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Disorders of sex development (DSD) are a heterogeneous group of pathologies that result in an alteration in sex determination or differentiation. DSD are estimated to affect 1: 4,500 newborns and according to the 2006 Chicago Consensus classification, DSD can be divided into three categories: those with a 46 XX karyotype, those with a 46 XY karyotype and those relating to sex chromosomes. It is crucial to correctly identify the pathology already in the first days of life to direct the patient and his family to the best path of care. For this reason, the role of the pediatrician is fundamental in the correct identification of the clinical picture and in supporting the family during the long process that involves the management of these patients. To make a diagnosis, it is necessary to follow a path led by a multidisciplinary team that includes several steps such as the execution of the genetic analysis, the evaluation with diagnostic imaging methods and laboratory evaluations. The therapeutic management, on the other hand, is still very complex even if in recent years we have moved from an attitude of early gender reassignment to an approach of watchful waiting to let the patient choose when she/he is mature enough to do so, which gender she/he feels to belong. It should not be forgotten that throughout this process the pediatrician must be both supportive and clinically active in the management of the child and his family.

The prevalence of Beckwith-Wiedemann spectrum (BWSp) is tenfold increased in children conceived through assisted reproductive techniques (ART). More than 90% of ART-BWSp patients reported so far display imprinting center 2 loss-of-methylations (IC2-LoM), versus 50% of naturally conceived BWSp patients. We describe a cohort of 74 ART-BWSp patients comparing their features with a cohort of naturally conceived BWSp patients, with the ART-BWSp patients previously described in literature, and with the general population of children born from ART. We found that the distribution of UPD(11)pat was not significantly different in ART and naturally conceived patients. We observed 68.9% of IC2-LoM and 16.2% of mosaic UPD(11)pat in our ART cohort, that strongly differ from the figure reported in other cohorts so far. Since UPD(11)pat likely results from post-fertilization recombination events, our findings allows to hypothesize that more complex molecular mechanisms, besides methylation disturbances, may underlie BWSp increased risk in ART pregnancies. Moreover, comparing the clinical features of ART and non-ART BWSp patients, we found that ART-BWSp patients might have a milder phenotype. Finally, our data show a progressive increase in the prevalence of BWSp over time, paralleling that of ART usage in the last decades.

Infertility is a worldwide health issue defined by the World Health Organization (WHO) as the inability to establish a pregnancy after 12 months or more of regular and unprotected sexual intercourse. Male infertility etiology can be related to either congenital or acquired factors. The therapeutical approach to male infertility depends on the underlying causes and includes medical and surgical treatments. In recent studies, the potential role of nerve growth factor (NGF) in male reproductive physiology has been proposed. It has been hypothesized that neurotrophins might be involved in testis morphogenesis and regulation of several aspects of spermatogenesis. Moreover, it has been shown that NGF exerts its role on gonadotropin-releasing hormone (GnRH) neurons through the activation of the PKC/p–ERK1/2/p–CREB cascade, which leads to the activation of hypothalamic cells and the consequent activation of hypothalamus–pituitary–gonadal axis (HPG) with the secretion of GnRH. Lastly, it has been shown that the physiology of mature sperm is affected by both exogenous and endogenous NGF. The NGF impact on the HPG axis and its effect on GnRH neurons might be exploited in the therapy of male hypogonadism or used as a protective strategy against gonadal dysfunction related to chemotherapeutic agents. Moreover, the improving effect of NGF on sperm motility and vitality could be useful to enhance assisted reproduction outcomes. NGF could be supplemented to cryopreserved sperm samples to counteract the oxidative stress induced by the frozen and thawing processes. Indeed, the potential clinical applications of NGF in male infertility treatment have been discussed.

Background Although children with special health care needs (CSHCN) represent a minority of the population, they go through more hospitalizations, more admissions to the Emergency Department (ED), and receive a major number of medical prescriptions, in comparison to general pediatric population. Objectives of the study were to determine the reasons for admission to the ED in Italian CSHCN, and to describe the association between patient’s demographic data, clinical history, and health services requirements. Methods Ad hoc web site was created to collect retrospective data of 3479 visits of CSHCN to the ED in 58 Italian Hospitals. Results Seventy-two percent of patients admitted to ED were affected by a previously defined medical condition. Most of the ED admissions were children with syndromic conditions (54%). 44.2% of the ED admissions were registered during the night-time and/or at the weekends. The hospitalization rate was of 45.6% among patients admitted to the ED. The most common reason for admission to the ED was the presence of respiratory symptoms (26.6%), followed by gastrointestinal problems (21.3%) and neurological disorders (18.2%). 51.4% of the access were classified as ‘urgent’, with a red/yellow triage code. Considering the type of ED, 61.9% of the visits were conducted at the Pediatric EDs (PedEDs), 33.5% at the Functional EDs (FunEDs) and 4.6% at the Dedicated EDs (DedEDs). Patients with more complex clinical presentation were more likely to be evaluated at the PedEDs. CSHCN underwent to a higher number of medical procedures at the PedEDs, more in comparison to other EDs. Children with medical devices were directed to a PedED quite exclusively when in need for medical attention. Subjects under multiple anti-epileptic drug therapy attended to PedEDs or FunEDs generally. Patients affected by metabolic diseases were more likely to look for medical attention at FunEDs. Syndromic patients mostly required medical attention at the DedEDs. Conclusions Access of CSHCN to an ED is not infrequent. For this reason, it is fundamental for pediatricians working in any kind of ED to increase their general knowledge about CHSCN and to gain expertise in the management of such patients and their related medical complexity.

Background and aims We previously demonstrated that children with Down syndrome (DS) exhibited a greater risk of steatosis than the general pediatric population. This trend was independent of obese phenotype, thus suggesting a role of genetic predisposition. Therefore, we investigated the prevalence of non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS) in function of genetic susceptibility and adipocytokine levels in children with DS. Methods and results A total of 84 Caucasian children with DS (age range 5–17 years), were included in this study. For all children, we collected data on anthropometric and biochemical parameters, and liver ultrasound (US). We also measured adipocytokines circulating levels and specific polymorphisms closed to NAFLD. We found a prevalence of 64.3% of liver steatosis at US, with a severe steatosis of about 4% in children with DS. The presence of steatosis in children with DS was associated with the presence of patatin-like phospholipase domain-containing 3 (PNPLA3) rs738409 variant, which also correlated with interleukin (IL)-6 levels. Moreover, we found that the 52.4% had a waist circumference > 90th percentile, 21.4% were hypertensive, 7.14% had hyperglycemia, 9.5% had hypertriglyceridemia, and 17.9% showed high-density lipoprotein cholesterol ≤ 40 mg/dl. Finally, the IL-6 and adiponectin levels correlated with steatosis, and several adipocytokines correlated with single MetS traits in children with DS. Conclusion The present study explores for the first time potential pathomechanisms connecting pediatric NAFLD and MetS in DS. We found that the PNPLA3 variant is associated with steatosis, but not with MetS, in children with DS.

Background: miRNAs are small non-coding RNAs with potential roles in the complications of pregnancy. We hypothesised links between polymorphisms in miRNA-196a2 and miRNA-499 in maternal blood and t...

