Sodium Intake and Sodium to Potassium Ratio among New York City Adults in the 2018 Heart Follow-Up Study.

Background: High sodium and low potassium intake are positively associated with blood pressure, a significant risk factor for cardiovascular disease. The mean intake of sodium among United States adults exceeds the chronic disease risk reduction level of 2300 mg/d, whereas potassium intake remains lower than the recommended levels. From 2008 through 2019, there were several local and national initiatives to reduce sodium in New York City (NYC). Objectives: We aimed to update and compare estimates of sodium intake among NYC adults overall and by covariates from the 2010 Heart Follow-Up Study (HFUS) with the 2018 HFUS. We also estimated the 2018 sodium-to-potassium ratio to understand overall diet quality among demographic groups. Methods: This cross-sectional study used sodium and potassium measurements from 24-h urine collection and self-reported data from 2509 and 1656 participants in the 2018 and 2010 HFUS, respectively. The weighted mean daily intake of sodium and the sodium-to-potassium ratio were estimated. T-tests and multivariable linear regression models with tests for interactions were used to compare changes in sodium intake. Results: The mean sodium intake of adult New Yorkers in 2018 was 3292 mg/d. Sodium intake did not change from 2010 (3234 mg/d, P = 0.45) to 2018 in the overall population, although there was a decrease in sodium intake among adults 18-24 y old (3445 mg/d to 2957 mg/d, P = 0.05). The daily mean sodium-to-potassium ratio was 1.7 mg/mg. The highest sodium-to-potassium ratios were among Black females 18-44 y old (2.0) and 45-64 y old (2.2) and Black (2.1) and Latino (2.1) males between 18 and 44 y old. Conclusions: The lack of population-level changes in sodium intake and the high sodium-to-potassium ratios among Black females and younger Black and Latino males suggest that further efforts to reduce sodium in the food supply and address persistent inequities are needed.

Independent and Combined Effects of Prenatal Alcohol Exposure and Prenatal Stress on Fetal HPA Axis Development.

Prenatal alcohol exposure (PAE) and prenatal stress (PS) are highly prevalent conditions known to affect fetal programming of the hypothalamic-pituitary-adrenal (HPA) axis. The objectives of this study were to assess the effect of light PAE, PS, and PAE-PS interaction on fetal HPA axis activity assessed via placental and umbilical cord blood biomarkers. Participants of the ENRICH-2 cohort were recruited during the second trimester and classified into the PAE and unexposed control groups. PS was assessed by the Perceived Stress Scale. Placental tissue was collected promptly after delivery; gene and protein analysis for 11ß-HSD1, 11ß-HSD2, and pCRH were conducted by qPCR and ELISA, respectively. Umbilical cord blood was analyzed for cortisone and cortisol. Pearson correlation and multivariable linear regression examined the association of PAE and PS with HPA axis biomarkers. Mean alcohol consumption in the PAE group was ~2 drinks/week. Higher PS was observed in the PAE group (p < 0.01). In multivariable modeling, PS was associated with pCRH gene expression (ß = 0.006, p < 0.01), while PAE was associated with 11ß-HSD2 protein expression (ß = 0.56, p < 0.01). A significant alcohol-by-stress interaction was observed with respect to 11ß-HSD2 protein expression (p < 0.01). Results indicate that PAE and PS may independently and in combination affect fetal programming of the HPA axis.

Experiences of neurofeedback therapists in treating attention-deficit hyperactivity disorder.

Background: Neurofeedback is a neurostimulatory biofeedback behavioural therapy that regulates brain wave levels for optimal cognitive functioning. It has shown promising results for the treatment of attention-deficit hyperactivity disorder (ADHD). Aim: To explore and describe the experiences of neurofeedback therapists (NTs) using neurofeedback to treat children and adults with ADHD and their experience of its role and value in treating this condition. Setting: Interviews were conducted in participants' private consultation rooms in Gauteng, South Africa. Methods: In this qualitative study using a descriptive phenomenological approach, six registered NTs with experience of treating ADHD were interviewed. Participants were asked: 'Tell me about your experiences of neurofeedback with ADHD patients in your practice.' Responses were audio-recorded, transcribed and underwent thematic analysis. Results: Participants experienced neurofeedback as an effective treatment for ADHD and other coexisting conditions, such as anxiety and insomnia. Participants felt that the neurofeedback process facilitates a beneficial therapeutic relationship and integrates well with other treatment methods. Challenges faced in practice included certain underlying comorbidities, home environment, poor patient compliance and NTs' level of expertise, which impact treatment outcomes. Conclusion: Neurofeedback therapists expressed an overall positive perception of the value of neurofeedback to reduce ADHD symptom severity and improve quality of life, particularly when used as part of a multimodal approach. Participants identified a need for further education and awareness regarding the use of neurofeedback for ADHD. Contribution: This study has contributed to our understanding of the role of neurofeedback in treating ADHD in the South African setting.

