The Differential Translation Capabilities of the Human DHFR2 Gene Indicates a Developmental and Tissue-Specific Endogenous Protein of Low Abundance.

A functional role has been ascribed to the human dihydrofolate reductase 2 (DHFR2) gene based on the enzymatic activity of recombinant versions of the predicted translated protein. However, the in vivo function is still unclear. The high amino acid sequence identity (92%) between DHFR2 and its parental homolog, DHFR, makes analysis of the endogenous protein challenging. This paper describes a targeted mass spectrometry proteomics approach in several human cell lines and tissue types to identify DHFR2-specific peptides as evidence of its translation. We show definitive evidence that the DHFR2 activity in the mitochondria is in fact mediated by DHFR, and not DHFR2. Analysis of Ribo-seq data and an experimental assessment of ribosome association using a sucrose cushion showed that the two main Ensembl annotated mRNA isoforms of DHFR2, 201 and 202, are differentially associated with the ribosome. This indicates a functional role at both the RNA and protein level. However, we were unable to detect DHFR2 protein at a detectable level in most cell types examined despite various RNA isoforms of DHFR2 being relatively abundant. We did detect a DHFR2-specific peptide in embryonic heart, indicating that the protein may have a specific role during embryogenesis. We propose that the main functionality of the DHFR2 gene in adult cells is likely to arise at the RNA level.

The burden of treatment of propranolol for infantile hemangiomas: A mixed methods study.

The burden of treatment (BOT) related to propranolol treatment for infantile hemangiomas (IH) has never previously been explored. A modified validated questionnaire, the Treatment Burden Questionnaire, and one-on-one semi-structured interviews were used to assess the BOT for propranolol for IH. Out of 80 caregivers, the overall burden score was very low at 1.2 out of 10; thematic analysis of interviews grouped themes into administration, monitoring, financial, and associated anomalies. The BOT of propranolol for IH is very low but could be reduced further by offering age-based risk stratification related to feeding frequency and risk of hypoglycemia, pragmatic advice around timing of doses before sleep, and reducing frequency of vital sign monitoring.

Pregnancy homocysteine and cobalamin status predict childhood metabolic health in the offspring.

BACKGROUND: Inadequate pregnancy cobalamin status has been associated with adverse offspring metabolic health in Indian and Nepalese studies. Studies of pregnancy cobalamin status and mid-childhood health outside of Asia are scarce. METHODS: Associations between pregnancy fasting plasma total homocysteine (tHcy), cobalamin status (plasma cobalamin, holotranscobalamin (holoTC), methylmalonic acid (MMA)) and mid-childhood metabolic score (MetSco) ((including fat mass index (zFMI), homeostatic model assessment of insulin resistance (zHOMA-IR) and dyslipidemia (zTG - zHDLc)/2) z-scores)) were investigated in a prospective study of 293 mother-child dyads. RESULTS: Highest versus low-mid pregnancy tHcy tertile was associated with higher mid-childhood MetSco, specifically with higher child zFMI. Stratifying by sex, the maternal tHcy-child MetSco association was limited to boys and confirmed for zFMI and zHOMA-IR. The maternal tHcy-child zFMI association was not mediated by birth weight z-score. First trimester plasma cobalamin was not associated with child outcomes, but other indicators of cobalamin status were. Lowest versus mid-high plasma holoTC tertile was associated with MetSco (specifically zFMI and zHOMA-IR) and highest versus low-mid plasma MMA tertile with higher MetSco and dyslipidemia in boys. CONCLUSIONS: Moderately elevated pregnancy tHcy and low cobalamin status were associated with mid-childhood metabolic score in boys. The pregnancy tHcy-child zFMI association was not mediated by birth weight. IMPACT: Fasting plasma total homocysteine (tHcy) during pregnancy and low cobalamin status during early pregnancy are associated with mid-childhood metabolic score and its components in the offspring. These findings were only significant in male offspring. The study provides new evidence that impaired one carbon metabolism during pregnancy is associated with negative health outcomes in the offspring, in a population with low prevalence of cobalamin deficiency. The maternal-offspring associations were observed in the functional markers of cobalamin status (holotranscobalamin and methylmalonic acid) and tHcy, not with plasma cobalamin concentration. Screening for low pregnancy cobalamin status should be considered.

