The influence of avoidant attachment and perceived support on disclosure about involvement in donor-assisted conception to family and friends.

STUDY QUESTION: Do the attachment-related dimensions Anxiety and Avoidance and perceived partner and social support in recipients and donors influence disclosure to others about their involvement in donor-assisted conception (DAC)? SUMMARY ANSWER: A higher global score on attachment Avoidance was associated with greater non-disclosure about involvement in DAC by participants to relationship-specific others. WHAT IS KNOWN ALREADY: Within the context of DAC, the topic of disclosure has been investigated in terms of the 'if', 'when', and the 'how' to disclose about circumstances of conception. Less focus, however, has been directed to investigating psychological theoretical frameworks that influence disclosure decisions to others, i.e. to whom information is disclosed and to what extent details are transparently revealed about the donor programme. STUDY DESIGN, SIZE, DURATION: The study was of a cross-sectional design and utilized a sample of 301 participants who were, or had been, involved in DAC, and were recruited across states of Australia. An online self-report questionnaire was completed between June 2014 and June 2017. PARTICIPANTS/MATERIALS, SETTING, METHODS: English speaking participants consisting of 209 female recipients and 92 donors (36 sperm; 48 egg; 8 embryo donors). Of the recipients, 104 had successfully conceived children via donated gametes (68 sperm, 23 eggs, 6 embryos, and 7 recipients where both gametes were donated from 2 donors to create the embryo). Participants anonymously completed an online questionnaire consisting of five sections: Demographics, Donor Conception and Disclosure Practices, the Experiences in Close Relationships-Relationships Structure, the Quality of Relationship Inventory, and the Multidimensional Scale of Perceived Social Support. Pearson correlations, independent samples t-tests, Chi-square, and ANOVA were used to explore the association between attachment Anxiety and Avoidance scores and disclosure about involvement in a DAC programme to significant others (i.e. parents, siblings, in-laws, and friends). MAIN RESULTS AND THE ROLE OF CHANCE: Compared to published community cohort data, participants reported lower global scores on attachment Anxiety and Avoidance and high levels of romantic partner and social network support, suggestive of secure relationships in the overall study sample. A higher score on attachment Avoidance was associated with less disclosure to significant others in their social network (i.e. parents, siblings, in-laws, and close friends), even in the presence of strong partner support (partial r = -0.248, P = 0.005). Higher scores on attachment Avoidance were inversely associated with level of perceived partner and social network support (all P < 0.05). Irrespective of attachment scores, more than 90% of all participants agreed that a child born of DAC should be told about mode of conception. LIMITATIONS, REASONS FOR CAUTION: This study utilized a cross-sectional design precluding causal inferences between dimensions of insecure attachment and disclosure practices. Participants were required to self-report on the quality of their relationships with the potential for social desirability respondent bias. The study's self-selecting sample may limit generalization to participants who were dis-inclined to participate. Specifically, respondents who have an Avoidant attachment style, may have elected not to participate in the study. WIDER IMPLICATIONS OF THE FINDINGS: Given the increased use of biotechnology and digital facial recognition enabling self-discovery of the donor and the donor's extended family, non-disclosure about involvement in DAC may have consequences. An 'Avoidant' attachment style is important to assess as a potential risk factor for non-disclosure about involvement in DAC across different relational contexts (e.g. close family members and friends). Fertility counsellors should consider introducing a measure of attachment screening as a pre-emptive psychoeducational strategy during donor implications counselling. This information could be used to offer patients insight into concerns they have about DAC disclosures to key important relationships, providing a target of clinical intervention. STUDY FUNDING/COMPETING INTEREST(S): No external funds were sought for this work. None of the authors have any competing interests to declare. TRIAL REGISTRATION NUMBER: N/A.

A new classification system for the anatomical variations of the human circle of Willis: A systematic review.