The maternal-placental-fetal interface: Adaptations of the HPA axis and immune mediators following maternal stress and prenatal alcohol exposure.

This review addresses underlying physiological, cellular, and molecular factors that alter the developing fetal brain stress circuits and responses of the hypothalamic-pituitary-adrenal (HPA) axis caused by maternal stress and prenatal alcohol exposure (PAE). An emphasis is placed on the contribution of the placenta following maternal stress separately, and as a co-occurrence with PAE. Altered fetal HPA axis ultimately results in dysregulation of the brain stress-response system long after birth and possibly lifelong. Additional consideration of the role of placentally-derived endocrine and sex hormones, as well as a brief discussion of epigenetic mechanisms of altered placental expression of genes encoding the glucocorticoid receptor and the enzymes 11ß-HSD that rapidly convert glucocorticoids into its active or inactive forms are reviewed. Data highlighting the strong, reciprocal interactions between the neuroimmune and neuroendocrine systems during fetal development that are impacted by maternal stress and PAE are considered, emphasizing the role of the placenta as a key contributor to the dysregulation of these systems. In view of the maternal-placental-fetal interface, important physiological, cellular, and molecular factors underlying later life dysregulated stress responses are additionally considered. Literature from animal models of PAE and maternal stress is reviewed that support clinical observations of the effect of maternal stress and alcohol exposure during fetal development on later-life adult stress responses and associated mood dysregulation. An appreciation of dysregulated stress responses in individuals with fetal alcohol spectrum disorders (FASD) are addressed given the greater prevalence of adult dysregulated stress responses and a greater co-occurrence of mood disorders in individuals diagnosed with FASD.

A novel method for the normalization of ChIP-qPCR data.

ChIP-qPCR permits the study of protein and chromatin interactions. The general technique can apply to the study of the interactions of protein with RNA, and the methylation state of genomic DNA. While the technique is vital to our understanding of epigenetic processes, there is much confusion around the proper normalization methods. Percent Input has recently emerged as a normalization standard, due to its reproducibility and accuracy. This method relies on the use of a constant volume of ChIP Isolate in each qPCR assay. Researchers may accidentally run qPCR assays with a constant amount of isolate, a common practice for RT-qPCR; however, the traditional Percent Input method cannot accurately normalize these data. We developed a novel method that can normalize these data to provide the same reproducible Percent Input value. Here, we present evidence that this novel method of normalizing ChIP-qPCR data works with real samples. Later, we present a mathematical proof which shows how a Percent Input value calculated from Cq (quantification cycle) values obtained from qPCR run with a constant amount (in nanograms of DNA in ChIP isolate) is equal to the traditional Percent Input calculated from quantification cycle (Cq) values obtained from running a constant volume of ChIP isolate.•Increases the number of possible data points per sample•End values are the same % Input values as the traditional normalization method.

Health supplements for allergic rhinitis: A mixed-methods systematic review.

Allergic rhinitis is a chronic inflammatory condition caused by an exaggerated response of the immune system to common allergens. Most pharmacological therapies tend to be palliative and in some cases are associated with adverse effects. There is a growing tendency for people to self-medicate with health supplements as they are generally considered safe, however clinical studies relating to their efficacy and safety are limited. This mixed-methods systematic review aims to synthesise the available evidence relating to the treatment of allergic rhinitis with a variety of health supplements. A total of 57 062 articles were derived from searching seven online databases and evidence from 48 RCTs and 10 observational studies were reviewed for methodological quality and risk of bias. No qualitative studies meeting the inclusion criteria could be found, therefore only a quantitative review was performed. Promising evidence for the following single supplements were found: apple polyphenols, tomato extract, spirulina, chlorophyll c2, honey, conjugated linoleic acid, MSM, isoquercitrin, vitamins C, D and E, as well as probiotics. Combination formulas may also be beneficial, particularly specific probiotic complexes, a mixture of vitamin D3, quercetin and Perilla frutescens, as well as the combination of vitamin D3 and L. reuteri. Owing to the paucity of good quality evidence, recommendations pertaining to the use of health supplements for allergic rhinitis should involve a shared decision-making process between the healthcare provider and the patient, taking into account their efficacy, safety and cost. Further good quality clinical studies and qualitative research would further our understanding of the role these health supplements may play in future treatment protocols.

