How young people find out about their family history of Huntington's disease

Family communication about adult-onset hereditary illness can be problematic, leaving some relatives inadequately informed or ignorant of their risk. Although studies have explored the barriers and facilitators in family communication about genetic risk, questions remain about when, what, how and indeed whether to tell relatives. The process of disclosure is also dependent upon the way in which genetic information is realized and understood by recipients, but research here is limited. Our paper explores young people’s experiences of finding out about a family history of the hereditary disorder Huntington’s disease (HD). In-depth interviews explored how and when young people found out, their reactions to different communication styles and any impact on family relations. We recruited young people through the North of Scotland regional genetics clinic and the Scottish Huntington’s Association (SHA). Thirtythree young people (aged 9–28) were interviewed. A qualitative analysis was undertaken which revealed four types of disclosure experiences: (1) having always been told, (2) gradually told, (3) HD was kept a secret, or (4) HD as a new diagnosis. In particular, the timing and style of disclosure from relatives, and one’s stage of awareness, were fundamental in structuring participants’ accounts. This article focuses on questions of when, how and indeed whether to tell children, and sits within a broader set of research and practice issues about what professionals and families (should) tell children about parental illness and genetic risk.Wellcome Trust’s Programme in Biomedical Ethic

Nutritional management of individuals with Huntington’s disease: nutritional guidelines

The delivery of good nutritional care is a fundamental element of the management of individuals with Huntington’s disease and all patients with Huntington’s disease will, at some time, need dietary intervention because of the sequela of the disease; yet there are no European nutritional guidelines. The European Huntington’s Disease Network Standards of Care Dietitians Group has brought together expert dietitians from across Europe to produce nutritional guidelines to improve the nutritional management of individuals with Huntington’s disease. The guidelines were developed to promote optimal nutritional screening, assessment and management of individuals throughout all stages of the disease, with the aim of improving the standard of nutritional care delivered. Literature was systematically searched in an attempt to ensure that the recommendations are based on sound evidence and where evidence is lacking, specific guidance is based on consensus expert dietetic opinion. The provision of nutritional care varies widely between countries. Implementation of these nutritional guidelines across Europe should improve the quality of nutritional care delivered to individuals with Huntington’s disease

Temporal whole field sawtooth flicker without a spatial component elicits a myopic shift following optical defocus irrespective of waveform direction in chicks

Purpose Myopia (short-sightedness) is the commonest visual disorder and greatest risk factor for sight threatening secondary pathologies. Myopia and hyperopia can be induced in animal models by rearing with optical lens defocus of opposite sign. The degree of refractive compensation to lens-induced defocus in chicks has been shown to be modified by directionally drifting sawtooth spatio-temporal luminance diamond plaids, with Fast-ON sawtooth spatio-temporal luminance profiles inhibiting the myopic shift in response to negative lenses, and Fast-OFF profiles inhibiting the hyperopic shift in response to positive lenses. What is unknown is whether similar sign-of-defocus dependent results produced by spatio-temporal modulation of sawtooth patterns could be achieved by rearing chicks under whole field low temporal frequency sawtooth luminance profiles at 1 or 4 Hz without a spatial component, or whether such stimuli would indiscriminately elicit a myopic shift such as that previously shown with symmetrical (or near-symmetrical) low frequency flicker across a range of species. Methods Hatchling chicks (n = 166) were reared from days five to nine under one of three defocus conditions (No Lens, +10D lens, or −10D lens) and five light conditions (No Flicker, 1 Hz Fast-ON/Slow-OFF sawtooth flicker, 4 Hz Fast-ON/Slow-OFF sawtooth flicker, 1 Hz Fast-OFF/Slow-ON sawtooth flicker, or 4Hz Fast-OFF/Slow-ON sawtooth flicker). The sawtooth flicker was produced by light emitting diodes (white LEDs, 1.2 –183 Lux), and had no measurable dark phase. Biometrics (refraction and ocular axial dimensions) were measured on day nine. Results Both 1 Hz and 4 Hz Fast-ON and Fast-OFF sawtooth flicker induced an increase in vitreous chamber depth that was greater in the presence of negative compared to positive lens defocus. Both sawtooth profiles at both temporal frequencies inhibited the hyperopic shift in response to +10D lenses, whilst full myopic compensation (or over-compensation) in response to −10D lenses was observed. Conclusions Whole field low temporal frequency Fast-ON and Fast-OFF sawtooth flicker induces a generalized myopic shift, similar to that previously shown for symmetrical sine-wave and square-wave flicker. Our findings highlight that temporal modulation of retinal ON/OFF pathways per se (without a spatial component) is insufficient to produce strong sign-of-defocus dependent effect

A population-based audit of surgical practice and outcomes of oncoplastic breast conservations in Scotland – an analysis of 589 patients

