Brain structure in asymptomatic FMR1 premutation carriers at risk for fragile X-associated tremor/ataxia syndrome

Fragile X-associated tremor/ataxia syndrome (FXTAS), a late-onset movement disorder affecting FMR1 premutation carriers, is associated with cerebral and cerebellar lesions. The aim of this study was to test whether computational anatomy can detect similar patterns in asymptomatic FMR1 premutation carriers (mean age 46.7 years) with qualitatively normal -appearing grey and white matter on brain MRI. We used a multimodal imaging protocol to characterize brain anatomy by automated assessment of gray matter volume and white matter properties. Structural changes in the hippocampus and in the cerebellar motor network with decreased gray matter volume in lobule VI and white matter alterations of the corresponding afferent projections through the middle cerebellar peduncles are demonstrated. Diffuse subcortical white matter changes in both hemispheres, without corresponding gray matter alterations, are only identified through age × group interactions. We interpret the hippocampal fimbria and cerebellar changes as early alterations with a possible neurodevelopmental origin. In contrast, progression of the diffuse cerebral hemispheric white matter changes suggests a neurodegenerative process, leading to late-onset lesions, which may mark the imminent onset of FXTAS.     

Toxicity of Amphotericin B Deoxycholate-Based Induction Therapy in Patients with HIV-Associated Cryptococcal Meningitis

Amphotericin B deoxycholate (AmBd) is the recommended induction treatment for HIV-associated cryptococcal meningitis (CM). Its use is hampered by toxicities that include electrolyte abnormalities, nephrotoxicity, and anemia. Protocols to minimize toxicity are applied inconsistently. In a clinical trial cohort of AmBd-based CM induction treatment, a standardized protocol of preemptive hydration and electrolyte supplementation was applied. Changes in blood counts, electrolyte levels, and creatinine levels over 14 days were analyzed in relation to the AmBd dose, treatment duration (short course of 5 to 7 days or standard course of 14 days), addition of flucytosine (5FC), and outcome. In the 368 patients studied, the hemoglobin levels dropped by a mean of 1.5 g/dl (95% confidence interval [CI], 1.0 to 1.9 g/dl) following 7 days of AmBd and by a mean of 2.3 g/dl (95% CI, 1.1 to 3.6 g/dl) after 14 days. Serum creatinine levels increased by 37 μmol/liter (95% CI, 30 to 45 μmol/liter) by day 7 and by 49 μmol/liter (95% CI, 35 to 64μmol/liter) by day 14 of AmBd treatment. Overall, 33% of patients developed grade III/IV anemia, 5.6% developed grade III hypokalemia, 9.5% had creatinine levels that exceeded 220 μmol, and 6% discontinued AmBd prematurely. The addition of 5FC was associated with a slight increase in anemia but not neutropenia. Laboratory abnormalities stabilized or reversed during the second week in patients on short-course induction. Grade III/IV anemia (adjusted odds ratio [aOR], 2.2; 95% CI, 1.1 to 4.3; P = 0.028) and nephrotoxicity (aOR, 4.5; 95% CI, 1.8 to 11; P = 0.001) were risk factors for 10-week mortality. In summary, routine intravenous saline hydration and preemptive electrolyte replacement during AmBd-based induction regimens for HIV-associated CM minimized the incidence of hypokalemia and nephrotoxicity. Anemia remained a concerning adverse effect. The addition of flucytosine was not associated with increased neutropenia. Shorter AmBd courses were less toxic, with rapid reversibility.     

SMS-based smartphone application for disease surveillance has doubled completeness and timeliness in a limited-resource setting – evaluation of a 15-week pilot program in Central African Republic (CAR)

Background

It is a challenge in low-resource settings to ensure the availability of complete, timely disease surveillance information. Smartphone applications (apps) have the potential to enhance surveillance data transmission.

Methods

The Central African Republic (CAR) Ministry of Health and Médecins Sans Frontières (MSF) conducted a 15-week pilot project to test a disease surveillance app, Argus, for 20 conditions in 21 health centers in Mambéré Kadéi district (MK 2016). Results were compared to the usual paper-based surveillance in MK the year prior (MK 2015) and simultaneously in an adjacent health district, Nana-Mambére (NM 2016). Wilcoxon rank sum and Kaplan-Meier analyses compared report completeness and timeliness; the cost of the app, and users’ perceptions of its usability were assessed.

Results

Two hundred seventy-one weekly reports sent by app identified 3403 cases and 63 deaths; 15 alerts identified 28 cases and 4 deaths. Median completeness (IQR) for MK 2016, 81% (81–86%), was significantly higher than in MK 2015 (31% (24–36%)), and NM 2016 (52% (48–57)) (p?<?0.01). Median timeliness (IQR) for MK 2016, 50% (39–57%) was also higher than in MK 2015, 19% (19–24%), and NM 2016 29% (24–36%) (p?<?0.01). Kaplan-Meier Survival Analysis showed a significant progressive reduction in the time taken to transmit reports over the 15-week period (p?<?0.01). Users ranked the app’s usability as greater than 4/5 on all dimensions. The total cost of the 15-week pilot project was US$40,575. It is estimated that to maintain the app in the 21 health facilities of MK will cost approximately US$18,800 in communication fees per year.

Conclusions

The app-based data transmission system more than doubled the completeness and timeliness of disease surveillance reports. This simple, low-cost intervention may permit the early detection of disease outbreaks in similar low-resource settings elsewhere.

