Safety, tolerability, and efficacy estimate of evoked gamma oscillation in mild to moderate Alzheimer's disease.

Background: Alzheimer's Disease (AD) is a multifactorial, progressive neurodegenerative disease that disrupts synaptic and neuronal activity and network oscillations. It is characterized by neuronal loss, brain atrophy and a decline in cognitive and functional abilities. Cognito's Evoked Gamma Therapy System provides an innovative approach for AD by inducing EEG-verified gamma oscillations through sensory stimulation. Prior research has shown promising disease-modifying effects in experimental AD models. The present study (NCT03556280: OVERTURE) evaluated the feasibly, safety and efficacy of evoked gamma oscillation treatment using Cognito's medical device (CogTx-001) in participants with mild to moderate AD. Methods: The present study was a randomized, double blind, sham-controlled, 6-months clinical trial in participants with mild to moderate AD. The trial enrolled 76 participants, aged 50 or older, who met the clinical criteria for AD with baseline MMSE scores between 14 and 26. Participants were randomly assigned 2:1 to receive self-administered daily, one-hour, therapy, evoking EEG-verified gamma oscillations or sham treatment. The CogTx-001 device was use at home with the help of a care partner, over 6 months. The primary outcome measures were safety, evaluated by physical and neurological exams and monthly assessments of adverse events (AEs) and MRI, and tolerability, measured by device use. Although the trial was not statistically powered to evaluate potential efficacy outcomes, primary and secondary clinical outcome measures included several cognitive and functional endpoints. Results: Total AEs were similar between groups, there were no unexpected serious treatment related AEs, and no serious treatment-emergent AEs that led to study discontinuation. MRI did not show Amyloid-Related Imaging Abnormalities (ARIA) in any study participant. High adherence rates (85-90%) were observed in sham and treatment participants. There was no statistical separation between active and sham arm participants in primary outcome measure of MADCOMS or secondary outcome measure of CDR-SB or ADAS-Cog14. However, some secondary outcome measures including ADCS-ADL, MMSE, and MRI whole brain volume demonstrated reduced progression in active compared to sham treated participants, that achieved nominal significance. Conclusion: Our results demonstrate that 1-h daily treatment with Cognito's Evoked Gamma Therapy System (CogTx-001) was safe and well-tolerated and demonstrated potential clinical benefits in mild to moderate AD.Clinical Trial Registration: www.ClinicalTrials.gov, identifier: NCT03556280.

Evaluation in a porcine wound model and long-term clinical assessment of an autologous heterogeneous skin construct used to close full-thickness wounds.

Acute and chronic wounds involving deeper layers of the skin are often not adequately healed by dressings alone and require therapies such as skin grafting, skin substitutes, or growth factors. Here we report the development of an autologous heterogeneous skin construct (AHSC) that aids wound closure. AHSC is manufactured from a piece of healthy full-thickness skin. The manufacturing process creates multicellular segments, which contain endogenous skin cell populations present within hair follicles. These segments are physically optimized for engraftment within the wound bed. The ability of AHSC to facilitate closure of full thickness wounds of the skin was evaluated in a swine model and clinically in 4 patients with wounds of different etiologies. Transcriptional analysis demonstrated high concordance of gene expression between AHSC and native tissues for extracellular matrix and stem cell gene expression panels. Swine wounds demonstrated complete wound epithelialization and mature stable skin by 4 months, with hair follicle development in AHSC-treated wounds evident by 15 weeks. Biomechanical, histomorphological, and compositional analysis of the resultant swine and human skin wound biopsies demonstrated the presence of epidermal and dermal architecture with follicular and glandular structures that are similar to native skin. These data suggest that treatment with AHSC can facilitate wound closure.

Avoiding future controversies in the Alzheimer's disease space through understanding the aducanumab data and FDA review.