The circle of Willis (CoW) is an anastomotic arterial network located on the base of the brain. Studies have shown that it demonstrates considerable anatomical variation in humans. This systematic review aimed to identify and catalogue the described anatomical variations of the CoW in humans to create a new, comprehensive variation classification system. An electronic literature search of five databases identified 5899 studies. A two-phase screening process was performed, and studies underwent quality assessment. A total of 42 studies were included in the review. Data were extracted and circles were reconstructed digitally using graphics software. The classification system contains 82 CoW variations in five continuous groups. Group one contains 24 circles with one or more hypoplastic segments only. Group two contains 11 circles with one or more absent segments only. Group three contains 6 circles with hypoplastic and absent segments only. Group four contains 26 circles with one or more accessory segments. Group five contains 15 circles with other types of anatomical variation. Within each group, circles were subcategorised according to the number or type of segments affected. An original coding system was created to simplify the description of anatomical variations of the CoW. The new classification system provides a comprehensive ontology of the described anatomical variations of the CoW in humans. When used with the coding system, it allows the description and categorisation of recorded and unrecorded variants identified in past and future studies. It is applicable to current clinical practice and the anatomical community, including human anatomy education and research.

The seasonal relationships between household dietary diversity and child growth in a rural Timor-Leste community.

Both child growth and dietary diversity are poor in rural Timor-Leste. The rainy season is associated with food scarcity, yet the association between seasonal scarcity, food diversity, and child growth is underdocumented. This study assesses the relationship between household dietary diversity and children's standardized growth across the 2018 food-scarce (April-May; post-rainy period) and post-harvest (October) seasons in the agricultural community of Natarbora, on the south-coastal plains of Timor-Leste. We conducted household interviews and collected anthropometric data across 98 and 93 households in the post-rainy and post-harvest periods, respectively. Consumed household foods were obtained via 24-h diet recalls and were subsequently categorized into a nine-food-group dietary diversity score (DDS; number of different food groups consumed). The DDS was related to children's standardized short-term growth (z-weight, z-body mass index [BMI] and percent change in weight over the harvest season) via linear mixed models. Across seasons, DDS increased from 3.9 (standard deviation [SD] = 1.0) to 4.3 (SD = 1.4; p < 0.05). In the post-rainy season, children in high DDS households had higher z-weight than those in low DDS households and higher z-BMI than children in medium and low DDS households. In the post-harvest period, household DDS did not predict children's z-weight but predicted z-BMI. Consumption of protein-rich foods, particularly animal-source foods and legumes, in low- and medium-DDS households may be associated with improved child growth. While consuming more animal-source foods in the post-rainy season would be ideal, promoting the consumption of locally grown legumes, such as beans and pulses, may facilitate better nutritional outcomes for more children in rural Timor-Leste.

Determinants of objectively measured physical activity in rural East Timorese children.

OBJECTIVES: The human juvenile period evolved as a period of learning and physical development in a family environment that subsidizes the costs of these processes. Children allocate energy to physical activity, maintenance, and growth. How energy is allocated has consequences for adult body size and other life-history traits. In subsistence agriculture populations, where child contributions to the household economy are common and energy availability is low, trade-offs in energy expenditure between activity and growth may help explain poor growth. METHODS: Using accelerometry, we measured physical activity over 2 years in 88 free-living children aged 5-19 years in two ecologically varying communities in rural Timor-Leste. We model characteristics related to variation in activity, and subsequently, activity is modeled against growth, illness, and aspects of household and local ecology using linear mixed models. RESULTS: Physical activity in Timorese children is characterized by high levels of moderate ( x ¯ = 8.8 h/day), no sustained vigorous, and little sedentary activity ( x ¯ = 4.6 h/day). Children in the mountainous community show a slight trade-off between activity and growth (P = .077). Males down-regulate both growth and activity relative to females. Variation in household characteristics does not predict child activity. Both activity and growth are lower in the mountainous community than in the flat, coastal community. CONCLUSIONS: Household demands on child behavior may constrain children's ability to moderate activity relative to nutritional status. Activity in this population is high relative to other subsistence populations, possibly because children face the dual pressures of contributing to household subsistence and attending school.

