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Background: Primary central nervous system melanoma is an extremely rare entity and even rarer in children and adolescents as compared to adults. It is often difficult to consider a diagnosis of intracranial melanoma pre-operatively without any clinical evidence of neurocutaneous melanosis. Case presentation: Herein, a case of primary melanoma of the brain is reported in a 17-year-old female who presented with headache, vomiting, and focal neurological deficit in the form of left-sided facial palsy and limb weakness. A contrast-enhanced computed tomography of head was performed which revealed a heterogeneously hyperattenuating mass lesion at left gangliocapsular region showing peripheral enhancement with internal non-enhancing cystic component. The patient underwent left frontotemporal craniotomy. The diagnosis was made on histopathological examination, which showed an invasive tumor comprising of epithelioid to spindled cells arranged in sheets, nests, and singly scattered. The special stains and immunohistochemical markers proved very helpful in establishing the diagnosis. Conclusions: The case highlights the uncommon occurrence of primary intracranial melanoma in the pediatric age group, the perplexing histological features, and the rapid and fatal course. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the present review is to analyze dynamic interactions between nutrigenomics, environmental cues, and parental influence, which can all lead to children's neophobic reactions and its persistence in time. Methods: We reviewed studies available on electronic databases, conducted on children aged from birth to 18 years. We also considered official websites of Italian Institutions, providing advice on healthy eating during infancy. Results: Modern day societies are faced with an eating paradox, which has severe and ever-growing implications for health. In face of a wider availability of healthy foods, individuals instead often choose processed foods high in fat, salt and sugar content. Economic reasons surely influence consumers' access to foods. However, there is mounting evidence that food choices depend on the interplay between social learning and genetic predispositions (e.g., individual eating traits and food schemata). Neophobia, the behavioral avoidance of new foods, represents an interesting trait, which can significantly influence children's food refusal. Early sensory experiences and negative cognitive schemata, in the context of primary caregiver–child interactions, importantly contribute to the priming of children's food rejection. Conclusions: As neophobia strongly affects consumption of healthy foods, it will be relevant to rule definitively out its role in the genesis of maladaptive food choices and weight status in longitudinal studies tracking to adulthood and, in meanwhile, implement early in life effective social learning strategies, to reduce long-term effects of neophobia on dietary patterns and weight status. Level of evidence: Level II, controlled trials without randomization. [ABSTRACT FROM AUTHOR]

The diagnosis of central pontine hyperintensities on cranial magnetic resonance imaging has wide-spectrum clinical entities, and the pro-type diagnosis of these is central pontine myelinolysis. The rapid changes in extracellular environment due to an imbalance of electrolytes or metabolic or toxic stress to the myelin sheath can cause demyelination of white matter tracts in pons, which is why this situation could have different etiologies than just rapid sodium changes. Central pontine myelinolysis can be presented with different clinical scenarios from asymptomatic to death. Here, we present eight patients who had central pontine hyperintensities on radiological imaging but showed various clinical symptoms and different etiologies. The etiologies of these cases are hypertriglyceridemia, alcohol consumption, antidepressant usage, immunocompromised situations, uncontrolled diabetes mellitus, liver and kidney failure, electrolyte changes, and adrenal insufficiency. We aimed to take attention with this case series to the fact that not only fast correction of hyponatremia is the cause of central pontine myelinolysis, but also different etiologies could play a role in this situation, and making the central pontine myelinolysis diagnosis considering different diagnosis is very important. [ABSTRACT FROM AUTHOR]

Background: The connectome, constituting a unique fingerprint of a person's brain, may be influenced by its prenatal environment, potentially affecting later-life resilience and mental health. Methods: We conducted a prospective resting-state functional Magnetic Resonance Imaging study in 28-year-old offspring (N = 49) of mothers whose anxiety was monitored during pregnancy. Two offspring anxiety subgroups were defined: "High anxiety" (n = 13) group versus "low-to-medium anxiety" (n = 36) group, based on maternal self-reported state anxiety at 12–22 weeks of gestation. To predict resting-state functional connectivity of 32 by 32 ROIs, maternal state anxiety during pregnancy was included as a predictor in general linear models for both ROI-to-ROI and graph theoretical metrics. Sex, birth weight and postnatal anxiety were included as covariates. Results: Higher maternal anxiety was associated with weaker functional connectivity of medial prefrontal cortex with left inferior frontal gyrus (t = 3.45, pFDR < 0.05). Moreover, network-based statistics (NBS) confirmed our finding and revealed an additional association of weaker connectivity between left lateral prefontal cortex with left somatosensory motor gyrus in the offspring. While our results showed a general pattern of lower functional connectivity in adults prenatally exposed to maternal anxiety, we did not observe significant differences in global brain networks between groups. Conclusions: Weaker (medial) prefrontal cortex functional connectivity in the high anxiety adult offspring group suggests a long-term negative impact of prenatal exposure to high maternal anxiety, extending into adulthood. To prevent mental health problems at population level, universal primary prevention strategies should aim at lowering maternal anxiety during pregnancy. [ABSTRACT FROM AUTHOR]

A vast body of research and theory underscores the importance of parental warmth/affection (hereby 'warmth' and 'warmth/affection' are used interchangeably) as a distinct relational process that is fundamental to core developmental processes including parent-child attachment, socialization, emotion recognition and responsivity, and empathic development. The increasing focus on parental warmth as a viable transdiagnostic and specific treatment target for Callous-Unemotional (CU) traits highlights the critical need for a reliable and valid tool for measuring this construct within clinical contexts. However, existing assessment methods have limitations in their ecological validity, clinical utility, and the comprehensiveness of their coverage of core warmth subcomponents. In response to this clinical and research need, the observational Warmth/Affection Coding System (WACS) was developed to comprehensively measure parent-to-child warmth/affection. This paper chronicles the conception and development of the WACS, which adopts a hybrid approach of utilizing both microsocial and macro-observational coding methods to capture key verbal and non-verbal subcomponents of warmth that are currently underrepresented or poorly captured by existing assessment tools. Recommendations for implementation and future directions are also discussed. [ABSTRACT FROM AUTHOR]

