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IntroductionPatient-centered care (PCC) is the preferred health policy approach that emphasizes responding to individual patient preferences, wishes, and needs. PCC requires active patient engagement. While there has been extensive research on physicians' robes, there is limited research on hospital-issued patient gowns during hospitalizations. How does the gown affect the cognitive–emotional experience of hospitalized patients? How is the gown associated with PCC?MethodsThe sample of this cross-sectional study consisted of 965 patients who were hospitalized at least once during the past year in a tertiary hospital. Measures were previously published.ResultsThe gown was strongly associated with lack of control and increased distress, and was negatively associated with patient proactiveness, engagement, and taking responsibility for self-management of chronic illness. Compared to male patients, female patients wearing the gown had stronger negative emotions and cognitively strong associations with the external locus of control, which inhibited engagement.DiscussionThe hospital gown is an unacknowledged barrier to achieving PCC, inhibits patient engagement, and reflects the paradoxes of inadvertently excluding patients' needs from hospital practice. The hospital gown must be modified to protect the patient's voice and enhance engagement. Policymakers are called to apply design thinking to facilitate patient participation in decision-making to accord hospital clothing to PCC and improve healthcare delivery.

The receipt of the white coat by medical students is a significant milestone. Extensive research has focused on the white coat, its purity, representation of authority and professionalism, its role in consolidating a medical hierarchy, and the professional status attributed to physicians wearing it. Studies suggest that the white coat is a symbol of medical competence, and patients expect physicians to wear it. Research, however, has paid little attention to what physicians think about their white coat, how they perceive the patient's view of the white coat and the hospital gown, within the patient–physician power asymmetry, which is the focus of the current study. In total, 85 physicians from three Israeli medical centers completed a questionnaire (62% Muslims, 33% Jewish, and 5% Christians; 68% men, ages ranging from 21 to 73 years). Employing the enclothed cognition theory and adopting a within-person approach, we found that the more physicians perceived the white coat as important, the more they attributed a positive view of the white coat to patients and the more they perceived the patient's view of the hospital gown as positive. In addition, the higher the perceived importance of the white coat, the higher the reported empathy of physicians toward inpatients, which is consistent with the hospital's values of care. Interestingly, although medicine is a symbol of protection and care for others, the symbolic meaning of the white coat was potent enough to elicit empathy only when physicians perceived it as important. This study extends the theoretical knowledge on the theory of enclothed cognition in healthcare regarding self-perceptions and professional conduct.

Abstract Background H. pylori infection has been linked to iron deficiency anemia, a risk factor of diminished cognitive development. The hypothesis on an association between H. pylori infection and cognitive function was examined in healthy children, independently of socioeconomic and nutritional factors. Methods A community-based study was conducted among 200 children aged 6-9 years, from different socioeconomic background. H. pylori infection was examined by an ELISA kit for detection of H. pylori antigen in stool samples. Cognitive function of the children was blindly assessed using Stanford-Benit test 5th edition, yielding IQ scores. Data on socioeconomic factors and nutritional covariates were collected through maternal interviews and from medical records. Multivariate linear regression analysis was performed to obtain adjusted beta coefficients. Results H. pylori infection was associated with lower IQ scores only in children from a relatively higher socioeconomic community; adjusted beta coefficient -6.1 (95% CI -11.4, -0.8) (P = 0.02) for full-scale IQ score, -6.0 (95% CI -11.1, -0.2) (P = 0.04) for non-verbal IQ score and -5.7 (95% CI -10.8, -0.6) (P = 0.02) for verbal IQ score, after controlling for potential confounders. Conclusions H. pylori infection might be negatively involved in cognitive development at early school age. Further studies in other populations with larger samples are needed to confirm this novel finding.