Key points of disagreement between the aducanumab FDA statistical review, which had primarily negative conclusions, and the clinical review, which had primarily positive conclusions, were investigated. Results from secondary endpoints in positive Study 302 were significant and these endpoints provided meaningful additional information. Findings indicate the statistical review of the aducanumab data was incorrect in a number of key areas. Greater placebo decline was not responsible for the significant results in Study 302. Correlations did exist between reduction in ß-amyloid and clinical outcomes. Missing data and functional unblinding did not likely bias results. In contrast, the clinical review went too far in saying the negative results in Study 301 did not detract from the positive results in Study 302, as all clinical data should be considered in the evaluation, and the clinical review accepted the company's explanation for divergence of the results between the studies although much of the divergence remained unexplained. Interestingly, both the statistical review and the clinical review considered the available efficacy evidence despite both studies being terminated early. Implications of these findings include that the divergence in results seen in the two phase 3 aducanumab studies can be expected in other studies with similar design and analysis. Therefore, further research is needed to determine if analysis methods other than MMRM and/or optimized outcomes will provide more consistent results across studies.

What are the barriers to sustaining a safe sleep program for infants within hospital settings: An integrative review of the literature.

PROBLEM: Safe sleep programs have been existing since the concept was first defined in 1969. The need for health care providers to model safe sleep practices is essential for successful adherence; however, barriers to promoting safe sleep practices hinder healthcare providers' ability to implement safe sleep in hospital settings. AIM: To determine the barriers to promoting safe sleep practices amongst healthcare workers in the hospital setting. METHODS: Whittemore & Knafl's framework (2005) guided this integrative review. CINAHL, PubMed, and Academic Search Complete databases were used as a search strategy. Inclusion criteria was limited to studies between 2010 and 2021, were peer-reviewed, in English, and quality improvement projects consisting of barriers to implementing safe sleep practices within hospitals. To assess quality of the included studies, the Mixed Methods Appraisal Tool and Standards for Quality Improvement Reporting Excellence were used. The studies were analyzed by two of the authors with data further categorized using the Social Ecological Model (SEM) to develop themes. RESULTS: Findings of the 10 included studies were presented in the form of a data display matrix. The authors used the SEM to categorize the findings under three main categories at the organizational, individual, and cultural levels. CONCLUSIONS: Barriers need to be addressed in hospital settings to reduce the risk of sudden infant death syndrome. Therefore, it is vital to consider those barriers while providing teaching programs in hospital settings. IMPLICATIONS: Findings from this review provide the core elements to consider for the development of safe sleep programs in the hospital setting.

The Experience of Palliative Care Nurses in Qatar During the Time of COVID-19: A Qualitative Study.

BACKGROUND: The COVID-19 pandemic has been a source of significant confusion and fear for healthcare workers as they try to maintain some sense of normalcy within their daily practices. One of the many areas affected by this pandemic has been palliative care. Palliative care nurses were thrust into a world of chaos as they faced increasing numbers of patients who were in the process of dying. PURPOSE: The aim of this research was to explore the caring experiences of palliative care nurses during the COVID-19 pandemic. METHODS: A qualitative interpretive description design was used to explore the experience of nurses caring for dying patients in a palliative care unit during the COVID-19 pandemic. Twenty-two nurses working in a palliative care unit participated in this study. Data were collected during 1.5- to 2-hour focus group sessions that were guided by open-ended questions. RESULTS: The collected data were analyzed and coded into themes, including (a) transitioning to the new normal, (b) ethical dilemmas, and (c) collaboration and support for fellow colleagues. CONCLUSIONS: Although the COVID-19 pandemic has not yet ended, this study provides relevant implications for practice. These implications include (a) holding continuing education sessions to help nurses better understand the meaning of pandemic conditions and how best to respond and (b) supporting nurses to better cope with the additional burdens faced because of increased patient loads. Overall, the nurses in this study were shown to have demonstrated reliance and resilience in the face of COVID-19.

Arabic translation, cultural adaptation, and pilot-testing of multimorbidity self-management self-efficacy scales.