Growth curves and the international standard: How children's growth reflects challenging conditions in rural Timor-Leste.

OBJECTIVES: Population-specific growth references are important in understanding local growth variation, especially in developing countries where child growth is poor and the need for effective health interventions is high. In this article, we use mixed longitudinal data to calculate the first growth curves for rural East Timorese children to identify where, during development, deviation from the international standards occurs. MATERIALS AND METHODS: Over an eight-year period, 1,245 children from two ecologically distinct rural areas of Timor-Leste were measured a total of 4,904 times. We compared growth to the World Health Organization (WHO) standards using z-scores, and modeled height and weight velocity using the SuperImposition by Translation And Rotation (SITAR) method. Using the Generalized Additive Model for Location, Scale and Shape (GAMLSS) method, we created the first growth curves for rural Timorese children for height, weight and body mass index (BMI). RESULTS: Relative to the WHO standards, children show early-life growth faltering, and stunting throughout childhood and adolescence. The median height and weight for this population tracks below the WHO fifth centile. Males have poorer growth than females in both z-BMI (p = .001) and z-height-for-age (p = .018) and, unlike females, continue to grow into adulthood. DISCUSSION: This is the most comprehensive investigation to date of rural Timorese children's growth, and the growth curves created may potentially be used to identify future secular trends in growth as the country develops. We show significant deviation from the international standard that becomes most pronounced at adolescence, similar to the growth of other Asian populations. Males and females show different growth responses to challenging conditions in this population.

Household resources and seasonal patterns of child growth in rural Timor-Leste.

OBJECTIVES: This study aimed to determine through detailed contextual investigation the effects of seasonal resource shortages, and household and individual level differences, on child growth in rural Timor-Leste. We compared trends in growth across two rural Timorese villages with different ecologies. METHODS: Heads of 104 households in Natarbora, Timor-Leste, were interviewed and resource levels assessed during the food shortage season. In these households, 337 children were measured for height, weight, and mid-upper arm circumference. World Health Organization standardized measures were calculated and compared with dry season measurements. Using hierarchical linear models, child growth was related to household resource levels. Results were then compared to data from rural mountainous Ossu, Timor-Leste. RESULTS: z BMI declined over the wet season when food resources were scarce compared with the dry season (P < .001). Both age and sex were strong predictors of child growth, with older children having worse z height-for-age (P = .001) and z weight-for-age (P < .001) and boys shorter for age than girls (P = .049). Children were taller in households with modern flushable toilets (P = .005). Agricultural strategies such as crop diversity and land cultivation were linked to child growth. Results parallel findings from Ossu on the effects of season, child age and sex, but not household level socioeconomic differences. CONCLUSIONS: Results highlight the importance of subsistence-based resource stabilization and of early intervention to prevent growth faltering. Predicting growth using ecological models requires small-scale investigation, as variation exists among rural areas within an ecologically and culturally diverse country.

Obesity and psychological wellbeing in patients undergoing fertility treatment.

Obesity negatively affects reproductive functioning and psychological wellbeing. Distress experienced by infertile women with elevated body mass index (BMI) was investigated. Infertile women (n = 403) were stratified according to World Health Organization (2000) BMI categories (normal, overweight and obese) and infertility category (polycystic ovary syndrome [PCOS] or non-PCOS). Participants anonymously completed a Demographics Questionnaire, International Physical Activity Questionnaire, Depression, Anxiety and Stress Scale, Positive and Negative Affect Schedule, Rosenberg Self Esteem Scale, Fertility Problem Inventory, Clinical Perfectionism Questionnaire and the Eating Disorder Examination Questionnaire. Women in the obese BMI group were no more psychologically vulnerable to general mood (depression, anxiety and stress) or fertility-specific distress than normal or overweight BMI women. Independent of their PCOS status, obese women reported more frequent episodes of binge eating, shape concerns and low self-esteem symptoms associated with disordered eating. Women with PCOS had elevated shape concerns and anxiety independent of their BMI category compared with women who did not have PCOS. Obese infertile women presenting with the characteristics of binge eating, low self-esteem and body shape concerns may represent a vulnerable subgroup that could benefit from accessing targeted psychological interventions as do women with PCOS who have body shape concerns.