Background: The long-term relations of socioeconomic status (SES) and early-life exposures with cognitive development at preadolescence are not fully understood, especially in low SES populations. We examined associations of SES and early-life exposures including feeding practices, physical growth and infections with cognitive development among preadolescents from underprivileged communities. Methods: A prospective study was conducted among 146 healthy children from two relatively low SES Arab villages in Israel, who were recruited at age 1–9 weeks and followed until age 18 months. Information was obtained on their feeding practices, health status and growth indicators. Cognitive development at age 10–12 years was assessed using the Wechsler Intelligence Scale, including the full-scale intelligence quotient (FSIQ) and scores of four cognitive domains. Multiple linear regression models were performed. Results: Nearly all the children (98%) were breastfed in infancy. Bivariate correlations were found of SES, growth indices and rates of diarrheal and respiratory illnesses in infancy, but not of feeding practices, with cognitive scores. In multivariable models, SES was positively (p

Background: Chronically ill elderly patients are concerned about losing the personal connection with clinicians in digital encounters and clinicians are concerned about missing nonverbal cues that are important for the diagnosis, thus jeopardizing quality of care. Aims: This study validated the expectations and preferences of chronically ill elderly patients regarding specific communication messages for communication with clinicians in telemedicine. Methods: The sample comprised 600 elderly chronically ill patients who use telehealth. We used a conjoint-based experimental design to test numerous messages. The outcome variable is elder patient expectations from communication with clinicians in telemedicine. The independent variables were known categories of patient–clinician communication. Respondents rated each of the 24 vignettes of messages. Results: Mathematical clustering yielded three mindsets, with statistically significant differences among them. Members of mindset 1 were most concerned with non-verbal communication, members of mindset 2 prefer communication that enhances the internal locus of control, and members of mindset 3 have an external locus of control and strongly oppose any dialogue about their expectations from communication. Conclusions: The use of the predictive algorithm that we developed enables clinicians to identify the belonging of each chronically ill elderly patient in the clinic to a sample mindset, and to accordingly personalize the communication in the digital encounters while structuring the encounter with greater specificity, therefore enhancing patient-centered care.

Background: Exposure in utero to certain medications can disrupt processes of fetal development, including brain development, leading to a continuum of neurodevelopmental difficulties. Recognizing the deficiency of neurodevelopmental investigations within pregnancy pharmacovigilance, an international Neurodevelopmental Expert Working Group was convened to achieve consensus regarding the core neurodevelopmental outcomes, optimization of methodological approaches and barriers to conducting pregnancy pharmacovigilance studies with neurodevelopmental outcomes.Methods: A modified Delphi study was undertaken based on stakeholder and expert input. Stakeholders (patient, pharmaceutical, academic and regulatory) were invited to define topics, pertaining to neurodevelopmental investigations in medication-exposed pregnancies. Experts were identified for their experience regarding neurodevelopmental outcomes following medicinal, substances of misuse or environmental exposures in utero. Two questionnaire rounds and a virtual discussion meeting were used to explore expert opinion on the topics identified by the stakeholders.Results: Twenty-five experts, from 13 countries and professionally diverse backgrounds took part in the development of 11 recommendations. The recommendations focus on the importance of neurodevelopment as a core feature of pregnancy pharmacovigilance, the timing of study initiation and a core set of distinct but interrelated neurodevelopmental skills or diagnoses which require investigation. Studies should start in infancy with an extended period of investigation into adolescence, with more frequent sampling during rapid periods of development. Additionally, recommendations are made regarding optimal approach to neurodevelopmental outcome measurement, comparator groups, exposure factors, a core set of confounding and mediating variables, attrition, reporting of results and the required improvements in funding for potential later emerging effects. Different study designs will be required depending on the specific neurodevelopmental outcome type under investigation and whether the medicine in question is newly approved or already in widespread use.Conclusion: An improved focus on neurodevelopmental outcomes is required within pregnancy pharmacovigilance. These expert recommendations should be met across a complementary set of studies which converge to form a comprehensive set of evidence regarding neurodevelopmental outcomes in pregnancy pharmacovigilance.