OBJECTIVE: This study aimed to translate to Arabic language and culturally adapt the Self-Efficacy for Managing Chronic Diseases Scale (SEMCD) and The Perceived Medical Condition Self-Management Scale (PMCSMS). DESIGN: The translation of the two scales was conducted according to the framework by Beaton et al. Then, these scales were tested in a cross-sectional correlational study with 85 Arabic-speaking participants with multimorbidities in Qatar. Psychometric tests to assess the reliability and validity of the translated scales were done. RESULTS: The internal consistency reliability (α) for the Arabic version of both PMCSMS and SEMCD scales was 0.953 and 0.949, respectively. Correlation coefficient (r) used to assess convergent validity between the PMCSMS and the SEMCD was 0.76 (p < 0.5). Number of morbidities negatively correlated with scores of self-management self- efficacy scores of the PMCSMS and the SEMCD (r = -0.50 and -0.51, respectively). DISCUSSION: The translated PMCSMS and SEMCD are valid and reliable scales that can be used by researchers and healthcare providers to assess levels of self-efficacy among individuals with multimorbidities. The translated scales can be employed in research or interventional programmes that aim to improve self-management or self-efficacy among individuals with multimorbidities.

DNA methylation signatures in airway cells from adult children of asthmatic mothers reflect subtypes of severe asthma.

Maternal asthma (MA) is among the most consistent risk factors for asthma in children. Possible mechanisms for this observation are epigenetic modifications in utero that have lasting effects on developmental programs in children of mothers with asthma. To test this hypothesis, we performed differential DNA methylation analyses of 398,186 individual CpG sites in primary bronchial epithelial cells (BECs) from 42 nonasthma controls and 88 asthma cases, including 56 without MA (NMA) and 32 with MA. We used weighted gene coexpression network analysis (WGCNA) of 69 and 554 differentially methylated CpGs (DMCs) that were specific to NMA and MA cases, respectively, compared with controls. WGCNA grouped 66 NMA-DMCs and 203 MA-DMCs into two and five comethylation modules, respectively. The eigenvector of one MA-associated module (turquoise) was uniquely correlated with 85 genes expressed in BECs and enriched for 36 pathways, 16 of which discriminated between NMA and MA using machine learning. Genes in all 16 pathways were decreased in MA compared with NMA cases (P = 7.1 × 10−3), a finding that replicated in nasal epithelial cells from an independent cohort (P = 0.02). Functional interpretation of these pathways suggested impaired T cell signaling and responses to viral and bacterial pathogens. The MA-associated turquoise module eigenvector was additionally correlated with clinical features of severe asthma and reflective of type 2 (T2)-low asthma (i.e., low total serum immunoglobulin E, fractional exhaled nitric oxide, and eosinophilia). Overall, these data suggest that MA alters diverse epigenetically mediated pathways that lead to distinct subtypes of severe asthma in adults, including hard-to-treat T2-low asthma.

GenoRisk: A polygenic risk score for Alzheimer's disease.

INTRODUCTION: Recent clinical trials are considering inclusion of more than just apolipoprotein E (APOE) ε4 genotype as a way of reducing variability in analysis of outcomes. METHODS: Case-control data were used to compare the capacity of age, sex, and 58 Alzheimer's disease (AD)-associated single nucleotide polymorphisms (SNPs) to predict AD status using several statistical models. Model performance was assessed with Brier scores and tenfold cross-validation. Genotype and sex × age estimates from the best performing model were combined with age and intercept estimates from the general population to develop a personalized genetic risk score, termed age, and sex-adjusted GenoRisk. RESULTS: The elastic net model that included age, age x sex interaction, allelic APOE terms, and 29 additional SNPs performed the best. This model explained an additional 19% of the heritable risk compared to APOE genotype alone and achieved an area under the curve of 0.747. DISCUSSION: GenoRisk could improve the risk assessment of individuals identified for prevention studies.

Cross-Sectional Exploration of Plasma Biomarkers of Alzheimer's Disease in Down Syndrome: Early Data from the Longitudinal Investigation for Enhancing Down Syndrome Research (LIFE-DSR) Study.