Background: Fetal alcohol spectrum disorders (FASD) are the manifestation of the damage caused by alcohol consumption during pregnancy. Children with fetal alcohol syndrome (FAS), the extreme FASD manifestation, show both facial dysmorphology and mental retardation. Alcohol consumed during gestational age prejudices brain development by reducing, among others, the synthesis and release of neurotrophic factors and neuroinflammatory markers. Alcohol drinking also induces oxidative stress. Hypothesis/Objective: The present study aimed to investigate the potential association between neurotrophins, neuroinflammation, and oxidative stress in 12 prepubertal male and female FASD children diagnosed as FAS or partial FAS (pFAS). Methods: Accordingly, we analyzed, in the serum, the level of BDNF and NGF and the oxidative stress, as free oxygen radicals test (FORT) and free oxygen radicals defense (FORD). Moreover, serum levels of inflammatory mediators (IL-1α, IL-2, IL-6, IL-10, IL-12, MCP-1, TGF-β, and TNF- α) involved in neuroinflammatory and oxidative processes have been investigated. Results: We demonstrated low serum levels of NGF and BDNF in pre-pubertal FASD children with respect to healthy controls. These changes were associated with higher serum presence of TNF- α and IL-1α. Quite interestingly, an elevation in the FORD was also found despite normal FORT levels. Moreover, we found a potentiation of IL-1α, IL-2, IL-10, and IL-1α1 in the analyzed female compared to male children. Conclusion: The present investigation shows an imbalance in the peripheral neuroimmune pathways that could be used in children as early biomarkers of the deficits observed in FASD.

SignificanceThe regulation of functional immune cell plasticity is poorly understood. Host environmental cues are critical, but the possible influence of pathogen-derived virulence factors has not been described. We have used reverse-engineered influenza A viruses that differ in PB1-F2 activity to analyze influenza in mice in the presence or absence of host interferon (IFN)-γ. In the absence of functional PB1-F2 and IFN-γ, lung ILC2s initiated robust IL-5 responses following viral challenge, which led to improved tissue integrity and survival. Conversely, functional PB1-F2 suppressed IL-5+ILC2 responses and induced a dominant IL-13+CD8 T cell response regardless of host IFN-γ. These findings demonstrate the critical interplay between the viral virulence factors and host cytokines in regulating protective pulmonary immunity during influenza virus infection.

Alcohol consumption during pregnancy and lactation is a widespread preventable cause of neurodevelopmental impairment in newborns. While the harmful effects of gestational alcohol use have been well documented, only recently the role of paternal preconceptual alcohol consumption (PPAC) prior to copulating has drawn specific epigenetic considerations. Solid human and animal model data demonstrated that PPAC may affect sperm function eliciting oxidative stress. In newborns, PPAC may induce changes in the behavior, cognitive functions and emotional responses. Furthermore, PPAC may elicit neurobiological disruptions, visuospatial impairments, hyperactivity disorders, motor skill disruptions, hearing loss, endocrine and immune alterations, reduced physical growth, placental disruptions and metabolic alterations. Neurobiological studies on PPAC disclosed also changes in brain function and structure by the disruption of the growth factors pathways. In particular, as shown in animal model studies PPAC alters brain nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) synthesis and release. This review shows that the crucial topic of lifelong disabilities induced by PPAC and/or gestational alcohol drinking is quite challenging at the individual, societal, and familial levels. Since a nontoxic drinking behavior before pregnancy (for both men and women) during pregnancy and lactation cannot be established the only suggestion for couples planning pregnancies is to completely avoid the consumption of alcoholic beverages.

BackgroundMost studies on the health impact of occupational stress use single-point measures of stress at work. This study analyses the associations of properties of entire employment trajectories over an extended time period with a composite score of allostatic load (AL).MethodsData come from the French CONSTANCES cohort, with information on adverse employment histories between ages 25 and 45 and a composite score of AL (based on 10 biomarkers, range 0–10) among people aged 45 or older (47 680 women and 45 035 men). Data were collected by questionnaires (including retrospective employment histories) or by health examinations (including blood-based biomarkers). We distinguish six career characteristics: number of temporary jobs, number of job changes, number of unemployment periods, years out of work, mode occupational position and lack of job promotion.ResultsFor both men and women, results of negative binomial regressions indicate that adverse employment histories are related to higher levels of AL, particularly histories that are characterised by a continued disadvantaged occupational position, repeated periods of unemployment or years out of work. Findings are adjusted for partnership, age and education, and respondents with a health-related career interruption or early retirement are excluded.ConclusionsOur study highlights physiological responses as a mechanism through which chronic stress during working life is linked to poor health and calls for intervention efforts among more disadvantaged groups at early stages of labour market participation.

Despite numerous studies on social relationships and health, the empirical focus has often been on middle-aged or older adults, even though young adulthood is a period of considerable change in social networks. We investigated whether the associations between social relationships and allostatic load, a multisystem physiological dysregulation index that reflects chronic stress responses, vary by type of relationship and stages of the lifecourse. Relationships with spouse/partner, immediate family and friends were assessed in terms of emotional support and social strain. Poisson regression models on multiple imputed data sets from waves 2-3 (2010-2012) of the UK Household Longitudinal Study (N = 10,380) were estimated. Social strain, particularly from partners and immediate family, appeared to elicit greater stress related dysregulation during early adulthood (age 21-34 years), corresponding to a predicted difference in the allostatic load index (range 0-12) between high and low strained relationships of 1.1 (95% CI: 0.5-1.6) among young women and 0.6 (95% CI: -0.04 to 1.2) among young men. There was little evidence of an association between allostatic load and any of the social relationships among older men and women. Models of social relationships over the lifecourse need to take account of how stressful social relationships become biologically embedded in early adulthood.

Background Assessment is a necessary part of training postgraduate medical residents. The implementation of methods located at the “shows how” level of Miller’s pyramid is believed to be more effective than previous conventional tools. In this study, we quantitatively compared electronic and conventional methods in assessing ophthalmology residents. Methods In this retrospective study, eight different conventional methods of assessment including residents’ attendance, logbook, scholarship and research skills, journal club, outpatient department participation, Multiple Choice Question (MCQ), Objective Structured Clinical Examination (OSCE), and professionalism/360-degree (as one complex) were used to assess 24 ophthalmology residents of all grades. Electronic media consisting of an online Patient Management Problem (e-PMP), and modified electronic OSCE (me-OSCE) tests performed 3 weeks later were also evaluated for each of the 24 residents. Quantitative analysis was then performed comparing the conventional and electronic assessment tools, statistically assessing the correlation between the two approaches. Results Twenty-four ophthalmology residents of different grades were included in this study. In the electronic assessment, average e-PMP scores (48.01 ± 12.40) were much lower than me-OSCE (65.34 ± 17.11). The total average electronic score was 56.67 ± 11.28, while the total average conventional score was 80.74 ± 5.99. Female and male residents’ average scores in the electronic and conventional method were (59.15 ± 12.32 versus 83.01 ± 4.95) and (55.19 ± 10.77 versus 79.38 ± 6.29), respectively. The correlation between modified electronic OSCE and all conventional methods was not statistically significant (P-value >0.05). Correlation between e-PMP and six conventional methods, consisting of professionalism/360-degree assessment tool, logbook, research skills, Multiple Choice Questions, Outpatient department participation, and Journal club active participation was statistically significant (P-value Conclusion In this study, we conclude that electronic PMP can be used alongside all conventional tools, and overall, e-assessment methods could replace currently used conventional methods. Combined electronic PMP and me-OSCE can be used as a replacement for currently used gold-standard assessment methods, including 360-degree assessment.

There has been limited theoretical and empirical research into the role of workplace accommodations in enabling workers with and without impairments to remain in work. This study used the International Classification of Functioning, Disability and Health (ICF) model to examine (a) whether workplace accommodations enable workers, particularly those with different impairments, to remain economically active; and (b) the predictors of the onset of work accommodations. Data from two waves of a large-scale longitudinal survey of disability in Great Britain, the Life Opportunities Survey (2009-2012) were analysed. 2307 workers with an impairment and 4308 workers without an impairment were followed up for a year. Work accommodations appear to enable workers with impairments to remain economically active, especially those with mental impairments. There was no difference in the employment rates of workers with and without mental impairments who had two or more work accommodations, in contrast to the 10% employment gap between workers with and without mental impairments who did not have any work accommodations. While there was no gender difference in the disability employment gap, barriers to employment related to caregiving were much greater for women compared to men. Moreover, only workers with incident pain impairments were associated with an increase in their work accommodations, not workers with incident mental impairments. Despite the evidence that workers with mental impairments could benefit considerably from workplace accommodations, they are less likely to have their workplace adjusted. The ICF model is particularly useful in analysing the role of work accommodations because it considers a much wider range of factors that are relevant not just to workers with different types of impairments, but are also relevant to the wider group of workers who use workplace accommodations.