Disordered eating attitudes and exercise in women undergoing fertility treatment.

BACKGROUND: Previous research has found a higher lifetime prevalence of eating disorders in women undergoing fertility treatment. AIMS: This study aimed to gauge the prevalence of eating disorders in women attending a fertility clinic and to compare current disordered eating attitudes and exercise amongst different infertility categories. MATERIALS AND METHODS: Three hundred and eighty-five women were grouped according to infertility diagnosis: male factor, unexplained infertility, ovulatory disorders, polycystic ovarian syndrome (PCOS) and heterogeneous causations. Participants anonymously completed the Eating Disorder Examination Questionnaire (EDE-Q), the International Physical Activity Questionnaire (IPAQ) and a Demographics questionnaire. RESULTS: The lifetime history of self-reported eating disorders for women in the sample was similar to Australian community rates. Profile analysis revealed on the EDE-Q that women with ovulatory disorders were not significantly different from women with PCOS; however, they were significantly different to women with other infertility diagnoses (all P < 0.05), suggesting increased vulnerability to disordered eating. There were no between-group differences in exercise quantity (IPAQ, P = 0.625) although women with ovulatory disorders and PCOS had a significantly higher risk of engaging in compulsive, 'driven' exercise (OR = 6.98, CI = 1.39, 34.90, P = 0.018) as a means to control weight or shape. CONCLUSIONS: Contrary to previous research, our findings do not confirm a greater lifetime prevalence rate of eating disorders in women attending an infertility clinic. This study does highlight the importance of screening women with forms of an ovulatory disorder for features of disordered eating attitudes and driven exercise behaviours.

Child size and household characteristics in rural Timor-Leste.

OBJECTIVES: The main objective was to determine those characteristics of the family and household that affects child health (as measured by child size for age) in the rural Ossu area of Timor-Leste. METHODS: Interviews of parents in 102 households assessed reproductive histories, the amount and type of resources available and family composition (number, sex, and age of members). Height, weight, and mid-upper arm circumference were measured for all children in the household. To standardize for age and sex, raw measures were transformed into WHO Z scores and compared across households. RESULTS: Children were low in both height and weight relative to international standards and older children compared with international standards more poorly than under-fives. There was no evidence of sex difference in relative growth. The number of children in a household was negatively associated with height but not weight and positively with BMI. Children living in the villages more distant from Ossu town center had significantly lower Z scores for height than children in town. No crop or livestock indices were related to growth. Fostered children did not show growth different from biological children, but biological children in households with fostered children were slightly larger for age. CONCLUSIONS: Short stature inflates BMI and harvest season measures may have captured short-term increases in children's energy balance. Social networks may increase child well-being by moving children toward resource richer households. Social and cultural factors influence resource allocations among children and their health in rural Timor-Leste.

Anatomy Nights: An international public engagement event increases audience knowledge of brain anatomy.