Introduction: The aim of this study was to evaluate the impact of minor trauma during pregnancy on maternal and fetal outcomes in patients managed in a tertiary setting. Materials and methods: A retrospective single centre case-controlled study was performed between 2005 and 2017 in a university affiliated tertiary obstetric and trauma centre. All pregnant women of 13–36 weeks gestation that presented to the department of emergency medicine with an Injury Severity Score of

BackgroundThe gut microbiome might play a role in neurodevelopment, however, evidence remains elusive. We aimed to examine the relationship between the intestinal microbiome and cognitive development of school-age children.MethodsThis cross-sectional study included healthy Israeli Arab children from different socioeconomic status (SES). The microbiome was characterized in fecal samples by implementing 16S rRNA gene sequencing. Cognitive function was measured using Stanford-Binet test, yielding full-scale Intelligence Quotient (FSIQ) score. Sociodemographics and anthropometric and hemoglobin measurements were obtained. Multivariate models were implemented to assess adjusted associations between the gut microbiome and FSIQ score, while controlling for age, sex, SES, physical growth, and hemoglobin levels.ResultsOverall, 165 children (41.2% females) aged 6–9 years were enrolled. SES score was strongly related to both FSIQ score and the gut microbiome. Measures of α-diversity were significantly associated with FSIQ score, demonstrating a more diverse, even, and rich microbiome with increased FSIQ score. Significant differences in fecal bacterial composition were found; FSIQ score explained the highest variance in bacterial β-diversity, followed by SES score. Several taxonomic differences were significantly associated with FSIQ score, including Prevotella, Dialister, Sutterella, Ruminococcus callidus, and Bacteroides uniformis.ConclusionsWe demonstrated significant independent associations between the gut microbiome and cognitive development in school-age children.

Valproic acid (VPA) is a very effective anticonvulsant and mood stabilizer with relatively few side effects. Being an epigenetic modulator, it undergoes clinical trials for the treatment of advanced prostatic and breast cancer. However, in pregnancy, it seems to be the most teratogenic antiepileptic drug. Among the proven effects are congenital malformations in about 10%. The more common congenital malformations are neural tube defects, cardiac anomalies, urogenital malformations including hypospadias, skeletal malformations and orofacial clefts. These effects are dose related; daily doses below 600 mg have a limited teratogenic potential. VPA, when added to other anti-seizure medications, increases the malformations rate. It induces malformations even when taken for indications other than epilepsy, adding to the data that epilepsy is not responsible for the teratogenic effects. VPA increases the rate of neurodevelopmental problems causing reduced cognitive abilities and language impairment. It also increases the prevalence of specific neurodevelopmental syndromes like autism (ASD) and Attention Deficit Hyperactivity Disorder (ADHD). High doses of folic acid administered prior to and during pregnancy might alleviate some of the teratogenic effect of VPA and other AEDs. Several teratogenic mechanisms are proposed for VPA, but the most important mechanisms seem to be its effects on the metabolism of folate, SAMe and histones, thus affecting DNA methylation. VPA crosses the human placenta and was found at higher concentrations in fetal blood. Its concentrations in milk are low, therefore nursing is permitted. Animal studies generally recapitulate human data.

The role of hippocampal monoamines and their related genes in the etiology and pathogenesis of depression-like behavior, particularly in impaired sociability traits and the meaning of changes in USVs emitted by pups, remains unknown. We assessed the effects of prenatal administration of S-adenosyl-methionine (SAMe) in Sub mice that exhibit depressive-like behavior on serotonergic, dopaminergic and noradrenergic metabolism and the activity of related genes in the hippocampus (HPC) in adulthood in comparison to saline-treated control Sub mice. During postnatal days 4 and 8, we recorded and analyzed the stress-induced USVs emitted by the pups and tried to understand how the changes in the USVs’ calls may be related to the changes in the monoamines and the activity of related genes. The recordings of the USVs showed that SAMe induced a reduction in the emitted flat and one-frequency step-up call numbers in PND4 pups, whereas step-down type calls were significantly increased by SAMe in PND8 pups. The reduction in the number of calls induced by SAMe following separation from the mothers implies a reduction in anxiety, which is an additional sign of decreased depressive-like behavior. Prenatal SAMe increased the concentrations of serotonin in the HPC in both male and female mice without any change in the levels of 5HIAA. It also decreased the level of the dopamine metabolite DOPAC in females. There were no changes in the levels of norepinephrine and metabolites. Several changes in the expression of genes associated with monoamine metabolism were also induced by prenatal SAMe. The molecular and biochemical data obtained from the HPC studies are generally in accordance with our previously obtained data from the prefrontal cortex of similarly treated Sub mice on postnatal day 90. The changes in both monoamines and their gene expression observed 2–3 months after SAMe treatment are associated with the previously recorded behavioral improvement and seem to demonstrate that SAMe is effective via an epigenetic mechanism.

