Sleep deficits but no metabolic deficits in premanifest Huntington's disease.

OBJECTIVE: Huntington disease (HD) is a fatal autosomal dominant, neurodegenerative condition characterized by progressively worsening motor and nonmotor problems including cognitive and neuropsychiatric disturbances, along with sleep abnormalities and weight loss. However, it is not known whether sleep disturbances and metabolic abnormalities underlying the weight loss are present at a premanifest stage. METHODS: We performed a comprehensive sleep and metabolic study in 38 premanifest gene carrier individuals and 36 age- and sex-matched controls. The study consisted of 2 weeks of actigraphy at home, 2 nights of polysomnography and multiple sleep latency tests in the laboratory, and body composition assessment using dual energy x-ray absorptiometry scanning with energy expenditure measured over 10 days at home by doubly labeled water and for 36 hours in the laboratory by indirect calorimetry along with detailed cognitive and clinical assessments. We performed a principal component analyses across all measures within each studied domain. RESULTS: Compared to controls, premanifest gene carriers had more disrupted sleep, which was best characterized by a fragmented sleep profile. These abnormalities, as well as a theta power (4-7Hz) decrease in rapid eye movement sleep, were associated with disease burden score. Objectively measured sleep problems coincided with the development of cognitive, affective, and subtle motor deficits and were not associated with any metabolic alterations. INTERPRETATION: The results show that among the earliest abnormalities in premanifest HD is sleep disturbances. This raises questions as to where the pathology in HD begins and also whether it could drive some of the early features and even possibly the pathology.The study was funded from a grant from CHDI Foundation, Inc.CHDI-RG50786. RAB received grants from NIHR BRC-RG64473. PS is funded by an MRC Programme grant (Physiological Modelling and Metabolic Risk: MC_UP_A090_1005).This is the final version of the article. It first appeared from Wiley via http://dx.doi.org/10.1002/ana.2449

Laparoscopic versus open left lateral segmentectomy

<p>Abstract</p> <p>Background</p> <p>Laparoscopic liver surgery is becoming increasingly common. This cohort study was designed to directly compare perioperative outcomes of the left lateral segmentectomy via laparoscopic and open approach.</p> <p>Methods</p> <p>Between 2002 and 2006 43 left lateral segmentectomies were performed at King's College Hospital. Those excluded from analysis included previous liver resections, polycystic liver disease, liver cirrhosis and synchronous operations. Of 20 patients analysed, laparoscopic (n = 10) were compared with open left lateral segmentectomy (n = 10). Both groups had similar patient characteristics.</p> <p>Results</p> <p>Morbidity rates were similar with no wound or chest infection in either group. The conversion rate was 10% (1/10). There was no difference in operating time between the groups (median time 220 minutes versus 179 minutes, p = 0.315). Surgical margins for all lesions were clear. Less postoperative opiate analgesics were required in the laparoscopic group (median 2 days versus 5 days, p = 0.005). The median postoperative in-hospital stay was less in the laparoscopic group (6 days vs 9 days, p = 0.005). There was no mortality.</p> <p>Conclusion</p> <p>Laparoscopic left lateral segmentectomy is safe and feasible. Laparoscopic patients may benefit from requiring less postoperative opiate analgesia and a shorter post-operative in-hospital stay.</p

Child DNA methylation in a randomized controlled trial of a video-feedback intervention to promote positive parenting and sensitive discipline (VIPP-SD)

A major modifiable risk factor for behavioural difficulties is harsh and insensitive parenting, and it has been hypothesised that the biological mechanism by which parenting influences child behaviour is via changes in the child’s DNA methylation. We attempted to, in part, address the hypothesis that parenting is associated with child DNA methylation and, in turn, behaviour. Primary caregivers of young children with behavioural difficulties (children aged 12-36 months) were randomised to receive Video-feedback Intervention to promote Positive Parenting and Sensitive Discipline (VIPP-SD) (n=151), or usual care (n=149). Child buccal samples were collected at a 2-year post-randomisation follow up (children aged 3-5 years, VIPP-SD group n=106, usual care group n=117) and were assessed for DNA methylation at the NR3C1, FKBP5 and OXYR genes. Child behaviour was assessed at baseline, post-intervention and 2-years post-randomisation using the Preschool Parental Account of Children’s Symptoms (PPACS). We examined group differences in DNA methylation, associations of DNA methylation with behaviour, and sex differences. For the NR3C1 and OXYR genes, there were no group differences, sex differences, or associations of DNA methylation with child behaviour, though all non-significant findings were in the hypothesised direction. For FKBP5 DNA methylation, there was a significant interaction between group and sex, such that males in the usual care group had higher DNA methylation than females, but in the intervention group females had higher DNA methylation than males. However, FKBP5 DNA methylation was not associated with behaviour in males or females. We provide the first evidence from a randomised controlled trial focused on improving parenting for sex-specific changes in child DNA methylation at a key gene involved in stress reactivity and psychopathology. This study adds to our understanding of causal mechanisms linking parenting with child behaviour, which is important to developing targeted interventions. A key limitation is that child DNA methylation was only assessed at one time point, so we were unable to assess change in DNA methylation over time. However, we demonstrate that is possible to collect and analyse DNA samples from families with young children receiving parenting interventions in the community, providing impetus for further research on this topic

Child DNA methylation in a randomised controlled trial of a video-feedback intervention to promote positive parenting and sensitive discipline (VIPP-SD)

Peer reviewed: TrueIntroductionA major modifiable risk factor for behavioural difficulties is harsh and insensitive parenting, and it has been hypothesised that the biological mechanism by which parenting influences child behaviour is via changes in the child's DNA methylation. We attempted to, in part, address the hypothesis that parenting is associated with child DNA methylation and, in turn, behaviour.MethodsPrimary caregivers of young children with behavioural difficulties (children aged 12–36 months) were randomised to receive a video-feedback Intervention to promote Positive Parenting and Sensitive Discipline (VIPP-SD) (n = 151), or usual care (n = 149). Child buccal samples were collected at a 2-year post-randomisation follow up (children aged 3–5 years, VIPP-SD group n = 106, usual care group n = 117) and were assessed for DNA methylation at the NR3C1, FKBP5 and OXYR genes. Child behaviour was assessed at baseline, post-intervention and 2-years post-randomisation using the Preschool Parental Account of Children's Symptoms (PPACS). We examined group differences in DNA methylation, associations of DNA methylation with behaviour, and sex differences.ResultsFor the NR3C1 and OXYR genes, there were no group differences, sex differences, or associations of DNA methylation with child behaviour, though all non-significant findings were in the hypothesised direction. For FKBP5 DNA methylation, there was a significant interaction between group and sex, such that males in the usual care group had higher DNA methylation than females, but in the intervention group females had higher DNA methylation than males. However, FKBP5 DNA methylation was not associated with behaviour in males or females.DiscussionWe provide the first evidence from a randomised controlled trial focused on improving parenting for sex-specific changes in child DNA methylation at a key gene involved in stress reactivity and psychopathology. This study adds to our understanding of causal mechanisms linking parenting with child behaviour, which is important for developing targeted interventions. A key limitation is that child DNA methylation was only assessed at one time point, so we were unable to assess change in DNA methylation over time. However, we demonstrate that is possible to collect and analyse DNA samples from families with young children receiving parenting interventions in the community, providing impetus for further research on this topic.</jats:sec