Dietary Patterns and Socioeconomic Status in the Very Old: The Newcastle 85+ Study

BackgroundDietary patterns (DP) are associated with health outcomes in younger adults but there is a lack of evidence in the very old (aged 85+) on DP and their association with sociodemographic factors, lifestyle, health and functioning measures. Higher socioeconomic status (SES) has been linked with healthier DP but it is not known whether these associations are sustained in the very old.ObjectiveWe aimed to (a) characterise DP in the very old and (b) assess the relationships between three SES indicators (education, occupational class and area-deprivation index [IMD]) and DP.MethodsComplete dietary data at baseline (2006/07) for 793 participants in the Newcastle 85+ Study were established through 24-hr multiple pass recall. We used Two-Step clustering and 30 food groups to derive DP, and multinomial logistic regression models to assess the association with SES.ResultsWe identified three distinct DP (characterised as ‘High Red Meat’, ‘Low Meat’, and ‘High Butter’) that varied with key sociodemographic, health and functioning measures. ‘Low Meat’ participants were more advantaged (i.e. higher education and occupational class, and lived in more affluent areas in owned homes), were least disabled, cognitively impaired, and depressed, and were more physically active than those in the other DP. After adjusting for other lifestyle factors, cognitive status and BMI, lower educational attainment remained a significant predictor of ‘High Red Meat’ and ‘High Butter’ membership compared with ‘Low Meat’ (‘High Red Meat’: OR [95% CI] for 0–9 and 10–11 years of education vs. ≥12 years: 5.28 [2.85–9.79], p<0.001 and 3.27 [1.65–6.51], p = 0.001, respectively; ‘High Butter’: 3.32 [1.89–5.82], p<0.001 and 2.83 [1.52–5.28], p = 0.001).ConclusionsIn this cohort of very old adults, we detected a favourable DP (‘Low Meat’), which was associated with better health and functioning and higher SES.     

Alzheimer’s Disease Susceptibility Genes APOE and TOMM40, and Hippocampal Volumes in the Lothian Birth Cohort 1936

The APOE ε and TOMM40 rs10524523 (‘523’) variable length poly-T repeat gene loci have been significantly and independently associated with Alzheimer’s disease (AD) related phenotypes such as age of clinical onset. Hippocampal atrophy has been significantly associated with memory impairment, a characteristic of AD. The current study aimed to test for independent effects of APOE ε and TOMM40 ‘523’ genotypes on hippocampal volumes as assessed by brain structural MRI in a relatively large sample of community-dwelling older adults. As part of a longitudinal study of cognitive ageing, participants in the Lothian Birth Cohort 1936 underwent genotyping for APOE ε2/ε3/ε4 status and TOMM40 ‘523’ poly-T repeat length, and detailed structural brain MRI at a mean age of 72.7 years (standard deviation = 0.7, N range = 624 to 636). No significant effects of APOE ε or TOMM40 523 genotype were found on hippocampal volumes when analysed raw, or when adjusted for either intracranial or total brain tissue volumes. In summary, in a large community-dwelling sample of older adults, we found no effects of APOE ε or TOMM40 523 genotypes on hippocampal volumes. This is discrepant with some previous reports of significant association between APOE and left/right hippocampal volumes, and instead echoes other reports that found no association. Previous significant findings may partly reflect type 1 error. Future studies should carefully consider: 1) their specific techniques in adjusting for brain size; 2) assessing more detailed sub-divisions of the hippocampal formation; and 3) testing whether significant APOE-hippocampal associations are independent of generalised brain atrophy.     

Association between Electronic Cigarette Use and Asthma among High School Students in South Korea

Objectives

Little is known about health outcomes related to electronic cigarette (EC) use, despite its growing popularity. The aim of this study is to investigate the association between EC use and asthma.

Methods

The study design is a cross-sectional study. A total of 35,904 high school students were included as the final study population. The presence of asthma was based on a student’s self-reported doctor diagnosis of asthma in the past 12 months.