Background: Mowat–Wilson syndrome (MWS; OMIM #235730) is a genetic condition caused by heterozygous mutations or deletions of the ZEB2 gene. It is characterized by moderate-severe intellectual disability, epilepsy, Hirschsprung disease and multiple organ malformations of which congenital heart defects and urogenital anomalies are the most frequent ones. To date, a clear description of the physical development of MWS patients does not exist. The aim of this study is to provide up-to-date growth charts specific for infants and children with MWS. Charts for males and females aged from 0 to 16 years were generated using a total of 2,865 measurements from 99 MWS patients of different ancestries. All data were collected through extensive collaborations with the Italian MWS association (AIMW) and the MWS Foundation. The GAMLSS package for the R statistical computing software was used to model the growth charts. Height, weight, body mass index (BMI) and head circumference were compared to those from standard international growth charts for healthy children.Results: In newborns, weight and length were distributed as in the general population, while head circumference was slightly smaller, with an average below the 30th centile. Up to the age of 7 years, weight and height distribution was shifted to slightly lower values than in the general population; after that, the difference increased further, with 50% of the affected children below the 5th centile of the general population. BMI distribution was similar to that of non-affected children until the age of 7 years, at which point values in MWS children increased with a less steep slope, particularly in males. Microcephaly was sometimes present at birth, but in most cases it developed gradually during infancy; many children had a small head circumference, between the 3rd and the 10th centile, rather than being truly microcephalic (at least 2 SD below the mean). Most patients were of slender build. Conclusions: These charts contribute to the understanding of the natural history of MWS and should assist pediatricians and other caregivers in providing optimal care to MWS individuals who show problems related to physical growth. This is the first study on growth in patients with MWS.

AimTo explore whether there are social inequalities in non‐diabetic hyperglycaemia (NDH) and in transitions to type 2 diabetes mellitus and NDH low‐risk status in England.MethodsSome 9143 men and women aged over 50 years were analysed from waves 2, 4, 6 and 8 (2004–2016) of the English Longitudinal Study of Ageing (ELSA). Participants were categorized as: NDH ‘low‐risk’ [HbA1c < 42 mmol/mol (< 6.0%)], NDH [HbA1c 42–47 mmol/mol (6.0–6.4%)] and type 2 diabetes [HbA1c > 47 mmol/mol )> 6.4%)]. Logistic regression models estimated the association between sociodemographic characteristics and NDH, and the transitions from NDH to diagnosed or undiagnosed type 2 diabetes andlow‐risk status in future waves.ResultsNDH was more prevalent in older participants, those reporting a disability, those living in deprived areas and in more disadvantaged social classes. Older participants with NDH were less likely to progress to undiagnosed type 2 diabetes [odds ratio (OR) 0.27, 95% confidence interval (CI) 0.08, 0.96]. NDH individuals with limiting long‐standing illness (OR 1.72, 95% CI 1.16, 2.53), who were economically inactive (OR 1.60, 95% CI 1.02, 2.51) or from disadvantaged social classes (OR 1.63, 95% CI 1.02, 2.61) were more likely to progress to type 2 diabetes. Socially disadvantaged individuals were less likely (OR 0.64, 95% CI 0.41, 0.98) to progress to NDH low‐risk status.ConclusionsThere were socio‐economic differences in NDH prevalence, transition to type 2 diabetes and transition to NDH low‐risk status. Disparities in transitions included the greater likelihood of disadvantaged social groups with NDH developing type 2 diabetes and greater likelihood of advantaged social groups with NDH becoming low‐risk. These socio‐economic differences should be taken into account when targeting prevention initiatives.

Papillary thyroid cancer (PTC) is the most common form of thyroid cancer, comprising 80% of all thyroid malignancies. The phosphoinositide-3-kinase-protein kinase B/Akt (PI3K-PKB/Akt) pathway is a main pathway in control of cell growth. Activated mTOR and Akt are involved in the development and progression of the PTC. This study aimed to evaluate the effects of MTOR (rs2536 and rs2295080) and AKT1 (rs2494732, rs1130214, and rs1130233) polymorphisms on PTC susceptibility. This study was conducted on 131 PTC patients and 144 healthy subjects. Genotype analysis was done using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. Our results showed no statistically significant association between MTOR rs2536, AKT1 rs2494732, and rs1130214 polymorphisms and PTC development. However, MTOR rs2295080 polymorphism was found to be associated with a decreased risk of PTC in dominant and allelic models. The TT genotype of AKT1 rs1130233 was significantly higher in the PTC group in comparison to the controls, with a 3.5-fold increased risk for developing PTC. Furthermore, the allelic distribution also showed the T allele of rs1130233 as a risk factor for PTC occurrence. In conclusion, our results suggest the MTOR rs2295080 and AkT1 rs1130233 as the protective and risk factors for PTC development, respectively.

Klinefelter syndrome (KS) is a genetic anomaly involving the presence of one or more supernumerary X chromosomes in male individuals. In the cognitive profile of these individuals, strengths are found in nonverbal abilities, whereas weaknesses are observed in executive function, language, and academic performance. Our study is based on a comparison between eight children diagnosed with KS (47,XXY) (age range: 9-13 years; IQ range: 80-123), with no delay in language development, and eight typically developing (TD) controls. We explored a range of high-level language competencies and Theory of Mind (ToM) in addition to basic language competency. High-level language competencies were assessed by a battery that measures pragmatic language skills and a metaphor comprehension test (MCT). To assess ToM, we administered the corresponding subtest of the NEPSY II. Basic language competence was assessed by the NEPSY II Comprehension of Instructions subtest. Although basic language performance did not differentiate the individuals with KS from the TD controls, relevant differences appeared in some of the high-level language competencies as well as in the ToM task. All tasks in which the individuals with KS performed less well were characterized by complex inferential processes. Some possible clinical and educational implications are discussed.

OBJECTIVES: Although adolescence is a sensitive developmental period in oral health, the social equalization hypothesis that suggests health inequalities attenuate in adolescence has not been examined. This study analyses whether the socioeconomic gap and ethnic disadvantage in oral health among children aged 5 reduces among adolescents aged 15.METHODS: Data from the cross-sectional Children's Dental Health Survey 2013 were analysed, comprising of 8541 children aged 5, 8, 12 and 15 attending schools in England, Wales and Northern Ireland. Oral health indicators included decayed and filled teeth, plaque, gingivitis and periodontal health. Ethnicity was measured using the 2011 UK census ethnic categories. Socioeconomic position was measured by family, school and residential deprivation. Negative binomial and probit regression models estimated the levels of oral health by ethnicity and socioeconomic position, adjusted for demographic and tooth characteristics.RESULTS: The predicted rate of decayed teeth for White British/Irish children aged 5 was 1.54 (95%CI 1.30-1.77). In contrast, the predicted rate for Indian and Pakistani children was about 2-2.5 times higher. At age 15, ethnic differences had reduced considerably. Family deprivation was associated with higher levels of tooth decay among younger children but not among adolescents aged 15. The influence of residential deprivation on the rate of tooth decay and filled teeth was similar among younger and older children. Moreover, inequalities in poor periodontal health by residential deprivation was significantly greater among 15-year-old children compared to younger children.CONCLUSIONS: This study found some evidence of smaller ethnic and family socioeconomic differences in oral health among British adolescents compared to younger children. However, substantial differences in oral health by residential deprivation remain among adolescents. Community levels of deprivation may be particularly important for the health of adolescents.