With improved healthcare, the Down syndrome (DS) population is both growing and aging rapidly. However, with longevity comes a very high risk of Alzheimer's disease (AD). The LIFE-DSR study (NCT04149197) is a longitudinal natural history study recruiting 270 adults with DS over the age of 25. The study is designed to characterize trajectories of change in DS-associated AD (DS-AD). The current study reports its cross-sectional analysis of the first 90 subjects enrolled. Plasma biomarkers phosphorylated tau protein (p-tau), neurofilament light chain (NfL), amyloid ß peptides (Aß1-40, Aß1-42), and glial fibrillary acidic protein (GFAP) were undertaken with previously published methods. The clinical data from the baseline visit include demographics as well as the cognitive measures under the Severe Impairment Battery (SIB) and Down Syndrome Mental Status Examination (DS-MSE). Biomarker distributions are described with strong statistical associations observed with participant age. The biomarker data contributes to understanding DS-AD across the spectrum of disease. Collectively, the biomarker data show evidence of DS-AD progression beginning at approximately 40 years of age. Exploring these data across the full LIFE-DSR longitudinal study population will be an important resource in understanding the onset, progression, and clinical profiles of DS-AD pathophysiology.

First-Person, Third-Person, or Bystander? Exploring the Persuasive Influence of Perspective in Mental Health Narratives.

As evidence suggests that college students are particularly vulnerable to mental health distress and illness, guidance for designing messages that inspire help-seeking behavior is needed. The purpose of this study was to evaluate the influence of perspective of storytelling on health message involvement and persuasion. A controlled experiment (N= 430) compared the influence of online mental health narratives targeted to college students that featured a bystander perspective to those that used first- and third-person perspectives. Evidence suggests that the bystander perspective was more effective for producing persuasive outcomes, including mental health information recall and beliefs. Results also indicate that self-referencing mediated the effects of message involvement on outcomes across all message conditions. People with experience with mental illness became involved with and were influenced by mental health narratives in different ways.

Perspectives of Healthcare Professionals Toward Interprofessional Collaboration in Primary Care Settings in a Middle Eastern Country.

BACKGROUND: Primary healthcare (PHC) setting is regarded as a central pillar to the healthcare system as it tends to be the first point of contact for patients. Interprofessional collaboration between healthcare professionals (HCP) in PHC settings remains unexplored in the Middle East. AIM: The objective of this study was to explore the perspectives of HCP in PHC centers towards interprofessional collaboration and to identify the facilitators and the barriers to collaborative practice. METHODS: A cross-sectional, web- and paper-based survey involving HCP in PHC centers was conducted in Qatar. Descriptive statistics as well as Student's t-test and One Way ANOVA test were performed to determine statistical differences in Readiness for Interprofessional Learning (RIPLs) scores between demographic groups. RESULTS: Overall, 1415 participants out of a potential 2500 HCP practicing in Qatar completed the survey (response rate, 56.6%). HCP generally indicated a positive attitude and readiness towards interprofessional collaboration. Furthermore, physicians had slightly more positive readiness towards understanding their professional identity than other healthcare professionals. Participants with previous interprofessional collaboration or interprofessional education experiences exhibited greater, but non-significant positive attitudes toward interprofessional collaboration compared to those without previous experiences. Identified barriers and facilitators included are conceptual rather than structural. Facilitating factors included HCP readiness and perceived benefit of interprofessional collaboration effectiveness in the work setting, increased professional satisfaction, respect between healthcare professions, appreciation of others' contribution, leadership, and institutional support. Top perceived barriers included leadership and support, time commitment, and resources constraints. CONCLUSION: HCP in PHC settings have demonstrated the willingness and readiness to engage in interprofessional collaboration. Recent reforms within the PHC setting consist of promoting interprofessional teams and collaborative culture. However, it is imperative to provide training and education to foster and support interprofessional collaborative practices.

Assessing primary health care nurses' knowledge toward immunizations: A quantitative study.