Results

Prevalence rates of asthmatics in ‘current EC users’ (n = 2,513), ‘former EC users’ (n = 2,078), and ‘never EC users’ (n = 31,313), were 3.9% (n = 98), 2.2% (n = 46) and 1.7% (n = 530), respectively. Comparing ‘current EC’ users with ‘never EC’ users, the unadjusted OR for asthma was 2.36 (95% CI: 1.89–2.94). In order to control for the effect of conventional cigarette (CC) smoking, after stratifying the subjects by the three CC smoking categories (never CC, former CC, and current CC), within the ‘never CC’ category, the unadjusted OR for asthma for ‘current EC’ users was 3.41 (95% CI: 1.79–6.49), and the adjusted OR was 2.74 (95% CI: 1.30–5.78). Severe asthma was reflected by the number of days absent from school due to asthma symptoms; current EC users had the highest adjusted OR for severe asthma compared to ‘never EC’ users.

Conclusions

When compared to a reference population of high school students in South Korea, EC users have an increased association with asthma and are more likely to have had days absent from school due to severe asthma symptoms. In conclusion, the results indicate that EC use may be a risk factor for asthma. The results may be useful in developing a scientific basis for the evaluation of a potential health hazard by EC.     

Eucalyptus Pollen Allergy and Asthma in Children: A Cross-Sectional Study in South-East Queensland,Australia

ObjectivesTo investigate Eucalyptus (gum tree) pollen allergy in children in relation to geography, particularly vegetation, and its relationship to asthma.MethodsMales (n = 180) and females (n = 200) aged 9 to 14 participated. Some were healthy (asymptomatic), some had asthma, and some had other symptoms associated with atopy. School students were from three urban coastal schools and one school from a nearby semi-rural elevated area (range) near Brisbane, Australia. Coastal and range locations featured different distributions of Myrtaceae family vegetation (including Eucalyptus, Melaleuca, Leptospermum species). Skin prick test (SPT) responses to 15 commercial allergens were compared. As well, responses from coast versus range groups, and ‘asthma’ (n = 97) versus ‘healthy’ status (n = 107) groups, were compared.ResultsSPT responses (≥3mm wheal diameter) indicate that children with asthma are 31.1 times more likely to be allergic to Eucalyptus pollen extract (OR: 31.1; 95%CI 4.1- 235.7) compared to healthy children. Dust mite (p = .018), Eucalyptus (p = .046) and cockroach (p = .047) allergen SPT responses (wheals ≥3mm) were significantly greater in participants located on the coast versus range as determined by Fisher’s Exact Test (α .05). For each location, percentage of positive responses (wheals ≥3mm) was greatest for ‘dust mite’ (30.9%-46%), ‘cockroach’ (18.1% -35%) and ‘Bermuda grass’ (10.6%-19.4%).ConclusionsThe results support the hypothesis that proximity to Myrtaceae vegetation is related to positive SPT response and that Eucalyptus is an important allergen for children with asthma. Substantial response to olive allergen, in the absence of olive trees, suggests that the response may be driven by substances in other plants, perhaps Melaleuca quinquenervia, which abounds in coastal areas.ImplicationsResponse to Eucalyptus allergen indicates that changes in gardening practice in schools and public areas may be appropriate. The findings pose validity questions regarding the use of some commercial allergens due to cross-reactive responses and the sources of those responses.     

Mobility Modification Alleviates Environmental Influence on Incident Mobility Difficulty among Community-Dwelling Older People: A Two-Year Follow-Up Study