Anatomy Nights is an international public engagement event created to bring anatomy and anatomists back to public spaces with the goal of increasing the public's understanding of their own anatomy by comparison with non-human tissues. The event consists of a 30-minute mini-lecture on the anatomy of a specific anatomical organ followed by a dissection of animal tissues to demonstrate the same organ anatomy. Before and after the lecture and dissection, participants complete research surveys designed to assess prior knowledge and knowledge gained as a result of participation in the event, respectively. This study reports the results of Anatomy Nights brain events held at four different venues in the UK and USA in 2018 and 2019. Two general questions were asked of the data: 1) Do participant post-event test scores differ from pre-event scores; and 2) Are there differences in participant scores based on location, educational background, and career. We addressed these questions using a combination of generalized linear models (R's glm function; R version 4.1.0 [R Core Team, 2014]) that assumed a binomial distribution and implemented a logit link function, as well as likelihood estimates to compare models. Survey data from 91 participants indicate that scores improve on post-event tests compared to pre-event tests, and these results hold irrespective of location, educational background, and career. In the pre-event tests, participants performed well on naming structures with an English name (frontal lobe and brainstem), and showed signs of improvement on other anatomical names in the post-test. Despite this improvement in knowledge, we found no evidence that participation in Anatomy Nights improved participants' ability to apply this knowledge to neuroanatomical contexts (e.g., stroke).

Clay-Based Modeling in the Anatomist's Toolkit: A Systematic Review.

Anatomical education has suffered from reduced teaching time and poor availability of staff and resources over the past thirty years. Clay-based modeling (CBM) is an alternative technique for teaching anatomy that can improve student knowledge and experience. This systematic review aimed to summarize and appraise the quality of the literature describing the uses, advantages, and limitations of CBM compared to alternative methods of teaching human gross anatomy to students or qualified healthcare professionals. A systematic search of Embase, MEDLINE, Scopus, and Web of Science databases was conducted, and the Medical Education Research Quality Instrument (MERSQI) was used to assess study quality. Out of the 829 studies identified, 12 papers met the inclusion criteria and were eligible for this review. The studies were of high quality, with a mean MERSQI score of 11.50/18. Clay-based modeling can be used to teach all gross anatomical regions, and 11 studies demonstrated a significant improvement in short-term knowledge gain in students who used CBM in comparison to other methods of learning anatomy. Eight studies that included subjective assessment showed that CBM is rated highly. However, some studies showed that students viewed CBM as juvenile and experienced difficulty making the models. Additionally, there is no evidence to suggest that CBM improves long-term knowledge. Clay-based modeling is an effective learning method for human gross anatomy and should be incorporated into the anatomists' toolkit. In the future, more randomized controlled studies with transparent study designs investigating the long-term impact of CBM are needed.

Epigenetic differences at the HTR2A locus in progressive multiple sclerosis patients.

The pathology of progressive multiple sclerosis (MS) is poorly understood. We have previously assessed DNA methylation in the CD4+ T cells of relapsing-remitting (RR) MS patients compared to healthy controls and identified differentially methylated regions (DMRs) in HLA-DRB1 and RNF39. This study aimed to investigate the DNA methylation profiles of the CD4+ T cells of progressive MS patients. DNA methylation was measured in two separate case/control cohorts using the Illumina 450K/EPIC arrays and data was analysed with the Chip Analysis Methylation Pipeline (ChAMP). Single nucleotide polymorphisms (SNPs) were assessed using the Illumina Human OmniExpress24 arrays and analysed using PLINK. Expression was assessed using the Illumina HT12 array and analysed in R using a combination of Limma and Illuminaio. We identified three DMRs at HTR2A, SLC17A9 and HDAC4 that were consistent across both cohorts. The DMR at HTR2A is located within the bounds of a haplotype block; however, the DMR remained significant after accounting for SNPs in the region. No expression changes were detected in any DMRs. HTR2A is differentially methylated in progressive MS independent of genotype. This differential methylation is not evident in RRMS, making it a potential biomarker of progressive disease.

Stress has a direct and indirect effect on eating pathology in infertile women: avoidant coping style as a mediator.