Introduction and aims Open injuries in children are rare compared to adults. In children with major open injuries, there is no specific scoring system to guide when to amputate or salvage the limb. The use of available adult scoring systems may lead to errors in management. The role of Ganga Hospital Open Injury Severity Scoring (GHOISS) for open injuries in adults is well established and its applicability for pediatric open injuries has not been studied. This study was done to analyse the usefulness of GHOISS in pediatric open injuries and to compare it with MESS(Mangled Extremity Severity Score). Methods All children (0–18 years) who were admitted with Open type IIIB injuries of lower limbs between January 2008 and March 2015 were included. MESS and GHOISS were calculated for all the patients. There were 50 children with 52 type IIIB Open injuries of which 39 had open tibial fractures and 13 had open femur fractures. Results Out of 52 type IIIB open injuries, 48 were salvaged and 4 were amputated. A MESS score of 7 and above had sensitivity of 25% for amputation while GHOISS of 17 and above was found to be more accurate for determining amputation with sensitivity of 75% and specificity of 93.75%. Conclusion GHOISS is a reliable predictor of injury severity in type IIIB open fractures in children and can be used as a guide for decision-making. The use of MESS score in children has a lower predictive value compared to GHOISS in deciding amputation versus salvage. A GHOISS of 17 or more has the highest sensitivity and specificity to predict amputation.

Objectives Early old age and the period around retirement are associated with a widening in socioeconomic inequalities in health. There are few studies that address the stress-biological factors related to this widening. This study examined whether retirement is associated with more advantageous (steeper) diurnal cortisol profiles, and differences in this association by occupational grade. Method Data from the 7th (2002–2004), 8th (2006), and 9th (2007–09) phases of the London-based Whitehall II civil servants study were analysed. Thousand hundred and forty three respondents who were employed at phase 8 (mean age 59.9 years) and who had salivary cortisol measured from five samples collected across the day at phases 7 and 9 were analysed. Results Retirement was associated with steeper diurnal slopes compared to those who remained in work. Employees in the lowest grades had flatter diurnal cortisol slopes compared to those in the highest grades. Low-grade retirees in particular had flatter diurnal slopes compared to high-grade retirees. Discussion Socioeconomic differences in a biomarker associated with stress increase, rather than decrease, around the retirement period. These biological differences associated with transitions into retirement for different occupational groups may partly explain the pattern of widening social inequalities in health in early old age.

Fetal Alcohol Spectrum Disorders (FASD) are a plethora of malformative conditions leading to mental retardation that affect newborns and children who have been exposed to alcohol during pregnancy or breastfeeding. FASD is a relevant topic for public health in Europe: European area is first in ranking for alcohol use during pregnancy with a prevalence of 25.2%. Italy ranked third among European countries with higher prevalence of FASD (45.0 per 1000 population). Furthermore, FASD could still be underestimated because of numerous undiagnosed and misdiagnosed cases. Aims of the study were to briefly summarize existing evidences about FASD and its psychiatric aspects to assess knowledge, attitudes and practice towards alcohol drinking during pregnancy in an Italian sample of health care professionals in order to provide information about FASD prevention. An anonymous online questionnaire containing the AUDIT-C, T-ACE model and the Drinking Motive Questionnaire was sent to 400 Italian healthcare professionals and students. The survey included socio-demographic information, questions about drinking habits and about knowledge, attitude and practice towards alcohol assumption during pregnancy. Among 320 respondents, 96.3% were women. AUDIT-C revealed that 52.4% were low risk drinkers but 27.6% were hazardous drinkers. The 90.6% of participants denied to ever attended a course about the fetus damage induced by alcohol consumption during pregnancy but 91.3% were willing to participate to professional update initiatives on the topic. Only 19.1% of participants talk regularly about the deleterious effects for the fetus of prenatal alcohol drinking to women and only 51.1% advise the 'zero alcohol' policy. Around 41% of participants tolerates the assumption of low-alcohol beverages. No differences were found between no drinkers and low and hazardous drinkers. In conclusion, data show that only specific and continuing updating for health care professionals about drinking habits may have impactful actions to prevent gestational alcohol intake in order to prevent the main cause of mental retardation in western countries.

Down Syndrome (DS) is the most common chromosomal disorder. Although DS individuals are mostly perceived as characterized by some distinct physical features, cognitive disabilities, and cardiac defects, they also show important dysregulations of immune functions. While critical information is available for adults with DS, little literature is available on the neuroinflammation in prepubertal DS children. We aimed to evaluate in prepubertal DS children the serum levels of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), oxidative stress as free oxygen radicals defense (FORD), free oxygen radicals test (FORT), and cytokines playing key roles in neuroinflammation and oxidative processes as TNF-α, TGF-β, MCP-1, IL-1α, IL-2, IL-6, IL-10, and IL-12. No differences were found in NGF between DS children and controls. However, BDNF was higher in DS subjects compared to controls. We also did not reveal changes in FORD and FORT. Quite interestingly, the serum of DS children disclosed a marked decrease in all analyzed cytokines with evident differences in serum cytokine presence between male and female DS children. In conclusion, the present study evidences in DS prepubertal children a disruption in the neurotrophins and immune system pathways.

Global ageing poses a substantial economic burden on health and social care costs. Enabling a greater proportion of older people to stay healthy for longer is key to the future sustainability of health, social and economic policy. Frailty and associated decrease in resilience plays a central role in poor health in later life. In this study, we present a population level assessment of the metabolic phenotype associated with frailty. Analysis of serum from 1191 older individuals (aged between 56 and 84 years old) and subsequent longitudinal validation (on 786 subjects) was carried out using liquid and gas chromatography-mass spectrometry metabolomics and stratified across a frailty index designed to quantitatively summarize vulnerability. Through multivariate regression and network modelling and mROC modeling we identified 12 significant metabolites (including three tocotrienols and six carnitines) that differentiate frail and non-frail phenotypes. Our study provides evidence that the dysregulation of carnitine shuttle and vitamin E pathways play a role in the risk of frailty., info:eu-repo/semantics/published

Background Prior analyses of class differences in health trajectories among employees have often omitted women and transitions to retirement. We examined social class trajectories in physical functioning among Finnish female employees from midlife to retirement age, and whether transitions to retirement modified these trajectories. Methods Data were derived from mail surveys at Phases 1–3 (2000–2012) among employees of the City of Helsinki, Finland, aged 40–60 at baseline (n = 8960, 80% women, response rates 69–83%). We included respondents to any of the Phases 1–3 aged 40–72 (n = 6976). We distinguished higher and lower social classes, and employment statuses, i.e. employed, mandatorily retired and disability-retired. Short Form 36 physical component summary was used to measure physical functioning. Mixed-effect growth curve models were used to assess the association of social class and employment status with functioning over age. Results For employed women, physical functioning deteriorated faster in the lower than in the higher class, with class trajectories widening in ages 40–65. After mandatory retirement, functioning deteriorated in both classes, whereas after disability retirement, functioning improved. Across employment statuses, functioning converged at older ages, and the disability-retired caught up with the better functioning of the employed and mandatorily retired. Employment status modified the trajectories, as among the continuously employed and mandatorily retired women functioning deteriorated, but among the disability-retired, trajectories improved and reached a similar level with employed and mandatorily retired women. Social class inequalities remained in all employment status groups. Conclusions Overall, our results suggest evidence for the cumulative disadvantage model, with accumulating work exposures among lower classes potentially contributing to their trajectories of ill health.