Exploring Social Subtypes in Autism Spectrum Disorder: A Preliminary Study.

Impairments in social functioning are considered a hallmark diagnostic feature of autism spectrum disorder (ASD). Yet, individuals diagnosed with ASD vary widely with respect to specific presentation, severity, and course across different dimensions of this complex symptom domain. The aim of this investigation was to utilize the Stanford Social Dimensions Scale (SSDS), a newly developed quantitative measure providing parental perspective on their child's social abilities, in order to explore the existence of homogeneous subgroups of ASD individuals who share unique profiles across specific dimensions of the social domain. Parents of 164 individuals with ASD (35 females, 129 males; meanage = 7.54 years, SD = 3.85) completed the SSDS, the Social Responsiveness Scale (SRS-2) and the Child Behavior Checklist (CBCL). Data on children's verbal and nonverbal intellectual functioning (FSIQ) were also collected. The Latent Profile Analysis was used to classify participants according to the pattern of SSDS subscale scores (Social Motivation, Social Affiliation, Expressive Social Communication, Social Recognition, and Unusual Approach). Five profiles were identified. Profiles did not differ in terms of chronological age nor gender distribution but showed distinct patterns of strengths and weaknesses across different social components rather than simply reflecting a severity gradient. Profiles were further differentiated in terms of cognitive ability, as well as ASD and internalizing symptom severity. The implications of current findings and the necessary further steps toward identifying subgroups of individuals with ASD who share particular constellation of strengths and weaknesses across key social domains as a way of informing personalized interventions are discussed. Autism Res 2020. © 2020 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: People with autism spectrum disorder (ASD) vary greatly in terms of their social abilities and social motivation. However, researchers lack measures that can fully assess different components of social functioning. This paper provides initial evidence for capturing subgroups of individuals with ASD with specific strengths and weakness across different aspects of social functioning. Autism Res 2020, 13: 1335-1342. © 2020 International Society for Autism Research, Wiley Periodicals, Inc.

Development of the Stanford Social Dimensions Scale: initial validation in autism spectrum disorder and in neurotypicals.

Background: The aim of this paper was to provide an initial validation of a newly developed parent questionnaire-the Stanford Social Dimensions Scale (SSDS), designed to capture individual differences across several key social dimensions including social motivation in children and adolescents with and without psychiatric disorders. Methods: The initial validation sample was comprised of parents of 175 individuals with autism spectrum disorder (ASD) (35 females, 140 males; Mage = 7.19 years, SDage = 3.96) and the replication sample consisted of 624 parents of children who were either typically developing or presented with a range of neurodevelopmental and neuropsychiatric disorders (302 females, 322 males; Mage = 11.49 years, SDage = 4.48). Parents from both samples completed the SSDS and the Social Responsiveness Scale (SRS-2). Results: Exploratory Structural Equation Modeling indicated that a 5-factor model provided adequate to excellent fit to the data in the initial ASD sample (comparative fit index [CFI] = .940, Tucker-Lewis Index [TLI] = .919, root mean square error of approximation [RMSEA] = .048, standardized root mean square residual [SRMR] = .038). The identified factors were interpreted as Social Motivation, Social Affiliation, Expressive Social Communication, Social Recognition, and Unusual Approach. This factor structure was further confirmed in Sample 2 (CFI = 946, TLI = .930, RMSEA = .044, SRMR = .026). Internal consistency for all subscales was in the good to excellent range across both samples as indicated by Composite Reliability scores of ≥ .72. Convergent and divergent validity was strong as indexed by the pattern of correlations with relevant SRS-2 and Child Behavior Checklist domains and with verbal and non-verbal intellectual functioning scores in Sample 1 and with the Need to Belong Scale and Child Social Preference Scale scores in Sample 2. Across both samples, females had higher social motivation and expressive social communication scores. Discriminant validity was strong given that across all SSDS subscales, the ASD sample had significantly higher impairment than both the typically developing group and the group with other clinical conditions, which in turn, had significantly higher impairment than the typically developing group. Conclusions: Our findings provide initial validation of a new scale designed to comprehensively capture individual differences in social motivation and other key social dimensions in ASD.

