Perinatal Gene Transfer to the Liver

The liver acts as a host to many functions hence raising the possibility that any one may be compromised by a single gene defect. Inherited or de novo mutations in these genes may result in relatively mild diseases or be so devastating that death within the first weeks or months of life is inevitable. Some diseases can be managed using conventional medicines whereas others are, as yet, untreatable. In this review we consider the application of early intervention gene therapy in neonatal and fetal preclinical studies. We appraise the tools of this technology, including lentivirus, adenovirus and adeno-associated virus (AAV)-based vectors. We highlight the application of these for a range of diseases including hemophilia, urea cycle disorders such as ornithine transcarbamylase deficiency, organic acidemias, lysosomal storage diseases including mucopolysaccharidoses, glycogen storage diseases and bile metabolism. We conclude by assessing the advantages and disadvantages associated with fetal and neonatal liver gene transfer

“You’ve Got to Pick Your Battles”: A Mixed-Methods Investigation of Physical Activity Counselling and Referral within General Practice

One in four people say they would be more active if advised by a general practitioner (GP), yet 72% of GPs do not discuss physical activity (PA) with patients and 80% of GPs are unaware of the PA guidelines. The aim of this study was therefore to investigate GP perspectives on PA counselling and referral and interpret these within the context of the socio-ecological model (SEM). Fifty-six GPs completed an online survey to investigate factors influencing PA counselling and referral. Semi-structured interviews were then conducted with seven GPs to explore topics in more depth. Interview data were analysed thematically and mapped to the SEM. GPs were more likely to discuss PA with patients if they were physically active themselves (p = 0.004). Influences on PA counselling and referral were identified at the policy (provision of education, priority), organisational (feedback, e-referral), interpersonal (PA as everybody’s business, patient factors) and intrapersonal (knowledge, GP PA levels) levels of the SEM. Multi-level strategies are required to help GPs promote PA and make use of exercise referral schemes, including making PA a strategic priority, introducing systems for feedback from referrals, and involving other members of the care team in PA counselling and referral

Auditory object cognition in dementia

The cognition of nonverbal sounds in dementia has been relatively little explored. Here we undertook a systematic study of nonverbal sound processing in patient groups with canonical dementia syndromes comprising clinically diagnosed typical amnestic Alzheimer's disease (AD; n = 21), progressive nonfluent aphasia (PNFA; n = 5), logopenic progressive aphasia (LPA; n = 7) and aphasia in association with a progranulin gene mutation (GAA; n = 1), and in healthy age-matched controls (n = 20). Based on a cognitive framework treating complex sounds as 'auditory objects', we designed a novel neuropsychological battery to probe auditory object cognition at early perceptual (sub-object), object representational (apperceptive) and semantic levels. All patients had assessments of peripheral hearing and general neuropsychological functions in addition to the experimental auditory battery. While a number of aspects of auditory object analysis were impaired across patient groups and were influenced by general executive (working memory) capacity, certain auditory deficits had some specificity for particular dementia syndromes. Patients with AD had a disproportionate deficit of auditory apperception but preserved timbre processing. Patients with PNFA had salient deficits of timbre and auditory semantic processing, but intact auditory size and apperceptive processing. Patients with LPA had a generalised auditory deficit that was influenced by working memory function. In contrast, the patient with GAA showed substantial preservation of auditory function, but a mild deficit of pitch direction processing and a more severe deficit of auditory apperception. The findings provide evidence for separable stages of auditory object analysis and separable profiles of impaired auditory object cognition in different dementia syndromes. (C) 2011 Elsevier Ltd. All rights reserved

A qualitative exploration of physical, mental and ocular fatigue in patients with primary Sjögren's Syndrome

Introduction Primary Sjögren's Syndrome (pSS) affects exocrine glands such as those producing the tear film, leading to dry and painful eyes, but is also associated with fatigue. The experience of fatigue in pSS, and its relationship with sicca symptoms, is poorly understood. Methods Twenty people diagnosed with pSS were recruited to participate in a semi-structured qualitative interview about their symptoms experience. Interviews were audio-recorded, transcribed verbatim and analysed using thematic analysis. Results People with pSS described physical tiredness, mental fatigue and ocular fatigue. Mental fatigue was characterised by difficulties in attention, particularly, the ability to follow conversations and short-term memory problems. Participants linked their experience of fatigue to feeling of depression, frustration, irritation and anxiety, and therefore, fatigue was suggested to have had a large impact on their psychological well-being. People with pSS also described a range of ocular symptoms including pain, dryness, and itching, which were compounded by fatigue. For some, eye fatigue was pervasive, and daily activities involving the eyes such as reading, using the computer and driving were impaired. In some cases, the level of ocular discomfort was so severe it prevented sleep, which in turn impacted on general fatigue levels. Conclusions People with pSS experience fatigue in a range of ways; physical, mental and ocular fatigue were described. Fatigue was suggested to exacerbate other ocular symptoms, posed serious physical limitations and caused psychological distress. Further research into the nature of fatigue and ocular symptoms in pSS is required