Background Recurrent spontaneous abortion (RSA) is a serious problem in pregnancy. The exact etiology of RSA is unknown in more than 50% of all the patients. However, genetic variations are known as susceptibility factors for idiopathic RSA. Considering the role of miRNA biosynthesis machinery in the miRNA production and effect of miRNAs on various diseases, this study aimed to evaluate the effects of DICER1 rs3742330 and DROSHA rs6877842 polymorphisms on RSA risk. Methods In this case‐control study, 150 RSA patients and 195 age‐matched healthy female controls were recruited. Both polymorphisms were genotyped using PCR‐RFLP method. Results The frequency of DICER1 rs3742330AG genotype was higher in the control group (P = .022). There was a statistically significant association between rs3742330 polymorphism and a reduced RSA risk in dominant and allelic models (P = .013 and P = .007, respectively). No statistically significant association was found between DROSHA rs6877842 variant and RSA risk. The combination of AG and GC genotypes and G‐G alleles of DICER1 rs3742330 and DROSHA rs6877842 polymorphisms led to a decreased RSA risk. However, the synergic effect of rs3742330A and rs6877842G alleles (A‐G) and AA‐GG genotypes was associated with an increased RSA risk. Conclusion the DICER1 rs3742330AG genotype and combination of AG and GC genotypes and G‐G alleles of DICER1 rs3742330 and DROSHA rs6877842 polymorphisms were associated with a reduced RSA risk.

DS86760016 is a new leucyl-tRNA-synthetase inhibitor at the preclinical development stage. DS86760016 showed potent activity against extended-spectrum multidrug-resistant Pseudomonas aeruginosa isolated from clinical samples and in vitro biofilms. In a murine catheter-associated urinary tract infection model, DS86760016 treatment resulted in significant eradication of P. aeruginosa from the kidney, bladder, and catheter without developing drug resistance. Our data suggest that DS86760016 has the potential to act as a new drug for the treatment of Pseudomonas infections.

PurposeMowat-Wilson syndrome (MWS) is a rare intellectual disability/multiple congenital anomalies syndrome caused by heterozygous mutation of the ZEB2 gene. It is generally underestimated because its rarity and phenotypic variability sometimes make it difficult to recognize. Here, we aimed to better delineate the phenotype, natural history, and genotype-phenotype correlations of MWS.MethodsIn a collaborative study, we analyzed clinical data for 87 patients with molecularly confirmed diagnosis. We described the prevalence of all clinical aspects, including attainment of neurodevelopmental milestones, and compared the data with the various types of underlying ZEB2 pathogenic variations.ResultsAll anthropometric, somatic, and behavioral features reported here outline a variable but highly consistent phenotype. By presenting the most comprehensive evaluation of MWS to date, we define its clinical evolution occurring with age and derive suggestions for patient management. Furthermore, we observe that its severity correlates with the kind of ZEB2 variation involved, ranging from ZEB2 locus deletions, associated with severe phenotypes, to rare nonmissense intragenic mutations predicted to preserve some ZEB2 protein functionality, accompanying milder clinical presentations.ConclusionKnowledge of the phenotypic spectrum of MWS and its correlation with the genotype will improve its detection rate and the prediction of its features, thus improving patient care.GENETICS in MEDICINE advance online publication, 4 January 2018; doi:10.1038/gim.2017.221. ispartof: Genetics in Medicine vol:20 issue:9 pages:965-975 ispartof: location:United States status: published

Background: Little is known about the role of sleep disturbance in relation to changes in depressive states. We used data obtained from the participants aged 65 and over in the English Longitudinal Study of Ageing (ELSA, waves 4 and 5, N=3108) and the Japan Gerontological Evaluation Study (JAGES, 2010 and 2013 sweeps, N=7527) to examine whether sleep disturbance is longitudinally associated with older adults’ patterns of depressive states. Methods: We created four patterns of depressive states (non-case, recovered, onset, repeatedly depressive) by combining responses to the measures (scoring four or more on seven items from the Center for Epidemiological Studies Depression Scale for the ELSA participants and scoring 5 or more for the Geriatric Depression Scale-15 for the JAGES participants) obtained at the baseline and follow-up. Sleep disturbance was assessed through responses to three questions on sleep problems. Age, sex, partnership status, household equivalised income, alcohol and cigarette use, and physical function were treated as confounders in this study. Additionally, information on sleep medication was available in JAGES and was included in the statistical models. Results: More ELSA participants were non-depressive cases and reported no sleep disturbances compared with the JAGES participants. Findings from multinomial logistic regression analysis showed that more sleep disturbance was associated with the onset group in ELSA (RRR=2.37, 95%CI=1.44-3.90) and JAGES (RRR=2.41, 95%CI=1.79-3.25) as well as the recovery (RRR=3.42, 95%CI=1.98-5.90, RRR=2.71, 95%CI=1.95-3.75) and repeatedly depressed group (RRR=7.24, 95%CI=3.91-13.40, RRR=5.16, 95%CI=3.82-6.98). Conclusions: Findings suggest that the association between sleep disturbance and depression in older adults is complex.Key words: Sleep; depressive states; cross-national comparisons; ELSA; JAGES

PURPOSE: Mowat-Wilson syndrome (MWS) is a genetic disease characterized by distinctive facial features, moderate to severe intellectual disability, and congenital malformations, including Hirschsprung disease, genital and eye anomalies, and congenital heart defects, caused by haploinsufficiency of the ZEB2 gene. To date, no characteristic pattern of brain dysmorphology in MWS has been defined.METHODS: Through brain magnetic resonance imaging (MRI) analysis, we delineated a neuroimaging phenotype in 54 MWS patients with a proven ZEB2 defect, compared it with the features identified in a thorough review of published cases, and evaluated genotype-phenotype correlations.RESULTS: Ninety-six percent of patients had abnormal MRI results. The most common features were anomalies of corpus callosum (79.6% of cases), hippocampal abnormalities (77.8%), enlargement of cerebral ventricles (68.5%), and white matter abnormalities (reduction of thickness 40.7%, localized signal alterations 22.2%). Other consistent findings were large basal ganglia, cortical, and cerebellar malformations. Most features were underrepresented in the literature. We also found ZEB2 variations leading to synthesis of a defective protein to be favorable for psychomotor development and some epilepsy features but also associated with corpus callosum agenesis.CONCLUSION: This study delineated the spectrum of brain anomalies in MWS and provided new insights into the role of ZEB2 in neurodevelopment.Genet Med advance online publication 10 November 2016Genetics in Medicine (2016); doi:10.1038/gim.2016.176.

Background: Little is known of how pension reforms affect the retirement decisions of people with different health statuses, although this is crucial for the understanding of the broader societal impact of pension policies and for future policy development. We assessed how the Finnish statutory pension age reform introduced in 2005 influenced the role of health as a predictor of retirement. Methods: We used register-based data and cox regression analysis to examine the association of health (measured by purchases of psychotropic medication, hospitalizations due to circulatory and musculoskeletal diseases, and the number of any prescription medications) with the risk of retirement at age 63-64 among those subject to the old pension system with fixed age limit at 65 (pre-reform group born in 1937-1941) and the new flexible system with 63 as the lower age limit (post-reform group born in 1941-1945) while controlling for socio-demographic factors. Results: Retirement at age 63-64 was more likely among the post- than the pre-reform group (HR = 1.50; 95% CI 1.43-1.57). This reform-related increase in retirement was more pronounced among those without a history of psychotropic medication or hospitalizations due to circulatory and musculoskeletal diseases, as well as among those with below median level medication use. As a result, poor health became a weaker predictor of retirement after the reform. Conclusion: Contrary to the expectations of the Finnish pension reform aimed at extending working lives, offering choice with respect to the timing of retirement may actually encourage healthy workers to choose earlier retirement regardless of the provided economic incentives for continuing in work. (C) 2016 The Authors. Published by Elsevier Ltd.