Crying Wolf: A Qualitative Review of Misinformation and Conspiracy Theories in Lupus Erythematosus.

BACKGROUND: Lupus comprises a complex group of inflammatory disorders including cutaneous lupus erythematosus (CLE) and systemic lupus erythematosus (SLE). The issue of health misinformation is increasingly problematic, although the content of misinformation related to lupus available online has not been deeply explored. This study aimed to qualitatively assess the type of misinformation related to lupus available online. METHODS: A literature search on PubMed was conducted, using search terms "cutaneous lupus" OR "discoid lupus" OR "lupus" AND "misinformation" OR "conspiracy" OR "disinformation." Further searches were also performed on Google, YouTube, Twitter, Facebook, Instagram, and TikTok. RESULTS: Published literature describing lupus-related misinformation was minimal, with only three manuscripts identified. Conversely, a variety of points of misinformation were identified online and on social media. Key themes identified in online content included suggestion of incorrect causes such as infection or aspartame consumption, false risk assessments such as lupus never developing in males, false claims about conventional treatments, and promotion of alternative treatments or "cures" without evidence. CONCLUSION: Dermatologists, rheumatologists, and all clinicians treating patients with lupus play an essential role in dispelling the pervasive misinformation surrounding the disease and its treatments, encouraging patients to seek reliable sources of information, and advocating for evidence-based guidance.

The importance of vitamin B12 for individuals choosing plant-based diets.

Vitamin B12 is an essential nutrient that is not made by plants; consequently, unfortified plant-based foods are not a reliable supply. Recent estimates suggest high rates of vitamin B12 deficiency among the vegetarian and vegan populations, particularly in pregnant women or women of child-bearing age who, for ethical and health reasons, are shifting towards higher consumption of plant-based foods in ever-increasing numbers. Vitamin B12 plays crucial metabolic roles across the life-course and in particular during pregnancy and in early development (first 1000 days of life). Evidence now implicates vitamin B12 deficiency with increased risk to a range of neuro, vascular, immune, and inflammatory disorders. However, the current UK recommended nutrient intake for vitamin B12 does not adequately consider the vitamin B12 deficit for those choosing a plant-based diet, including vegetarianism and in particular veganism, representing a hidden hunger. We provide a cautionary note on the importance of preventing vitamin B12 deficits for those individuals choosing a plant-based diet and the health professionals advising them.

#corticophobia: a review on online misinformation related to topical steroids.

Misinformation in healthcare is at crisis level worldwide, with the internet as primary source of prevarication. Topical corticosteroids (TCS) are a safe and effective treatment used in multiple dermatological conditions. Nonadherence to prescribed TCS can be due to phobia secondary to misinformation. TCS phobia is a complex multifaceted phenomenon that exploits patients with skin disease, creates cognitive dissonance and can obstruct successful treatment. This study aimed to examine the content of TCS-related misinformation available online. A formal review of PubMed was performed using the terms 'topical corticosteroids' AND 'misinformation' OR 'disinformation' OR 'conspiracy theory, along with an informal Google search using combinations of these terms and further targeted searches on social media applications including Facebook™, Twitter™, Instagram™ and TikTok™. 'Topical steroid withdrawal', 'red skin syndrome' or 'TCS addiction' is a particularly prevalent myth currently being propagated on social media, with most content suggesting that eczema is due to a 'leaky gut' or food intolerance and not to skin inflammation. The risks of potential adverse effects such as skin thinning and stunted growth/development are often exaggerated. Multiple websites promoting misinformation were frequently endorsed by companies advertising consultations or testing to identify 'underlying causes', or 'natural' products as alternative treatments, including 'herbal' remedies, which can contain significant quantities of corticosteroids or other potent ingredients. The dermatology community should be vigilant of the type of TCS-related misinformation online and be active in attempts to counteract it with evidence-based advice.