BackgroundEnvironmental barriers increase risk for mobility difficulties in old age. Mobility difficulty is preceded by a phase where people try to postpone a difficulty through mobility modification. We studied whether perceived environmental mobility barriers outdoors correlate with mobility modification and mobility difficulty, predict development of mobility difficulty over a two-year follow-up, and whether mobility modification alleviates the risk for difficulty.MethodsAt baseline, 848 people aged 75–90 were interviewed face-to-face. Telephone follow-up interviews were conducted one (n = 816) and two years (n = 761) later. Environmental barriers to mobility were self-reported using a15-item structured questionnaire at baseline, summed and divided into tertiles (0, 1 and 2 or more barriers). Mobility difficulty was assessed as self-reported ability to walk 2 km at all assessment points and categorized into ‘no difficulty’, ‘no difficulty but mobility modifications’ (reducing frequency, stopping walking, using an aid, slowing down or resting during the performance) and ‘difficulty’.ResultsAt baseline, 212 participants reported mobility modifications and 356 mobility difficulties. Those reporting one or multiple environmental barriers had twice the odds for mobility modifications and up to five times the odds for mobility difficulty compared to those reporting no environmental barriers. After multiple adjustments for health and functioning, reporting multiple environmental barriers outdoors continued to predict the development of incident mobility difficulty over the two-year follow-up. Mobility modifications attenuated the association.ConclusionFor older people who successfully modify their performance, environmental influence on incident mobility difficulty can be diminished. Older people use mobility modification to alleviate environmental press on mobility.     

Genomic insights on the ethno-history of the Maya and the ‘Ladinos’ from Guatemala

Background

Guatemala is a multiethnic and multilingual country located in Central America. The main population groups separate ‘Ladinos’ (mixed Native American-African-Spanish), and Native indigenous people of Maya descent. Among the present-day Guatemalan Maya, there are more than 20 different ethnic groups separated by different languages and cultures. Genetic variation of these communities still remains largely unexplored. The principal aim of this study is to explore the genetic variability of the Maya and ‘Ladinos’ from Guatemala by means of uniparental and ancestry informative markers (AIMs).

Results

Analyses of uniparental genetic markers indicate that Maya have a dominant Native American ancestry (mitochondrial DNA [mtDNA]: 100%; Y-chromosome: 94%). ‘Ladino’, however, show a clear gender-bias as indicated by the large European ancestry observed in the Y-chromosome (75%) compared to the mtDNA (0%). Autosomal polymorphisms (AIMs) also mirror this marked gender-bias: (i) Native American ancestry: 92% for the Maya vs. 55% for the ‘Ladino’, and (ii) European ancestry: 8% for the Maya vs. 41% for the ‘Ladino’. In addition, the impact of the Trans-Atlantic slave trade on the present-day Guatemalan population is very low (and only occurs in the ‘Ladino’; mtDNA: 9%; AIMs: 4%), in part mirroring the fact that Guatemala has a predominant orientation to the Pacific Ocean instead of a Caribbean one. Sequencing of entire Guatemalan mitogenomes has led to improved Native American phylogeny via the addition of new haplogroups that are mainly observed in Mesoamerica and/or the North of South America.

Conclusions

The data reveal the existence of a fluid gene flow in the Mesoamerican area and a predominant unidirectional flow towards South America, most likely occurring during the Pre-Classic (1800 BC-200 AD) and the Classic (200–1000 AD) Eras of the Mesoamerican chronology, coinciding with development of the most distinctive and advanced Mesoamerican civilization, the Maya. Phylogenetic features of mtDNA data also suggest a demographic scenario that is compatible with moderate local endogamy and isolation in the Maya combined with episodes of gene exchange between ethnic groups, suggesting an ethno-genesis in the Guatemalan Maya that is recent and supported on a cultural rather than a biological basis.

Electronic supplementary material

The online version of this article (doi:10.1186/s12864-015-1339-1) contains supplementary material, which is available to authorized users.     

The Obesogenic Quality of the Home Environment: Associations with Diet,Physical Activity,TV Viewing,and BMI in Preschool Children

Objectives

The home environment is thought to play a key role in early weight trajectories, although direct evidence is limited. There is general agreement that multiple factors exert small individual effects on weight-related outcomes, so use of composite measures could demonstrate stronger effects. This study therefore examined whether composite measures reflecting the ‘obesogenic’ home environment are associated with diet, physical activity, TV viewing, and BMI in preschool children.

Methods

Families from the Gemini cohort (n = 1096) completed a telephone interview (Home Environment Interview; HEI) when their children were 4 years old. Diet, physical activity, and TV viewing were reported at interview. Child height and weight measurements were taken by the parents (using standard scales and height charts) and reported at interview. Responses to the HEI were standardized and summed to create four composite scores representing the food (sum of 21 variables), activity (sum of 6 variables), media (sum of 5 variables), and overall (food composite/21 + activity composite/6 + media composite/5) home environments. These were categorized into ‘obesogenic risk’ tertiles.

