No excess of mitochondrial DNA deletions within muscle in progressive multiple sclerosis

BACKGROUND: Mitochondrial dysfunction is an established feature of multiple sclerosis (MS). We recently described high levels of mitochondrial DNA (mtDNA) deletions within respiratory enzyme-deficient (lacking mitochondrial respiratory chain complex IV with intact complex II) neurons and choroid plexus epithelial cells in progressive MS. OBJECTIVES: The objective of this paper is to determine whether respiratory enzyme deficiency and mtDNA deletions in MS were in excess of age-related changes within muscle, which, like neurons, are post-mitotic cells that frequently harbour mtDNA deletions with ageing and in disease. METHODS: In progressive MS cases (n=17), known to harbour an excess of mtDNA deletions in the central nervous system (CNS), and controls (n=15), we studied muscle (paraspinal) and explored mitochondria in single fibres. Histochemistry, immunohistochemistry, laser microdissection, real-time polymerase chain reaction (PCR), long-range PCR and sequencing were used to resolve the single muscle fibres. RESULTS: The percentage of respiratory enzyme-deficient muscle fibres, mtDNA deletion level and percentage of muscle fibres harbouring high levels of mtDNA deletions were not significantly different in MS compared with controls. CONCLUSION: Our findings do not provide support to the existence of a diffuse mitochondrial abnormality involving multiple systems in MS. Understanding the cause(s) of the CNS mitochondrial dysfunction in progressive MS remains a research priority

Variations in disability and quality of life with age and sex between eight Lower and Middle Income Countries:data from the INDEPTH WHO-SAGE collaboration

Background: Disability and quality of life are key outcomes for older people. Little is known about how these measures vary with age and gender across lower income and middle-income countries; such information is necessary to tailor health and social care policy to promote healthy ageing and minimise disability. Methods: We analysed data from participants aged 50 years and over from health and demographic surveillance system sites of the International Network for the Demographic Evaluation of Populations and their Health Network in Ghana, Kenya, Tanzania, South Africa, Vietnam, India, Indonesia and Bangladesh, using an abbreviated version of the WHO Study on global AGEing survey instrument. We used the eight-item WHO Quality of Life (WHOQoL) tool to measure quality of life and theWHO Disability Assessment Schedule, version 2 (WHODAS-II) tool to measure disability. We collected selected health status measures via the survey instrument and collected demographic and socioeconomic data from linked surveillance site information. We performed regression analyses to quantify differences between countries in the relationship between age, gender and both quality of life and disability, and we used anchoring vignettes to account for differences in interpretation of disability severity. Results: We included 43 935 individuals in the analysis. Mean age was 63.7 years (SD 9.7) and 24 434 (55.6%) were women. In unadjusted analyses across all countries, WHOQoL scores worsened by 0.13 points (95% CI 0.12 to 0.14) per year increase in age and WHODAS scores worsened by 0.60 points (95% CI 0.57 to 0.64). WHODAS-II and WHOQoL scores varied markedly between countries, as did the gradient of scores with increasing age. In regression analyses, differences were not fully explained by age, socioeconomic status, marital status, education or health factors. Differences in disability scores between countries were not explained by differences in anchoring vignette responses. Conclusions: The relationship between age, sex and both disability and quality of life varies between countries. The findings may guide tailoring of interventions to individual country needs, although these associations require further study

An investigation of factors associated with the health and well-being of HIV-infected or HIV-affected older people in rural South Africa

BackgroundDespite the severe impact of HIV in sub-Saharan Africa, the health of older people aged 50+ is often overlooked owing to the dearth of data on the direct and indirect effects of HIV on older people's health status and well-being. The aim of this study was to examine correlates of health and well-being of HIV-infected older people relative to HIV-affected people in rural South Africa, defined as participants with an HIV-infected or death of an adult child due to HIV-related cause. MethodsData were collected within the Africa Centre surveillance area using instruments adapted from the World Health Organization (WHO) Study on global AGEing and adult health (SAGE). A stratified random sample of 422 people aged 50+ participated. We compared the health correlates of HIV-infected to HIV-affected participants using ordered logistic regressions. Health status was measured using three instruments: disability index, quality of life and composite health score. ResultsMedian age of the sample was 60 years (range 50-94). Women HIV-infected (aOR 0.15, 95% confidence interval (CI) 0.08-0.29) and HIV-affected (aOR 0.20, 95% CI 0.08-0.50), were significantly less likely than men to be in good functional ability. Women's adjusted odds of being in good overall health state were similarly lower than men's; while income and household wealth status were stronger correlates of quality of life. HIV-infected participants reported better functional ability, quality of life and overall health state than HIV-affected participants. Discussion and Conclusions The enhanced healthcare received as part of anti-retroviral treatment as well as the considerable resources devoted to HIV care appear to benefit the overall well-being of HIV-infected older people; whereas similar resources have not been devoted to the general health needs of HIV uninfected older people. Given increasing numbers of older people, policy and programme interventions are urgently needed to holistically meet the health and well-being needs of older people beyond the HIV-related care system. <br/