Red-faced lies: a qualitative analysis of online misinformation and conspiracy theories in rosacea.

Rosacea is a common chronic inflammatory skin disease with a complex aetiology and major psychological impact, rendering patients susceptible to misinformation. We aimed to assess the content of rosacea-related misinformation online. A formal review of PubMed was performed, using the terms 'rosacea' AND 'misinformation' OR 'disinformation' OR 'conspiracy theory', along with informal Google searches using combinations of these terms, and further targeted searches on Twitter, Facebook, Instagram and TikTok. Key areas of misinformation identified in the search included mislabelling of rosacea as adult acne; falsehoods about rosacea only occurring in older adults or in individuals with lightly pigmented skin; incorrect causes of rosacea such as makeup or diet; and misleading 'cures', some of which may lead to exacerbation of the underlying rosacea. Dermatologists must be aware of the large amount of rosacea misinformation trending online and be prepared to counteract them with evidence to optimize patient care.

Pooling the evidence: A review of swimming and atopic dermatitis.

Swimming is an excellent form of aerobic exercise and is an essential life skill. Many children with atopic dermatitis (AD) are advised not to swim because of concerns about negative impacts on their skin disease, and some children with AD do not swim because they are self-conscious about the appearance of their skin. We aimed to perform a narrative review of the available literature on swimming and AD and scientifically analyze the potential impact of all components of swimming in AD-water, skin barrier, swimming gear, and exercise. Studies examined the impact of swimming on the skin barrier and the relative contraindications to swimming. Constituents of water which may affect AD include hardness, pH, temperature, antiseptics, and other chemicals. Potential interventions to reduce damage included emollient application, special swim gear, and showering post-submersion. The benefits of swimming as a form of exercise in AD included reduced sweating, cardiorespiratory fitness, and maintenance of healthy weight. Drawbacks of swimming as a form of exercise in AD included the limited benefit on bone mineral density. Future research should examine the impact of swimming on flares of AD using noninvasive biomarkers as well as clinical severity assessment and assess the role for different types of emollient as an intervention for optimal eczema control. This review highlights gaps in the scientific literature on swimming and AD and provides evidence-based guidance on interventions to minimize deleterious effects on skincare and maximize opportunities for children with AD to swim.

Exploring progressive mental model representation of core physiology concepts in physician assistant students through word frequency and association analyses.

A well-developed mental model is crucial for effectively studying physiology core concepts. However, mental models can be difficult for students to represent and for instructors to evaluate and correct. Systems modeling as a visualization cognitive tool may facilitate mental model development. On the other hand, evidence of mental model development may also be represented verbally, in writing, and therefore, be evaluated. In this study, analysis of writing prompt completions illustrated progress in physician assistant student mental model formation of physiology core concepts, such as homeostasis and cell-cell communication, over time. Two cohorts of physician assistant students were invited to voluntarily submit completions of writing prompts five times over 16 months. Sessions included submissions pre- and post-small group systems modeling participation. Word frequency and word association cluster dendrogram analyses were conducted on submissions using the tm text mining package in R to provide insight into progressive changes in core concepts of word use and associations. Students demonstrated expanded core concepts systems thinking over time. This was apparent through the increased use of systems process terms, such as homeostasis, in submissions immediately following systems modeling activities. Students also increasingly included terms and associations emphasizing cell-cell communication and systems integration. The inclusion of these concepts within student mental models was demonstrably enhanced by participation in systems modeling activities.NEW & NOTEWORTHY This study applies text mining, an artificial intelligence form of natural language processing, to evaluate a series of physiology student-written prompt completions. Text mining of student writing in physiology has not yet been reported in the literature. Through the application of this technique, longitudinal trends in student development of mental models of core concepts were identified and visualized through word frequency distributions and cluster dendrograms.