Results

Children in ‘higher-risk’ food environments consumed less fruit (OR; 95% CI = 0.39; 0.27–0.57) and vegetables (0.47; 0.34–0.64), and more energy-dense snacks (3.48; 2.16–5.62) and sweetened drinks (3.49; 2.10–5.81) than children in ‘lower-risk’ food environments. Children in ‘higher-risk’ activity environments were less physically active (0.43; 0.32–0.59) than children in ‘lower-risk’ activity environments. Children in ‘higher-risk’ media environments watched more TV (3.51; 2.48–4.96) than children in ‘lower-risk’ media environments. Neither the individual nor the overall composite measures were associated with BMI.

Conclusions

Composite measures of the obesogenic home environment were associated as expected with diet, physical activity, and TV viewing. Associations with BMI were not apparent at this age.     

Polymorphisms of Renin-Angiotensin-Aldosterone System Gene in Chinese Han Patients with Nonfamilial Atrial Fibrillation

BackgroundAtrial fibrillation(AF) is the most common arrhythmia in the adult population. The activated renin-angiotensin-aldosterone system (RAS) has been reported to play an important role in the pathogenesis of atrial fibrillation. The aim of this study was to investigate the association between nonfamilial AF and polymorphisms in RAS gene.MethodsA total of 931 patients with nonfamilial AF, 663 non-AF heart disease patients and 727 healthy subjects were selected. 10 tagSNPs (tSNPs) (ACE gene rs8066114, AGT gene rs7539020, rs3789678, rs2478544, rs11568023, rs2478523, rs4762, rs699 and CYP11B2 rs3802230, rs3097) were chosen and genotyped in our study. Single-locus analysis and haplotype analysis were used in this study.ResultsIn single-locus analysis, we found rs11568023 and rs3789678 in AGT gene were associated with nonfamilial AF in Chinese Han population. AF risk was associated with rs3789678 between the AF group and control groups. Under dominant model, the significant AF risk was observed in rs3789678 between the AF group and non AF heart control group; And the protective effect was found in rs11568023, compared with the non-AF heart disease control group. In multilocus haplotype analysis, the association between frequencies of the haplotypes and AF risk was showed in AGT gene (rs7539020-rs3789678), compared ‘TT’ haplotype with the common ‘TC’ haplotype, adjusted for age, gender, LVEF, LVEDD, LAD and frequency of hypertension and diabetes. The diplotype with ‘TC’, carrying rs3789678-C-allele, was associated with reduced risk of AF between the AF group and the healthy control group. The diplotype with ‘TT’ haplotype in the same block, carrying rs3789678-T-allele, was associated with increased risk of AF.ConclusionsVia a large-scale case-control study, we found that rs3789678 site was potential susceptible locus of AF whereas rs11568023 was protective factor.     

A Novel Objective Method of Estimating the Age of Mandibles from African Elephants (Loxodonta africana Africana)

The importance of assigning an accurate estimate of age and sex to elephant carcasses found in the wild has increased in recent years with the escalation in levels of poaching throughout Africa. Irregularities identified in current ageing techniques prompted the development of a new method to describe molar progression throughout life. Elephant mandibles (n = 323) were studied and a point near the distal dental alveolus was identified as being most useful in ranking each jaw according to molar progression. These ‘Age Reference Lines’ were then associated with an age scale based on previous studies and Zimbabwean mandibles of known age. The new ranking produced a single age scale that proved useful for both male and female mandibles up to the maximum lifespan age of 70–75 years. Methods to aid in molar identification and the sexing of found jaws were also identified.     