Purpose: To provide an overview of the discovery, presentation, and management of Rapid-onset Obesity with Hypothalamic dysfunction, Hypoventilation, and Autonomic Dysregulation (ROHHAD). To discuss a search for causative etiology spanning multiple disciplines and continents. Methods: The literature (1965–2022) on the diagnosis, management, pathophysiology, and potential etiology of ROHHAD was methodically reviewed. The experience of several academic centers with expertise in ROHHAD is presented, along with a detailed discussion of scientific discovery in the search for a cause. Results: ROHHAD is an ultra-rare syndrome with fewer than 200 known cases. Although variations occur, the acronym ROHHAD is intended to alert physicians to the usual sequence or unfolding of the phenotypic presentation, including the full phenotype. Nearly 60 years after its first description, more is known about the pathophysiology of ROHHAD, but the etiology remains enigmatic. The search for a genetic mutation common to patients with ROHHAD has not, to date, demonstrated a disease-defining gene. Similarly, a search for the autoimmune basis of ROHHAD has not resulted in a definitive answer. This review summarizes current knowledge and potential future directions. Conclusion: ROHHAD is a poorly understood, complex, and potentially devastating disorder. The search for its cause intertwines with the search for causes of obesity and autonomic dysregulation. The care for the patient with ROHHAD necessitates collaborative international efforts to advance our knowledge and, thereby, treatment, to decrease the disease burden and eventually to stop, and/or reverse the unfolding of the phenotype. [ABSTRACT FROM AUTHOR]

Purpose: Congenital central hypoventilation syndrome (CCHS) and rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) are rare disorders of autonomic regulation with risk for disrupted neurocognitive development. Our aim is to summarize research on neurocognitive outcomes in these conditions, advance understanding of how to best support these individuals throughout development, and facilitate future research. Methods: We conducted a narrative review of literature on neurocognitive outcomes in CCHS and ROHHAD, supplemented with previously unpublished data from patients with CCHS and ROHHAD at our Center for Autonomic Medicine in Pediatrics (CAMP). Results: Individuals with CCHS and ROHHAD experience a wide range of neurocognitive functioning ranging from above average to below average, but are at particular risk for difficulties with working memory, processing speed, perceptual reasoning, and visuographic skills. An assessment framework emphasizing fluid cognition seems especially appropriate for these conditions. Owing to small cohorts and varied methods of data collection, it has been difficult to identify associations between disease factors (including CCHS PHOX2B genotypes) and cognitive outcomes. However, results suggest that early childhood is a period of particular vulnerability, perhaps due to the disruptive impact of recurrent intermittent hypoxic episodes on brain and cognitive development. Conclusion: Neurocognitive monitoring is recommended as a component of routine clinical care in CCHS and ROHHAD as a marker of disease status and to ensure that educational support and disability accommodations are provided as early as possible. Collaborative efforts will be essential to obtain samples needed to enhance our understanding of neurocognitive outcomes in CCHS and ROHHAD. [ABSTRACT FROM AUTHOR]

Clinical studies have found that ketamine has a rapid and lasting antidepressant effect, especially in the case of patients with major depressive disorder (MDD). The molecular mechanisms, however, remain unclear. In this study, we observe the effects of S-Ketamine on the expression of Rac1, neuronal morphology, and synaptic transmission function in the hippocampus of stressed rats. Chronic unpredictable mild stress (CUMS) was used to construct stressed rats. The rats were given a different regimen of ketamine (20 mg/kg, i.p.) and Rac1 inhibitor NSC23766 (50 µg, ICV) treatment. The depression-like behavior of rats was evaluated by sucrose preference test and open-field test. The protein expression of Rac1, GluA1, synapsin1, and PSD95 in the hippocampus was detected by Western blot. Pull-down analysis was used to examine the activity of Rac1. Golgi staining and electrophysiological study were used to observe the neuronal morphology and long-term potentiation (LTP). Our results showed that ketamine can up-regulate the expression and activity of Rac1; increase the spine density and the expression of synaptic-related proteins such as GluA1, Synapsin1, and PSD95 in the hippocampus of stressed rats; reduce the CUMS-induced LTP impairments; and consequently improve depression-like behavior. However, Rac1 inhibitor NSC23766 could have effectively reversed ketamine-mediated changes in the hippocampus of rats and counteracted its antidepressant effects. The specific mechanism of S-Ketamine's antidepressant effect may be related to the up-regulation of the expression and activity of Rac1 in the hippocampus of stressed rats, thus enhancing synaptic plasticity. [ABSTRACT FROM AUTHOR]

Macrosomia in neonates of diabetic women is a risk factor for neonatal hypoglycemia, with an over-risk for asymmetric macrosomia. This study aimed to study the association between anthropometric measurements and hypoglycemia in neonates of mothers treated for gestational diabetes. This is a secondary analysis of the INDAO trial study conducted between May 2012 and November 2016 in 13 French tertiary care university hospitals in 890 pregnant women with gestational diabetes treated with either insulin or glyburide. Neonatal anthropometric measurements were birthweight and weight-length ratio (WLR, defined as birth weight/length). Neonatal hypoglycemia was defined as capillary blood glucose below 36 mg/dL (2 mmol/L) or below 45 mg/dL (2.5 mmol/L) associated with clinical signs after 2 h of life. Their relationships were modeled with logistic regressions using fractional polynomials. Extreme categories of birthweight or WLR adjusted for gestational age at birth and sex were defined as Z-score < −1.28 or > 1.28. These categories were compared to Z-score between −1.28 and 1.28 by estimating odds ratios and confidence intervals for neonatal hypoglycemia. Neonatal hypoglycemia occurred in 9.1% of cases. The relationship between birthweight and WLR Z-scores and neonatal risk of hypoglycemia adjusted for maternal treatment was a U-shaped curve. Adjusted odds ratios for the risk of hypoglycemia were 9.6 (95% CI 3.5, 26.8) and 2.3 (95% CI 1.1, 4.9) for WLR Z-score below −1.28 and above 1.28, respectively, compared with WLR Z-score between −1.28 and 1.28. Conclusion: Birthweight Z-score was associated with the risk of neonatal hypoglycemia in neonates from mothers treated for gestational diabetes. The risk of neonatal hypoglycemia was increased for both extreme birthweight Z-scores, regardless of maternal treatment. Small for gestational age neonates of diabetic mothers require special attention for the risk of neonatal hypoglycemia. What is Known: • Macrosomia in neonates of diabetic women is a risk factor for neonatal hypoglycemia, with an over-risk for asymmetric macrosomia. Few retrospective studies have assessed the risk for neonatal hypoglycemia among small for gestational age neonates born to diabetic mothers. What is New: • The risk of neonatal hypoglycemia among neonates of diabetic mothers increased for both low and high weight-length ratio, regardless of maternal medicinal treatment, gestational age at birth, and sex of the newborn. [ABSTRACT FROM AUTHOR]

