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Abstract Background People with neurodegenerative disorders show diverse clinical syndromes, genetic heterogeneity, and distinct brain pathological changes, but studies report overlap between these features. DNA methylation (DNAm) provides a way to explore this overlap and heterogeneity as it is determined by the combined effects of genetic variation and the environment. In this study, we aim to identify shared blood DNAm differences between controls and people with Alzheimer’s disease, amyotrophic lateral sclerosis, and Parkinson’s disease. Results We use a mixed-linear model method (MOMENT) that accounts for the effect of (un)known confounders, to test for the association of each DNAm site with each disorder. While only three probes are found to be genome-wide significant in each MOMENT association analysis of amyotrophic lateral sclerosis and Parkinson’s disease (and none with Alzheimer’s disease), a fixed-effects meta-analysis of the three disorders results in 12 genome-wide significant differentially methylated positions. Predicted immune cell-type proportions are disrupted across all neurodegenerative disorders. Protein inflammatory markers are correlated with profile sum-scores derived from disease-associated immune cell-type proportions in a healthy aging cohort. In contrast, they are not correlated with MOMENT DNAm-derived profile sum-scores, calculated using effect sizes of the 12 differentially methylated positions as weights. Conclusions We identify shared differentially methylated positions in whole blood between neurodegenerative disorders that point to shared pathogenic mechanisms. These shared differentially methylated positions may reflect causes or consequences of disease, but they are unlikely to reflect cell-type proportion differences.

Parkinson’s disease (PD) is a common neurodegenerative disorder with a complex etiology involving genetics and the environment. Here, Vallerga et al. identify two CpG probes associated with PD in a blood cell type-corrected epigenome-wide meta-analysis, implicating the SLC7A11 gene as a plausible biological target.

Abstract Background DNA methylation changes with age. Chronological age predictors built from DNA methylation are termed ‘epigenetic clocks’. The deviation of predicted age from the actual age (‘age acceleration residual’, AAR) has been reported to be associated with death. However, it is currently unclear how a better prediction of chronological age affects such association. Methods In this study, we build multiple predictors based on training DNA methylation samples selected from 13,661 samples (13,402 from blood and 259 from saliva). We use the Lothian Birth Cohorts of 1921 (LBC1921) and 1936 (LBC1936) to examine whether the association between AAR (from these predictors) and death is affected by (1) improving prediction accuracy of an age predictor as its training sample size increases (from 335 to 12,710) and (2) additionally correcting for confounders (i.e., cellular compositions). In addition, we investigated the performance of our predictor in non-blood tissues. Results We found that in principle, a near-perfect age predictor could be developed when the training sample size is sufficiently large. The association between AAR and mortality attenuates as prediction accuracy increases. AAR from our best predictor (based on Elastic Net, https://github.com/qzhang314/DNAm-based-age-predictor) exhibits no association with mortality in both LBC1921 (hazard ratio = 1.08, 95% CI 0.91–1.27) and LBC1936 (hazard ratio = 1.00, 95% CI 0.79–1.28). Predictors based on small sample size are prone to confounding by cellular compositions relative to those from large sample size. We observed comparable performance of our predictor in non-blood tissues with a multi-tissue-based predictor. Conclusions This study indicates that the epigenetic clock can be improved by increasing the training sample size and that its association with mortality attenuates with increased prediction of chronological age.