Patient-perceived stress and avoidance-oriented coping strategies are mental health risk factors well documented within the infertility literature. Relatedly, these factors are associated with maladaptive eating behaviours known to influence reproductive functioning. This study aims to investigate the interconnection between perceived stress, avoidant coping style and eating pathology in infertile women, and to determine whether avoidant coping style mediates the relationship between stress and eating pathology. A multicentre cross-sectional study of 416 women (aged 20-47 years) was completed. Women were assessed on the Eating Disorder Examination Questionnaire, the Perceived Stress Scale and the Brief COPE. Correlational matrices, principal components analysis and structural equation modelling were used to develop a measurement model to test the avoidant coping style mediation hypothesis. Results showed that perceived stress had a direct effect on maladaptive eating behaviours [ß = 0.21; 95% confidence interval (CI) 0.065-0.346; P = 0.005]. Furthermore, a statistically significant indirect effect between perceived stress and maladaptive eating via avoidant coping style was also observed (ß = 0.14; 95% CI = 0.017-0.267; P = 0.018), indicating partial mediation. These findings highlight that both perceived stress and avoidant coping style are important psychotherapy targets to consider in infertile women presenting with eating pathology.

Genome-wide DNA methylation changes in CD19+ B cells from relapsing-remitting multiple sclerosis patients.

Multiple Sclerosis (MS) is an inflammatory and neurodegenerative disease of the central nervous system. The inflammatory process in MS is driven by both T and B cells and current therapies are targeted to each of these cell types. Epigenetic mechanisms may provide a valuable link between genes and environment. DNA methylation is the best studied epigenetic mechanism and is recognized as a potential contributor to MS risk. The objective of this study was to identify DNA methylation changes associated with MS in CD19+ B-cells. We performed an epigenome-wide association analysis of DNA methylation in the CD19+ B-cells from 24 patients with relapsing-remitting MS on various treatments and 24 healthy controls using Illumina 450 K arrays. A large differentially methylated region (DMR) was observed at the lymphotoxin alpha (LTA) locus. This region was hypermethylated and contains 19 differentially methylated positions (DMPs) spanning 860 bp, all of which are located within the transcriptional start site. We also observed smaller DMRs at 4 MS-associated genes: SLC44A2, LTBR, CARD11 and CXCR5. These preliminary findings suggest that B-cell specific DNA-methylation may be associated with MS risk or response to therapy, specifically at the LTA locus. Development of B-cell specific epigenetic therapies is an attractive new avenue of research in MS treatment. Further studies are now required to validate these findings and understand their functional significance.

DNA methylation changes in CD4+ T cells isolated from multiple sclerosis patients on dimethyl fumarate.

BACKGROUND: Dimethyl fumarate is an oral treatment for multiple sclerosis, whose mechanism of action is not fully understood. OBJECTIVE: To investigate the effects of dimethyl fumarate on DNA methylation in the CD4+ T cells of multiple sclerosis patients. METHODS: We performed Illumina EPIC arrays to investigate the DNA methylation profiles of CD4+ T cells derived from multiple sclerosis patients before and after dimethyl fumarate treatment. RESULTS: Treatment with dimethyl fumarate resulted in 97% of differentially methylated positions showing hypermethylation. Four genes, SNORD1A, SHTN1, MZB1 and TNF had a differentially methylated region located within the transcriptional start site. CONCLUSION: This study investigates the effect of dimethyl fumarate on DNA methylation in multiple sclerosis patients.

Erythrocyte microRNA sequencing reveals differential expression in relapsing-remitting multiple sclerosis.