Studies show robust links between disorganized attachment in infancy and socioemotional maladjustment in childhood. Little is known, however, about the links between disorganized attachment and brain development, and whether attachment-related differences in brain morphology translate into meaningful variations in child socioemotional functioning. This study examined the links between infants' disorganized attachment behaviors toward their mothers, whole-brain regional grey matter volume and thickness, and peer rejection in late childhood. Thirty-three children and their mothers took part in this study. The Strange Situation Procedure was used to assess mother–infant attachment when infants were 18 months old. Magnetic resonance imaging was performed when they were 10 years old to assess cortical thickness and grey matter volumes. Children and teachers reported on peer rejection 1 year later, as an indicator of socioemotional maladjustment. Results indicated that disorganized attachment was not associated with grey matter volumes. However, children who exhibited more disorganized attachment behaviors in infancy had significantly thicker cortices in bilateral middle and superior frontal gyri, and extending to the inferior frontal gyrus, as well as the orbitofrontal and insular cortices in the right hemisphere in late childhood. Moreover, children with thicker cortices in these regions experienced greater peer rejection, as rated by themselves and their teachers. Although preliminary, these results are the first to indicate that disorganized attachment may play a role in cortical thickness development and that changes in cortical thickness are associated with differences in child socioemotional functioning. [ABSTRACT FROM AUTHOR]

Purpose: There is altered breastmilk composition among mothers with gestational diabetes and conflicting evidence on whether breastfeeding is beneficial or detrimental to their offspring's cardiometabolic health. We aimed to investigate associations between breastfeeding and offspring's cardiometabolic health across the range of gestational glycemia. Methods: We included 827 naturally conceived, term singletons from a prospective mother–child cohort. We measured gestational (26–28 weeks) fasting plasma glucose (FPG) and 2-h plasma glucose (2 hPG) after an oral glucose tolerance test as continuous variables. Participants were classified into 2 breastfeeding categories (high/intermediate vs. low) according to their breastfeeding duration and exclusivity. Main outcome measures included magnetic resonance imaging (MRI)-measured abdominal fat, intramyocellular lipids (IMCL), and liver fat, quantitative magnetic resonance (QMR)-measured body fat mass, blood pressure, blood lipids, and insulin resistance at 6 years old (all continuous variables). We evaluated if gestational glycemia (FPG and 2 hPG) modified the association of breastfeeding with offspring outcomes after adjusting for confounders using a multiple linear regression model that included a 'gestational glycemia × breastfeeding' interaction term. Results: With increasing gestational FPG, high/intermediate (vs. low) breastfeeding was associated with lower levels of IMCL (p-interaction = 0.047), liver fat (p-interaction = 0.033), and triglycerides (p-interaction = 0.007), after adjusting for confounders. Specifically, at 2 standard deviations above the mean gestational FPG level, high/intermediate (vs. low) breastfeeding was linked to lower adjusted mean IMCL [0.39% of water signal (0.29, 0.50) vs. 0.54% of water signal (0.46, 0.62)], liver fat [0.39% by weight (0.20, 0.58) vs. 0.72% by weight (0.59, 0.85)], and triglycerides [0.62 mmol/L (0.51, 0.72) vs. 0.86 mmol/L (0.75, 0.97)]. 2 hPG did not significantly modify the association between breastfeeding and childhood cardiometabolic risk. Conclusion: Our findings suggest breastfeeding may confer protection against adverse fat partitioning and higher triglyceride concentration among children exposed to increased glycemia in utero. [ABSTRACT FROM AUTHOR]

It is well established that exercise can improve depressive symptoms in the general population; however, it is not clear if these benefits are also seen in pregnancy. This review aimed to synthesize the evidence that examines whether exercise during pregnancy impacts depressive and associated symptoms (e.g. anxiety) during the perinatal period. The review was conducted in accordance with PRISMA guidelines and reporting criteria; literature was searched using PubMed, Scopus and Web of Science database engines. Clinical trials published in English evaluating the effects of a defined exercise protocol during pregnancy on depressive and/or anxiety symptoms during the perinatal period were included. Studies without a control group were excluded. Risk of bias was conducted by Cochrane assessment to appraise the quality of the included studies. Twenty-seven articles, between 1994 and 2019, were included. Of these, only 5 specifically recruited women with depression (n = 334), which all assessed a yoga-based intervention; 4 of these studies showed a statistically significant improvement in depressive and/or anxiety symptoms in the intervention group compared to baseline; however, 2 of these studies also showed an improvement in the control group. The remaining 22 studies used various exercise interventions in pregnant women (n = 4808) with 20 studies reporting that exercise during pregnancy has the ability to improve depressive and/or anxiety measures in the perinatal period compared to either baseline or control. The evidence suggests that exercise of various types in pregnancy can reduce depressive and/or anxiety symptoms in the perinatal period in otherwise healthy women. Specifically in women with antenatal depression, the incorporation of yoga in pregnancy can improve depressive/anxiety symptoms in the perinatal period; however, this is based on a small number of studies, and it is not clear whether this is superior to non-exercise controls. Further studies are needed to determine the potential therapeutic effects of exercise of various types during pregnancy on symptoms of antenatal depression. [ABSTRACT FROM AUTHOR]

Background: There is increasing appreciation of the association of obesity beyond co-morbidities, such as cancers, Type 2 diabetes, hypertension, and stroke to also impact upon the muscle to give rise to sarcopenic obesity. Phenotypic knowledge of obesity is crucial for profiling and management of obesity, as different fat—subcutaneous adipose tissue depots (SAT) and visceral adipose tissue depots (VAT) have various degrees of influence on metabolic syndrome and morbidities. Manual segmentation is time consuming and laborious. Study focuses on the development of a deep learning-based, complete data processing pipeline for MRI-based fat analysis, for large cohort studies which include (1) data augmentation and preprocessing (2) model zoo (3) visualization dashboard, and (4) correction tool, for automated quantification of fat compartments SAT and VAT. Methods: Our sample comprised 190 healthy community-dwelling older adults from the Geri-LABS study with mean age of 67.85 ± 7.90 years, BMI 23.75 ± 3.65 kg/m2, 132 (69.5%) female, and mainly Chinese ethnicity. 3D-modified Dixon T1-weighted gradient-echo MR images were acquired. Residual global aggregation-based 3D U-Net (RGA-U-Net) and standard 3D U-Net were trained to segment SAT, VAT, superficial and deep subcutaneous adipose tissue depots (SSAT and DSAT). Manual segmentation from 26 subjects was used as ground truth during training. Data augmentations, random bias, noise and ghosting were carried out to increase the number of training datasets to 130. Segmentation accuracy was evaluated using Dice and Hausdorff metrics. Results: The accuracy of segmentation was SSAT:0.92, DSAT:0.88 and VAT:0.9. Average Hausdorff distance was less than 5 mm. Automated segmentation significantly correlated R2 > 0.99 (p < 0.001) with ground truth for all 3-fat compartments. Predicted volumes were within ± 1.96SD from Bland–Altman analysis. Conclusions: DL-based, comprehensive SSAT, DSAT, and VAT analysis tool showed high accuracy and reproducibility and provided a comprehensive fat compartment composition analysis and visualization in less than 10 s. [ABSTRACT FROM AUTHOR]