Measuring Health-Related Quality of Life in Strabismus: A Modification of the Adult Strabismus-20 (AS-20) Questionnaire Using Rasch Analysis

PurposeTo evaluate the psychometric properties of the Adult Strabismus-20 (AS-20)- a health-related quality of life (HRQoL) questionnaire in adults with strabismus, and if flawed, to revise the AS-20 and its subscales creating valid measurement scales.Methods584 adults (meanage, 27.5 years) with strabismus were recruited from an outpatient clinic at a South Indian tertiary eye care centre and were administered the AS-20 questionnaire.The AS-20 was translated and back translated into two Indian languages. The AS-20 and its two 10-item subscales – ‘psychosocial’ and ‘function’were assessed separately for fit to the Rasch model, including an assessment of the rating scale, unidimensionality (by principal components analysis), measurement precision by person separation reliability, PSR, targeting, and differential item functioning (DIF; notable > 1.0 logits).ResultsResponse categories were not used as intended, thereby, required re-organization and reducing their number from 5 to 3. The AS-20 had adequate measurement precision (PSR = 0.87) but lacked unidimensionality; however, deletion of the six multi-dimensionality causing items and an additional three misfitting items resulted in 11-item unidimensional questionnaire (AS-11). Two items failed to satisfy the model expectations in the ‘psychosocial’ subscale and were deleted – resulting in an 8-item unidimensional scale with adequate PSR (0.81) and targeting (0.23 logits). One item misfit in the ‘function’ subscale and was deleted—resulting in a 9 item Rasch-revised unidimensional subscale with acceptable PSR (0.80) and targeting (0.97 logits).None of the items displayed notable DIF by age, gender and level of education.ConclusionsThe AS-11 and its two Rasch-revised subscales – 8-item psychosocial and 9-item function subscale may be more appropriate than the original AS-20 and its two 10-item subscales for use as unidimensional measures of HRQoL in adults with strabismus in India. Further work is required to establish the validity of the revised rating scale.     

Eight-Shaped Hatching Increases the Risk of Inner Cell Mass Splitting in Extended Mouse Embryo Culture

Increased risk of monozygotic twinning (MZT) has been shown to be associated with assisted reproduction techniques, particularly blastocyst culture. Interestingly, inner cell mass (ICM) splitting in human ‘8’-shaped hatching blastocysts that resulted in MZT was reported. However, the underlying cause of MZT is not known. In this study, we investigated in a mouse model whether in vitro culture leads to ICM splitting and its association with hatching types. Blastocyst hatching was observed in: (i) in vivo developed blastocysts and (ii–iii) in vitro cultured blastocysts following in vivo or in vitro fertilization. We found that ‘8’-shaped hatching occurred with significantly higher frequency in the two groups of in vitro cultured blastocysts than in the group of in vivo developed blastocysts (24.4% and 20.4% versus 0.8%, respectively; n = 805, P < 0.01). Moreover, Oct4 immunofluorescence staining was performed to identify the ICM in the hatching and hatched blastocysts. Scattered and split distribution of ICM cells was observed around the small zona opening of ‘8’-shaped hatching blastocysts. This occurred at a high frequency in the in vitro cultured groups. Furthermore, we found more double OCT4-positive masses, suggestive of increased ICM splitting in ‘8’-shaped hatching and hatched blastocysts than in ‘U’-shaped hatching and hatched blastocysts (12.5% versus 1.9%, respectively; n = 838, P < 0.01). Therefore, our results demonstrate that extended in vitro culture can cause high frequencies of ‘8’-shaped hatching, and ‘8’-shaped hatching that may disturb ICM herniation leading to increased risk of ICM splitting in mouse blastocysts. These results may provide insights into the increased risk of human MZT after in vitro fertilization and blastocyst transfer.     

Use of Brain MRI Atlases to Determine Boundaries of Age-Related Pathology: The Importance of Statistical Method