The etiology of autism spectrum disorder (ASD) is genetic, environmental, and epigenetic. In addition to sex differences in the prevalence of ASD, which is 3–4 times more common in males, there are also distinct clinical, molecular, electrophysiological, and pathophysiological differences between sexes. In human, males with ASD have more externalizing problems (i.e., attention-deficit hyperactivity disorder), more severe communication and social problems, as well as repetitive movements. Females with ASD generally exhibit fewer severe communication problems, less repetitive and stereotyped behavior, but more internalizing problems, such as depression and anxiety. Females need a higher load of genetic changes related to ASD compared to males. There are also sex differences in brain structure, connectivity, and electrophysiology. Genetic or non-genetic experimental animal models of ASD-like behavior, when studied for sex differences, showed some neurobehavioral and electrophysiological differences between male and female animals depending on the specific model. We previously carried out studies on behavioral and molecular differences between male and female mice treated with valproic acid, either prenatally or early postnatally, that exhibited ASD-like behavior and found distinct differences between the sexes, the female mice performing better on tests measuring social interaction and undergoing changes in the expression of more genes in the brain compared to males. Interestingly, co-administration of S-adenosylmethionine alleviated the ASD-like behavioral symptoms and the gene-expression changes to the same extent in both sexes. The mechanisms underlying the sex differences are not yet fully understood.

The receipt of the white coat by medical students is a significant milestone. Extensive research has focused on the white coat, its purity, representation of authority and professionalism, its role in consolidating a medical hierarchy, and the professional status attributed to physicians wearing it. Studies suggest that the white coat is a symbol of medical competence, and patients expect physicians to wear it. Research, however, has paid little attention to what physicians think about their white coat, how they perceive the patient's view of the white coat and the hospital gown, within the patient--physician power asymmetry, which is the focus of the current study. In total, 85 physicians from three Israeli medical centers completed a questionnaire (62% Muslims, 33% Jewish, and 5% Christians; 68% men, ages ranging from 21 to 73 years). Employing the enclothed cognition theory and adopting a within-person approach, we found that the more physicians perceived the white coat as important, the more they attributed a positive view of the white coat to patients and the more they perceived the patient's view of the hospital gown as positive. In addition, the higher the perceived importance of the white coat, the higher the reported empathy of physicians toward inpatients, which is consistent with the hospital's values of care. Interestingly, although medicine is a symbol of protection and care for others, the symbolic meaning of the white coat was potent enough to elicit empathy only when physicians perceived it as important. This study extends the theoretical knowledge on the theory of enclothed cognition in healthcare regarding self-perceptions and professional conduct. [ABSTRACT FROM AUTHOR]

Childhood obesity is a major health problem. We examined differences between children with obesity and normal weight in nutritional and inflammation biomarkers. A cross-sectional study was conducted among healthy children aged 10–12 years from Arab villages in Israel. Parents were interviewed regarding sociodemographic and children’s health status. Body weight and height measurements were performed and weight categories were defined using the 2007 WHO growth curves. Blood samples were tested for complete blood count, levels of iron, ferritin, lipids, uric acid, and C-reactive protein (CRP). Overall, 146 children (59.0% males, mean age = 11.3 [SD = 0.5]) were enrolled. In total 43.8%, 14.1% and 42.3% of the participants had normal weight, overweight and obesity, respectively. A multivariable logistic regression model showed that children with overweight and obesity had lower iron, and HDL-C levels than children with normal weight. Levels of CRP, uric acid, LDL-C and lymphocytes were higher among children with overweight and obesity. In conclusion, our findings highlight the worse metabolic and nutritional status in overweight and obese children. Such markers play a role in metabolic syndrome, thus suggesting that metabolic syndrome might start in childhood.