"His first word was 'cream'." The burden of treatment in pediatric atopic dermatitis-A mixed methods study.

The burden of treatment (BOT) is the workload of health care experienced by patients with chronic conditions and consequences on well-being. This study aimed to assess the BOT of atopic dermatitis (AD) on children and caregivers using mixed methods. The quantitative component of this mixed methods study involved the Treatment Burden Questionnaire. The qualitative component involved interviews with parents of children with moderate-severe AD. The questionnaire was completed by 168 parents; 32.1% had mild AD, 39.9% had moderate AD, and 28% had severe AD. The average burden score was 3.5 (out of 10). Average burden scores were low in mild AD (1.0 out of 10) and were proportionally higher in moderate (3.9 out of 10) and severe (5.8 out of 10) AD (p < 0.001). Increased frequency of therapy had increased perceived burden. In moderate-severe AD, oral therapy was rated as less burdensome than topical therapies. Semi-structured interviews were conducted with 15 parents of children with moderate-severe AD. Thematic analysis grouped experiences into health care burden, treatment burden, and financial burden. Insights from health care burden analysis included "mixed messages," "treatment futility," and "expectant resolution." Insights from treatment burden included treatment routine, schooling impact, and "topical-sparing" with systemic treatment. Factors of financial burden included topical treatments, clothing, and health care visits. Moderate-severe AD is associated with high BOT, particularly related to topical therapies, which may be reduced by systemic treatment. All physicians treating children with AD should avoid potentially damaging communication regarding mixed messages, treatment futility, and expectant resolution.

A qualitative review of misinformation and conspiracy theories in skin cancer.

Misinformation on diseases and treatments is a worldwide threat and can lead to worse outcomes for patients with skin cancer. The aim of this study was to qualitatively assess the content of online misinformation related to skin cancer. Searches were performed via PubMed and Google using the terms 'skin cancer' OR 'melanoma' OR 'non-melanoma skin cancer' OR 'SCC' OR 'BCC' AND 'misinformation' OR 'disinformation' OR 'conspiracy theories'. The most common themes of misinformation related to skin cancer included assertions of the 'dangers' of using sunscreen and alternative sunscreen practices; promotion of tanning and Melanotan (an unlicensed and untested form of α-melanocyte-stimulating hormone) as safe practices; claims that risk of skin cancer are limited to people who are older or have fair skin; and assertions of alternative 'causes' and alternative 'cures' for skin cancer. Sunscreen was particularly vilified as being an ineffective prophylactic measure and a cause of skin cancer. Dermatologists should be aware of misinformation available online relating to skin cancer, and refute and rebut misleading health information.

Spotting fake news: a qualitative review of misinformation and conspiracy theories in acne vulgaris.

Acne vulgaris is an extremely common disorder of the pilosebaceous unit, typically manifest as a highly visible facial and upper trunk dermatosis, with teenagers most frequently affected. This cohort is markedly susceptible to misinformation, given their impressionable age, distress about their appearance and high internet usage. This study aimed to assess the content of acne-related misinformation available online. A formal review of PubMed was performed in March 2022, using the terms 'acne' AND 'misinformation' OR 'disinformation' OR 'conspiracy theory', along with an informal Google search using combinations of these terms, and further targeted searches on TikTok, Twitter, Facebook and Instagram. Key themes of acne-related misinformation included diet and other 'causes' of acne, unconventional acne 'cures' and a distrust of conventional acne treatments. Websites promoting misinformation were frequently affiliated with companies selling products that promised to cure acne, often in a remarkably short time. Dermatologists should be aware of the nature of acne-related misinformation available online and be prepared to counter it with scientific principles and facts.

Study protocol: assessing SleeP IN infants with early-onset atopic Dermatitis by Longitudinal Evaluation (The SPINDLE study).