     

Magnetic resonance imaging as a tool for in vivo and ex vivo anatomical phenotyping in experimental genetic models

This article describes a suite of computational approaches suitable for deriving various quantitative phenotypes from structural magnetic resonance (MR) images obtained in rodents and used subsequently in genetic studies of complex traits. We begin by introducing the basic principles of genetic studies of complex traits in experimental models. We then illustrate the use of MR-based computational anatomy in vivo and ex vivo, and in combination with histology. This work was carried out in two inbred strains of rats, namely spontaneously hypertensive rats and Brown Norway rats; these are parental strains of the only existing panel of recombinant inbred strains of rats. The rats were scanned in vivo at two time points (at 8 and 12 weeks of age) and ex vivo (at 12 weeks of age). We describe between-strain differences and across-time changes in brain and kidney volumes, as well as regional variations in brain structure using surface- and deformation-based approaches. We conclude by discussing the power of the population-based computational analysis of MR images, and their fusion with histology, in studies of complex traits.     

Phenol esters and other constituents from the stem barks of Stereospermum acuminatissimum

A new ester, 2-(4'-hydroxyphenyl)ethyl dotriacontanoate (1), and a new inseparable mixture of octacosan-1,28-dioldiferulate and triacontan-1,30-dioldiferulate (2) were isolated from the stem barks of Stereospermum acuminatissimum, along with 24 known compounds including 4 triterpenoids, 11 anthraquinones, 2 lignans, 3 phenylpropanoids, 2 4-hydroxyphenethyl esters, 1 methoxyphenol, and 1 iridoid. The structures of the new metabolites were determined with the help of spectroscopic data including extensive 2D NMR spectroscopy. The known compounds were identified by comparison of their physical and spectroscopic data with those reported in the literature. The compounds were tested against Candida albicans ATCC 24433, C. albicans ATCC 90028, Candida glabrata ATCC 90030, Candida krusei ATCC 6258, and Candida parapsilosis ATCC 22019. Some of them were moderately active.     

Social reasoning skills in adults with Down syndrome: the role of language,executive functions and socio‐emotional behaviour

Background Although the prevalence of mental illness and behaviour problems is lower in adults with Down syndrome (DS) than in other populations with intellectual disabilities, they do present emotional and relational problems, as well as social integration difficulties. However, studies reporting on specific competences known to be central in developing appropriate social relationships (e.g. social reasoning, emotion processing, theory of mind) remain rare in the adult DS population and the mechanisms underlying these people's emotional and relational difficulties are unclear. Method The present study investigated the ability to understand the appropriateness of others' social behaviour in 34 adults with DS, using the Social Resolution Task (SRT). Their results were compared with those of 34 typically developing (TD) children matched for gender and receptive vocabulary. The relationships among the SRT experimental task, cognitive competences (receptive and productive vocabulary, non‐verbal reasoning, inhibition, selective attention) and a caregiver‐rated measure of socio‐emotional behaviour were examined in the DS group. Results The DS participants' global SRT scores did not differ from those of the controls. However, analyses of the SRT subscores revealed that the DS group identified significantly fewer inappropriate situations than the control group. Nevertheless, when they correctly identified the behaviour as inappropriate, they were as well as the controls to explain the rules underlying their responses. Regression analyses showed that receptive vocabulary and selective attention and a specific dimension of the socio‐emotional profile (social relating skills) constituted the best predictors of the DS adults' performance on the SRT. Conclusions The main findings show that the DS participants demonstrate relatively good social reasoning skills in comparison with TD children matched for verbal age. However, the two groups present distinctions in their response patterns, and the influence of cognitive variables on success on the SRT also appears different. While selective attention skills are found to be significant predictors for both groups, the influence of receptive vocabulary level is much stronger in the DS group. The implications of particular cognitive and socio‐emotional factors for success on the SRT in this group are considered in more detail.     

Perception of the risk of sexual transmission of HIV among Congolese and Japanese university students

Objective

Sub-Saharan Africa remains the region most heavily affected by HIV infection. This study aimed to evaluate the knowledge, attitudes, and practices of Congolese students of risk behaviors for sexual transmission of HIV in comparison with their Japanese counterparts.

Methods

Of the 1,747 undergraduate students who participated in the survey, there were 1,326 respondents (752 Japanese, 574 Congolese) who voluntarily and fully filled out the auto-administered questionnaire.

Results

The proportion of Congolese respondents who do not always use condoms with an occasional sex partner was significantly higher, 57%, as compared with their Japanese counterparts (15%; p < 0.001). Fewer than 40% (9.9–39.7%) of Congolese respondents had accurate knowledge about multiple sex partnership (MSP), men sex with men (MSM), precocious sex, and commercial sex work (CSW) being high-risk behaviors (p < 0.001) for the sexual transmission of HIV infection. However, the proportion of Congolese tested or willing to get tested for HIV was significantly higher (97.2%) than that in the Japanese group (72.4%, p < 0.001). In Congolese students, we observed an absence of adherence to preventive measures such as condom use with an occasional sex partner, and a greater proportion of students having inaccurate knowledge of major risk behaviors such as MSM, precocious sex, and MSP, compared with their Japanese counterparts.

Conclusions

This study showed that, though sexual contact remains the main mode of HIV transmission in the region, Congolese students tend to have inaccurate knowledge of risk behaviors that expose people to the sexual transmission of HIV. This suggests that continuous education targeting those risk behaviors is of great importance to reduce the spread of the HIV epidemic.