Sex-specific deficits in biochemical but not behavioral responses to delay fear conditioning in prenatal alcohol exposure mice.

BACKGROUND: Studies in clinical populations and preclinical models have shown that prenatal alcohol exposure (PAE) is associated with impairments in the acquisition, consolidation and recall of information, with deficits in hippocampal formation-dependent learning and memory being a common finding. The glucocorticoid receptor (GR), mineralocorticoid receptor (MR), and extracellular signal-regulated kinase 2 (ERK2) are key regulators of hippocampal formation development, structure and functioning and, thus, are potential mediators of PAE's effects on this brain region. In the present studies, we employed a well-characterized mouse model of PAE to identify biochemical mechanisms that may underlie activity-dependent learning and memory deficits associated with PAE. METHODS: Mouse dams consumed either 10% (w/v) ethanol in 0.066% (w/v) saccharin (SAC) or 0.066% (w/v) SAC alone using a limited (4-h) access, drinking-in-the-dark paradigm. Male and female offspring (∼180-days of age) were trained using a delay conditioning procedure and contextual fear responses (freezing behavior) were measured 24 h later. Hippocampal formation tissue and blood were collected from three behavioral groups of animals: 20 min following conditioning (conditioning only group), 20 min following the re-exposure to the context (conditioning plus re-exposure group), and behaviorally naïve (naïve group) mice. Plasma corticosterone levels were measured by enzyme immunoassay. Immunoblotting techniques were used to measure protein levels of the GR, MR, ERK1 and ERK2 in nuclear and membrane fractions prepared from the hippocampal formation. RESULTS: Adult SAC control male and female mice displayed similar levels of contextual fear. However, significant sex differences were observed in freezing exhibited during the conditioning session. Compared to same-sex SAC controls, male and female PAE mice demonstrated context fear deficits While plasma corticosterone concentrations were elevated in PAE males and females relative to their respective SAC naïve controls, plasma corticosterone concentrations in the conditioning only and conditioning plus re-exposure groups were similar in SAC and PAE animals. Relative to the respective naïve group, nuclear GR protein levels were increased in SAC, but not PAE, male hippocampal formation in the conditioning only group. In contrast, no difference was observed between nuclear GR levels in the naïve and conditioning plus re-exposure groups. In females, nuclear GR levels were significantly reduced by PAE but there was no effect of behavioral group or interaction between prenatal treatment and behavioral group. In males, nuclear MR levels were significantly elevated in the SAC conditioning plus re-exposure group compared to SAC naïve mice. In PAE females, nuclear MR levels were elevated in both the conditioning only and conditioning plus re-exposure groups relative to the naïve group. Levels of activated ERK2 (phospho-ERK2 expressed relative to total ERK2) protein were elevated in SAC, but not PAE, males following context re-exposure, and a significant interaction between prenatal exposure group and behavioral group was found. No main effects or interactions of behavioral group and prenatal treatment on nuclear ERK2 were found in female mice. These findings suggest a sex difference in which molecular pathways are activated during fear conditioning in mice. CONCLUSIONS: In PAE males, the deficits in contextual fear were associated with the loss of responsiveness of hippocampal formation nuclear GR, MR and ERK2 to signals generated by fear conditioning and context re-exposure. In contrast, the contextual fear deficit in PAE female mice does not appear to be associated with activity-dependent changes in GR and MR levels or ERK2 activation during training or memory recall, although an overall reduction in nuclear GR levels may play a role. These studies add to a growing body of literature demonstrating that, at least partially, different mechanisms underlie learning, memory formation and memory recall in males and females and that these pathways are differentially affected by PAE.

Sex-Dependent Effects of the Histone Deacetylase Inhibitor, Sodium Valproate, on Reversal Learning After Developmental Arsenic Exposure.