Temporal estimation in prediction motion tasks is biased by a moving destination

© 2018 The Authors. An ability to predict the time-to-contact (TTC) of moving objects that become momentarily hidden is advantageous in everyday life and could be particularly so in fast-ball sports. Prediction motion (PM) experiments have sought to test this ability using tasks where a disappearing target moves toward a stationary destination. Here, we developed two novel versions of the PM task in which the destination either moved away from (Chase) or toward (Attract) the moving target. The target and destination moved with different speeds such that collision occurred 750, 1,000 or 1,250 ms after target occlusion. To determine if domain-specific experience conveys an advantage in PM tasks, we compared the performance of different sporting groups ranging from internationally competing athletes to nonsporting controls. There was no difference in performance between sporting groups and non-sporting controls but there were significant and independent effects on response error by target speed, destination speed, and occlusion period. We simulated these findings using a revised version of the linear TTC model of response timing for PM tasks (Yakimoff, Bocheva, & Mitrania, 1987; Yakimoff, Mateeff, Ehrenstein, & Hohnsbein, 1993) in which retinal input from the moving destination biases the internal representation of the occluded target. This revision closely reproduced the observed patterns of response error and thus describes a means by which the brain might estimate TTC when the target and destination are in motion

Faster visual reaction times in elite athletes are not linked to better gaze stability

The issue of whether visually-mediated, simple reaction time (VRT) is faster in elite athletes is contentious. Here, we examined if and how VRT is affected by gaze stability in groups of international cricketers (16 females, 28 males), professional rugby-league players (21 males), and non-sporting controls (20 females, 30 males). VRT was recorded via a button-press response to the sudden appearance of a stimulus (circular target - diameter 0.8°), that was presented centrally, or 7.5° to the left or right of fixation. The incidence and timing of saccades and blinks occurring from 450ms before stimulus onset to 225ms after onset were measured to quantify gaze stability. Our results show that 1) cricketers have faster VRT than controls; 2) blinks and, in particular, saccades are associated with slower VRT regardless of the level of sporting ability; 3) elite female cricketers had steadier gaze (fewer saccades and blinks) compared to female controls; 4) When we accounted for the presence of blinks and saccades, our group comparisons of VRT were virtually unchanged. The stability of gaze is not a factor that explains the difference between elite and control groups in VRT. Thus we conclude that better gaze stability cannot explain faster VRT in elite sports players

Using the Receptivity model to uncover 'urine blindness': perceptions on the re-use of urine

Population growth, climatic changes and over-exploitation of natural resources are at the basis of the world’s food crisis, which counts almost one million people without sufficient food sustenance. These changes require novel environmental practices which are based on nutrient recovery and management in agriculture. This contribution analyses and discusses users’ perceptions on re-use of urine as fertilizer through the lenses of the Receptivity model. A search was performed on Scopus (as well as other web search engines) using the keywords: urine, nutrient recovery and sanitation. Results shows how questions related to awareness, association, acquisition and application of the environmental change can represent hurdles to novel models of nutrient recovery and the use of urine in agriculture. Examples of hurdles identified from the literature relate to poor understanding of potential for urine reuse, social stigma attached to using dry sanitation and applying urine in agriculture and poor operational knowledge of application of urine in agriculture. Conclusion relates to the illustration of implications of such challenges on the design of environmental interventions

The Language Profile of Behavioral Variant Frontotemporal Dementia

BACKGROUND: The language profile of behavioral variant frontotemporal dementia (bvFTD) remains to be fully defined. OBJECTIVE: We aimed to quantify the extent of language deficits in this patient group. METHODS: We assessed a cohort of patients with bvFTD (n = 24) in relation to patients with semantic variant primary progressive aphasia (svPPA; n = 14), nonfluent variant primary progressive aphasia (nfvPPA; n = 18), and healthy age-matched individuals (n = 24) cross-sectionally and longitudinally using a comprehensive battery of language and general neuropsychological tests. Neuroanatomical associations of language performance were assessed using voxel-based morphometry of patients' brain magnetic resonance images. RESULTS: Relative to healthy controls, and after accounting for nonverbal executive performance, patients with bvFTD showed deficits of noun and verb naming and single word comprehension, diminished spontaneous propositional speech, and deterioration in naming performance over time. Within the bvFTD group, patients with MAPT mutations had more severe impairments of noun naming and single word comprehension than patients with C9orf72 mutations. Overall the bvFTD group had less severe language deficits than patients with PPA, but showed a language profile that was qualitatively similar to svPPA. Neuroanatomical correlates of naming and word comprehension performance in bvFTD were identified predominantly in inferior frontal and antero-inferior temporal cortices within the dominant hemispheric language network. CONCLUSIONS: bvFTD is associated with a language profile including verbal semantic impairment that warrants further evaluation as a novel biomarker