BACKGROUND: Atopic dermatitis (AD) is the most common chronic inflammatory skin condition in childhood. Most (50-60%) children with AD report sleep disturbance, which is secondary to itch, dry skin, inflammation, and abnormal circadian rhythm. Sleep is essential for brain development, learning, and growth. Sleep disruption in early life is associated with cognitive and psychological dysfunction in later life. The aim of this study is to describe in detail the sleep architecture of infants with early-onset atopic dermatitis (AD), compared to controls, by using EEG polysomnography, sleep actigraphy, and parental reporting. METHODS: This observational study will recruit six- to eight-month old infants with moderate to severe AD and age-matched control infants who do not have AD. At six-eight months diurnal sleep electroencephalography and polysomnography will be performed in our research center. Nocturnal sleep actigraphy will be performed at home for five consecutive nights at six-eight months and 12 months. Between six and 12 months, monthly questionnaires will capture data on quantitative sleep and parental sleep. Skin barrier and immune profiles will be captured at six-eight and 12 months. AD will be assessed using standardized severity assessment tools and treated according to protocol. A neurodevelopmental assessment will be performed at 18 months to assess cognition and behaviour. An estimated sample size of 50 participants in each group is required to power the primary outcome of disturbed macrostructure of sleep and secondary outcomes of disturbed microstructure of sleep, and disturbed parental sleep, assuming an attrition rate of 60%. Potential confounding factors which will be controlled for in the data analysis will include parental educational level, parental depression, feeding practice, and number of siblings. DISCUSSION: This study will provide a rich analysis of sleep in infants with AD in the first year of life using detailed electroencephalography, novel actigraphy techniques, and longitudinal parent-reported data. It may provide guidance on the optimal treatment of AD to prevent or reduce sleep disruption. TRIAL REGISTRATION: clinicaltrials.gov NCT05031754 , retrospectively registered on September 2nd, 2021.

Stroke affects intestinal immune cell trafficking to the central nervous system.

Stroke is an acute neurological disease with a strong inflammatory component that can be regulated by the intestinal microbiota and intestinal immune cells. Although stroke has been shown to alter immune cell populations in the gut, the dynamics of cell trafficking have not been elucidated. To study the trafficking of gut-derived immune cells after stroke, we used mice expressing the photoconvertible protein Kikume Green-Red, which turns form green to red when exposed to violet light. Mice underwent laparotomy and the small intestine was exposed to violet laser light. Immune cells were isolated from the small intestine immediately after photoconversion and 2 days later. Percentage of immune cells (CD45+KikR+) that expressed the red variant of the protein (KikR) was higher immediately after photoconversion than 2 days later, indicating cell egress from the small intestine. To investigate whether intestinal immune cells traffic to the periphery and/or the central nervous system (CNS) after stroke, we analyzed KikR+ immune cells (2 days after photoconversion) in peripheral lymphoid organs, meninges and brain, 3 and 14 days after transient occlusion of the middle cerebral artery (tMCAo) or sham-surgery. Although migration was observed in naïve and sham animals, stroke induced a higher mobilization of gut KikR+ immune cells, especially at 3 days after stroke, to all the organs analyzed. Notably, we detected a significant migration of CD45hi immune cells from the gut to the brain and meninges at 3 days after stroke. Comparison of cell trafficking between organs revealed a significant preference of intestinal CD11c+ cells to migrate from the small intestine to brain and meninges after stroke. We conclude that stroke increases immune cell trafficking from the small intestine to peripheral lymphoid organs and the CNS where they might contribute to post-stroke inflammation.

Novel agents for atopic dermatitis in patients over 50 years of age: A case series.

Lan et al recently highlighted the under-representation of older adults in clinical trials of systemic therapies for atopic dermatitis (AD). Late-onset AD is increasingly recognized in older adults. Spontaneous remission is uncommon with this phenotype. Existing drug treatments such as corticosteroids, methotrexate, ciclosporin, and azathioprine are complicated by adverse effects including increased malignancy risk, immunosuppression in the context of immunosenescence, and drug interactions in the setting of polypharmacy. A case series is presented of seven patients over 50 years of age with AD who were prescribed dupilumab or tofacitinib or upadacitinib for at least 6 months. All patients were clear or almost clear (investigator global assessment score 0/1) after 1 month of therapy. No significant adverse events were seen. This case series provides preliminary evidence about the safety and efficacy of these novel drugs for AD in older adults. Further studies with higher numbers of participants are needed to obtain real-world evidence for these drugs in older adults, given the limited data in clinical trials.