A family history of mood and anxiety disorders is one of the most well-established risk factors for these disorders in offspring. A family history of these disorders has also been linked to alterations in brain regions involved in cognitive-affective processes broadly, and mood and anxiety disorders specifically. Results from studies of brain structure of children of parents with a history of mood or anxiety disorders (high-risk offspring) have been inconsistent. We followed the PRISMA protocol to conduct a scoping review of the literature linking parental mood and anxiety disorders to offspring brain structure to examine which structures in offspring brains are linked to parental major depressive disorder (MDD), anxiety, or bipolar disorder (BD). Studies included were published in peer-reviewed journals between January 2000 and July 2021. Thirty-nine studies were included. Significant associations between parental BD and offspring caudate volume, inferior frontal gyrus thickness, and anterior cingulate cortex thickness were found. Associations were also identified between parental MDD and offspring amygdala and hippocampal volumes, fusiform thickness, and thickness in temporoparietal regions. Few studies have examined associations between parental anxiety and high-risk offspring brain structure; however, one study found associations between parental anxiety symptoms and offspring amygdala structure, and another found similar associations with the hippocampus. The direction of grey matter change across studies was inconsistent, potentially due to the large age ranges for each study and the non-linear development of the brain. Children of parents with MDD and bipolar disorders, or elevated anxiety symptoms, show alterations in a range of brain regions. Results may further efforts to identify children at high risk for affective disorders and may elucidate whether alterations in specific brain regions represent premorbid markers of risk for mood and anxiety disorders. [ABSTRACT FROM AUTHOR]

Given that human infants are almost fully reliant on caregivers for survival, the presence of parents who provide sensitive, responsive care support infants and young children in developing the foundation for optimal biological functioning. Conversely, when parents are unavailable or insensitive, there are consequences for infants' and children's attachment and neurobiological development. In this paper, we describe effects of inadequate parenting on children's neurobiological and behavioral development, with a focus on developing capacities for executive functioning, emotion regulation, and other important cognitive-affective processes. Most prior research has examined correlational associations among these constructs. Given that interventions tested through randomized clinical trials allow for causal inferences, we review longitudinal intervention effects on children's biobehavioral and cognitive-affective outcomes. In particular, we provide an overview of the Bucharest Early Intervention Project, a study in which children were randomized to continue in orphanage care (typically the most extreme condition of privation) or were placed into the homes of trained, supported foster parents. We also discuss findings regarding Attachment and Biobehavioral Catch-up, an intervention enhancing sensitivity among high-risk parents. We conclude by suggesting future directions for research in this area. [ABSTRACT FROM AUTHOR]

FK506-binding protein 51 (encoded by Fkpb51, also known as Fkbp5) has been associated with stress-related mental illness. To investigate its function, we studied the morphological consequences of Fkbp51 deletion. Artificial Intelligence-assisted morphological analysis revealed that male Fkbp51 knock-out (KO) mice possess more elongated dentate gyrus (DG) but shorter hippocampal height in coronal sections when compared to WT. Primary cultured Fkbp51 KO hippocampal neurons were shown to exhibit larger dendritic outgrowth than wild-type (WT) controls and pharmacological manipulation experiments suggest that this may occur through the regulation of microtubule-associated protein. Both in vitro primary culture and in vivo labeling support a role for FKBP51 in the regulation of microtubule-associated protein expression. Furthermore, Fkbp51 KO hippocampi exhibited decreases in βIII-tubulin, MAP2, and Tau protein levels, but a greater than 2.5-fold increase in Parkin protein. Overexpression and knock-down FKBP51 demonstrated that FKBP51 negatively regulates Parkin in a dose-dependent and ubiquitin-mediated manner. These results indicate a potential novel post-translational regulatory mechanism of Parkin by FKBP51 and the significance of their interaction on disease onset. KO has more flattened hippocampus using AI-assisted measurement Both pyramidal cell layer (PCL) of CA and granular cell layer (GCL) of DG distinguishable as two layers: deep cell layer and superficial layer. Distinct MAP2 expression between deep and superficial layer between KO and WT, Higher Parkin expression in KO brain Mechanism of FKBP51 inhibition resulting in Parkin, MAP2, Tau, and Tubulin expression differences between KO and WT mice, and resulting neurite outgrowth differences. [ABSTRACT FROM AUTHOR]

Purpose: Few studies have described adherence to dietary patterns over time in women of childbearing age. This study aims to describe, examine the stability and changes in dietary patterns between pregnancy and 6 years post-pregnancy and the sociodemographic and lifestyle factors influencing the adherence over time. Methods: During pregnancy and at 6 years post-pregnancy, 24-h recalls and food frequency questionnaires were collected, respectively, from 709 women. Data on sociodemographic and lifestyle factors were collected via questionnaires. Dietary patterns were identified using principal component analysis and stability assessed using Pearson's correlation coefficients (r) and Cohen's weighted kappa (κ). Associations with sociodemographic characteristics were assessed by multiple logistic regression. Results: The 'Fruits, Vegetables and Legumes' (FVL) and 'Seafood, Noodle, Soup' (SNS) patterns were identified at both time points, with low correlation for the dietary pattern z scores (r 0.2 and 0.3, respectively) and modest agreement in tertile assignment, suggesting poor stability. An 'unhealthy' pattern was only observed at 6 years post-pregnancy. Women who showed increased adherence to FVL pattern had higher educational attainment and exhibited healthy lifestyle behaviours. Women who had gestational diabetes during pregnancy were less likely to decrease adherence to FVL pattern over time. Women who adhered more closely to the 'unhealthy' pattern at 6 years post-pregnancy tended to be younger, of Malay ethnicity, had lower socioeconomic status, were less physically active and had additional pregnancies. Conclusions: Dietary habits of women became less healthy during the transition from pregnancy to 6 years post-pregnancy. However, results should be interpreted with caution due to the different dietary assessment tools used at the two time points. [ABSTRACT FROM AUTHOR]