Several studies have demonstrated that exposure to arsenic in drinking water adversely affects brain development and cognitive function in adulthood. While the mechanism by which arsenic induces adverse neurological outcomes remains elusive, studies suggest a link between reduced levels of histone acetylation and impaired performance on a variety of behavioral tasks following arsenic exposure. Using our developmental arsenic exposure (DAE) paradigm, we have previously reported reduced histone acetylation and associated histone acetyltransferase enzyme expression in the frontal cortex of C57BL/6J adult male mice, with no changes observed in the female frontal cortex. In the present study, we sought to determine if DAE produced sex-dependent deficits in frontal cortical executive function using the Y-maze acquisition and reversal learning tasks, which are specific for assessing cognitive flexibility. Further, we tested whether the administration of valproic acid, a class I-IIa histone deacetylase inhibitor, was able to mitigate behavioral and biochemical changes resulting from DAE. As anticipated, DAE inhibited acquisition and reversal learning performance in adult male, but not female, mice. Valproate treatment for 2 weeks restored reversal performance in the male arsenic-exposed offspring, while not affecting female performance. Protein levels of HDACs 1, 2, and 5 were elevated following behavioral assessment but only in DAE male mice; restoration of appropriate HDAC levels occurred after valproate treatment and was concurrent with improved behavioral performance, particularly during reversal learning. Female frontal cortical levels of HDAC enzymes were not impacted by DAE or valproate treatment. Finally, mRNA expression levels of brain-derived neurotrophic factor, Bdnf, which has been implicated in the control of frontal cortical flexibility and is regulated by HDAC5, were elevated in DAE male mice and restored to normal levels following HDACi treatment. Levels of mRNA encoding glutamate receptor ionotropic NMDA type subunits, which have been linked to cognitive flexibility, were not related to the reversal learning deficit in the DAE mice and were not altered by HDACi treatments. These findings demonstrate that DAE alters frontal cortical HDAC levels and Bdnf expression in males, but not females, and that these molecular changes are associated with sex-dependent differences in cognitive flexibility in a reversal-learning task.

Arsenic exposure during embryonic development alters the expression of the long noncoding RNA growth arrest specific-5 (Gas5) in a sex-dependent manner.

Our previous studies suggest that prenatal arsenic exposure (50ppb) modifies epigenetic control of the programming of the glucocorticoid receptor (GR) signaling system in the developing mouse brain. These deficits may lead to long-lasting consequences, including deficits in learning and memory, increased depressive-like behaviors, and an altered set-point of GR feedback throughout life. To understand the arsenic-induced changes within the GR system, we assessed the impact of in utero arsenic exposure on the levels of the GR and growth arrest-specific-5 (Gas5), a noncoding RNA, across a key gestational period for GR programming (gestational days, GD 14-18) in mice. Gas5 contains a glucocorticoid response element (GRE)-like sequence that binds the GR, thereby decreasing GR-GRE-dependent gene transcription and potentially altering GR programming. Prenatal arsenic exposure resulted in sex-dependent and age-dependent shifts in the levels of GR and Gas5 expression in fetal telencephalon. Nuclear GR levels were reduced in males, but unchanged in females, at all gestational time points tested. Total cellular Gas5 levels were lower in arsenic-exposed males with no changes seen in arsenic-exposed females at GD16 and 18. An increase in total cellular Gas-5 along with increased nuclear levels in GD14 arsenic-exposed females, suggests a differential regulation of cellular compartmentalization of Gas5. RIP assays revealed reduced Gas5 associated with the GR on GD14 in the nuclear fraction prepared from arsenic-exposed males and females. This decrease in levels of GR-Gas5 binding continued only in the females at GD18. Thus, nuclear GR signaling potential is decreased in prenatal arsenic-exposed males, while it is increased or maintained at levels approaching normal in prenatal arsenic-exposed females. These findings suggest that females, but not males, exposed to arsenic are able to regulate the levels of nuclear free GR by altering Gas5 levels, thereby keeping GR nuclear signaling closer to control (unexposed) levels.

Prenatal arsenic exposure alters REST/NRSF and microRNA regulators of embryonic neural stem cell fate in a sex-dependent manner.