IntroductionNeurodegenerative disease diagnoses may be supported by the comparison of an individual patient’s brain magnetic resonance image (MRI) with a voxel-based atlas of normal brain MRI. Most current brain MRI atlases are of young to middle-aged adults and parametric, e.g., mean ±standard deviation (SD); these atlases require data to be Gaussian. Brain MRI data, e.g., grey matter (GM) proportion images, from normal older subjects are apparently not Gaussian. We created a nonparametric and a parametric atlas of the normal limits of GM proportions in older subjects and compared their classifications of GM proportions in Alzheimer’s disease (AD) patients.MethodsUsing publicly available brain MRI from 138 normal subjects and 138 subjects diagnosed with AD (all 55–90 years), we created: a mean ±SD atlas to estimate parametrically the percentile ranks and limits of normal ageing GM; and, separately, a nonparametric, rank order-based GM atlas from the same normal ageing subjects. GM images from AD patients were then classified with respect to each atlas to determine the effect statistical distributions had on classifications of proportions of GM in AD patients.ResultsThe parametric atlas often defined the lower normal limit of the proportion of GM to be negative (which does not make sense physiologically as the lowest possible proportion is zero). Because of this, for approximately half of the AD subjects, 25–45% of voxels were classified as normal when compared to the parametric atlas; but were classified as abnormal when compared to the nonparametric atlas. These voxels were mainly concentrated in the frontal and occipital lobes.DiscussionTo our knowledge, we have presented the first nonparametric brain MRI atlas. In conditions where there is increasing variability in brain structure, such as in old age, nonparametric brain MRI atlases may represent the limits of normal brain structure more accurately than parametric approaches. Therefore, we conclude that the statistical method used for construction of brain MRI atlases should be selected taking into account the population and aim under study. Parametric methods are generally robust for defining central tendencies, e.g., means, of brain structure. Nonparametric methods are advisable when studying the limits of brain structure in ageing and neurodegenerative disease.     

Transmission of ‘Candidatus Anaplasma camelii’ to mice and rabbits by camel-specific keds,Hippobosca camelina

Anaplasmosis, caused by infection with bacteria of the genus Anaplasma, is an important veterinary and zoonotic disease. Transmission by ticks has been characterized but little is known about non-tick vectors of livestock anaplasmosis. This study investigated the presence of Anaplasma spp. in camels in northern Kenya and whether the hematophagous camel ked, Hippobosca camelina, acts as a vector. Camels (n = 976) and > 10,000 keds were sampled over a three-year study period and the presence of Anaplasma species was determined by PCR-based assays targeting the Anaplasmataceae 16S rRNA gene. Camels were infected by a single species of Anaplasma, ‘Candidatus Anaplasma camelii’, with infection rates ranging from 63–78% during the dry (September 2017), wet (June-July 2018), and late wet seasons (July-August 2019). 10–29% of camel keds harbored ‘Ca. Anaplasma camelii’ acquired from infected camels during blood feeding. We determined that Anaplasma-positive camel keds could transmit ‘Ca. Anaplasma camelii’ to mice and rabbits via blood-feeding. We show competence in pathogen transmission and subsequent infection in mice and rabbits by microscopic observation in blood smears and by PCR. Transmission of ‘Ca. Anaplasma camelii’ to mice (8–47%) and rabbits (25%) occurred readily after ked bites. Hence, we demonstrate, for the first time, the potential of H. camelina as a vector of anaplasmosis. This key finding provides the rationale for establishing ked control programmes for improvement of livestock and human health.     

Cost-free lifespan extension via optimization of gene expression in adulthood aligns with the developmental theory of ageing

Ageing evolves because the force of selection on traits declines with age but the proximate causes of ageing are incompletely understood. The ‘disposable soma’ theory of ageing (DST) upholds that competitive resource allocation between reproduction and somatic maintenance underpins the evolution of ageing and lifespan. In contrast, the developmental theory of ageing (DTA) suggests that organismal senescence is caused by suboptimal gene expression in adulthood. While the DST predicts the trade-off between reproduction and lifespan, the DTA predicts that age-specific optimization of gene expression can increase lifespan without reproduction costs. Here we investigated the consequences for lifespan, reproduction, egg size and individual fitness of early-life, adulthood and post-reproductive onset of RNAi knockdown of five ‘longevity’ genes involved in key biological processes in Caenorhabditis elegans. Downregulation of these genes in adulthood and/or during post-reproductive period increases lifespan, while we found limited evidence for a link between impaired reproduction and extended lifespan. Our findings demonstrate that suboptimal gene expression in adulthood often contributes to reduced lifespan directly rather than through competitive resource allocation between reproduction and somatic maintenance. Therefore, age-specific optimization of gene expression in evolutionarily conserved signalling pathways that regulate organismal life histories can increase lifespan without fitness costs.     

