Cardio-Dance Exercise to Improve Cognition and Mood in Older African Americans: A Propensity-Matched Cohort Study.

The current study sought to determine the influence of initial sleep quality and body mass index on the cognitive and mood outcomes of a community-based cardio-dance exercise program. Thirty-two older African Americans who participated in a 5-month cardio-dance exercise program were propensity-matched to 32 no-contact controls. Participants completed neuropsychological tests of attention, executive function, and memory and a self-reported depression measure at baseline and post-test. Among exercise participants, we observed significant improvements in depression (baseline = 6.16 ± 5.54, post-test = 4.66 ± 4.89, ηp2=.12, p = .009) and attention (baseline = 40.53 ± 14.01, post-test = 36.63 ± 13.29, ηp2=.12, p = .009) relative to controls. Improvements in executive function and attention were most pronounced among exercise participants with poor sleep quality (baseline = 7.71 ± 1.25, post-test = 8.29 ± 2.06, ηp2=.41, p = .04) and with obesity (baseline = 38.05 ± 12.78, post-test = 35.67 ± 13.82, ηp2=.30, p = .001), respectively. This study provides novel evidence that exercise has the potential to improve depression in older African Americans. For those with poor sleep quality or obesity, exercise can also improve some cognitive outcomes.

New GJA8 variants and phenotypes highlight its critical role in a broad spectrum of eye anomalies.

GJA8 encodes connexin 50 (Cx50), a transmembrane protein involved in the formation of lens gap junctions. GJA8 mutations have been linked to early onset cataracts in humans and animal models. In mice, missense mutations and homozygous Gja8 deletions lead to smaller lenses and microphthalmia in addition to cataract, suggesting that Gja8 may play a role in both lens development and ocular growth. Following screening of GJA8 in a cohort of 426 individuals with severe congenital eye anomalies, primarily anophthalmia, microphthalmia and coloboma, we identified four known [p.(Thr39Arg), p.(Trp45Leu), p.(Asp51Asn), and p.(Gly94Arg)] and two novel [p.(Phe70Leu) and p.(Val97Gly)] likely pathogenic variants in seven families. Five of these co-segregated with cataracts and microphthalmia, whereas the variant p.(Gly94Arg) was identified in an individual with congenital aphakia, sclerocornea, microphthalmia and coloboma. Four missense variants of unknown or unlikely clinical significance were also identified. Furthermore, the screening of GJA8 structural variants in a subgroup of 188 individuals identified heterozygous 1q21 microdeletions in five families with coloboma and other ocular and/or extraocular findings. However, the exact genotype-phenotype correlation of these structural variants remains to be established. Our data expand the spectrum of GJA8 variants and associated phenotypes, confirming the importance of this gene in early eye development.

A prospective study of time to healing and hypertrophic scarring in paediatric burns: every day counts.

BACKGROUND: It is commonly accepted that burns taking longer than 3 weeks to heal have a much higher rate of hypertrophic scarring than those which heal more quickly. However, some of our patients develop hypertrophic scars despite healing within this 3-week period. METHODS: We performed a prospective study of 383 paediatric burns treated non-operatively at a regional burns centre over a 2-year period from May 2011 to April 2013. Scar assessment was performed by a senior burns therapist using the Vancouver Scar Scale. RESULTS: Overall rates of hypertrophic scarring were 17.2%. Time to healing was the strongest predictor of developing hypertrophic scarring, and the earliest hypertrophic scar developed in a patient who was healed after 8 days. The risk of hypertrophic scarring was multiplied by 1.138 for every additional day taken for the burn wound to heal. There was a trend towards higher rates of hypertrophic scarring in non-white skin types but this did not reach statistical significance. CONCLUSIONS: The risk of hypertrophic scarring increases with every day and, therefore, every effort should be made to get the wound healed as quickly as possible, even within the traditional 3-week period usually allowed for healing. We believe that the traditional dogma of aiming for healing within 3 weeks is overly simplistic and should be abandoned: in paediatric burns, every day counts. TRIAL REGISTRATION: Not applicable.

Monitoring of Persons with Risk for Exposure to Ebola Virus - United States, November 3, 2014-December 27, 2015.