Exposure to arsenic, a common environmental toxin found in drinking water, leads to a host of neurological pathologies. We have previously demonstrated that developmental exposure to a low level of arsenic (50ppb) alters epigenetic processes that underlie deficits in adult hippocampal neurogenesis leading to aberrant behavior. It is unclear if arsenic impacts the programming and regulation of embryonic neurogenesis during development when exposure occurs. The master negative regulator of neural-lineage, REST/NRSF, controls the precise timing of fate specification and differentiation of neural stem cells (NSCs). Early in development (embryonic day 14), we observed increased expression of Rest, its co-repressor, CoREST, and the inhibitory RNA binding/splicing protein, Ptbp1, and altered expression of mRNA spliced isoforms of Pbx1 that are directly regulated by these factors in the male brain in response to prenatal 50ppb arsenic exposure. These increases were concurrent with decreased expression of microRNA-9 (miR-9), miR-9*, and miR-124, all of which are REST/NRSF targets and inversely regulate Rest expression to allow for maturation of NSCs. Exposure to arsenic decreased the formation of neuroblasts in vitro from NSCs derived from male pup brains. The female response to arsenic was limited to increased expression of CoREST and Ptbp2, an RNA binding protein that allows for appropriate splicing of genes involved in the progression of neurogenesis. These changes were accompanied by increased neuroblast formation in vitro from NSCs derived from female pups. Unexposed male mice express transcriptomic factors to induce differentiation earlier in development compared to unexposed females. Thus, arsenic exposure likely delays differentiation of NSCs in males while potentially inducing precocious differentiation in females early in development. These effects are mitigated by embryonic day 18 of development. Arsenic-induced dysregulation of the regulatory loop formed by REST/NRSF, its target microRNAs, miR-9 and miR-124, and RNA splicing proteins, PTBP1 and 2, leads to aberrant programming of NSC function that is perhaps perpetuated into adulthood inducing deficits in differentiation we have previously observed.

Physiotherapy and a Homeopathic Complex for Chronic Low-back Pain Due to Osteoarthritis: A Randomized, Controlled Pilot Study.

CONTEXT: Osteoarthritis (OA) is a common cause of chronic low-back pain (CLBP) and can be managed with drug therapy and physiotherapy. Homeopathic remedies may assist managing OA; however, research that supports their effectiveness is limited. OBJECTIVES: The study aimed to investigate the efficacy of a homeopathic complex in combination with physiotherapy in treating CLBP due to OA. DESIGN: The study was a 6-wk, randomized, double-blind, placebo-controlled pilot. SETTING: The study took place in a private physiotherapy practice in Gauteng, South Africa. PARTICIPANTS: The participants were 30 males and females, aged 45-75 y, who were receiving physiotherapy treatment for OA of the lumbar spine from a therapist in private practice. INTERVENTIONS: The intervention and control groups both received standard physiotherapy treatment-massage, thermal therapy, and joint mobilization-every 2 wk. In addition, the treatment group received a homeopathic complex-6cH each of Arnica montana, Bryonia alba, Causticum, Kalmia latifolia, Rhus toxicodendron, and Calcarea fluorica. The control group a received a placebo. OUTCOME MEASURES: The primary measure was a visual analogue scale (VAS) for pain. Secondary outcome measures included the Oswestry Disability Index (ODI), an evaluation of each patient's range of motion (ROM) of the lumbar spine, and a determination of each patient's need for pain medication. RESULTS: Intergroup analysis revealed that the treatment group significantly outperformed the control group with regard to pain, daily functioning, and ROM. No difference existed between the groups, however, in the need for conventional pain medication. CONCLUSIONS: The study was too small to be conclusive, but results suggest the homeopathic complex, together with physiotherapy, can significantly improve symptoms associated with CLBP due to OA.

Developmental exposure to 50 parts-per-billion arsenic influences histone modifications and associated epigenetic machinery in a region- and sex-specific manner in the adult mouse brain.