Chronic anticoagulation is not associated with a reduced risk of acute kidney injury in hospitalised Covid-19 patients.

BACKGROUND: Coronavirus-19 (COVID-19) has been declared a global pandemic by the World Health Organisation. Severe disease typically presents with respiratory failure but Acute Kidney Injury (AKI) and a hypercoagulable state can also occur. Early reports suggest that thrombosis may be linked with AKI. We studied the development of AKI and outcomes of patients with COVID-19 taking chronic anticoagulation therapy. METHODS: Electronic records were reviewed for all adult patients admitted to Manchester University Foundation Trust Hospitals between March 10 and April 302,020 with a diagnosis of COVID-19. Patients with end-stage kidney disease were excluded. AKI was classified as per KDIGO criteria. RESULTS: Of the 1032 patients with COVID-19 studied,164 (15.9%) were taking anticoagulant therapy prior to admission. There were similar rates of AKI between those on anticoagulants and those not anticoagulated (23.8% versus 19.7%) with no difference in the severity of AKI or requirement of renal replacement therapy between groups (1.2% versus 3.5%). Risk factors for AKI included hypertension, pre-existing renal disease and male sex. There was a higher mortality in those taking anticoagulant therapy (40.2% versus 30%). Patients taking anticoagulants were less likely to be admitted to the Intensive Care Unit (8.5% versus 17.4%) and to receive mechanical ventilation (42.9% versus 78.1%). CONCLUSION: Patients on chronic anticoagulant therapy did not have a reduced incidence or severity of AKI suggesting that AKI is unlikely to be thrombotic in nature. Therapeutic anticoagulation is currently still under investigation in randomised controlled studies to determine whether it has a potential role in COVID-19 treatment.

Reactive infectious mucocutaneous eruption in children diagnosed with COVID-19.

We describe the cases of two immunocompetent children who developed mucositis with oral, ocular, and genital involvement during acute COVID-19 illness. The pattern of mucosal involvement with no other cutaneous involvement was consistent with reactive infectious mucocutaneous eruption (RIME). No other intercurrent infections or new medications were identified, suggesting that COVID-19 was causative. Both patients noted improvement with systemic corticosteroid therapy.

Distinct Commensal Bacterial Signature in the Gut Is Associated With Acute and Long-Term Protection From Ischemic Stroke.

Background and Purpose- Commensal gut bacteria have a profound impact on stroke pathophysiology. Here, we investigated whether modification of the microbiota influences acute and long-term outcome in mice subjected to stroke. Methods- C57BL/6 male mice received a cocktail of antibiotics or single antibiotic. After 4 weeks, fecal bacterial density of the 16S rRNA gene was quantitated by qPCR, and phylogenetic classification was obtained by 16S rRNA gene sequencing. Infarct volume and hemispheric volume loss were measured 3 days and 5 weeks after middle cerebral artery occlusion, respectively. Neurological deficits were tested by the Tape Test and the open field test. Results- Mice treated with a cocktail of antibiotics displayed a significant reduction of the infarct volume in the acute phase of stroke. The neuroprotective effect was abolished in mice recolonized with a wild-type microbiota. Single antibiotic treatment with either ampicillin or vancomycin, but not neomycin, was sufficient to reduce the infarct volume and improved motorsensory function 3 days after stroke. This neuroprotective effect was correlated with a specific microbial population rather than the total bacterial density. In particular, random forest analysis trained for the severity of the brain damage revealed that Bacteroidetes S24.7 and the enzymatic pathway for aromatic metabolism discriminate between large versus small infarct size. Additionally, the microbiota signature in the ampicillin-treated mice was associated with a reduced gut inflammation, long-term favorable outcome shown by an amelioration of the stereotypic behavior, and a reduction of brain tissue loss in comparison to control and was predictive of a regulation of short-chain fatty acids and tryptophan pathways. Conclusions- The findings highlight the importance of the intestinal microbiota in short- and long-term outcomes of ischemic stroke and raises the possibility that targeted modification of the microbiome associated with specific microbial enzymatic pathways may provide a preventive strategy in patients at high risk for stroke. Visual Overview- An online visual overview is available for this article.

