Wiessam Abu Ahmad

Premature aging of leukocyte DNA methylation is associated with type 2 diabetes prevalence.

BackgroundType 2 diabetes mellitus (T2D) is highly prevalent in Middle-Eastern and North African Arab populations, but the molecular basis for this susceptibility is unknown. Altered DNA methylation levels were reported in insulin-secreting and responding tissues, but whether methylation in accessible tissues such as peripheral blood is associated with T2D risk remains an open question. Age-related alteration of DNA methylation level was reported in certain methylation sites, but no association with T2D has been shown. Here we report on a population-based study of 929 men and women representing the East Jerusalem Palestinian (EJP) Arab population and compare with the findings among Israeli Ashkenazi Jews. This is the first reported epigenetic study of an Arab population with a characteristic high prevalence of T2D.ResultsWe found that DNA methylation of a prespecified regulatory site in peripheral blood leukocytes (PBLs) is associated with impaired glucose metabolism and T2D independent of sex, body mass index, and white blood cell composition. This CpG site (Chr16: 53,809,231-2; hg19) is located in a region within an intron of the FTO gene, suspected to serve as a tissue-specific enhancer. The association between PBL hypomethylation and T2D varied by age, revealing differential patterns of methylation aging in healthy and diabetic individuals and between ethnic groups: T2D patients displayed prematurely low methylation levels, and this hypomethylation was greater and occurred earlier in life among Palestinian Arabs than Ashkenazi Jews.ConclusionsOur study suggests that premature DNA methylation aging is associated with increased risk of T2D. These findings should stimulate the search for more such sites and may pave the way to improved T2D risk prediction within and between human populations.

Gum chewing and gastrointestinal function following caesarean delivery: a systematic review and meta‐analysis

AIMS AND OBJECTIVES The aims of this systematic review and meta-analysis were to summarise current knowledge regarding gum chewing intervention for activation of the gastrointestinal (GI) system following caesarean delivery. BACKGROUND GI symptoms such as nausea, vomiting and defecatory difficulties are bothersome for women following a caesarean delivery. There is category A recommendation to not withhold oral intake postoperatively. However, current practice guidelines vary widely on time to initiate oral feeding post caesarean delivery, and additional research is needed. Gum chewing has been shown to stimulate the GI system in other postoperative patient populations. DESIGN A systematic review and meta-analysis. METHODS An electronic review was undertaken using the following resources: PubMed (Medline), CINAHL, EMBASE and ClinicalTrials.gov databases. Key words used in various combinations included cesarean section; cesarean delivery; postoperative chewing gum; bowel movement; bowel function and complications. RESULTS A total of 171 articles were found of which 166 were excluded: 157 were duplicates and the remainder did not meet the inclusion criteria. Five randomised control trials were included in the meta-analysis, focusing on gum chewing as an intervention as compared with a nongum chewing intervention, with a total of 846 participants. Compared with the nongum chewing group, gum chewing showed a beneficial impact on the major outcomes of digestive system activation, including bowel sound, gas passage and defecation. CONCLUSIONS This meta-analysis supports the effectiveness of gum chewing post caesarean delivery as a noninvasive/nonpharmacological intervention for reactivation of bowel movement. RELEVANCE TO CLINICAL PRACTICE Gum chewing in the immediate postoperative period following caesarean delivery may provide a socially acceptable, low-cost and safe intervention to reduce postcaesarean delivery GI complications and restore GI function.

Beta-carotene as a novel therapy for the treatment of “Autistic like behavior” in animal models of Autism

HighlightsAutism characterized by lower plasma oxytocin and its ectoenzyme regulator CD38.The role of beta‐ carotene in rescuing autistic‐like behavior in mice investigated.Beta‐carotene reduced stereotyped behaviors & increased social interactions.Elevated CD38, oxytocin, oxytocin receptor, BDNF, retinoic acid, serum oxytocin.Beta‐carotene may prevent/ameliorate autistic symptoms in predisposed newborns. &NA; Autism‐affected individuals are characterized by lower plasma oxytocin and its ectoenzyme regulator CD38. Oxytocin, a hypothalamic hormone secreted upon the release of CD38, plays a role in social behavior and bonding. All‐trans retinoic acid is a potent inducer of CD38 and can be used as a novel therapeutic strategy in autism. We investigated the role of beta‐carotene in rescuing autistic‐like behavior in BALB/c and BTBR mice. Beta‐carotene derivatives are preferred as they are neither toxic nor teratogenic. Beta‐carotene at 0.1–5.0 mg/kg was administered orally to BALB/c and BTBR newborn mice on days 1–7. They were tested at age 2–3 months for five behavioral tests for “autism”; in addition, brain CD38, oxytocin, oxytocin receptor, Brain Derived Neurotrophic Factor (BDNF) and retinoic acid receptor gene expression, serum oxytocin levels, and neurological score were evaluated. Beta‐carotene administered at birth significantly increased T‐maze alternations and led to longer time spent with an unfamiliar mouse in the “three‐chamber test” and less time spent in the empty chamber. Furthermore, enhanced activity in the open field test; increased time spent in the reciprocal social interaction test; decreased grooming and bedding behaviors; and enhanced brain CD38, oxytocin, oxytocin receptor, BDNF, retinoic acid gene expression, and serum oxytocin levels. No changes in neurological score were observed. Beta‐carotene oral supplementation to BALB/c and BTBR mice at birth significantly reduced restricted and stereotyped behaviors and interests, increased social interactions and communication, CD38, and oxytocin, probably by enhancing brain neuroplasticity without toxicity. Thus, beta‐carotene administered after birth to newborns of families predisposed to “autism” has the potential to prevent/ameliorate “autistic like behavior”. These results support further clinical studies.