During November 3, 2014-December 27, 2015, CDC implemented guidance on movement and monitoring of persons in the United States with potential exposure to Ebola virus (Ebola) (1). Monitoring was concluded in December 2015. After CDC modified the guidance for monitoring travelers from Guinea (the last country for which monitoring of travelers was recommended) in late December 2015, jurisdictional reports were no longer collected by CDC. This report documents the number of persons monitored as part of the effort to isolate, test, and, if necessary, treat symptomatic travelers and other persons in the United States who had risk for exposure to Ebola during the period the guidance was in effect. Sixty jurisdictions, including all 50 states, two local jurisdictions, and eight territories and freely associated states, reported a total of 29,789 persons monitored, with >99% completing 21-day monitoring with no loss to follow-up exceeding 48 hours. No confirmed cases of imported Ebola were reported once monitoring was initiated. This landmark public health response demonstrates the robust infrastructure and sustained monitoring capacity of local, state, and territorial health authorities in the United States as a part of a response to an international public health emergency.

Reducing Health Disparities and Improving Health Equity in Saint Lucia.

St. Lucia is an island nation in the Eastern Caribbean, with a population of 179,000 people, where chronic health conditions, such as hypertension and diabetes, are significant. The purpose of this pilot study is to create a model for community health education, tracking, and monitoring of these health conditions, research training, and policy interventions in St. Lucia, which may apply to other Caribbean populations, including those in the U.S. This paper reports on phase one of the study, which utilized a mixed method analytic approach. Adult clients at risk for, or diagnosed with, diabetes (n = 157), and health care providers/clinic administrators (n = 42), were recruited from five healthcare facilities in St. Lucia to assess their views on health status, health services, and improving health equity. Preliminary content analyses indicated that patients and providers acknowledge the relatively high prevalence of diabetes and other chronic illnesses, recognize the impact that socioeconomic status has on health outcomes, and desire improved access to healthcare and improvements to healthcare infrastructures. These findings could inform strategies, such as community education and workforce development, which may help improve health outcomes among St. Lucians with chronic health conditions, and inform similar efforts among other selected populations.

Tissue expansion in burn reconstruction: what can the child and family expect?

A child with a burn injury often has to go through reconstructive surgery after it has healed to improve function and cosmetic appearance. Tissue expansion is one of the procedures commonly used in the reconstructive process. It requires commitment from the child and the family, because it involves several hospital visits, including at least two surgical episodes, in addition to a change in lifestyle during the process, and there are time and costs involved in travelling, including time off work and school. However, most families think that the final improvement achieved is worthwhile. Multidisciplinary pre-reconstruction clinics offer information and individualised support on the clinical, practical and psychological aspects of the procedures. The audit presented in this article found that attendance at the clinics can improve patient education, reduce complications and enhance the experience of the children and their families.

Translocation breakpoint at 7q31 associated with tics: further evidence for IMMP2L as a candidate gene for Tourette syndrome.

Gilles de la Tourette syndrome is a complex neuropsychiatric disorder with a strong genetic basis. We identified a male patient with Tourette syndrome-like tics and an apparently balanced de novo translocation [46,XY,t(2;7)(p24.2;q31)]. Further analysis using array comparative genomic hybridisation (CGH) revealed a cryptic deletion at 7q31.1-7q31.2. Breakpoints disrupting this region have been reported in one isolated and one familial case of Tourette syndrome. In our case, IMMP2L, a gene coding for a human homologue of the yeast inner mitochondrial membrane peptidase subunit 2, was disrupted by the breakpoint on 7q31.1, with deletion of exons 1-3 of the gene. The IMMP2L gene has previously been proposed as a candidate gene for Tourette syndrome, and our case provides further evidence of its possible role in the pathogenesis. The deleted region (7q31.1-7q31.2) of 7.2 Mb of genomic DNA also encompasses numerous genes, including FOXP2, associated with verbal dyspraxia, and the CFTR gene.

The deployment of adenovirus-containing gene activated matrices onto severed axons after central nervous system injury leads to transgene expression in target neuronal cell bodies.

BACKGROUND: In previous studies, we showed that gene activated matrices (GAMs) containing nonviral vectors successfully deliver genes to neurons after optic nerve and spinal cord injury. In the present study, we evaluated whether adenoviral vectors delivered within a GAM increase the efficiency of local gene delivery to injured CNS neurons. Lyophilized GAMs containing collagen and adenoviral vectors were assessed in vitro and in vivo. METHODS: We evaluated viral vector stability, release kinetics and efficiency of transduction for this GAM formulation in vitro using the quantitative polymerase chain reaction (qPCR), flow cytometry and fluorescence microscopy. Using PCR, reverse transcriptase-PCR and confocal microscopy, we assessed viral DNA retrograde axonal transport, green fluorescent protein (GFP) expression in retinal ganglion cells (RGCs) after GAM implantation into the wound of the rat transected optic nerve. RESULTS: qPCR analyses demonstrated that 100% of viral particles were retained within the collagen after lyophilization. In vitro studies demonstrated that 60% of the particles within the GAM were infective and not released from the collagen matrix when placed in water. By 24 h, GFP expression was detected within cells that have invaded the GAM. In vivo studies demonstrated that adenoviral particles were retrogradely transported in axons from the GAM implanted at the lesion site to the RGC in the retina where the corresponding mRNA was expressed. Analysis of the efficiency of cell transduction indicated that 69% of RGC express GFP. CONCLUSIONS: These studies demonstrate that lyophilized GAMs containing adenoviral particles within collagen are stable, retain a significant proportion of their infectivity and successfully and efficiently deliver genes to neurons after central nervous system injury.