Epidemiological studies report that arsenic exposure via drinking water adversely impacts cognitive development in children and, in adults, can lead to greater psychiatric disease susceptibility, among other conditions. While it is known that arsenic toxicity has a profound effect on the epigenetic landscape, very few studies have investigated its effects on chromatin architecture in the brain. We have previously demonstrated that exposure to a low level of arsenic (50ppb) during all three trimesters of fetal/neonatal development induces deficits in adult hippocampal neurogenesis in the dentate gyrus (DG), depressive-like symptoms, and alterations in gene expression in the adult mouse brain. As epigenetic processes control these outcomes, here we assess the impact of our developmental arsenic exposure (DAE) paradigm on global histone posttranslational modifications and associated chromatin-modifying proteins in the dentate gyrus and frontal cortex (FC) of adult male and female mice. DAE influenced histone 3K4 trimethylation with increased levels in the male DG and FC and decreased levels in the female DG (no change in female FC). The histone methyltransferase MLL exhibited a similar sex- and region-specific expression profile as H3K4me3 levels, while histone demethylase KDM5B expression trended in the opposite direction. DAE increased histone 3K9 acetylation levels in the male DG along with histone acetyltransferase (HAT) expression of GCN5 and decreased H3K9ac levels in the male FC along with decreased HAT expression of GCN5 and PCAF. DAE decreased expression of histone deacetylase enzymes HDAC1 and HDAC2, which were concurrent with increased H3K9ac levels but only in the female DG. Levels of H3 and H3K9me3 were not influenced by DAE in either brain region of either sex. These findings suggest that exposure to a low, environmentally relevant level of arsenic during development leads to long-lasting changes in histone methylation and acetylation in the adult brain due to aberrant expression of epigenetic machinery based on region and sex.

Some intrapersonal qualities of SA homeopaths who have established successful private practices.

PURPOSE: The purpose of the study was to explore the experiences of homeopaths who have established successful private practices in South Africa (SA) with the aim of identifying some of their intrapersonal qualities which may have contributed to their establishing a successful practice. METHOD: This was a qualitative phenomenological research design using in-depth interviews with homeopaths running successful private practices across 5 provinces in SA, which were digitally recorded. Of these, 18 were transcribed and analysed using a descriptive coding approach and strategies for phenomenological analysis. Themes and supporting categories are identified and described. FINDINGS: Homeopaths experiences suggest that they are authentic, self-aware, self-reflective and proactive. They experienced a need for self-care and support and further found that their integrity, positive attitude, self-discipline and passion, contributed to their success in practice. CONCLUSION: The intrapersonal qualities can be roughly divided between those that generate inner-support and those which aid homeopaths attain their goal of establishing a practice and are therefore crucial aspects of success generation.

Sex-Dependent effects of developmental arsenic exposure on methylation capacity and methylation regulation of the glucocorticoid receptor system in the embryonic mouse brain.

Previously we have shown that prenatal moderate arsenic exposure (50 ppb) disrupts glucocorticoid receptor (GR) programming and that these changes continue into adolescence in males. However, it was not clear what the molecular mechanisms were promoting these GR programming changes or if these changes occurred in arsenic-exposed females. In the present studies, we assessed the effects of arsenic on protein and mRNA of the glucocorticoid receptor (GR) and 11ß-hydroxysteroid dehydrogenase (Hsd) isozymes and compared the levels of methylation within the promoters of the Nr3c1 and Hsd11b1 genes in female fetal brain at embryonic days (E) 14 and 18. Prenatal arsenate exposure produced sex specific effects on the glucocorticoid system. Compared to males, females were resistant to arsenic induced changes in GR, 11ß-Hsd-1 and 11ß-Hsd-2 protein levels despite observed elevations in Nr3c1 and Hsd11b2 mRNA. This sex-specific effect was not due to differences in the methylation of the GR promoter as methylation of the Nr3c1 gene was either unchanged (region containing the egr-1 binding site) or similarly reduced (region containing the SP-1 transcription factor binding site) in both males and females exposed to arsenic. Arsenic did produce sex and age-specific changes in the methylation of Hsd11b1 gene, producing increased methylation in females at E14 and decreased methylation at E18. These changes were not attributed to changes in DNMT levels. Since arsenate metabolism could interfere with the generation of methyl donor groups, we assessed glutathione (GSH), s-adenosylmethionine (SAM) and As 3 methyltransferase (As3MT). Exposed males and females had similar levels of As3MT and SAM; however, females had higher levels of GSH/GSSH. It is possible that this greater anti-oxidative capacity within the females provides protection against low to moderate arsenate. Our data suggest that the GR signaling system in female offspring was not as affected by prenatal arsenic and predicts that female arsenic-exposed mice should have normal GR feedback regulation.

Efficacy of a homeopathic complex on acute viral tonsillitis.