Background: The current nursing workforce needs to be skilled, confident, and competent to address the rapid change in Primary Health Care services, to align with the National Vision of Qatar. This is emphasized in the Primary Health Care Strategy 2018-2023. This strategy outlines the need of having a skilled nursing workforce to administer and educate the public about the importance of immunizations. Primary Health Care nurses emanate from several nationalities and hence possess various level of knowledge and background related to immunization administration. Design and methods: To assess Primary Health Care nurses' knowledge before and after the delivered immunization education program in Qatar. The study was part of a Sequential mixed method research study that aimed to assess the Primary Health Care nurses' knowledge, attitude, and practice of nurses before and after the conducted training program. A self-administered survey, specifically developed for the research project was loaded in Qualtrics and sent to participants of the immunization education program before and after training. Participants were trained in two cohorts from October to December, 2018 in Qatar. For the purposes of this paper, data about the immunization knowledge was statistically analyzed using the SPSS Software version 25 and Microsoft Excel. Results: Specific areas were identified as knowledge gaps among the participants of the two cohorts. Moreover, the developed education program showed overall improvement in the participants' knowledge. Conclusions: The study results have demonstrated that the delivered immunization education program significantly increases the participants' knowledge about immunization in certain areas of the primary healthcare clinics they work, including vaccine safety, efficiency, and contraindications in the delivery of vaccines to the public.

Gender and Age Stratified Analyses of Nutrient and Dietary Pattern Associations with Circulating Lipid Levels Identify Novel Gender and Age-Specific Correlations.

Dyslipidemia is a precursor to a myriad of cardiovascular diseases in the modern world. Age, gender, and diet are known modifiers of lipid levels, however they are not frequently investigated in subset analyses. Food and nutrient intakes from National Health and Nutrition Examination Study 2001⁻2013 were used to assess the correlation between lipid levels (high-density lipoprotein (HDL) cholesterol, triglycerides (TG), low-density lipoprotein (LDL) cholesterol, and total cholesterol (TC):HDL cholesterol ratio) and nutritional intake using linear regression. Associations were initially stratified by gender and significant gender correlations were further stratified by age. Analyses were performed at both the dietary pattern and nutrient level. Dietary pattern and fat intake correlations agreed with the literature in direction and did not demonstrate gender or age effects; however, we observed gender and age interactions among other dietary patterns and individual nutrients. These effects were independent of ethnicity, caloric intake, socioeconomic status, and physical activity. Elevated HDL cholesterol levels correlated with increasing vitamin and mineral intake in females of child bearing age but not males or older females (≥65 years). Moreover, increases in magnesium and retinol intake correlated with HDL cholesterol improvement only in females (all age groups) and males (35⁻64), respectively. Finally, a large amount of gender-specific variation was associated with TG levels. Females demonstrated positive associations with sugar and carbohydrate while males show inverse associations with polyunsaturated fatty acid (PUFA) intake. The female-specific association increased with the ratio of carbohydrate: saturated fatty acid (SFA) intake, suggesting that gender specific dietary habits may underlie the observed TG-nutrient correlations. Our study provides evidence that a subset of previously established nutrient-lipid associations may be gender or age-specific. Such discoveries provide potential new avenues for further research into personalized nutritional approaches to treat dyslipidemia.

Global DNA methylation changes spanning puberty are near predicted estrogen-responsive genes and enriched for genes involved in endocrine and immune processes.