The value of CCTV surveillance cameras as an investigative tool: an empirical analysis

There has been extensive research on the value of closed-circuit television (CCTV) for preventing crime, but little on its value as an investigative tool. This study sought to establish how often CCTV provides useful evidence and how this is affected by circumstances, analysing 251,195 crimes recorded by British Transport Police that occurred on the British railway network between 2011 and 2015. CCTV was available to investigators in 45% of cases and judged to be useful in 29% (65% of cases in which it was available). Useful CCTV was associated with significantly increased chances of crimes being solved for all crime types except drugs/weapons possession and fraud. Images were more likely to be available for more-serious crimes, and less likely to be available for cases occurring at unknown times or in certain types of locations. Although this research was limited to offences on railways, it appears that CCTV is a powerful investigative tool for many types of crime. The usefulness of CCTV is limited by several factors, most notably the number of public areas not covered. Several recommendations for increasing the usefulness of CCTV are discussed

A Case of a Nonpetrous Cholesterol Granuloma Presenting as a Temporal Mass

Objective. A case of a skull base cholesterol granuloma (CG) of the squamosal temporal bone. This is the first ever reported case of CG in a well-pneumatized squamous temporal bone. Design. Case report and review of the literature. Discussion. CG is a cystic mass typically found in the petrous apex and occasionally in the paranasal sinuses and orbit. Experience with the treatment of these expansile and inflammatory processes has largely been garnered from those occurring in the petrous apex, where they are surgically drained, via a transtympanic, transmastoid, or middle fossa approach. We report a case of cholesterol granuloma situated in the temporal fossa presenting as a temporal mass. The accessible location of this particular lesion made it amenable to total excision, avoiding the need for surgical drainage and possibility for recurrence. Conclusion. This case supports the theory of pathogenesis of such lesions typically occurring where pneumatized air spaces interface with bone marrow, in this case, where the reaches of pneumatized cells in the squamous portion of the temporal bone meet diploic bone

Academic goals, student homework engagement, and academic achievement in elementary school

There seems to be a general consensus in the literature that doing homework is beneficial for students. Thus, the current challenge is to examine the process of doing homework to find which variables may help students to complete the homework assigned. To address this goal, a path analysis model was fit. The model hypothesized that the way students engage in homework is explained by the type of academic goals set, and it explains the amount of time spend on homework, the homework time management, and the amount of homework done. Lastly, the amount of homework done is positively related to academic achievement. The model was fit using a sample of 535 Spanish students from the last three courses of elementary school (aged 9 to 13). Findings show that: (a) academic achievement was positively associated with the amount of homework completed, (b) the amount of homework completed was related to the homework time management, (c) homework time management was associated with the approach to homework, (d) and the approach to homework, like the rest of the variables of the model (except for the time spent on homework), was related to the student's academic motivation (i.e., academic goals).This work was developed through the funding of the research project EDU2013-44062-P, of the State Plan of Scientific and Technical Research and Innovation 2013-2016 (MINECO) and to the financing received by one of the authors in the FPU program of the Ministry of Education, Culture, and Sport.info:eu-repo/semantics/publishedVersio

Development and implementation of rapid metabolic engineering tools for chemical and fuel production in Geobacillus thermoglucosidasius NCIMB 11955

Background The thermophile Geobacillus thermoglucosidasius has considerable attraction as a chassis for the production of chemicals and fuels. It utilises a wide range of sugars and oligosaccharides typical of those derived from lignocellulose and grows at elevated temperatures. The latter improves the rate of feed conversion, reduces fermentation cooling costs and minimises the risks of contamination. Full exploitation of its potential has been hindered by a dearth of effective gene tools. Results Here we designed and tested a collection of vectors (pMTL60000 series) in G. thermoglucosidasius NCIMB 11955 equivalent to the widely used clostridial pMTL80000 modular plasmid series. By combining a temperature-sensitive replicon and a heterologous pyrE gene from Geobacillus kaustophilus as a counter-selection marker, a highly effective and rapid gene knock-out/knock-in system was established. Its use required the initial creation of uracil auxotroph through deletion of pyrE using allele-coupled exchange (ACE) and selection for resistance to 5-fluoroorotic acid. The turnaround time for the construction of further mutants in this pyrE minus strain was typically 5 days. Following the creation of the desired mutant, the pyrE allele was restored to wild type, within 3 days, using ACE and selection for uracil prototrophy. Concomitant with this process, cargo DNA (pheB) could be readily integrated at the pyrE locus. The system’s utility was demonstrated through the generation in just 30 days of three independently engineered strains equivalent to a previously constructed ethanol production strain, TM242. This involved the creation of two in-frame deletions (ldh and pfl) and the replacement of a promoter region of a third gene (pdh) with an up-regulated variant. In no case did the production of ethanol match that of TM242. Genome sequencing of the parental strain, TM242, and constructed mutant derivatives suggested that NCIMB 11955 is prone to the emergence of random mutations which can dramatically affect phenotype. Conclusions The procedures and principles developed for clostridia, based on the use of pyrE alleles and ACE, may be readily deployed in G. thermoglucosidasius. Marker-less, in-frame deletion mutants can be rapidly generated in 5 days. However, ancillary mutations frequently arise, which can influence phenotype. This observation emphasises the need for improved screening and selection procedures at each step of the engineering processes, based on the generation of multiple, independent strains and whole-genome sequencing