Homocysteine, the methylenetetrahydrofolate reductase 677C>T polymorphism and hypertension: effect modifiers by lifestyle factors and population subgroups.

Evidence linking fasting plasma total homocysteine (tHcy) and methylenetetrahydrofolate reductase (MTHFR) 677C>T genotype with hypertension is inconsistent. Differences in B vitamin status, other lifestyle factors or their consideration in analyses might explain this. We investigated these associations in the absence of mandatory fortification with folic acid and B vitamin supplement use. A cross-sectional study was conducted in 788 adults, aged 18-75 years, randomly selected from three Catalonian town population registers. Fasting plasma folate, cobalamin, tHcy, erythrocyte folate, erythrocyte glutathione reductase activation coefficient (EGRAC, functional riboflavin status indicator; increasing EGRAC indicates worsening riboflavin status), MTHFR 677C>T and solute carrier family 1 (SLC19A1) 80 G>A genotypes were determined. Medical history and lifestyle habits were recorded. Principal tHcy determinants differed between women (age, plasma folate, plasma cobalamin, cigarettes/d) and men (MTHFR 677TT genotype, plasma folate, plasma cobalamin and CT genotype). The MTHFR 677C>T polymorphism-tHcy association (ß standardised regression coefficients) was stronger in male smokers (0·52, P < 0·001) compared with non-smokers (0·21, P = 0·001) and weaker in participants aged >50 years (0·19, P = 0·007) compared with ≤50 years (0·31, P < 0·001). Hypertension was more probable in the third tHcy tertile compared with other tertiles (OR 1·9; 95 % CI 1·2, 3·0), and in participants aged ≤50 years, for the MTHFR 677TT genotype compared with the CC genotype (OR 4·1; 95 % CI 1·0, 16·9). EGRAC was associated with increased probability of hypertension in participants aged >50 years (OR 6·2; 95 % CI 1·0, 38·7). In conclusion, moderately elevated tHcy and the MTHFR 677CT genotype were associated with hypertension. The MTHFR 677C>T genotype-hypertension association was confined to adults aged ≤50 years.

The effect of prenatal smoke exposure on child neuropsychological function: a prospective mother-child cohort study.

Objective: To study prospectively the effect of prenatal smoke exposure (PSE) on child neuropsychological function and intelligence quotient (IQ).Background: PSE has been associated with adverse effects on child neurodevelopment. However, some studies reported that these associations disappear after adjustment for potential confounders.Methods: A cohortof 248 mothers-child dyad was followed from the first trimester of pregnancy until children were 7.5 years old. PSE was recorded during pregnancy by questionnaire and plasma cotinine. The Wechsler Intelligence Scale for Children, the Neuropsychological Assessment of Executive Functions for Children (ENFEN) and the School Neuropsychological Maturity Questionnaire were administered at 7.5 years of age. The effect of PSE on child IQ and neuropsychological function was assessed with ANCOVA, adjusting for obstetric, neonatal and sociodemographic factors.Results: Children whose mothers smoked throughout pregnancy scored lower in interference (ENFEN) compared to unexposed children (F = 4.1; p = .008). The results showed no differences in other executive functions, verbal and visual memory and IQ between the PSE groups.Conclusion: PSE had little effect on child neuropsychological outcome and was limited to mental flexibility. Nevertheless, these findings support further efforts aimed at encouraging mothers to quit smoking in pregnancy.