Asymmetry characterizes the brain in both structure and function. Anatomical asymmetries explain only a fraction of functional variability in lateralization, with structural and functional asymmetries developing at different periods of life and in different ways. In this work, we perform a scoping review of the cerebral asymmetries in the first brain development phases. We included all English-written studies providing direct evidence of hemispheric asymmetries in full-term neonates, foetuses, and premature infants, both at term post-conception and before. The final analysis included 57 studies. The reviewed literature shows large variability in the used techniques and methodological procedures. Most structural studies investigated the temporal lobe, showing a temporal planum more pronounced on the left than on the right (although not all data agree), a morphological asymmetry already present from the 29th week of gestation. Other brain structures have been poorly investigated, and the results are even more discordant. Unlike data on structural asymmetries, functional data agree with each other, identifying a leftward dominance for speech stimuli and an overall dominance of the right hemisphere in all other functional conditions. This generalized dominance of the right hemisphere for all conditions (except linguistic stimuli) is in line with theories stating that the right hemisphere develops earlier and that its development is less subject to external influences because it sustains functions necessary to survive. [ABSTRACT FROM AUTHOR]

Adult abilities in complex cognitive domains such as music appear to depend critically on the age at which training or experience begins, and relevant experience has greater long-term effects during periods of peak maturational change. Previous work has shown that early trained musicians (ET; < age 7) out-perform later-trained musicians (LT; > age 7) on tests of musical skill, and also have larger volumes of the ventral premotor cortex (vPMC) and smaller volumes of the cerebellum. These cortico-cerebellar networks mature and function in relation to one another, suggesting that early training may promote coordinated developmental plasticity. To test this hypothesis, we examined structural covariation between cerebellar volume and cortical thickness (CT) in sensorimotor regions in ET and LT musicians and non-musicians (NMs). Results show that ETs have smaller volumes in cerebellar lobules connected to sensorimotor cortices, while both musician groups had greater cortical thickness in right pre-supplementary motor area (SMA) and right PMC compared to NMs. Importantly, early musical training had a specific effect on structural covariance between the cerebellum and cortex: NMs showed negative correlations between left lobule VI and right pre-SMA and PMC, but this relationship was reduced in ET musicians. ETs instead showed a significant negative correlation between vermal IV and right pre-SMA and dPMC. Together, these results suggest that early musical training has differential impacts on the maturation of cortico-cerebellar networks important for optimizing sensorimotor performance. This conclusion is consistent with the hypothesis that connected brain regions interact during development to reciprocally influence brain and behavioral maturation. [ABSTRACT FROM AUTHOR]

Perinatal maternal symptoms of depression and anxiety compromise psychosocial function and influence developmental outcomes in the offspring. The onset of symptoms remains unclear with findings that suggest a preconceptual origin. We addressed this issue with a prospective analysis of anxiety and depressive symptom profiles from preconception through to parturition. Women were recruited into a preconception study to assess (a) variation in symptom levels of depression and anxiety from pre- to post-conception and (b) if the symptom network profiles of depression and anxiety change from pre-conception to post-conception. A within-subject intraclass correlation analyses revealed that symptoms of depression or anxiety in the preconception phase strongly predicted those across pregnancy and into the early postnatal period. The symptom network analysis revealed that the symptom profiles remained largely unchanged from preconception into the second trimester. Our findings suggest that for a significant portion of women, maternal mental health remains stable from preconception into pregnancy. This finding highlights the need for early intervention studies on women's mental health to be targeted during the preconception period and to be extended across the population. [ABSTRACT FROM AUTHOR]

Greedy individuals often exhibit more impulsive decision-making and short-sighted behaviors. It has been assumed that altered reward circuitry and prospection network is associated with greed personality trait (GPT). In this study, we first explored the morphological characteristics (i.e., gray matter volume; GMV) of GPT combined with univariate and multivariate pattern analysis (MVPA) approaches. Second, we adopted a revised version of inter-temporal choice task and independently manipulated the amount and delay time of future rewards. Using brain-imaging design, reward- and prospection-related brain activations were assessed and their associations with GPT were further examined. The MVPA results showed that GPT was associated with the GMVs in the right lateral frontal pole cortex, left ventromedial prefrontal cortex, right lateral occipital cortex, and right occipital pole. Additionally, we observed that the amount-relevant brain activations (responding to reward circuitry) in the lateral orbitofrontal cortex were negatively associated with individual's variability in GPT scores, whereas the delay time-relevant brain activations (responding to prospection network system) in the dorsolateral prefrontal cortex, dorsomedial prefrontal cortex, superior parietal lobule, and anterior cingulate cortex were positively associated with individual's variability in GPT scores. These findings not only provide novel insights into the neuroanatomical substrates underlying the human dispositional greed, but also suggest the critical roles of reward and prospection processing on the greed. [ABSTRACT FROM AUTHOR]

Aims: To determine predictors of neonatal adiposity and differences in associations by fetal sex in women with gestational diabetes mellitus (GDM), normal-weight and overweight (BMI ≥ 25 kg/m2) normal glucose-tolerant women (NGT). Methods: Skinfold thickness was measured in 576 newborns, and cord blood leptin, c-peptide and lipids in 327 newborns in a multi-centric prospective cohort study. Results: Compared to neonates of normal-weight NGT women (327), neonates of women with GDM (97) were more often large-for-gestational age (LGA) (16.5% vs 8.6%, p = 0.024) ,but the macrosomia rate (8.2% vs 5.8%, p = 0.388), sum of skinfolds (13.9 mm ± 2.9 vs 13.3 mm ± 2.6, p = 0.067), neonatal fat mass (1333.0 g ± 166.8 vs 1307.3 g ± 160.9, p = 0.356), and cord blood biomarkers were not significantly different. Compared to neonates of normal-weight NGT women, neonates of overweight NGT women (152) had higher rates of macrosomia (12.5% vs 5.8%, p = 0.012), LGA (17.1% vs 8.6%, p = 0.006), higher sum of skinfolds (14.3 mm ± 2.6 vs 13.2 mm ± 2.6, p < 0.001), neonatal fat mass (1386.0 g ± 168.6 vs 1307.3 g ± 160.9, p < 0.001), % neonatal fat mass > 90th percentile (15.2% vs 7.1%, p < 0.001), without significant differences in cord blood biomarkers. Maternal BMI, fasting glycemia, triglycerides, gestational weight gain, cord blood leptin ,and cord blood triglycerides were independent predictors for neonatal adiposity. Gestational weight gain was positively associated with adiposity in boys only. Conclusion: Compared to neonates of normal-weight NGT women, neonates of GDM women have higher LGA rates but similar adiposity, while neonates of overweight NGT women have increased adiposity. Limiting gestational weight gain might be especially important in the male fetus to reduce neonatal adiposity. [ABSTRACT FROM AUTHOR]