A qualitative study into the personal factors influencing secondary school teachers’ motivating styles

Background: All teachers aspire to create the most motivating classroom climate for their students. This is because students who are motivated demonstrate superior learning outcomes relative to students who are not motivated. According to the Self-Determination Theory (SDT), when teachers establish an autonomy-supportive climate in their classrooms, their students can benefit in numerous developmentally and educationally important ways. Whilst most teachers have an understanding that autonomy-supportive teaching can benefit their students, many of them are unwilling or unable to carry out autonomy-supportive strategies. This can be explained by the implicit and explicit forces (e.g., teaching philosophies and beliefs, personal experiences) imposed on them by their internal (namely, intrapsychic) and external (namely, social) environments. This paper focuses on the personal factors that influence teachers’ adoption and employment of autonomy-supportive instructional behaviours. Method: Following a 10-week intervention program on implementing six autonomy-supportive instructional behaviours, we interviewed 59 teachers from 17 secondary schools in Singapore on their adoption and employment of the teaching strategies. Their number of years of teaching experience ranged from 1 to 31 years with a mean of 10.8 years of teaching experience, and 62.71% of them were female. Finding: From the interviews, we identified several teacher-related personal factors which we labelled “teaching philosophies and beliefs,” “personal experiences,” “motivation to teach,” “personality,” “teachers’ mental and emotional states” and “teaching efficacy.” Through identifying the personal factors, we hope to raise awareness amongst the teachers on the inner forces that can foster or frustrate their own expression of autonomy-supportive instructional behaviours. Given the many plausible benefits that can be derived from autonomy-supportive teaching, we hope that the information gained from this qualitative study can path the way for greater willingness and effort in implementing autonomy-supportive teaching in the classrooms

A three-year longitudinal study of retinal function and structure in patients with multiple sclerosis

BACKGROUND Researchers have in recent years begun to investigate ophthalmological manifestations of multiple sclerosis (MS) other than optic neuritis (ON), and it is now clear that changes to retinal function (measured using the electroretinogram, ERG) and structure (measured using optical coherence tomography, OCT) are found in MS patients irrespective of prior ON episodes. ERG results are consistent with dysfunctional bipolar cells, as in other autoimmune diseases. To date, studies have presented only cross-sectional data regarding ERG and OCT. We, therefore, studied the longitudinal course of ERG and OCT in patients with MS, as well as the effect of disability changes and non-ON clinical relapses on these functional and structural measures. METHODS MS patients (n = 23) participating in an ongoing longitudinal observational study were invited to take part in a 3-year ophthalmological substudy. ERG and OCT were performed, and measures of MS-related disability and relapse history were obtained. Study visits were repeated annually. ERG peak times, rod b-wave amplitude, mixed rod/cone and cone b-/a-wave amplitude ratios, thickness of the peripapillary retinal nerve fibre layer, and volumes of the segmented retinal layers/complexes were analysed. Using generalised estimating equation models adjusted for age, ON, and MS treatment status, we assessed changes to ERG and OCT over the study duration, the effect of changes in disability and recent non-ON MS relapses on ERG and OCT, and the effect of selected OCT parameters on corresponding ERG parameters. RESULTS At the group level, small fluctuations of several ERG peak times were recorded, with OCT values remaining stable. Increased disability between visits was associated with significant prolongation of mixed rod-cone ERG b-wave peak times. No evidence of associations between OCT and ERG parameters was observed. CONCLUSIONS Retinal bipolar cell function may be affected by changes in disability in patients with MS; however, recent non-ON MS clinical relapses appear not to affect ERG or OCT results. As ERG changes in MS patients over 3 years are likely to be small and of uncertain clinical relevance, longitudinal studies of retinal function in MS should be planned over an extended period