Investigation of Repeat Client Drop-Out and Re-Enrolment Cycles in Fourteen Methadone Maintenance Treatment Clinics in Guangdong,China

ObjectiveClient adherence is vital for effective methadone maintenance treatment (MMT). This study explores the pattern and associated factors of client adherence, drop-out and re-enrolment in the Chinese MMT programme over the period of 2006–2013.MethodsThis retrospective study was conducted in 14 MMT clinics in Guangdong Province, China. We employed Kaplan-Meier survival analysis to estimate the rates of drop-out and re-enrolment of MMT clients and multivariate Cox regression to identify associated factors.ResultsAmong 1,512 study participants, 79% have experienced ‘drop-out’ during the 7-year study period. However, 82% ‘dropped-out’ clients resumed treatment at a later time. Low education level (junior high or below versus otherwise, HR = 1.21, 1.05–1.40), low methadone dosage in the first treatment episode (<50 ml versus ≥50 ml, HR = 1.84, 1.64–2.06) and higher proportion of positive urine test (≥50% versus<50%, HR = 3.72, 3.30–4.20) during the first treatment episode were strong predictors of subsequent drop-outs of the participants. Among the ‘dropped-out’ clients, being female (HR = 1.40, 1.23–1.60), being married (HR = 1.19, 1.09–1.30), and having a higher proportion of positive urine tests in the first treatment episode (≥50% versus<50%, HR = 1.35, 1.20–1.51) had greater likelihood of subsequent re-enrolment in MMT. Clients receiving lower methadone dosage (first treatment episode <50 ml versus ≥50 ml, HR = 1.12, 1.03–1.23; the last intake before drop-out <50 ml versus ≥50 ml, HR = 1.16, 1.04–1.30) were also more likely to re-enrol.ConclusionPersistent cycling in-and-out of clients in MMT programmes is common. Insufficient dosage and higher proportion of positive urine samples in the first treatment episode are the key determinants for subsequent client drop-out and re-enrolment. Interventions should target clients in their early stage of treatment to improve retention in the long term.     

Sporadic outbreaks of crimean-congo haemorrhagic fever in Uganda,July 2018-January 2019

IntroductionCrimean-Congo haemorrhagic fever (CCHF) is a tick-borne, zoonotic viral disease that causes haemorrhagic symptoms. Despite having eight confirmed outbreaks between 2013 and 2017, all within Uganda’s ‘cattle corridor’, no targeted tick control programs exist in Uganda to prevent disease. During a seven-month-period from July 2018-January 2019, the Ministry of Health confirmed multiple independent CCHF outbreaks. We investigated to identify risk factors and recommend interventions to prevent future outbreaks.MethodsWe defined a confirmed case as sudden onset of fever (≥37.5°C) with ≥4 of the following signs and symptoms: anorexia, vomiting, diarrhoea, headache, abdominal pain, joint pain, or sudden unexplained bleeding in a resident of the affected districts who tested positive for Crimean-Congo haemorrhagic fever virus (CCHFv) by RT-PCR from 1 July 2018–30 January 2019. We reviewed medical records and performed active case-finding. We conducted a case-control study and compared exposures of case-patients with age-, sex-, and sub-county-matched control-persons (1:4).ResultsWe identified 14 confirmed cases (64% males) with five deaths (case-fatality rate: 36%) from 11 districts in western and central region. Of these, eight (73%) case-patients resided in Uganda’s ‘cattle corridor’. One outbreak involved two case-patients and the remainder involved one. All case-patients had fever and 93% had unexplained bleeding. Case-patients were aged 6–36 years, with persons aged 20–44 years more affected (AR: 7.2/1,000,000) than persons ≤19 years (2.0/1,000,000), p = 0.015. Most (93%) case-patients had contact with livestock ≤2 weeks before symptom onset. Twelve (86%) lived <1 km from grazing fields compared with 27 (48%) controls (OR_M-H = 18, 95% CI = 3.2-∞) and 10 (71%) of 14 case-patients found ticks attached to their bodies ≤2 weeks before symptom onset, compared to 15 (27%) of 56 control-persons (OR_M-H = 9.3, 95%CI = 1.9–46).ConclusionsCCHF outbreaks occurred sporadically during 2018–2019, both within and outside ‘cattle corridor’ districts of Uganda. Most cases were associated with tick exposure. The Ministry of Health should partner with the Ministry of Agriculture, Animal Industry and Fisheries to develop joint nationwide tick control programs and strategies with shared responsibilities through a One Health approach.     