Highlights • We examined the association between adolescent non-cognitive skills and adult health, using both subjective and objective measures of health. • Conscientiousness is positively associated with your ability to cope with stress and negatively associated with cardiovascular risk. • Agreeableness is positively associated with health-related quality of life and negatively associated with physiological ‘wear and tear’, however is negatively associated with your ability to cope with stress. • Neuroticism is negatively associated with health-related quality of life, and positively associated with physiological ‘wear and tear’ and cardiovascular risk. • All of these associations are stronger at the end of the health distribution that indicates poorer health, except for the cardiovascular risk biomarkers., Several studies have established associations between early-life non-cognitive skills and later-life health and health behaviours. However, no study addresses the more important policy concern about how this relationship varies along the health distribution. We use unconditional quantile regression to analyse the effects of adolescent non-cognitive skills across the distributions of the health-related quality of life at age 50 and biomarkers at age 45 years. We examine the effects of measures of conscientiousness, agreeableness and neuroticism recorded at age 16 for 3585 individuals from the National Child Development Study. Adolescent conscientiousness is positively associated with ability to cope with stress and negatively associated with risk of cardiovascular disease in middle-age. Adolescent agreeableness is associated with higher health-related quality of life and lower physiological ‘wear and tear’, but negatively associated with ability to cope with stress in middle-age. Adolescent neuroticism is associated with lower health-related quality of life, higher physiological ‘wear and tear’, and a higher risk of cardiovascular disease in middle-age. All of these associations are stronger at the lower end of the health distribution except for the cardiovascular risk biomarkers. These associations are robust to correcting for attrition using inverse probability weighting and consistent with causal bounds assuming proportional selection on observables and unobservables. They suggest policies that improve non-cognitive skills in adolescence could offer most long-term health benefit to those with the poorest health.

Objectives This study examined whether oral health is a neglected aspect of subjective well-being (SWB) among older adults. The key research question was whether deterioration in oral health among dentate older adults living in England was associated with decreases in SWB, using measures of eudemonic, evaluative, and affective dimensions of well-being. Methods This secondary analysis used data from the third (2006–2007) and fifth (2010–2011) waves of respondents aged 50 and older from the English Longitudinal Study of Ageing (ELSA). We fitted multivariable regression models to examine the effects of changes in oral impacts on daily life and edentulism (complete tooth loss) on SWB (quality of life, life satisfaction, and depressive symptomatology). Results A worsening in both oral health measures was associated with an increase in depressive symptoms even after adjusting for time-varying confounders including declining health, activities of daily living, and reduced social support. Becoming edentate was also associated with decreases in quality of life and life satisfaction. Discussion A deterioration in oral health and oral health–related quality of life increases the risk of depressive symptoms among older adults and highlights the importance of oral health as a determinant of subjective well-being in later life.

Objectives Little is known about which component, such as social contact of social networks is associated with mental health or whether such an association can be observed across countries. This study examined whether the association between frequent social contact and mental health differs by composition (relatives or friends) and whether the associations are similar across three occupational cohorts from Great Britain, Japan, and Finland. Study design Cross-sectional analysis of data from three prospective cohort studies. Methods Participants were civil servants of a prospective cohort study based in London (Men: n = 4519; Women: n = 1756), in the West Coast of Japan (Men: n = 2571; Women: n = 1102), and in Helsinki, Finland (Men: n = 1181; Women: n = 5633); we included the information on study variables which is complete. Mental health function was the study outcome, indicated by the total score from the Mental Health Component on the Short Form Health Survey36. Participants reported frequencies of contacts with their relatives or friends via a questionnaire. Age, marital status, and occupational position were treated as confounders in this study. Results Findings from multiple regression showed that the associations between social contact and mental health function were different depending on country of origin and gender. Among British or Japanese men, frequent contact with both friends and relatives was positively associated with their mental health function, while only social contact with friends was significantly associated with mental health of Finnish men. In women, the patterns of the associations between social contact and mental health were more distinctive: friends for Great Britain, relatives for Japan, and friends and relatives for Finland. These significant associations were independent of the confounders. Conclusions Social contact was related to mental health of working people; however, culture and gender are likely to be tapped into.

ObjectiveChina’s internal migration has left 61 million children living apart from their parent(s) in rural areas. The present study aimed to examine whether the relative contributions of macronutrients (protein, fat and carbohydrate) to total energy intake differ between children left behind by the father or mother, compared with children from intact families.DesignDrawing on a longitudinal study, the China Health and Nutrition Survey (1997–2009), multilevel modelling analyses (level 1: occasions; level 2: children; level 3: villages) were performed.SettingData from rural communities in nine provinces in China.SubjectsRural children (n975; 555 boys and 420 girls) from 140 villages.ResultsAmong boys of school age, being left behind by the father tended to reduce the relative protein intake by 0·70 % (PPPConclusionsPublic health policies should recognise the influences of parental migration on boys, especially maternal migration, and encourage a more balanced diet for children in rural China.

The rapid advancement of next-generation sequencing (NGS) technology and the decrease in costs for whole-exome sequencing (WES) and whole-genome sequening (WGS), has prompted its clinical application in several fields of medicine. Currently, there are no specific guidelines for the use of NGS in the field of neonatal medicine and in the diagnosis of genetic diseases in critically ill newborn infants. As a consequence, NGS may be underused with reduced diagnostic success rate, or overused, with increased costs for the healthcare system. Most genetic diseases may be already expressed during the neonatal age, but their identification may be complicated by nonspecific presentation, especially in the setting of critical clinical conditions. The differential diagnosis process in the neonatal intensive care unit (NICU) may be time-consuming, uncomfortable for the patient due to repeated sampling, and ineffective in reaching a molecular diagnosis during NICU stay. Serial gene sequencing (Sanger sequencing) may be successful only for conditions for which the clinical phenotype strongly suggests a diagnostic hypothesis and for genetically homogeneous diseases. Newborn screenings with Guthrie cards, which vary from country to country, are designed to only test for a few dozen genetic diseases out of the more than 6000 diseases for which a genetic characterization is available. The use of WES in selected cases in the NICU may overcome these issues. We present an intersociety document that aims to define the best indications for the use of WES in different clinical scenarios in the NICU. We propose that WES is used in the NICU for critically ill newborn infants when an early diagnosis is desirable to guide the clinical management during NICU stay, when a strong hypothesis cannot be formulated based on the clinical phenotype or the disease is genetically heterogeneous, and when specific non-genetic laboratory tests are not available. The use of WES may reduce the time for diagnosis in infants during NICU stay and may eventually result in cost-effectiveness.

Beckwith-Wiedemann syndrome (BWS) is characterized by cancer predisposition, overgrowth and highly variable association of macroglossia, abdominal wall defects, nephrourological anomalies, nevus flammeus, ear malformations, hypoglycemia, hemihyperplasia, and organomegaly. BWS molecular defects, causing alteration of expression or activity of the genes regulated by two imprinting centres (IC) in the 11p15 chromosomal region, are also heterogeneous. In this paper we define (epi)genotype-phenotype correlations in molecularly confirmed BWS patients. The characteristics of 318 BWS patients with proven molecular defect were compared among the main four molecular subclasses: IC2 loss of methylation (IC2-LoM, n=190), IC1 gain of methylation (IC1-GoM, n=31), chromosome 11p15 paternal uniparental disomy (UPD, n=87), and cyclin-dependent kinase inhibitor 1C gene (CDKN1C) variants (n=10). A characteristic growth pattern was found in each group; neonatal macrosomia was almost constant in IC1-GoM, postnatal overgrowth in IC2-LoM, and hemihyperplasia more common in UPD (P

Objectives Although urbanisation is generally associated with poverty reduction in low-income and middle-income countries, it also results in increased socioeconomic segregation of the poor. Cities with higher levels of socioeconomic segregation tend to have higher mortality rates, although the evidence is based on ecological associations. The paper examines whether socioeconomic segregation of the poor is associated with higher under-60 years (‘premature’) mortality risk in Indian cities and whether this association is confounded by contextual and compositional sociodemographic and socioeconomic factors. Setting and participants A population representative sample of over one million from 39 427 households living in 1876 urban wards within 59 Indian districts (cities) from the third (2008) District Level Household Survey (DLHS-3). Primary outcome and other measures The outcome was any death under the age of 60 reported by households in the preceding 4years of the DLHS-3. Socioeconomic segregation, estimated at the district (city) level, was measured using an isolation index of the poor and the index of dissimilarity. Results Poor households living in cities where the poor were more isolated had higher probabilities of premature mortality than poor households living in cities where the poor were less isolated. In contrast, it did not matter whether rich households lived in more or less socioeconomically segregated cities. A 1 SD increase in the isolation index was associated with an absolute increase of 1.1% in the probability of premature mortality for the poorest households. Conclusion Increasing segregation of the poor may result in higher premature mortality. As low-income and middle-income countries become increasingly urbanised, there is a risk that this may lead to increased segregation of the poor as well as increased premature mortality.