Reduction in the levels of monoamines, such as serotonin and dopamine in the brain, were reported in patients and animals with depression. SAMe, a universal methyl donor and an epigenetic modulator, is successfully used as an adjunct treatment of depression. We previously found that prenatal treatment with SAMe of Submissive (Sub) mice that serve as a model for depression alleviated many of the behavioral depressive symptoms. In the present study, we treated pregnant Sub mice with 20 mg/kg of SAMe on days 12–15 of gestation and studied the levels of monoamines and the expression of genes related to monoamines metabolism in their prefrontal cortex (PFC) at the age of 3 months. The data were compared to normal saline-treated Sub mice that exhibit depressive-like symptoms. SAMe increased the levels of serotonin in the PFC of female Sub mice but not in males. The levels of 5-HIAA were not changed. SAMe increased the levels of dopamine and of DOPAC in males and females but increased the levels of HVA only in females. The levels of norepinephrine and its metabolite MHPG were unchanged. SAMe treatment changed the expression of several genes involved in the metabolism of these monoamines, also in a sex-related manner. The increase in several monoamines induced by SAMe in the PFC may explain the alleviation of depressive-like symptoms. Moreover, these changes in gene expression more than 3 months after treatment probably reflect the beneficial effects of SAMe as an epigenetic modulator in the treatment of depression.

Objectives: Our objective was to estimate the likelihood of abnormal development among institutionalized children, addressing either the risk in general, or the risk for fetal alcohol spectrum disorder (FASD). Methods: Narrative review of studies measuring developmental effects of these populations. We identified all systematic reviews and meta analyses dealing with the associations between institutionalization of children and their neurodevelopment in general, or between institunalization of children and their likelihood of suffering from FASD. Results: a) In a published meta-analysis the mean IQ/DQ was 84 among institutionalized children, as compared to 104 among children raised in families. Favorable caregiver-child ratios appeared to have a protective effect, whereas longer stays in institutions had a detrimental effect on IQ/ DQ. b) A further meta- analysis has shown a positive impact of adoption on children’s cognitive development with adopted children’s displaying remarkably normal cognitive competence as compared to their non-adopted peers. c) The overall pooled prevalence was 6% (60 per 1,000, 95% CI 38-85) for full blown fetal alcohol syndrome (FAS), and 16.9% (95% CI 109-238 per 1,000) for the whole range of FASD. d) The estimated prevalence of FASD was 10-40 fold higher than the 7.7 per 1000 in the general population. Conclusions: A large proportion of adopted institutionalized children may not follow a normal developmental trajectory. If not afflicted by FASD, there is a positive impact of adoption on children’s cognitive development and in general they are comparable to their non- adopted peers.

In this review, we discuss the functions and main effects on pregnancy outcomes of three agents that have the ability to induce epigenetic modifications: valproic acid (VPA), a well-known teratogen that is a histone deacetylase inhibitor; S-adenosylmethionine (SAMe), the most effective methyl donor; and choline, an important micronutrient involved in the one methyl group cycle and in the synthesis of SAMe. Our aim was to describe the possible effects of these compounds when administered during pregnancy on the developing embryo and fetus or, if administered postnatally, their effects on the developing child. These substances are able to modify gene expression and possibly alleviate neurobehavioral changes in disturbances that have epigenetic origins, such as autism spectrum disorder (ASD), depression, Rett syndrome, and fetal alcohol spectrum disorder (FASD). Valproic acid and SAMe are antagonistic epigenetic modulators whether administered in utero or postnatally. However, VPA is a major human teratogen and, whenever possible, should not be used by pregnant women. Most currently relevant data come from experimental animal studies that aimed to explore the possibility of using these substances as epigenetic modifiers and possible therapeutic agents. In experimental animals, each of these substances was able to alleviate the severity of several well-known diseases by inducing changes in the expression of affected genes or by other yet unknown mechanisms. We believe that additional studies are needed to further explore the possibility of using these substances, and similar compounds, for the treatment of ”epigenetic human diseases”.