BACKGROUND: Acute viral tonsillitis is an upper respiratory tract infection prevalent in school-aged children. Because this condition is self-limiting, conventional treatment options are usually palliative. Homeopathic remedies are a useful alternative to conventional medications in acute uncomplicated upper respiratory tract infections in children, offering earlier symptom resolution, cost-effectiveness, and fewer adverse effects. This study aimed to determine the efficacy of a homeopathic complex on the symptoms of acute viral tonsillitis in African children in South Africa. METHODS: This was a randomized, double-blind, placebo-controlled, 6-day pilot study. Thirty children, age 6 to 12 years, with acute viral tonsillitis were recruited from a primary school in Gauteng, South Africa. Participants took two tablets of the medication four times daily. The treatment group received lactose tablets medicated with the homeopathic complex (Atropa belladonna D4, Calcarea phosphoricum D4, Hepar sulphuris D4, Kalium bichromat D4, Kalium muriaticum D4, Mercurius protoiodid D10, and Mercurius biniodid D10). The placebo consisted of the unmedicated vehicle only. The Wong-Baker FACES Pain Rating Scale measured pain intensity, and a Symptom Grading Scale assessed changes in tonsillitis signs and symptoms. RESULTS: The treatment group had a statistically significant improvement in the following symptoms compared with the placebo group: pain associated with tonsillitis, pain on swallowing, erythema and inflammation of the pharynx, and tonsil size. CONCLUSION: The homeopathic complex used in this study exhibited significant anti-inflammatory and pain-relieving qualities in children with acute viral tonsillitis. No patients reported any adverse effects. These preliminary findings are promising; however, the sample size was small and therefore a definitive conclusion cannot be reached. A larger, more inclusive research study should be undertaken to verify the findings of this study.

The effect of a homeopathic complex on psychophysiological onset insomnia in males: a randomized pilot study.

CONTEXT: Psychophysiological onset insomnia (PI) is defined as sleeplessness exceeding 30 min due to learned, sleep-preventing behaviors and hyperarousal at bedtime. This common condition significantly impacts sufferers' health, occupational performance, and interpersonal relationships. Conventional treatment with hypnotics has many shortcomings. Homeopathic medication may present an alternative treatment for this condition. OBJECTIVE: The study intended to determine the effect of a homeopathic complex on PI. DESIGN: The research team designed a randomized, double-blind, placebo-controlled, 4-wk pilot study, using matched pairs. SETTING: The study took place at the Homeopathy Health Clinic at the University of Johannesburg in Johannesburg, South Africa. PARTICIPANTS: Forty-six males aged between 18 and 40 y with chronic PI were recruited; 28 completed the study- placebo group (n = 14) and experimental group (n = 14). INTERVENTIONS: The homeopathic complex was made in 20% alcohol. The placebo consisted of the unmedicated vehicle only. OUTCOME MEASURES: The study used the Pre-sleep Arousal Scale (PSAS) and the Sleep Diary (SD), which assessed sleep-onset latency. RESULTS: The experimental group showed a statistically significant improvement in presleep arousal as well as sleep onset latency over the 4 wks of the study. The Wilcoxon signed-rank test revealed that the improvement occurred gradually. Intergroup analysis showed through both the PSAS and the SD that the experimental group had outperformed the placebo group by day 28 of the study. CONCLUSION: Findings suggest that daily use of the homeopathic complex does have an effect over a 4-wk period on physiological and cognitive arousal at bedtime as well as on sleep onset latency in PI sufferers. Further research on the use of this complex for PI is warranted before any definitive conclusions can be drawn.

Complementary and alternative medical therapies for children with attention-deficit/hyperactivity disorder (ADHD).

Attention-deficit/hyperactivity disorder (ADHD) is a commonly diagnosed childhood disorder characterized by impulsivity, inattention, and hyperactivity. ADHD affects up to 1 in 20 children in the United States. The underlying etiologies of ADHD may be heterogeneous and diverse, and many possible risk factors in the development of ADHD have been identified. Conventional treatment usually consists of behavioral accommodations and medication, with stimulant medication most commonly being prescribed. Parents concerned about the side effects and long-term use of conventional medications are increasingly seeking alternatives to pharmacologic treatment. Complementary and alternative medicine (CAM) offers parents various treatment options for this condition, including dietary modifications, nutritional supplementation, herbal medicine, and homeopathy. CAM appears to be most effective when prescribed holistically and according to each individual's characteristic symptoms. Possible etiologies and risk factors for the condition also need to be considered when developing a treatment plan. This article serves to highlight the latest research regarding the most commonly used CAM for children with ADHD.