Although associations between work stressors and stress-related biomarkers have been reported in cross-sectional studies, the use of single time measurements of work stressors could be one of the reasons for inconsistent associations. This study examines whether repeated reports of work stress towards the end of the working career predicts allostatic load, a measure of chronic stress related physiological processes. Data from waves 2 to 6 of the English Longitudinal Study of Ageing (ELSA) were analysed, with a main analytical sample of 2663 older adults (aged 50+) who had at least one measurement of effort-reward imbalance between waves 2–6 and a measurement of allostatic load at wave 6. Cumulative work stress over waves 2–6 were measured by the effort-reward imbalance model. ELSA respondents who had reported two or more occasions of imbalance had a higher (0.3) estimate of the allostatic load index than those who did not report any imbalance, controlling for a range of health and socio-demographic factors, as well as allostatic load at baseline. More recent reports of imbalance were significantly associated with a higher allostatic load index, whereas reports of imbalance from earlier waves of ELSA were not. The accumulation of work related stressors could have adverse effects on chronic stress biological processes.

Objectives Although there is some evidence that public transport use confers public health benefits, the evidence is limited by cross-sectional study designs and health-related confounding factors. This study examines the effect of public transport use on changes in walking speed among older adults living in England, comparing frequent users of public transport to their peers who did not use public transport because of structural barriers (poor public transport infrastructure) or through choice. Design Prospective cohort study. Setting England, UK. Participants Older adults aged ≥60 years eligible for the walking speed test. 6246 individuals at wave 2 (2004-2005); 5909 individuals at wave 3 (2006-2007); 7321 individuals at wave 4 (2008-2009); 7535 individuals at wave 5 (2010-2011) and 7664 individuals at wave 6 (2012-2013) of the English Longitudinal Study of Ageing. Main outcome measure The walking speed was estimated from the time taken to walk 2.4 m. Fixed effects models and growth curve models were used to examine the associations between public transport use and walking speed. Results Older adults who did not use public transport through choice or because of structural reasons had slower walking speeds (â '0.02 m/s (95% CI â '0.03 to-0.003) and â '0.02 m/s (95% CI â '0.03 to-0.01), respectively) and took an extra 0.07 s to walk 2.4 m compared with their peers who used public transport frequently. The age-related trajectories of decline in walking speed were slower for frequent users of public transport compared with non-users. Conclusions Frequent use of public transport may prevent age-related decline in physical capability by promoting physical activity and lower limb muscle strength among older adults. The association between public transport use and slower decline in walking speed among older adults is unlikely to be confounded by health-related selection factors. Improving access to good quality public transport could improve the health of older adults.

Background There is little evidence on whether becoming re-employed in poor quality work is better for health and well-being than remaining unemployed. We examined associations of job transition with health and chronic stress-related biomarkers among a population-representative cohort of unemployed British adults. Methods A prospective cohort of 1116 eligible participants aged 35 to 75 years, who were unemployed at wave 1 (2009/10) of the UK Household Longitudinal Study, were followed up at waves 2 (2010/11) and 3 (2011/12) for allostatic load biomarkers and self-reported health. Negative binomial and multiple regression models estimated the association between job adversity and these outcomes. Results Compared with adults who remained unemployed, formerly unemployed adults who transitioned into poor quality jobs had higher levels of overall allostatic load (0.51, 0.32–0.71), log HbA1c (0.06

BACKGROUND: China's unprecedented internal migration has left 61 million rural children living apart from parents. This study investigates how being left behind is associated with children's growth, by examining children's height and weight trajectories by age, testing the accumulation and critical period life course hypotheses. METHODS: Data were drawn from five waves of the China Health and Nutrition Survey (CHNS). Multiple cohorts of children under 6 years old from 1997-2009 were examined (N = 2,555). Growth curve models investigated whether height and weight trajectories differ for children who were left behind at different stages of the life course: in early childhood (from ages 0-5 but not afterwards), in later childhood (from ages 6 to 17 only), and in both early and later childhood (from ages 0-5 and from ages 6-17), compared to their peers from intact households. RESULTS: Boys who were left behind at different life stages of childhood differed in height and weight growth compared with boys from intact families. No significant associations were found for girls. As young boys turned into adolescents, those left behind in early childhood tended to have slower height growth and weight gain than their peers from intact households. There was a 2.8 cm difference in the predicted heights of boys who were left behind in early childhood compared to boys from intact households, by the age of 14. Similarly, the difference in weight between the two groups of boys was 5.3 kg by the age of 14. CONCLUSIONS: Being left behind during early childhood, as compared to not being left behind, could lead to slower growth rates of height and weight for boys. The life course approach adopted in this study suggests that early childhood is a critical period of children's growth in later life, especially for boys who are left behind. The gender paradox in China, where sons are preferred, but being left behind appears to affect boys more than girls, needs further exploration.

The deleterious effects exerted by prenatal ethanol exposure include physical, mental, behavioral, and/or learning disabilities that are included in the term fetal alcohol spectrum disorder. The measurement of ethylglucuronide (EtG) in alternative biological matrices, including neonatal and maternal hair, neonatal meconium, and maternal nails, is receiving increasing interest for the accurate evaluation of the in utero exposure to alcohol.To evaluate the correlation between EtG in maternal hair and nails with EtG in neonatal meconium to further explore the suitability of these biomarkers in disclosing prenatal exposure to ethanol.A total of 151 maternal hair strands (0-6 cm), nail clips (2-6 mm), and corresponding neonatal meconium and nails samples were obtained from neonatal wards of 4 Mediterranean public hospitals: Rome, Florence, and Belluno in Italy and Barcelona in Spain. Hair, nails, and meconium were analyzed for the presence of EtG by validated liquid chromatography mass spectrometry assay. Meconium was also analyzed for the presence of fatty acid ethyl esters (FAEEs) as a complementary biomarker of potential in utero exposure to alcohol.Eighteen newborns resulted in utero exposed to maternal alcohol consumption by FAEE testing in meconium with EtG values between 0.5 and 1.5 nmol/g. Unfortunately, none of these cases were confirmed by the presence of EtG in maternal hair and nails samples, which resulted all negative to this biomarker.The results confirm that FAEEs and EtG in meconium are the best biomarkers to assess in utero exposure to maternal alcohol. EtG in hair and nails are not good biomarkers to disclose alcohol consumption lower than on daily basis and lower than 1-2 alcoholic units per day.