BACKGROUND: There is a paucity of knowledge concerning erythrocytes in the aetiology of Multiple Sclerosis (MS) despite their potential to contribute to disease through impaired antioxidant capacity and altered haemorheological features. Several studies have identified an abundance of erythrocyte miRNAs and variable profiles associated with disease states, such as sickle cell disease and malaria. The aim of this study was to compare the erythrocyte miRNA profile of relapsing-remitting MS (RRMS) patients to healthy sex- and age-matched controls. METHODS: Erythrocytes were purified by density-gradient centrifugation and RNA was extracted. Following library preparation, samples were run on a HiSeq4000 Illumina instrument (paired-end 100 bp sequencing). Sequenced erythrocyte miRNA profiles (9 patients and 9 controls) were analysed by DESeq2. Differentially expressed miRNAs were validated by RT-qPCR using miR-152-3p as an endogenous control and replicated in a larger cohort (20 patients and 18 controls). After logarithmic transformation, differential expression was determined by two-tailed unpaired t-tests. Logistic regression analysis was carried out and receiver operating characteristic (ROC) curves were generated to determine biomarker potential. RESULTS: A total of 236 erythrocyte miRNAs were identified. Of twelve differentially expressed miRNAs in RRMS two showed increased expression (adj. p < 0.05). Only modest fold-changes were evident across differentially expressed miRNAs. RT-qPCR confirmed differential expression of miR-30b-5p (0.61 fold, p < 0.05) and miR-3200-3p (0.36 fold, p < 0.01) in RRMS compared to healthy controls. Relative expression of miR-3200-5p (0.66 fold, NS p = 0.096) also approached significance. MiR-3200-5p was positively correlated with cognition measured by audio-recorded cognitive screen (r = 0.60; p < 0.01). MiR-3200-3p showed greatest biomarker potential as a single miRNA (accuracy = 75.5%, p < 0.01, sensitivity = 72.7%, specificity = 84.0%). Combining miR-3200-3p, miR-3200-5p, and miR-30b-5p into a composite biomarker increased accuracy to 83.0% (p < 0.05), sensitivity to 77.3%, and specificity to 88.0%. CONCLUSIONS: This is the first study to report differences in erythrocyte miRNAs in RRMS. While the role of miRNAs in erythrocytes remains to be elucidated, differential expression of erythrocyte miRNAs may be exploited as biomarkers and their potential contribution to MS pathology and cognition should be further investigated.

Eating disorders in the context of preconception care: fertility specialists' knowledge, attitudes, and clinical practices.

OBJECTIVE(S): To gauge fertility specialists' knowledge, clinical practices, and training needs in regard to eating disorders. DESIGN: Cross-sectional study. SETTINGS: Fertility clinics. PARTICIPANTS: Eighty Australian and New Zealand fertility specialists who were members of the Fertility Society of Australia. INTERVENTION(S): None. MAIN OUTCOME MEASURES(S): Responses to an anonymously completed online questionnaire. RESULT(S): Approximately 54% of doctors correctly identified the body mass index relevant to anorexia nervosa, and 30% identified menstrual disturbances for anorexia, while 63.8% of doctors incorrectly nominated maladaptive weight control behaviors as a characteristic of binge eating disorder. While clinicians (83.7%) agreed it was important to screen for eating disorders during preconception assessments, 35% routinely screened for eating disorders and 8.8% indicated that their clinics had clinical practice guidelines for management of eating disorders. A minority of participants (13.8%) felt satisfied with their level of university training in eating disorders, 37.5% of doctors felt confident in their ability to recognize symptoms of an eating disorder, and 96.2% indicated a need for further education and clinical guidelines. On most items examined, knowledge and clinical practices regarding eating disorders did not differ according to doctor gender or years of clinical experience working as a fertility specialist. CONCLUSION(S): Knowledge about eating disorders in the context of fertility treatment is important. This study highlights the uncertainty among fertility specialists in detecting features of eating disorders. The findings point to the importance of further education and training, including the development of clinical guidelines specific to fertility health care providers.

Differential methylation at MHC in CD4+ T cells is associated with multiple sclerosis independently of HLA-DRB1.