Zika pandemic online trends, incidence and health risk communication: a time trend study

Objectives We aimed to describe the online search trends of Zika and examine their association with Zika incidence, assess the content of Zika-related press releases issued by leading health authorities and examine the association between online trends and press release timing. Design Using Google Trends, the 1 May 2015 to 30 May 2016 online trends of Zika and associated search terms were studied globally and in the five countries with the highest numbers of suspected cases. Correlations were then examined between online trends and Zika incidence in these countries. All Zika-related press releases issued by WHO/Pan America Health Organization (PAHO) and Centers for Disease Control and Prevention (CDC) during the study period were assessed for transparency, uncertainty and audience segmentation. Wittes Extended Parallel Process Model was applied to assess self-efficacy, response efficacy, susceptibility and severity. AutoRegressive Integrated Moving Average with an eXogenous predictor variable (ARIMAX) (p,d,q) regression modelling was used to quantify the association between online trends and the timing of press releases. Results Globally, Zika online search trends were low until the beginning of 2016, when interest rose steeply. Strong correlations (r=0.748–0.922; p<0.001) were observed between online trends and the number of suspected Zika cases in four of the five countries studied. Compared with press releases issued by WHO/PAHO, CDC press releases were significantly more likely to provide contact details and links to other resources, include figures/graphs, be risk-advisory in nature and be more readable and briefer. ARIMAX modelling results indicate that online trends preceded by 1 week press releases by WHO (stationary-R2=0.345; p<0.001) and CDC (stationary-R2=0.318; p=0.014). Conclusions These results suggest that online trends can aid in pandemic surveillance. Identification of shortcomings in the content and timing of Zika press releases can help guide health communication efforts in the current pandemic and future public health emergencies.

Diabetic macular edema treated with ranibizumab following bevacizumab failure in Israel (DERBI study)

Purpose: To evaluate the outcome of second-line intravitreal ranibizumab treatment in eyes with diabetic macular edema having persistent edema following initial therapy with intravitreal bevacizumab. Methods: Diabetic macular edema treated with ranibizumab following bevacizumab failure in Israel was a retrospective, multi-center study. Consecutive eyes with persistent diabetic macular edema following at least three previous intravitreal bevacizumab injections prior to intravitreal ranibizumab, at least three-monthly intravitreal ranibizumab injections and at least 12 months of follow-up were included. Data collected included demographics, ocular findings, diabetes control, details of intravitreal bevacizumab and ranibizumab injections, and visual and anatomical measurements before and after intravitreal ranibizumab treatment. Results: In total, 202 eyes of 162 patients treated at 11 medical centers across Israel were included. Patients received a mean (±standard deviation) of 8.8 ± 4.9 intravitreal bevacizumab injections prior to the switch to intravitreal ranibizumab. A mean of 7.0 ± 2.7 intravitreal ranibizumab injections were given during the 12 months following the switch to intravitreal ranibizumab. The median central subfield retinal thickness (±interquartile range) by spectral-domain optical coherence tomography decreased from 436 ± 162 µm at baseline to 319 ± 113 µm at month 12 (p < 0.001). Median logMAR visual acuity (±interquartile range) improved from 0.40 ± 0.48 at baseline to 0.38 ± 0.40 at month 12 (p = 0.001). Linear regression suggested that higher number of intravitreal ranibizumab injections and higher pre-switch central subfield retinal thickness were associated with favorable visual outcome. Higher number of intravitreal bevacizumab injections and the presence of intraretinal fluid before the switch lessened the odds of favorable outcome. Conclusion: Switching from bevacizumab to ranibizumab in persistent diabetic macular edema was associated with anatomical improvement in the majority of eyes and ⩾2 lines of vision improvement in 22% of eyes.

