Delivering a disease-modifying treatment for Huntington’s disease

Huntington's disease (HD) is an incurable genetic neurodegenerative disorder that leads to motor and cognitive decline. It is caused by an expanded polyglutamine tract within the Huntingtin (HTT) gene, which translates into a toxic mutant HTT protein. Although no cure has yet been discovered, novel therapeutic strategies, such as RNA interference (RNAi), antisense oligonucleotides (ASO), ribozymes, DNA enzymes, and genome-editing approaches, aimed at silencing or repairing the mutant HTT gene hold great promise. Indeed, several preclinical studies have demonstrated the utility of such strategies to improve HD neuropathology and symptoms. In this review, we critically summarise the main advances and limitations of each gene-silencing technology as an effective therapeutic tool for the treatment of HD.

Optimising protocol of acquisition and post-processing procedures in the assessment of coronary artery disease by computed tomography

Coronary artery disease (CAD) is currently one of the most prevalent diseases in the world population and calcium deposits in coronary arteries are one direct risk factor. These can be assessed by the calcium score (CS) application, available via a computed tomography (CT) scan, which gives an accurate indication of the development of the disease. However, the ionising radiation applied to patients is high. This study aimed to optimise the protocol acquisition in order to reduce the radiation dose and explain the flow of procedures to quantify CAD. The main differences in the clinical results, when automated or semiautomated post-processing is used, will be shown, and the epidemiology, imaging, risk factors and prognosis of the disease described. The software steps and the values that allow the risk of developingCADto be predicted will be presented. A64-row multidetector CT scan with dual source and two phantoms (pig hearts) were used to demonstrate the advantages and disadvantages of the Agatston method. The tube energy was balanced. Two measurements were obtained in each of the three experimental protocols (64, 128, 256 mAs). Considerable changes appeared between the values of CS relating to the protocol variation. The predefined standard protocol provided the lowest dose of radiation (0.43 mGy). This study found that the variation in the radiation dose between protocols, taking into consideration the dose control systems attached to the CT equipment and image quality, was not sufficient to justify changing the default protocol provided by the manufacturer.

Psychological well-being and perception of disease severity in people with multiple sclerosis, who underwent a program of self-regulation to promote physical activity

Rehabilitation is very important for in the results of treatment in individuals with multiple sclerosis. Rehabilitation processes occur through gradual changes. These changes integrate intrinsic and extrinsic mechanisms of the individual, promoting adaptations to the needs and activities of daily living according to individual goals. Recommendations for exercise in multiple sclerosis: these recommendations apply only to patients with EDSS less than 7; moderate intensity aerobic exercise for a total of 20 to 30 minutes, twice or three times for week; the resistance training with low or moderate intensity is well tolerated by patients with MS; associated with these exercises were recommended flexibility exercises of moderate intensity, as well as strengthening exercises. The aim of this study is to examine the implications of the program of self-regulation in the perception of illness and mental health (psychological well-being domain) in multiple sclerosis patients.

Beach sand and the potential for infectious disease transmission: observations and recommendations

Recent studies suggest that sand can serve as a vehicle for exposure of humans to pathogens at beach sites, resulting in increased health risks. Sampling for microorganisms in sand should therefore be considered for inclusion in regulatory programmes aimed at protecting recreational beach users from infectious disease. Here, we review the literature on pathogen levels in beach sand, and their potential for affecting human health. In an effort to provide specific recommendations for sand sampling programmes, we outline published guidelines for beach monitoring programmes, which are currently focused exclusively on measuring microbial levels in water. We also provide background on spatial distribution and temporal characteristics of microbes in sand, as these factors influence sampling programmes. First steps toward establishing a sand sampling programme include identifying appropriate beach sites and use of initial sanitary assessments to refine site selection. A tiered approach is recommended for monitoring. This approach would include the analysis of samples from many sites for faecal indicator organisms and other conventional analytes, while testing for specific pathogens and unconventional indicators is reserved for high-risk sites. Given the diversity of microbes found in sand, studies are urgently needed to identify the most significant aetiological agent of disease and to relate microbial measurements in sand to human health risk.

Assessment of the quality of brain regions and neuroimaging metrics as biomarkers of Alzheimer’s disease

Alzheimer Disease (AD) is characterized by progressive cognitive decline and dementia. Earlier diagnosis and classification of different stages of the disease are currently the main challenges and can be assessed by neuroimaging. With this work we aim to evaluate the quality of brain regions and neuroimaging metrics as biomarkers of AD. Multimodal Imaging Brain Connectivity Analysis (MIBCA) toolbox functionalities were used to study AD by T1weighted, Diffusion Tensor Imaging and 18FAV45 PET, with data obtained from the AD Neuroimaging Initiative database, specifically 12 healthy controls (CTRL) and 33 patients with early mild cognitive impairment (EMCI), late MCI (LMCI) and AD (11 patients/group). The metrics evaluated were gray-matter volume (GMV), cortical thickness (CThk), mean diffusivity (MD), fractional anisotropy (FA), fiber count (FiberConn), node degree (Deg), cluster coefficient (ClusC) and relative standard-uptake-values (rSUV). Receiver Operating Characteristic (ROC) curves were used to evaluate and compare the diagnostic accuracy of the most significant metrics and brain regions and expressed as area under the curve (AUC). Comparisons were performed between groups. The RH-Accumbens/Deg demonstrated the highest AUC when differentiating between CTRLEMCI (82%), whether rSUV presented it in several brain regions when distinguishing CTRL-LMCI (99%). Regarding CTRL-AD, highest AUC were found with LH-STG/FiberConn and RH-FP/FiberConn (~100%). A larger number of neuroimaging metrics related with cortical atrophy with AUC>70% was found in CTRL-AD in both hemispheres, while in earlier stages, cortical metrics showed in more confined areas of the temporal region and mainly in LH, indicating an increasing of the spread of cortical atrophy that is characteristic of disease progression. In CTRL-EMCI several brain regions and neuroimaging metrics presented AUC>70% with a worst result in later stages suggesting these indicators as biomarkers for an earlier stage of MCI, although further research is necessary.

Non-colorectal intestinal tract carcinomas in inflammatory bowel disease: results of the 3rd ECCO Pathogenesis Scientific Workshop (II)

Patients with inflammatory bowel diseases (IBD) have an excess risk of certain gastrointestinal cancers. Much work has focused on colon cancer in IBD patients, but comparatively less is known about other more rare cancers. The European Crohn's and Colitis Organization established a pathogenesis workshop to review what is known about these cancers and formulate proposals for future studies to address the most important knowledge gaps. This article reviews the current state of knowledge about small bowel adenocarcinoma, ileo-anal pouch and rectal cuff cancer, and anal/perianal fistula cancers in IBD patients.