Background: The changes that occur during puberty have been implicated in susceptibility to a wide range of diseases later in life, many of which are characterized by sex-specific differences in prevalence. Both genetic and environmental factors have been associated with the onset or delay of puberty, and recent evidence has suggested a role for epigenetic changes in the initiation of puberty as well. Objective: To identify global DNA methylation changes that arise across the window of puberty in girls and boys. Methods: Genome-wide DNA methylation levels were measured using the Infinium 450K array. We focused our studies on peripheral blood mononuclear cells (PBMCs) from 30 girls and 25 boys pre- and post-puberty (8 and 14 years, respectively), in whom puberty status was confirmed by Tanner staging. Results: Our study revealed 347 differentially methylated probes (DMPs) in females and 50 DMPs in males between the ages of 8 and 14 years (FDR 5%). The female DMPs were in or near 312 unique genes, which were over-represented for having high affinity estrogen response elements (permutation P < 2.0 × 10-6), suggesting that some of the effects of estrogen signaling in puberty are modified through epigenetic mechanisms. Ingenuity Pathway Analysis (IPA) of the 312 genes near female puberty DMPs revealed significant networks enriched for immune and inflammatory responses as well as reproductive hormone signaling. Finally, analysis of gene expression in the female PBMCs collected at 14 years revealed modules of correlated transcripts that were enriched for immune and reproductive system functions, and include genes that are responsive to estrogen and androgen receptor signaling. The male DMPs were in or near 48 unique genes, which were enriched for adrenaline and noradrenaline biosynthesis (Enrichr P = 0.021), with no significant networks identified. Additionally, no modules were identified using post-puberty gene expression levels in males. Conclusion: Epigenetic changes spanning the window of puberty in females may be responsive to or modify hormonal changes that occur during this time and potentially contribute to sex-specific differences in immune-mediated and endocrine diseases later in life.

Effects of a Meal Replacement on Body Composition and Metabolic Parameters among Subjects with Overweight or Obesity.

Meal replacement plans are effective tools for weight loss and improvement of various clinical characteristics but not sustainable due to the severe energy restriction. The aim of the study was to evaluate the impact of meal replacement, specifically 388 kcal in total energy, on body composition and metabolic parameters in individuals with overweight and obesity from a Chinese population. A parallel, randomized controlled trial was performed with 174 participants (ChiCTR-OOC-17012000). The intervention group (N=86) was provided with a dinner meal replacement, and the control group (N=88) continued their routine diet as before. Body composition and blood parameters were assessed at 0, 4, 8, and 12 weeks. A post hoc analysis (least significant difference (LSD) test), repeated measurements, and paired T-test were used to compare each variable within and between groups. Significant (p < 0.001) improvements in body composition components were observed among the intervention group, including body weight (-4.3 ± 3.3%), body mass index (-4.3 ± 3.3%), waist circumference (-4.3 ± 4.4%), fat-free mass (-1.8 ± 2.9%), and body fat mass (-5.3 ± 8.8%). Body composition improvements corresponded with significant metabolic improvements of blood glucose (-4.7 ± 9.8%). Further improvements in visceral fat area (-7.7 ± 10.1%), accompanying with improvements in systolic (-3.7 ± 6.9%) and diastolic (-5.3 ± 7.7%) blood pressure, were only found in male subjects. To conclude, meal replacement intake with 388 kcal in total energy at dinner time for 12 weeks contributed to improvement in body composition and clinically significant metabolic parameters in both male and female participants with overweight/obesity. Additionally, glucose and blood pressure reduction were gender-specific highlighting the importance of gender stratification for design of nutritional intervention studies for improvement of health.

Correction: Nicodemus-Johnson, J.; et al. Fruit and Juice Epigenetic Signatures Are Associated with Independent Immunoregulatory Pathways. Nutrients 2017, 9, 752.

We would like to submit the following correction to our recently published paper [1] due to the error in illustration of the abbreviation eFORGE. The details are as follows:[...].

Fruit and Juice Epigenetic Signatures Are Associated with Independent Immunoregulatory Pathways.