BACKGROUND: Although many genetic variants have been associated with multiple sclerosis (MS) risk, they do not explain all the disease risk and there remains uncertainty as to how these variants contribute to disease. DNA methylation is an epigenetic mechanism that can influence gene expression and has the potential to mediate the effects of environmental factors on MS. In a previous study, we found a differentially methylation region (DMR) at MHC HLA-DRB1 that was associated within relapsing-remitting MS (RRMS) patients in CD4+ T cells. This study aimed to confirm this earlier finding in an independent RRMS cohort of treatment-naïve female patients. METHODS: Total genomic DNA was extracted from CD4+ T cells of 28 female RRMS and 22 age-matched healthy controls subjects. DNA was bisulfite-converted and hybridised to Illumina 450K arrays. Beta values for all CpGs were analysed using the DMPFinder function in the MINFI program, and a follow-up prioritisation process was applied to identify the most robust MS-associated DMRs. RESULTS: This study confirmed our previous findings of a hypomethylated DMR at HLA-DRB1 and a hypermethylated DMR at HLA-DRB5 in this RRMS patient cohort. In addition, we identified a large independent DMR at MHC, whereby 11 CpGs in RNF39 were hypermethylated in MS cases compared to controls (max. ∆beta = 0.19, P = 2.1 × 10-4). We did not find evidence that SNP genotype was influencing the DMR in this cohort. A smaller MHC DMR was also identified at HCG4B, and two non-MHC DMRs at PM20D1 on chr1 and ERICH1 on chr8 were also identified. CONCLUSIONS: The findings from this study confirm our previous results of a DMR at HLA-DRB1 and also suggest hypermethylation in an independent MHC locus, RNF39, is associated with MS. Taken together, our results highlight the importance of epigenetic factors at the MHC locus in MS independent of treatment, age and sex. Prospective studies are now required to discern whether methylation at MHC is involved in influencing risk of disease onset or whether the disease itself has altered the methylation profile.

Erythrocytes in multiple sclerosis - forgotten contributors to the pathophysiology?

Multiple sclerosis (MS) is an autoimmune disease characterised by lymphocytic infiltration of the central nervous system and subsequent destruction of myelin and axons. On the background of a genetic predisposition to autoimmunity, environmental triggers are assumed to initiate the disease. The majority of MS research has focused on the pathological involvement of lymphocytes and other immune cells, yet a paucity of attention has been given to erythrocytes, which may play an important role in MS pathology. The following review briefly summarises how erythrocytes may contribute to MS pathology through impaired antioxidant capacity and altered haemorheological features. The effect of disease-modifying therapies on erythrocytes is also reviewed. It may be important to further investigate erythrocytes in MS, as this could broaden the understanding of the pathological mechanisms of the disease, as well as potentially lead to the discovery of novel and innovative targets for future therapies.

Next-generation sequencing reveals broad down-regulation of microRNAs in secondary progressive multiple sclerosis CD4+ T cells.

BACKGROUND: Immunoactivation is less evident in secondary progressive MS (SPMS) compared to relapsing-remitting disease. MicroRNA (miRNA) expression is integral to the regulation of gene expression; determining their impact on immune-related cell functions, especially CD4+ T cells, during disease progression will advance our understanding of MS pathophysiology. This study aimed to compare miRNA profiles of CD4+ T cells from SPMS patients to healthy controls (HC) using whole miRNA transcriptome next-generation sequencing (NGS). Total RNA was extracted from CD4+ T cells and miRNA expression patterns analyzed using Illumina-based small-RNA NGS in 12 SPMS and 12 HC samples. Results were validated in a further cohort of 12 SPMS and 10 HC by reverse transcription quantitative polymerase chain reaction (RT-qPCR). RESULTS: The ten most dysregulated miRNAs identified by NGS were selected for qPCR confirmation; five (miR-21-5p, miR-26b-5p, miR-29b-3p, miR-142-3p, and miR-155-5p) were confirmed to be down-regulated in SPMS (p < 0.05). SOCS6 is targeted by eight of these ten miRNAs. Consistent with this, SOCS6 expression is up-regulated in SPMS CD4+ T cells (p < 0.05). This is of particular interest as SOCS6 has previously been shown to act as a negative regulator of T cell activation. CONCLUSIONS: Ninety-seven percent of miRNA candidates identified by NGS were down-regulated in SPMS. The down-regulation of miRNAs and increased expression of SOCS6 in SPMS CD4+ T cells may contribute to reduced immune system activity in progressive MS.