Purpose: Current literature on the roles of α-, β-carotene and β-cryptoxanthin in neurocognitive function has largely focused on preventing cognitive decline in older people, and less on neuro-development in children. We examined the relations of maternal plasma carotenoids concentrations with offspring cognitive development up to age 4.5 years in the Growing Up in Singapore Towards healthy Outcomes mother–offspring cohort study. Methods: Maternal plasma α-, β-carotene and β-cryptoxanthin concentrations at delivery were determined by ultra-performance liquid chromatography. Children's cognition was assessed at ages 2 (Bayley Scales of Infant and Toddler Development) and 4.5 (Kaufman Brief Intelligence Test) years. Associations were examined in 419 mother–offspring pairs using linear regressions adjusting for key confounders. Results: Median and interquartile range of maternal plasma concentrations (mg/L) were: α-carotene 0.052 (0.032, 0.081), β-carotene 0.189 (0.134, 0.286), and β-cryptoxanthin 0.199 (0.123, 0.304). In 2 years old children, higher maternal carotenoids [per standard deviation (SD) log-concentration] were positively associated with neurocognitive functions: β-cryptoxanthin with higher scores in cognitive [β = 0.18, (0.08, 0.28) SD], receptive language [β = 0.17 (0.07, 0.27) SD], fine motor [β = 0.16 (0.05, 0.26) SD], and gross motor [β = 0.16 (0.06, 0.27) SD] scales; β-carotene with higher cognitive score [β = 0.17 (0.05, 0.29) SD]. No significant associations were observed with neurocognitive functions at age 4.5 years. Conclusion: Our study provides novel data suggesting a potential role of prenatal carotenoids, particularly β-cryptoxanthin, on early offspring cognitive and motor development. Whether the prenatal influences sustain beyond early childhood requires further investigation in longer term studies. [ABSTRACT FROM AUTHOR]

Obesity is defined as an abnormal/excessive accumulation of body fat, associated with health consequences. Although overall obesity does confer a significant threat to the health of individuals, the distribution of body fat, especially abdominal/central obesity is of greater importance. For practical reasons, proxy anthropometric measurements have been developed to identify central obesity, however, major limitations are noted in these traditional measurements. The present study aims to evaluate the literature, to identify and describe non-traditional anthropometric measurements of overweight and obesity in children. The current systematic review was conducted in accordance with the PRISMA guidelines, and the search was undertaken in the PubMed® database, using MeSH (Medical Subject Headings) terms. Data extracted from each study were: (a) details of the study, (b) anthropometric parameter(s) evaluated in the study and its details, (c) study methods, (d) objectives of the study and/or comparisons, and (e) main findings/conclusions of the study. The search yielded a total of 3697 articles, of which 31 studies were deemed eligible to be included. The literature search identified 13 non-traditional anthropometric parameters. Data on non-traditional anthropometric parameters were derived from 24 countries. Majority were descriptive cross-sectional studies (n = 29), while sample size varied from 65 to 23,043. Non-traditional anthropometric parameters showed variable correlation with obesity and/or related metabolic risk factors. Some parameters involved complex calculations, while others were based on a single anthropometric measurement or derived from traditional measures. Most studies lacked comparison with a 'gold standard' assessment of body fat, hence further research is required to determine their accuracy and precision. [ABSTRACT FROM AUTHOR]

Basic psychological needs lie at the heart of the self-determination theory (SDT) explanatory framework. SDT researchers have recently undertaken neuroscientific programs of research to investigate the neural bases of psychological need satisfaction, and many have done so by using functional neuroimaging data collection methods. According to these studies, the activities of the striatum, orbitofrontal cortex (OFC), insula, and anterior cingulate cortex (ACC) represent central neural mechanisms of psychological need satisfaction. These findings led us to now investigate the possibility that people might possess individual differences in the capacity to experience need satisfaction and that these individual differences would be based on differences in their structural brain volumes in these brain areas. Region of interest and whole-brain voxel-based morphometry analyses of 50 participants' anatomic MRI scans to predict their self-reported need satisfaction over the last year found that only ventral striatum gray matter volume, but not the gray matter volumes of the dorsal striatum, OFC, insula, and ACC, positively correlated with extent of psychological need satisfaction. These neuroanatomic findings offer unique insights to understand the neuroanatomic bases of psychological need satisfaction. [ABSTRACT FROM AUTHOR]

Childhood obesity has reached pandemic proportions, and youth-onset type 2 diabetes is following suit. This review summarises the literature on the influence of developmental overnutrition, resulting from maternal diabetes, obesity, maternal dietary intake during pregnancy, excess gestational weight gain, and infant feeding practices, on the aetiology of obesity and type 2 diabetes risk during childhood and adolescence. Key goals of this review are: (1) to summarise evidence to date on consequences of developmental overnutrition; (2) describe shared and distinct biological pathways that may link developmental overnutrition to childhood obesity and youth-onset type 2 diabetes; and (3) to translate current knowledge into clinical and public health strategies that not only target primary prevention in youth, but also encourage primordial prevention during the perinatal period, with the aim of breaking the intergenerational cycle of obesity and diabetes. [ABSTRACT FROM AUTHOR]

Despite many studies reporting a variety of alterations in brain networks in patients with attention deficit hyperactivity disorder (ADHD), alterations in hemispheric anatomical networks are still unclear. In this study, we investigated topology alterations in hemispheric white matter in patients with ADHD and the relationship between these alterations and clinical features of the illness. Weighted hemispheric brain anatomical networks were first constructed for each of 40 right-handed patients with ADHD and 53 matched normal controls. Then, graph theoretical approaches were utilized to compute hemispheric topological properties. The small-world property was preserved in the hemispheric network. Furthermore, a significant group-by-hemisphere interaction was revealed in global efficiency, local efficiency and characteristic path length, attributed to the significantly reduced hemispheric asymmetry of global and local integration in patients with ADHD compared with normal controls. Specifically, reduced asymmetric regional efficiency was found in three regions. Finally, we found that the abnormal asymmetry of hemispheric brain anatomical network topology and regional efficiency were both associated with clinical features (the Adult ADHD Self-Report Scale and Wechsler Adult Intelligence Scale) in patients. Our findings provide new insights into the lateralized nature of hemispheric dysconnectivity and highlight the potential for using brain network measures of hemispheric asymmetry as neural biomarkers for ADHD and its clinical features. [ABSTRACT FROM AUTHOR]