Environmental exposures and fetal growth: the Haifa pregnancy cohort study

BackgroundThe developing fetus is susceptible to environmental insults. Studying the effects of environmental exposures on fetal growth is essential for understanding the causal pathway between prenatal exposures and pregnancy outcomes. Here we describe the Haifa Pregnancy Cohort Study (HPCS) and discuss challenges and opportunities in applying “big data” paradigm.MethodsMaccabi Healthcare Services (MHS), is the second largest Israeli health maintenance organization (HMO) providing care services to two million beneficiaries. The HPCS cohort potentially includes ~750,000 newborns born between 1998 and 2017. We will estimate daily exposures to air pollutants, temperature and greenness, using satellite-based data and models. We hypothesize that residents of Haifa have higher exposures to environmental pollutants and that in pregnant women this higher exposure is associated with poorer fetal growth. We will evaluate outcomes such as birth-weight, head-circumference and gestational age at birth. We will adjust for pregnancy complications such as pre-eclampsia and gestational diabetes and parental variables, such as maternal weight, age and smoking habits as potential confounders. In addition, we will conduct a multi-tiered field study, nested within this population, among 150 pregnant women residing in two geographical regions-one in the polluted Haifa area, and one in a relatively unpolluted area in central Israel. Blood and urinary samples will be collected, as well as personal and indoor exposure to air pollution.DiscussionEvaluating environmental exposures of pregnant women and assessing in utero growth over the course of the pregnancy during different exposure windows, is of great scientific and public health interest. Recent advances in data collection and analysis pose great promise to provide insights into contribution of environment to the health of the developing fetus, but also pose major challenges and pitfalls, such as data management, proper statistical framework and integration of data in the population-based study and selectiveness in the nested field study. Yet the continuing follow-up of the study cohort, integrating data from different services, health-promotion, and eventually, application later in real life of our main promises. Our study aims to meet these challenges and to provide evidence of the environmental exposures associated with fetal growth.

Questionnaire-based study showed that neonatal chest radiographs could be reliably interpreted using the WhatsApp messaging application

We surveyed whether clinicians used the WhatsApp messaging application to view neonatal chest radiographs and asked a sub‐sample to compare them with computer screen viewings.

Using anaerobic blood cultures for infants younger than 90 days rarely showed anaerobic infections but increased yields of bacterial growth

The use of anaerobic blood cultures in infants suspected of bacteraemia is controversial. Our childrens hospital uses both aerobic and anaerobic media, regardless of the risk of anaerobic infection, and the aim of this study was to re‐evaluate the use of anaerobic cultures in infants.

National Evidence in Israel Supporting Reevaluation of Respiratory Syncytial Virus Prophylactic Guidelines

Background: The American Academy of Pediatrics (AAP) recently narrowed the indications for respiratory syncytial virus (RSV) prophylaxis, while in Israel the guidelines have not changed. Objective: To compare the prevalence and severity of RSV infection among preterm infants born earlier than 340/7 weeks of gestation (PI), late preterm infants born at 340/7-366/7 weeks (LPTI), and term infants born after 370/7 weeks of gestation (TI) and to determine whether the results support a change in local policy. Methods: Data of all children aged 0-14 years hospitalized with PCR-positive RSV in a single tertiary center from 2010 to 2014 were collected. A total of 793 children were included and divided into 3 groups: 637 were TI, 105 were LPTI, and 50 were PI. These groups were compared regarding incidence of hospitalization due to RSV infection, intensive care unit (ICU) hospitalization, and length of hospitalization. Results: The hospitalization rate due to RSV infection was 5.2, 3.5, and 1.3% among PI, LPTI, and TI, respectively (p < 0.01). The hospitalization rate in the ICU was 24, 7.6, and 3% among PI, LPTI, and TI, respectively (p < 0.001). The length (days) of hospitalization was significantly longer among PI compared with LPTI and TI (p < 0.001). Overall, the hospitalization rate and disease severity were significantly higher for infants born earlier than 35 weeks of gestation compared with more maturely born infants. Conclusion: RSV infection remains a major cause of morbidity among children born prematurely even after RSV prophylaxis and would probably be greater were prophylaxis curtailed. Our results do not support applying the current AAP guidelines in Israel. Further local studies are needed to optimize prophylaxis for both PI and LPTI.

Development of a nomogram for prediction of successful membrane sweeping

Abstract Objective: To evaluate the association of obstetric, maternal, and fetal variables with successful membrane sweeping and to develop a calculator that can predict spontaneous delivery within 24 hours of membrane sweeping. Methods: This secondary analysis of the STRIP-G Study included all singleton term parturients who underwent membrane sweeping in a tertiary center in October 2011 to July 2013. Primary end point was a 24-hour time interval from sweeping to delivery. Women who delivered without formal induction within the 24-hour interval were included in the “successful sweeping group”. Stepwise logistic regression was used to calculate the adjusted odds ratio (aOR) for successful membrane sweeping and to create the calculator. The predictive power of the calculator was evaluated by area under the curve (AUC) of the receiver operating characteristic (ROC) curve and by Nagelkerke R-square. The model was validated by the Hosmer–Lemeshow test and by these validation measures: sensitivity, specificity, and positive and negative predictive value. Results: We analyzed data from 542 women. Parity (aOR = 1.66, 95% confidence interval [CI] 1.1–2.54), cervical dilation (aOR = 3.33, 95%CI 2.04–5.44), and gestational age (aOR = 1.44, 95%CI 1.21–1.72) were independent predictors of spontaneous delivery during the first 24 hours. A cross validation procedure showed that the calculator had a good accuracy (68%). Conclusions: A simple calculator based on maternal age, parity, gestational age, cervical dilatation, effacement and station, can accurately predict the chances of delivery within 24 hours of membrane sweeping. This may assist physicians better counseling of women regarding the likelihood of successful membrane sweeping.