Background: The main aim of the study was to improve the general health status of the jail prisoners. Specific objectives were to assess the knowledge of HIV/AIDS among prison inmates and to explore the perceptions of risk factors related to HIV /AIDS spread in prison inmates of district Jail Sargodha. Material & Methods: It was a Cross Sectional study conducted in district jail Sargodha from 1st October to 31st December 2013. The sample size estimated to carry out this study was n=180. Data was collected through Systematic sampling and for its entry and analysis SPSS 16.0 software was used. Results: In this study the upper and lower bound of age groups was between 18 to 78 years. Average age of participants included was 35 years. Both married (56.1%) and unmarried (41.7%) respondents were contained within the study. During data collection all illiterate (42.2%) and literate (57.8%) prisoners from both urban (80.2%) and rural (15.6%) area were considered resulting in a large number of illiterate respondents belonging from urban area. Study statistics indicated that the ratio of low income levels of respondents was very high, which was 66.7%, between 5,000 to 10,000 rupees per month and only 15.6% respondents had income level above 20,000 rupees. Awareness regarding sexually transmitted diseases (STDs) out of total respondents, 126 were aware while 112 had only heard about HIV/AIDS disease. Study explored that a big ratio of respondents had no knowledge about casual relation with HIV infected person. It was found that the overall knowledge of respondents was reasonable e.g. by sharing needles, sexual intercourse, blood transmission, pregnant mother transmit to her new born child, through breast feeding, homosexual, shaving instruments. This study showed that about 83% of literate and illiterate having no knowledge about difference in between HIV and AIDs. Conclusion: The prison inmates may have HIV/AIDs inside the Jail or import from outside. The health setup in Pakistani jails cannot be beneficial for the health of prisoners if necessary codal formalities will not be fulfilled. Even though Supreme Court and High Court have recommended implementing the proper health procedure but still there is no proper mechanism to monitor the implementation of the recommendations. [ABSTRACT FROM AUTHOR]

The aim was to assess the role of platform switching ( PS) in minimising crestal bone loss around dental implants through a systematic review of the currently available clinical evidence. To address the focused question 'Does PS minimise crestal bone loss compared with non-platform-switched ( NPS) implants?', Pub Med/ Medline and Google Scholar databases were explored from 1986 up to and including December 2013 using the following key words in different combinations: 'bone loss', 'dental implant', 'diameter', 'mandible', 'maxilla' and 'platform switching'. Letters to the Editor, unpublished data, historical reviews, case reports and articles published in languages other than English were excluded. Fifteen clinical studies were included. In seven studies, PS and NPS implants were placed in both the maxilla and mandible. In 13 studies, implants were placed at crestal bone levels whereas in one study, implants were placed supracrestally. Three studies reported the bucco-lingual (or transversal) width of the alveolar ridge which ranged between 7-8 mm. Seven studies reported that implants placed according to the PS concept did not minimise crestal bone loss as compared with NPS implants. 3 D- Implant positioning, width of alveolar ridge and control of micromotion at the implant-abutment interface are the more critical factors that influence crestal bone levels than PS. [ABSTRACT FROM AUTHOR]

Abstract: In order to design a solar energy system with optimized performance a through knowledge of solar radiation data for a considerably long period (20-25 years) is a pre-requisite. For developing countries like Pakistan, the need of empirical models to assess the feasibility of solar energy utilization seems inevitable due to the absence and scarcity of trust-worthy solar radiation data. We present such models for the capital city of Pakistan, Islamabad to estimate global and diffuse solar radiation. It is found that with the exception of monsoon month, solar energy can be utilized very efficiently throughout the year. The models suggested could be used for most of the north-eastern areas of Pakistan, which are similar to Islamabad with respect to the climate and the availability of solar radiation but lack in the record of solar radiation data. [Copyright &y& Elsevier]

Background: Areca-nut (AN) chewing habit has been associated with oral diseases including oral cancer, oral submucous fibrosis and periodontal disease; however, some authors have reported that the AN-chewing abuse may also jeopardize the systemic health among its users. Objectives: The objective was to review any reported association between AN-chewing and the metabolic syndrome (MetS). Methods: To address the research question “Is there an association between areca-nut chewing habit and the MetS?” the MEDLINE and PubMed databases were searched from 1991 up to and including April 2010. The search criteria included: human studies, metabolic syndrome, diabetes, areca nut (AN). Only articles published in English were included. Results: Eight cohort studies were included in the review. The sample size of the selected studies ranged from 210 to 56,116 individuals (age range 15-83 years). The daily frequencies of AN-chewing reported by the users ranged between once a day to 76 times daily. The duration of use ranged from 6 years to ≥ 20 years. Two studies associated AN-chewing habit with hyperglycemia and type 2 diabetes while five studies studies reported an association between AN-chewing and metabolic syndrome. Four studies related AN-chewing with obesity and an increased body mass index. Higher triacylglycerol levels were reported in one study among AN-chewers compared to non-chewers. Though the numbers of publications on this subject are limited, the available studies indicate that AN-chewing could be associated with the metabolic syndrome, and individually with two of the recognized components of the syndrome i.e. diabetes mellitus and central obesity. [ABSTRACT FROM AUTHOR]