Background Since 2002, Afghanistan has made much effort to achieve universal health coverage. According to the UN Sustainable Development Goal 3, target eight, the provision of quality care to all must include usually underserved groups, including people with disabilities. We investigated whether a decade of international investment in the Afghan health system has brought quality health care to this group. Methods We used data from two representative household surveys, one done in 2005 and one in 2013, in 13 provinces of Afghanistan, that included questions about activity limitations and functioning difficulties, socioeconomic factors, perceived availability of health care, and experience with coverage of health-care needs. We used multilevel modelling and tests for interaction to investigate factors associated with differences in perception between timepoints and whether village remoteness affected changes in perception. Findings The 2005 survey included 334 people, and the 2013 survey included 961 people. Mean age, employment, and asset levels of participants with disabilities increased slightly between 2005 and 2013, but the level of education decreased. Formal education and higher asset level were associated with improved availability of health care and positive experience with coverage of health-care needs, whereas being employed was only associated with the latter. Perceived availability of health care and positive experience with coverage of health-care needs significantly worsened in 2013 compared with in 2005 (227 [69%] perceived that services were available in 2005 vs 405 [44%] in 2013, p

OBJECTIVE: This study assessed associations between social relationships and oral health outcomes and whether these associations were explained by demographic, socioeconomic, and behavioral factors, and physical health. METHODS: We used the National Health and Nutrition Examination Survey (1999-2004) data on 4014 adults aged 60 years or older. Oral health outcomes were edentulism, number of decayed teeth, root decay, number of sound or filled teeth, and self-rated oral health. Social relationships referred to social networks (marital status, number of close friends) and social support (emotional support need, provision of financial support). Analyses consisted of regression models sequentially adjusting for demographic, socioeconomic, behavioral, and physical health confounders. RESULTS: In fully adjusted models, widowed or divorced/separated individuals had fewer sound or filled teeth than those married or living with a partner: rate ratio (95% confidence interval)=0.89 (0.82 to 0.97) and 0.90 (0.83 to 0.97), respectively. People with four to six close friends had fewer decayed teeth and lower probability for root decay than those with fewer friends. Emotional support need was associated with 1.41 (1.05 to 1.90) higher odds for root decay and 1.18 (1.04 to 1.35) higher odds for poorer self-rated oral health. Lack of financial support was associated with more decayed teeth. Edentulism was not related to any social network and social support markers. CONCLUSIONS: Social relationships are associated with clinical measures of current disease, markers of good oral function, and subjective oral health, but not with clinical measures of a lifetime history of oral disease among older Americans.

Juvenile Polyposis (JP) is a rare hereditary condition characterized by diffuse hamartomatous gastrointestinal polyposis, associated with a significantly increased risk of neoplastic transformation. Most of the cases are caused by SMAD and BMPR1A mutations, while 10q23 microdeletions, encompassing both PTEN and BMPR1A oncogenes, are extremely rare, typically associated with more aggressive JP, and extraintestinal features overlapping with PTEN Hamartoma Tumor Syndrome. We present the first case of a young female with multiple autoimmune disorders (i.e. thyroiditis and celiac disease), associated with JP, cardiac defects and epilepsy, who carries a de novo heterozygous 10q23.1q23.31 deletion. The dysregulation of the PI3K/Akt pathway is advanced as the putative mechanism connecting autoimmune, malformative and neoplastic disorders. A literature review of clinical manifestation, gene alterations and the treatment of patients with 10q23 deletion is also provided, highlighting the importance of comprehensive, long-term, multi-disciplinary management, aimed at early identification and treatment of both intestinal and extraintestinal disorders.

PurposeParents face an increased risk of psychological distress compared with adults without children, and families with children also have lower average household incomes. Past research suggests that absolute income (material position) and income status (psychosocial position) influence psychological distress, but their combined effects on changes in psychological distress have not been examined. Whether absolute income interacts with income status to influence psychological distress are also key questions.MethodsWe used fixed-effects panel models to examine longitudinal associations between psychological distress (measured on the Kessler scale) and absolute income, distance from the regional mean income, and regional income rank (a proxy for status) using data from 29,107 parents included in the UK Millennium Cohort Study (2003–2012).ResultsPsychological distress was determined by an interaction between absolute income and income rank: higher absolute income was associated with lower psychological distress across the income spectrum, while the benefits of higher income rank were evident only in the highest income parents. Parents’ psychological distress was, therefore, determined by a combination of income-related material and psychosocial factors.ConclusionsBoth material and psychosocial factors contribute to well-being. Higher absolute incomes were associated with lower psychological distress across the income spectrum, demonstrating the importance of material factors. Conversely, income status was associated with psychological distress only at higher absolute incomes, suggesting that psychosocial factors are more relevant to distress in more advantaged, higher income parents. Clinical interventions could, therefore, consider both the material and psychosocial impacts of income on psychological distress.

There has been considerable debate over the importance of the health selection hypothesis for explaining social gradients in health. Although studies have argued that it may not be an important explanation of social gradients in health, previous analyses have not estimated, simultaneously, the relative effect of health on changes in social position and of social position on changes in health (social causation). Cross-lagged longitudinal analyses using structural equation models enable the estimation of the relative size of these pathways which would be useful in determining the relative importance of the health selection hypothesis over the social causation hypothesis. Data from four phases of the Whitehall II study (initially consisting of 10,308 men and women aged 35-55 in the British civil service) were collected over a 10 year period. There was no evidence for an effect of mental (GHQ-30 and SF36) or physical health (SF-36) on changes in employment grade. When financial deprivation was used as a measure of social position, there was a significant effect of mental health on changes in social position among men although this health selection effect was over two and a half times smaller than the effect of social position on changes in health. The results suggest that the development of social gradients in health in the Whitehall II study may not be primarily explained in terms of a health selection effect.

Objectives: All health care providers in England are required to conduct surveys of their patients' experience of health care. Data from such surveys contribute to the 'star rating' performance indicators. However, there are concerns that these subjective measures may be influenced more by characteristics of patients than by true variations in the quality of care. The purpose of this paper is threefold: to determine the relationship between demographic characteristics and an index measure of patients' reported experience; to explore the extent to which patients' experiences may be accounted for by the particular National Health Service (NHS) trust they attended; and to assess how meaningful a summary index is in terms of its ability to discriminate between providers. Methods: Data from patients in the National Survey of National Health Service Patients treated for coronary heart disease in 194 NHS trusts. Patients were sent questionnaires after discharge, with a covering letter and a prepaid stamped addressed envelope. Up to two reminders were sent to non-responders. Multi-level linear regression models were used to estimate the extent to which patients' experiences differed between trusts and the association of demographic variables with the summary index. Results: In total, 116 872 patients were sent questionnaires, but 3399 proved to be ineligible for the survey. Responses were gained from 84 310 (74.3% of eligible respondents). Age and sex were most strongly associated with reported patients' experiences. However, the actual impact of age and sex on patients' experience is small, accounting for less than 3% of the variance. The proportion of the variance that was accounted for by the hospital trust in which patients were treated was only 5%. Conclusions: Demographic characteristics do not appear to account for differences between hospital trusts in patients' experience of health care. However, there is considerable variation in patients' experience within each provider. This would suggest that summary indices of patients' experience should not be used to rank providers, although detailed information from patient surveys have a useful role in determining priorities for quality improvement within individual hospitals and for assessing changes over time.

Children living in low-income households face elevated risks of behavioral problems, but the impact of absolute and relative income to this risk remains unexplored. Using the U.K. Millennium Cohort Study data, longitudinal associations between Strengths and Difficulties Questionnaire scores and absolute household income, distance from the regional median and mean income, and regional income rank were examined in 3- to 12-year-olds (n = 16,532). Higher absolute household incomes were associated with lower behavioral problems, while higher income rank was associated with lower behavioral problems only at the highest absolute incomes. Higher absolute household incomes were associated with lower behavioral problems among children in working households, indicating compounding effects of income and socioeconomic advantages. Both absolute and relative incomes therefore appear to influence behavioral problems.