Maternal care influences child hippocampal development. The hippocampus is functionally organized along an anterior–posterior axis. Little is known with regards to the extent maternal care shapes offspring anterior and posterior hippocampal (aHPC, pHPC) functional networks. This study examined maternal behavior, especially maternal sensitivity, at 6 months postpartum in relation to aHPC and pHPC functional networks of children at age 4 and 6 years. Maternal sensitivity was assessed at 6 months via the "Maternal Behavior Q Sort (MBQS) mini for video". Subsequently, 61 and 76 children underwent resting-state functional magnetic resonance imaging (rs-fMRI), respectively, at 4 and 6 years of age. We found that maternal sensitivity assessed at 6 months postpartum was associated with the right aHPC functional networks in children at both 4 and 6 years of age. At age 4 years, maternal sensitivity was associated positively with the right aHPC's functional connectivity with the sensorimotor network and negatively with the aHPC's functional connectivity with the top–down cognitive control network. At 6 years of age, maternal sensitivity was linked positively with the right aHPC's functional connectivity with the visual-processing network. Our findings suggested that maternal sensitivity in infancy has a long-term impact on the anterior hippocampal functional network in preschool children, implicating a potential role of maternal care in shaping child brain development in early life. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: We aimed to determine the association of maternal metabolites with newborn adiposity and hyperinsulinaemia in a multi-ethnic cohort of mother-newborn dyads.Methods: Targeted and non-targeted metabolomics assays were performed on fasting and 1 h serum samples from a total of 1600 mothers in four ancestry groups (Northern European, Afro-Caribbean, Mexican American and Thai) who participated in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) study, underwent an OGTT at ~28 weeks gestation and whose newborns had anthropometric measurements at birth.Results: In this observational study, meta-analyses demonstrated significant associations of maternal fasting and 1 h metabolites with birthweight, cord C-peptide and/or sum of skinfolds across ancestry groups. In particular, maternal fasting triacylglycerols were associated with newborn sum of skinfolds. At 1 h, several amino acids, fatty acids and lipid metabolites were associated with one or more newborn outcomes. Network analyses revealed clusters of fasting acylcarnitines, amino acids, lipids and fatty acid metabolites associated with cord C-peptide and sum of skinfolds, with the addition of branched-chain and aromatic amino acids at 1 h.Conclusions/interpretation: The maternal metabolome during pregnancy is associated with newborn outcomes. Maternal levels of amino acids, acylcarnitines, lipids and fatty acids and their metabolites during pregnancy relate to fetal growth, adiposity and cord C-peptide, independent of maternal BMI and blood glucose levels. [ABSTRACT FROM AUTHOR]

Opinion Statement: Pathologies of pediatric brain tumors are more varied than those diagnosed in adults and survival outcomes more optimistic. Therapies for pediatric brain tumors are also diverse and treatment options are expanding. The growing number of adult survivors of childhood brain tumors is quite diverse. Medical management of these adults requires understanding the tumor diagnosis and location, the modalities used to treat the tumor, the age of the survivor at the time of diagnosis and treatment, any complications of treatment, and, most importantly, the baseline medical condition and neurological function of each adult survivor. A network of medical, neurological, and mental health providers is critical in the care of a child with a brain tumor. A comparable network should be available to survivors of these tumors since they may transition to adulthood with medical and neurological deficits and can acquire additional late effects of treatments as they age. Optimally, each survivor will have an individualized survivor health plan (SHP) that concisely summarizes the tumor, treatments, potential late effects, and screening that may identify evolving late effects before they impact mental, social or physical functioning. This plan helps patients, families, and the medical team advocate for surveillance aiming to optimize the survivor's quality of life. Failure to support the health and function of these heroic cancer survivors renders the medical advances, the courage, and the struggle that permitted survival meaningless. [ABSTRACT FROM AUTHOR]

Two separate lines of inquiry indicate (a) that prenatal stress is associated with heightened behavioral and physiological reactivity, and (b) that these postnatal phenotypes are associated with increased susceptibility to both positive and negative developmental experiences and environmental exposures. This research considered together raises the intriguing hypothesis first advanced by Pluess and Belsky (Dev Psychopathol 23:29-38, 2011) that prenatal-stress fosters, promotes or “programs” postnatal developmental plasticity. In this paper, we review further evidence consistent with this proposition, including a novel animal study which experimentally manipulated both prenatal stress and postnatal rearing. Directions for future work focused on mechanisms mediating the plasticity-inducing effects of prenatal stress and the moderators of such effects are outlined. [ABSTRACT FROM AUTHOR]

This paper is based on a literature review from 2011 to 2016. The paper is divided into two main sections. The first section relates to technical advances in fetal imaging techniques, including fetal motion compensation, imaging at 3.0 T, 3-D T2-weighted MRI, susceptibility-weighted imaging, computed tomography, morphometric analysis, diffusion tensor imaging, spectroscopy and fetal behavioral assessment. The second section relates to clinical updates, including cerebral lamination, migrational anomalies, midline anomalies, neural tube defects, posterior fossa anomalies, sulcation/gyration and hypoxic-ischemic insults. [ABSTRACT FROM AUTHOR]

In today's global economy and affordable vacation travel, it is increasingly important that visitors to another country and their physician be familiar with emerging infections, infections unique to a specific geographic region, and risks related to the process of travel. This is never more important than for patients with primary immunodeficiency disorders (PIDD). A recent review addressing common causes of fever in travelers provides important information for the general population Thwaites and Day (N Engl J Med 376:548-560, 2017). This review covers critical infectious and management concerns specifically related to travel for patients with PIDD. This review will discuss the context of the changing landscape of infections, highlight specific infections of concern, and profile distinct infection phenotypes in patients who are immune compromised. The organization of this review will address the environment driving emerging infections and several concerns unique to patients with PIDD. The first section addresses general considerations, the second section profiles specific infections organized according to mechanism of transmission, and the third section focuses on unique phenotypes and unique susceptibilities in patients with PIDDs. This review does not address most parasitic diseases. Reference tables provide easily accessible information on a broader range of infections than is described in the text. [ABSTRACT FROM AUTHOR]

This case-series analyzed the outcome of live donor liver transplantation (LT) performed in children <7.5kg from January 2008 to June 2009 at our center. Five patients (3 males, 2 females, mean age, 8.2 ± .4 months; mean weight 6.8 ± 0.4 kg) underwent LT. The indications of LT included biliary atresia (3) and idiopathic neonatal hepatitis (2). Postoperative complications included acute rejection (1), portal venous thrombosis (1), bile leak (1), severe hypertension (1) and bacterial sepsis (4). There were no donor related complications. The median follow-up duration is 11 months with patient and graft survival rates of 100% each, respectively. [ABSTRACT FROM AUTHOR]

A 48-year-old-man in the first chronic phase of chronic myeloid leukaemia developed a central nervous system complication on day + 57 after HLA-identical peripheral blood progenitor cell (PBPC) transplantation. The clinical picture evolved to a reversible pseudobulbar palsy requiring mechanical ventilation. MRI examination disclosed lesions typical of central and extrapontine myelinolysis (CEPM), which disappeared on a repeat examination 20 days later. The patient had received cyclosporiue A (CsA) as GVHD prophylaxis and severe hyponatremia was detected 7 days after the first neurological sign. CEPM has been described in alcohol-induced liver disease, following rapidly corrected hyponatremia and associated with CsA in orthotopic liver transplantation. This is the first reported case of CEPM in PBPC transplantation, and CsA seems to have played a role in the development of this very serious complication. [ABSTRACT FROM AUTHOR]