Epidemiological evidence strongly suggests that fruit consumption promotes many health benefits. Despite the general consensus that fruit and juice are nutritionally similar, epidemiological results for juice consumption are conflicting. Our objective was to use DNA methylation marks to characterize fruit and juice epigenetic signatures within PBMCs and identify shared and independent signatures associated with these groups. Genome-wide DNA methylation marks (Illumina Human Methylation 450k chip) for 2,148 individuals that participated in the Framingham Offspring exam 8 were analyzed for correlations between fruit or juice consumption using standard linear regression. CpG sites with low P-values (P < 0.01) were characterized using Gene Set Enrichment Analysis (GSEA), Ingenuity Pathway Analysis (IPA), and epigenetic Functional element Overlap analysis of the Results of Genome Wide Association Study Experiments (eFORGE). Fruit and juice-specific low P-value epigenetic signatures were largely independent. Genes near the fruit-specific epigenetic signature were enriched among pathways associated with antigen presentation and chromosome or telomere maintenance, while the juice-specific epigenetic signature was enriched for proinflammatory pathways. IPA and eFORGE analyses implicate fruit and juice-specific epigenetic signatures in the modulation of macrophage (fruit) and B or T cell (juice) activities. These data suggest a role for epigenetic regulation in fruit and juice-specific health benefits and demonstrate independent associations with distinct immune functions and cell types, suggesting that these groups may not confer the same health benefits. Identification of such differences between foods is the first step toward personalized nutrition and ultimately the improvement of human health and longevity.

Epigenome-wide analysis links SMAD3 methylation at birth to asthma in children of asthmatic mothers.

BACKGROUND: The timing and mechanisms of asthma inception remain imprecisely defined. Although epigenetic mechanisms likely contribute to asthma pathogenesis, little is known about their role in asthma inception. OBJECTIVE: We sought to assess whether the trajectory to asthma begins already at birth and whether epigenetic mechanisms, specifically DNA methylation, contribute to asthma inception. METHODS: We used the Methylated CpG Island Recovery Assay chip to survey DNA methylation in cord blood mononuclear cells from 36 children (18 nonasthmatic and 18 asthmatic subjects by age 9 years) from the Infant Immune Study (IIS), an unselected birth cohort closely monitored for asthma for a decade. SMAD3 methylation in IIS (n = 60) and in 2 replication cohorts (the Manchester Asthma and Allergy Study [n = 30] and the Childhood Origins of Asthma Study [n = 28]) was analyzed by using bisulfite sequencing or Illumina 450K arrays. Cord blood mononuclear cell-derived IL-1ß levels were measured by means of ELISA. RESULTS: Neonatal immune cells harbored 589 differentially methylated regions that distinguished IIS children who did and did not have asthma by age 9 years. In all 3 cohorts methylation in SMAD3, the most connected node within the network of asthma-associated, differentially methylated regions, was selectively increased in asthmatic children of asthmatic mothers and was associated with childhood asthma risk. Moreover, SMAD3 methylation in IIS neonates with maternal asthma was strongly and positively associated with neonatal production of IL-1ß, an innate inflammatory mediator. CONCLUSIONS: The trajectory to childhood asthma begins at birth and involves epigenetic modifications in immunoregulatory and proinflammatory pathways. Maternal asthma influences epigenetic mechanisms that contribute to the inception of this trajectory.

Optimizing the Presentation of Mental Health Information in Social Media: The Effects of Health Testimonials and Platform on Source Perceptions, Message Processing, and Health Outcomes.

Using social media for the purpose of disseminating mental health information is a critical area of scientific inquiry for health communication professionals. The purpose of this study was to investigate whether the presence of a first-person testimonial in educational mental health information placed in Facebook and Twitter messages influenced college students' (N = 257) source perceptions, information processing, cognitive elaboration, health information recall, beliefs, and behavioral intentions. Results show that exposure to social media messages that featured mental health information embedded with a testimonial predicted less source homophily and more critical thoughts about the social media source, less systematic message processing, and less cognitive elaboration. Health information recall was significantly impacted by both the social media platform and message content such that participants in the testimonial condition on Facebook were more likely to recall the health facts in those messages whereas participants who viewed the testimonial in Twitter were less likely to recall the facts in those tweets. Compared to those who read Facebook messages, participants who read Twitter messages reported higher levels of systematic message processing. These findings suggest that the integration of health testimonials into social media messages might inadvertently provoke psychological resistance to mental health information, thereby reducing the persuasive impact of those messages.