Introduction: Current evidence for oncoplastic breast conservation (OBC) is based on single institutional series. Therefore, we carried out a population-based audit of OBC practice and outcomes in Scotland. Methods: A predefined database of patients treated with OBC was completed retrospectively in all breast units practicing OBC in Scotland. Results: 589 patients were included from 11 units. Patients were diagnosed between September 2005 and March 2017. High volume units performed a mean of 19.3 OBCs per year vs. low volume units who did 11.1 (p = 0.012). 23 different surgical techniques were used. High volume units offered a wider range of techniques (8–14) than low volume units (3–6) (p = 0.004). OBC was carried out as a joint operation involving a breast and a plastic surgeon in 389 patients. Immediate contralateral symmetrisation rate was significantly higher when OBC was performed as a joint operation (70.7% vs. not joint operations: 29.8%; p < 0.001). The incomplete excision rate was 10.4% and was significantly higher after surgery for invasive lobular carcinoma (18.9%; p = 0.0292), but was significantly lower after neoadjuvant chemotherapy (3%; p = 0.031). 9.2% of patients developed major complications requiring hospital admission. Overall the complication rate was significantly lower after neoadjuvant chemotherapy (p = 0.035). The 5 year local recurrence rate was 2.7%, which was higher after OBC for DCIS (8.3%) than invasive ductal cancer (1.6%; p = 0.026). 5-year disease-free survival was 91.7%, overall survival was 93.8%, and cancer-specific survival was 96.1%. Conclusion: This study demonstrated that measured outcomes of OBC in a population-based multi-centre setting can be comparable to the outcomes of large volume single centre series

Noncoronary Gated Transcatheter Aortic Valve Replacement Computed Tomography Scans Can Safely Replace Invasive Coronary Angiography Pre-Transcatheter Aortic Valve Replacement

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Mutations in SLC20A2 are a major cause of familial idiopathic basal ganglia calcification

Familial idiopathic basal ganglia calcification (IBGC) or Fahr's disease is a rare neurodegenerative disorder characterized by calcium deposits in the basal ganglia and other brain regions, which is associated with neuropsychiatric and motor symptoms. Familial IBGC is genetically heterogeneous and typically transmitted in an autosomal dominant fashion. We performed a mutational analysis of SLC20A2, the first gene found to cause IBGC, to assess its genetic contribution to familial IBGC. We recruited 218 subjects from 29 IBGC-affected families of varied ancestry and collected medical history, neurological exam, and head CT scans to characterize each patient's disease status. We screened our patient cohort for mutations in SLC20A2. Twelve novel (nonsense, deletions, missense, and splice site) potentially pathogenic variants, one synonymous variant, and one previously reported mutation were identified in 13 families. Variants predicted to be deleterious cosegregated with disease in five families. Three families showed nonsegregation with clinical disease of such variants, but retrospective review of clinical and neuroimaging data strongly suggested previous misclassification. Overall, mutations in SLC20A2 account for as many as 41 % of our familial IBGC cases. Our screen in a large series expands the catalog of SLC20A2 mutations identified to date and demonstrates that mutations in SLC20A2 are a major cause of familial IBGC. Non-perfect segregation patterns of predicted deleterious variants highlight the challenges of phenotypic assessment in this condition with highly variable clinical presentation

Mutation of HIV-1 Genomes in a Clinical Population Treated with the Mutagenic Nucleoside KP1461

The deoxycytidine analog KP1212, and its prodrug KP1461, are prototypes of a new class of antiretroviral drugs designed to increase viral mutation rates, with the goal of eventually causing the collapse of the viral population. Here we present an extensive analysis of viral sequences from HIV-1 infected volunteers from the first “mechanism validation” phase II clinical trial of a mutagenic base analog in which individuals previously treated with antiviral drugs received 1600 mg of KP1461 twice per day for 124 days. Plasma viral loads were not reduced, and overall levels of viral mutation were not increased during this short-term study, however, the mutation spectrum of HIV was altered. A large number (N = 105 per sample) of sequences were analyzed, each derived from individual HIV-1 RNA templates, after 0, 56 and 124 days of therapy from 10 treated and 10 untreated control individuals (>7.1 million base pairs of unique viral templates were sequenced). We found that private mutations, those not found in more than one viral sequence and likely to have occurred in the most recent rounds of replication, increased in treated individuals relative to controls after 56 (p = 0.038) and 124 (p = 0.002) days of drug treatment. The spectrum of mutations observed in the treated group showed an excess of A to G and G to A mutations (p = 0.01), and to a lesser extent T to C and C to T mutations (p = 0.09), as predicted by the mechanism of action of the drug. These results validate the proposed mechanism of action in humans and should spur development of this novel antiretroviral approach.Koronis Pharmaceutical

27 years of prenatal diagnosis for Huntington disease in the United Kingdom.

PURPOSE: There is little long-term, population-based data on uptake of prenatal diagnosis for Huntington disease (HD), a late-onset autosomal dominant neurodegenerative disorder, and the effect of the availability of preimplantation genetic diagnosis (PGD) on families' decisions about conventional prenatal diagnosis is not known. We report trends in prenatal diagnosis and preimplantation diagnosis for HD in the United Kingdom since services commenced. METHODS: Long-term UK-wide prospective case record-based service evaluation in 23 UK Regional Genetic Centres 1988-2015, and four UK PGD centers 2002-2015. RESULTS: From 1988 to 2015, 479 prenatal diagnoses were performed in the UK for HD. An exclusion approach was used in 150 (31%). The annual rate of HD prenatal diagnosis has remained around 18 (3.5/million) over 27 years, despite a steady increase in the use of PGD for HD since 2002. CONCLUSION: Although increasing number of couples are choosing either direct or exclusion PGD to prevent HD in their offspring, both direct and exclusion prenatal diagnosis remain important options in a health system where both PGD and prenatal diagnosis are state funded. At-risk couples should be informed of all options available to them, preferably prepregnancy