In vitro evaluation of a 'stealth' adenoviral vector for targeted gene delivery to adult mammalian neurones.

BACKGROUND: Polymer coating of adenovirus type 5 (Ad5) particles produces a 'stealth' Ad5 (sAd5) that confers protection from immune recognition, blocks receptor-mediated uptake, and favours uptake into pinocytic cells. METHODS: In mixed cultures of primary adult rat dorsal root ganglion neurones (DRGN), rat C6 glioma cells, A9 non-Coxsackie and Ad Receptor (CAR)- and CAR-expressing fibroblasts, reporter gene expression after sAd5 pinocytotic uptake was monitored using the green fluorescent protein (gfp) gene, and viral particle trafficking and polymer coat dismantling was followed using Yoyo-1 tagged Ad5 DNA and Texas Red (TR) to label the coat. RESULTS: sAd5.gfp was pinocytosed by significantly higher proportions of neurones, than other cells, but GFP was not expressed. The TR-labelled coat remained co-localised with tagged viral DNA within transfected DRGN, showing that sAd5 did not uncoat and viral DNA did not traffic to the nucleus. Noncoated Ad5 transduced non-neuronal DRG cells more efficiently than DRGN, whereas A9(CAR) cells were more significantly transduced than any other cell type. Retargeting of the sAd5.gfp with either fibroblast growth factor-2 or nerve growth factor (NGF) enhanced internalisation by DRGN into endocytic vesicles allowing uncoating and thus GFP expression. Retargeting with NGF resulted in significantly higher numbers of DRGN expressing GFP than non-neuronal DRG cells. CONCLUSIONS: These findings indicate that DRGN pinocytose atropic genetic particles at higher levels than non-neuronal DRG cells and the environment of pinocytic vesicles is not conducive to sAd5 uncoating and capsid dismantling, requiring reformulation of sAd5 with either a neurone specific ligand or a self-dismantling coat to target sAd5 transgene expression to neurones.

Targeting adenoviral transgene expression to neurons.

Adenovirus (Ad) is an efficient and safe vector for CNS gene delivery since it infects non-replicating neurons and does not cause insertional mutagenesis of host cell genomes. However, the promiscuous Ad CAR receptor targets cells non-specifically and activates a host immune response. Using Ad5 containing an expression cassette encoding the gene for green fluorescent protein, gfp, regulated by the neuron specific promoter synapsin-1 and the woodchuck post-transcriptional regulatory element (WPRE), we demonstrate efficient, prolonged and promoter-restricted gfp expression in neurons of mixed primary adult rat dorsal root ganglion (DRG) and retinal cell cultures. We also demonstrate restricted gfp expression in DRG neurons after direct injections of Ad5 containing the synapsin-1(gfp)/WPRE construct into L4 DRG in vivo, while Ad5 CMV(gfp) transfected both DRG glia and neurons. Moreover, since the effective titres of delivered Ad5 are reduced with this neuron specific promoter/WPRE expression cassette, the viral immune challenge should be attenuated when used in vivo.

Aluminium in human breast tissue.

Aluminium is omnipresent in everyday life and increased exposure is resulting in a burgeoning body burden of this non-essential metal. Personal care products are potential contributors to the body burden of aluminium and recent evidence has linked breast cancer with aluminium-based antiperspirants. We have used graphite furnace atomic absorption spectrometry (GFAAS) to measure the aluminium content in breast biopsies obtained following mastectomies. The aluminium content of breast tissue and breast tissue fat were in the range 4-437 nmol/g dry wt. and 3-192 nmol/g oil, respectively. The aluminium content of breast tissue in the outer regions (axilla and lateral) was significantly higher (P=0.033) than the inner regions (middle and medial) of the breast. Whether differences in the regional distribution of aluminium in the breast are related to the known higher incidence of tumours in the outer upper quadrant of the breast remains to be ascertained.