214 research outputs found

    Mood Management Intervention for College Smokers with Elevated Depressive Symptoms: A Pilot Study

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    Objective This pilot study examined smoking reduction and cessation among college smokers with elevated depressive symptomatology participating in a group-based behavioral counseling, mood management, and motivational enhancement combined intervention (CBT). Participants & Methods Fifty-eight smokers (smoked ≄ 6 days in the past 30) were randomized to six sessions of CBT (n=29) or a nutrition-focused attention-matched control group (CG, n=29). Results Relative to CG participants, significantly more CBT participants reduced smoking intensity by 50% (χ2(1, N=58)=4.86, p=.028) at end of treatment. Although CBT participants maintained smoking reductions at 3- and 6-month follow-up, group differences were no longer significant. No group differences in cessation emerged. Finally, participants in both groups evidenced increased motivation to reduce smoking at end of treatment (F(1, 44)=11.717, p=.001, ηp2=.207). Conclusions Findings demonstrate the utility of this intervention for smoking reduction and maintenance of reductions over time among a population of college students with elevated depressive symptomatology

    A multiple sclerosis-like disorder in patients with OPA1 mutations.

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    We describe three unrelated patients presenting with a spinal cord syndrome and neuroimaging features consistent with multiple sclerosis (MS). All harbored a pathogenic OPA1 mutation. Although the neurological phenotype resembled neuromyelitis optica (NMO), anti-aquaporin 4 antibodies were not detected and the disorder followed a slow progressive course. The coincidental occurrence of OPA1 mutations and an MS-like disorder is likely to have modulated the phenotypic manifestations of both disorders, but unlike the previously reported association of Leber hereditary optic neuropathy and MS (Harding disease), the optic neuropathy in patients with OPA1 mutations and an MS-like disorder can be mild with a good visual prognosis.PYWM is supported by a Clinician Scientist Fellowship Award (G1002570) from the Medical Research Council (UK), and also receives funding from Fight for Sight (UK), the UK National Institute of Health Research (NIHR) as part of the Rare Diseases Translational Research Collaboration, and the NIHR Biomedical Research Centre based at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology. PFC is a Wellcome Trust Senior Fellow in Clinical Science (101876/Z/13/ Z), and a UK NIHR Senior Investigator. PFC receives additional support from the Medical Research Council Mitochondrial Biology Unit (MC_UP_1501/2), the Wellcome Trust Centre for Mitochondrial Research (096919Z/11/Z), the Medical Research Council (UK) Centre for Translational Muscle Disease (G0601943), the Medical Research Council (UK) Centre for Translational Muscle Disease research (G0601943), and EU FP7 TIRCON

    Diverse interventions that extend mouse lifespan suppress shared age-associated epigenetic changes at critical gene regulatory regions

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    Background: Age-associated epigenetic changes are implicated in aging. Notably, age-associated DNA methylation changes comprise a so-called aging “clock”, a robust biomarker of aging. However, while genetic, dietary and drug interventions can extend lifespan, their impact on the epigenome is uncharacterised. To fill this knowledge gap, we defined age-associated DNA methylation changes at the whole-genome, single-nucleotide level in mouse liver and tested the impact of longevity-promoting interventions, specifically the Ames dwarf Prop1 df/df mutation, calorie restriction and rapamycin. Results: In wild-type mice fed an unsupplemented ad libitum diet, age-associated hypomethylation was enriched at super-enhancers in highly expressed genes critical for liver function. Genes harbouring hypomethylated enhancers were enriched for genes that change expression with age. Hypermethylation was enriched at CpG islands marked with bivalent activating and repressing histone modifications and resembled hypermethylation in liver cancer. Age-associated methylation changes are suppressed in Ames dwarf and calorie restricted mice and more selectively and less specifically in rapamycin treated mice. Conclusions: Age-associated hypo- and hypermethylation events occur at distinct regulatory features of the genome. Distinct longevity-promoting interventions, specifically genetic, dietary and drug interventions, suppress some age-associated methylation changes, consistent with the idea that these interventions exert their beneficial effects, in part, by modulation of the epigenome. This study is a foundation to understand the epigenetic contribution to healthy aging and longevity and the molecular basis of the DNA methylation clock

    WFS1-Associated Optic Neuropathy : Genotype-Phenotype Correlations and Disease Progression

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    center dot OBJECTIVE: To evaluate the pattern of vision loss and genotype-phenotype correlations in WFS1-associated optic neuropathy (WON).center dot DESIGN: Multicenter cohort study. center dot METHODS: The study involved 37 patients with WON carrying pathogenic or candidate pathogenic WFS1 variants. Genetic and clinical data were retrieved from the medical records. Thirteen patients underwent additional comprehensive ophthalmologic assessment. Deep phenotyping involved visual electrophysiology and advanced psychophysical testing with a complementary metabolomic study. Main Outcome Measures: WFS1 variants, functional and structural optic nerve and retinal parameters, and metabolomic profile.center dot RESULTS: Twenty-two recessive and 5 dominant WFS1 variants were identified. Four variants were novel. All WFS1 variants caused loss of macular retinal ganglion cells (RGCs) as assessed by optical coherence tomography (OCT) and visual electrophysiology. Advanced psychophysical testing indicated involvement of the major RGC subpopulations. Modeling of vision loss showed an accelerated rate of deterioration with increasing age. Dominant WFS1 variants were associated with abnormal reflectivity of the outer plexiform layer (OPL) on OCT imaging. The dominant variants tended to cause less severe vision loss compared with recessive WFS1 variants, which resulted in more variable phenotypes ranging from isolated WON to severe multisystem disease depending on the WFS1 alleles. The metabolomic profile included markers seen in other neurodegenerative diseases and type 1 diabetes mellitus. center dot CONCLUSIONS: WFS1 variants result in heterogenous phenotypes influenced by the mode of inheritance and the disease-causing alleles. Biallelic WFS1 variants cause more variable, but generally more severe, vision and RGC loss compared with heterozygous variants. Abnormal cleftlike lamination of the OPL is a distinctive OCT feature that strongly points toward dominant WON. (Am J Ophthalmol 2022;241: 927. (c) 2022 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license ( http://creativecommons.org/licenses/by/4.0/ ))Peer reviewe

    An investigation of overlap in children's speech

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    The simultaneous speech of six 4-year-old girls was investigated within three-party conversation. The data reveal two major types of overlap, one providing instances of turn completion projections and the other reflecting tension for the turn at speaking. The data are discussed in terms of the Sacks, Schegloff, and Jefferson (1974) model of conversational interaction.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45101/1/10936_2005_Article_BF01067502.pd
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