This narrative review presents the emerging published evidence on the existence of a phenotypic behavior in children with fetal alcohol spectrum behavior. Such a phenotype, exhibiting high sensitivity, specificity, and predictive values, may assist clinicians and families in identifying children who often miss some of the information needed for full diagnosis, but who may benefit from these screening tools in mobilizing help to these youngsters and their families.

Valproic acid (VPA) is a very effective anticonvulsant and mood stabilizer with relatively few side effects. Being an epigenetic modulator, it undergoes clinical trials for the treatment of advanced prostatic and breast cancer. However, in pregnancy, it seems to be the most teratogenic antiepileptic drug. Among the proven effects are congenital malformations in about 10%. The more common congenital malformations are neural tube defects, cardiac anomalies, urogenital malformations including hypospadias, skeletal malformations and orofacial clefts. These effects are dose related; daily doses below 600 mg have a limited teratogenic potential. VPA, when added to other anti-seizure medications, increases the malformations rate. It induces malformations even when taken for indications other than epilepsy, adding to the data that epilepsy is not responsible for the teratogenic effects. VPA increases the rate of neurodevelopmental problems causing reduced cognitive abilities and language impairment. It also increases the prevalence of specific neurodevelopmental syndromes like autism (ASD) and Attention Deficit Hyperactivity Disorder (ADHD). High doses of folic acid administered prior to and during pregnancy might alleviate some of the teratogenic effect of VPA and other AEDs. Several teratogenic mechanisms are proposed for VPA, but the most important mechanisms seem to be its effects on the metabolism of folate, SAMe and histones, thus affecting DNA methylation. VPA crosses the human placenta and was found at higher concentrations in fetal blood. Its concentrations in milk are low, therefore nursing is permitted. Animal studies generally recapitulate human data. [ABSTRACT FROM AUTHOR]

The intestinal microbiome continues to shift and develop throughout youth and could play a pivotal role in health and wellbeing throughout adulthood. Environmental and interpersonal determinants are strong mediators of the intestinal microbiome during the rapid growth period of preadolescence. We aim to delineate associations between the gut microbiome composition, body mass index (BMI), dietary intake and socioeconomic status (SES) in a cohort of ethnically homogenous preadolescents. This cohort included 139 Arab children aged 10–12 years, from varying socioeconomic strata. Dietary intake was assessed using the 24-h recall method. The intestinal microbiome was analyzed using 16S rRNA gene amplicon sequencing. Microbial composition was associated with SES, showing an overrepresentation of Prevotella and Eubacterium in children with lower SES. Higher BMI was associated with lower microbial diversity and altered taxonomic composition, including higher levels of Collinsella, especially among participants from lower SES. Intake of polyunsaturated fatty acids was the strongest predictor of bacterial alterations, including an independent association with Lachnobacterium and Lactobacillus. This study demonstrates that the intestinal microbiome in preadolescents is associated with socioeconomic determinants, BMI and dietary intake, specifically with higher consumption of polyunsaturated fatty acids. Thus, tailored interventions during these crucial years have the potential to improve health disparities throughout the lifespan.

Understanding the role in pediatric obesity of early life feeding practices and dietary intake at school age is essential for early prevention. The study aimed to examine associations of early life feeding practices, environmental and health-related exposures, and dietary intake at school age as determinants of obesity in children aged 10–12 years. In an earlier study of 233 healthy infants in two Arab towns in northern Israel, neonatal history, feeding practices, and health information were obtained up to age 18 months. This follow-up study assessed dietary intake and anthropometric measurements at age 10–12 years using the 24 h recall method. Overall, 174 children participated in this study. Almost all (98%) the children were breastfed. The prevalence of obesity at school age was 42%. A multivariable model adjusted for energy intake and socioeconomic status showed positive associations of total fat intake and of weight-for-height z score, but not feeding practices in infancy, with obesity. Higher gestational age at birth was associated with lower odds of obesity at age 10–12 years. In conclusion, in a population with near universal breastfeeding, gestational age at birth, weight indicators but not feeding practices in infancy, and total fat intake at school age were associated with increased likelihood of obesity.