Characterization of age signatures of DNA methylation in normal and cancer tissues from multiple studies

Background

DNA methylation (DNAm) levels can be used to predict the chronological age of tissues; however, the characteristics of DNAm age signatures in normal and cancer tissues are not well studied using multiple studies.

Results

We studied approximately 4000 normal and cancer samples with multiple tissue types from diverse studies, and using linear and nonlinear regression models identified reliable tissue type-invariant DNAm age signatures. A normal signature comprising 127 CpG loci was highly enriched on the X chromosome. Age-hypermethylated loci were enriched for guanine–and-cytosine-rich regions in CpG islands (CGIs), whereas age-hypomethylated loci were enriched for adenine–and-thymine-rich regions in non-CGIs. However, the cancer signature comprised only 26 age-hypomethylated loci, none on the X chromosome, and with no overlap with the normal signature. Genes related to the normal signature were enriched for aging-related gene ontology terms including metabolic processes, immune system processes, and cell proliferation. The related gene products of the normal signature had more than the average number of interacting partners in a protein interaction network and had a tendency not to interact directly with each other. The genomic sequences of the normal signature were well conserved and the age-associated DNAm levels could satisfactorily predict the chronological ages of tissues regardless of tissue type. Interestingly, the age-associated DNAm increases or decreases of the normal signature were aberrantly accelerated in cancer samples.

Conclusion

These tissue type-invariant DNAm age signatures in normal and cancer can be used to address important questions in developmental biology and cancer research.

Electronic supplementary material

The online version of this article (doi:10.1186/1471-2164-15-997) contains supplementary material, which is available to authorized users.     

Untargeted Metabolomic Analysis of Human Plasma Indicates Differentially Affected Polyamine and L-Arginine Metabolism in Mild Cognitive Impairment Subjects Converting to Alzheimer’s Disease

This study combined high resolution mass spectrometry (HRMS), advanced chemometrics and pathway enrichment analysis to analyse the blood metabolome of patients attending the memory clinic: cases of mild cognitive impairment (MCI; n = 16), cases of MCI who upon subsequent follow-up developed Alzheimer’s disease (MCI_AD; n = 19), and healthy age-matched controls (Ctrl; n = 37). Plasma was extracted in acetonitrile and applied to an Acquity UPLC HILIC (1.7μm x 2.1 x 100 mm) column coupled to a Xevo G2 QTof mass spectrometer using a previously optimised method. Data comprising 6751 spectral features were used to build an OPLS-DA statistical model capable of accurately distinguishing Ctrl, MCI and MCI_AD. The model accurately distinguished (R2 = 99.1%; Q2 = 97%) those MCI patients who later went on to develop AD. S-plots were used to shortlist ions of interest which were responsible for explaining the maximum amount of variation between patient groups. Metabolite database searching and pathway enrichment analysis indicated disturbances in 22 biochemical pathways, and excitingly it discovered two interlinked areas of metabolism (polyamine metabolism and L-Arginine metabolism) were differentially disrupted in this well-defined clinical cohort. The optimised untargeted HRMS methods described herein not only demonstrate that it is possible to distinguish these pathologies in human blood but also that MCI patients ‘at risk’ from AD could be predicted up to 2 years earlier than conventional clinical diagnosis. Blood-based metabolite profiling of plasma from memory clinic patients is a novel and feasible approach in improving MCI and AD diagnosis and, refining clinical trials through better patient stratification.