PROPPIN [beta-propeller(s) that bind PPIn] proteins and the epsin-like proteins Ent3p and Ent5p, whereas others remain to be defined. One of the principal functions of PtdIns(3,5)P(2) is to regulate the fission/fragmentation of endo-lysosomal sub-compartments. PtdIns(3,5)P(2) is required for vesicle formation during protein trafficking between endo-lysosomes and also for fragmentation of endo-lysosomes into smaller compartments. In yeast, hyperosmotic stress accelerates the latter process. In the present review we highlight and discuss recent studies that reveal the role of the HOPS-CORVET complex and the vacuolar H(+)-ATPase in the process of endo-lysosome fission, and speculate on connections between these machineries and the Fab1p pathway. We also discuss new evidence linking PtdIns(3,5)P(2) and PtdIns5P to the regulation of exocytosis.

A case control study of factors associated with congenital syphilis

Congenital syphilis now occupies a high priority as a public health concern. In 1994, a case control study was conducted to elucidate factors associated with congenital syphilis. Cases (n=61) were obtained from the Bustamante Hospital for Children, Victoria Jubilee Hospital and the University Hospital of the West Indies. Data collection was done by hospital records review. Results indicate that mothers of cases were more likely to be unmarried (p<0.005), unemployed and unskilled (p<0.03). The time of mother's first antenatal visit (p<0.03) and, the type of health care facility where antenatal service was sought were significantly associated with congenital syphilis (p<0.0001). Cases were predominantly from the parish of Kingston & St. Andrew and were more likely to have been of low birth weight, less than 2.5 kilograms (p<0.0001). As expected, cases were significantly associated with mothers who were positive for syphilis (p<0.0001). Recommendations are to develop strategies for reduction in the vulnerability of the "at risk" population as well as promotion of early antenatal attendance of pregnant females thereby facilitating early treatment of maternal syphilis (AU)