Cyclosporin is a lipophilic cyclic polypeptide immunosuppressant that interferes with the activity of T cells chiefly via calcineurin inhibition. The original oil-based oral formulation of this drug (Sandimmun)l was characterised by high intra- and interpatient pharmacokinetic variability, with poor bioavailability in many patients; a novel microemulsion formulation (Neoral)1 was therefore developed to circumvent these problems. Studies show increases, attributable chiefly to improved absorption in patients who absorb the drug only poorly from the original formulation, in mean systemic exposure to cyclosporin with the microemulsion, with no clinically significant differences in tolerability or drug interaction profiles. Cyclosporin microemulsion is at least as effective as the oil-based formulation in renal, liver and heart transplant recipients, with trends towards decreased incidence of acute rejection with the microemulsion formulation in some (statistically significant in a few) trials. Cyclosporin microemulsion and tacrolimus appear to have similar efficacy in preventing acute rejection episodes in most renal, pancreas-kidney, liver and heart transplant recipients. However, there are indications of superior efficacy for tacrolimus in some trials, particularly in the prevention of severe acute rejection and in Black transplant recipients. Current 12-month data also indicate equivalent efficacy of sirolimus in renal transplantation. Conversion from the oil-based to microemulsion formulation in stable renal, liver and heart transplant recipients is achievable with no change in acute rejection rates. The addition of an anti-interleukin-2 receptor monoclonal antibody and/or mycophenolate mofetil to cyclosporin microemulsion plus corticosteroids decreases rates of acute rejection; corticosteroid withdrawal without increased acute rejection rates was also achieved on the addition of these agents in some trials. Pharmacoeconomic analyses have shown savings in direct healthcare costs in kidney or liver transplantation when cyclosporin microemulsion is used in preference to the oil-based formulation, although studies incorporating indirect costs or expressing costs in terms of therapeutic outcomes are currently unavailable. CONCLUSIONS: The introduction of cyclosporin microemulsion has consolidated the place of the drug as a mainstay of therapy in all types of solid organ transplantation; research into optimisation of outcomes through more effective therapeutic monitoring in patients receiving this formulation is ongoing. Several novel immunosuppressants have been introduced in recent years: further clinical and pharmacoeconomic research will be needed to clarify the relative positioning of these agents, particularly with respect to specific patient groups. Other new drugs (basiliximab/daclizumab and mycophenolate mofetil) offer particular advantages when used in combination with cyclosporin. [ABSTRACT FROM AUTHOR]

Cyclosporin is a lipophilic cyclic polypeptide immunosuppressant that interferes with the activity of T cells chiefly via calcineurin inhibition. The original oil-based oral formulation of this drug (Sandimmun) was characterised by high intra- and interpatient pharmacokinetic variability, with poor bioavailability in many patients; a novel microemulsion formulation (Neoral) was therefore developed to circumvent these problems. Studies show increases, attributable chiefly to improved absorption in patients who absorb the drug only poorly from the original formulation, in mean systemic exposure to cyclosporin with the microemulsion, with no clinically significant differences in tolerability or drug interaction profiles. Cyclosporin microemulsion is at least as effective as the oil-based formulation in renal, liver and heart transplant recipients, with trends towards decreased incidence of acute rejection with the microemulsion formulation in some (statistically significant in a few) trials. Cyclosporin microemulsion and tacrolimus appear to have similar efficacy in preventing acute rejection episodes in most renal, pancreas-kidney, liver and heart transplant recipients. However, there are indications of superior efficacy for tacrolimus in some trials, particularly in the prevention of severe acute rejection and in Black transplant recipients. Current 12-month data also indicate equivalent efficacy of sirolimus in renal transplantation. Conversion from the oil-based to microemulsion formulation in stable renal, liver and heart transplant recipients is achievable with no change in acute rejection rates. The addition of an anti-interleukin-2 receptor monoclonal antibody and/or mycophenolate mofetil to cyclosporin microemulsion plus corticosteroids decreases rates of acute rejection; corticosteroid withdrawal without increased acute rejection rates was also achieved on the addition of these agents in some trials. Pharmacoeconomic analyses have shown savings in direct healthcare costs in kidney or liver transplantation when cyclosporin microemulsion is used in preference to the oil-based formulation, although studies incorporating indirect costs or expressing costs in terms of therapeutic outcomes are currently unavailable. Conclusions: The introduction of cyclosporin microemulsion has consolidated the place of the drug as a mainstay of therapy in all types of solid organ transplantation; research into optimisation of outcomes through more effective therapeutic monitoring in patients receiving this formulation is ongoing. Several novel immunosuppressants have been introduced in recent years: further clinical and pharmacoeconomic research will be needed to clarify the relative positioning of these agents, particularly with respect to specific patient groups. Other new drugs (basiliximab/daclizumab and mycophenolate mofetil) offer particular advantages when used in combination with cyclosporin. [ABSTRACT FROM AUTHOR]

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Purpose Of Review: A growing body of epidemiological and experimental data indicate that nutritional or environmental stressors during early development can induce long-term adaptations that increase risk of obesity, diabetes, cardiovascular disease, and other chronic conditions-a phenomenon termed "developmental programming." A common phenotype in humans and animal models is altered body composition, with reduced muscle and bone mass, and increased fat mass. In this review, we summarize the recent literature linking prenatal factors to future body composition and explore contributing mechanisms.Recent Findings: Many prenatal exposures, including intrauterine growth restriction, extremes of birth weight, maternal obesity, and maternal diabetes, are associated with increased fat mass, reduced muscle mass, and decreased bone density, with effects reported throughout infancy and childhood, and persisting into middle age. Mechanisms and mediators include maternal diet, breastmilk composition, metabolites, appetite regulation, genetic and epigenetic influences, stem cell commitment and function, and mitochondrial metabolism. Differences in body composition are a common phenotype following disruptions to the prenatal environment, and may contribute to developmental programming of obesity and diabetes risk. [ABSTRACT FROM AUTHOR]

Purpose Of Review: Prenatal maternal psychological distress is an established risk factor for the development of psychopathology in offspring. The purpose of this review is to evaluate whether sex differences in fetal responses to maternal distress contribute to sex differences in subsequent psychopathology.Recent Findings: Male and female fetuses respond differently to stress signals. We review recent evidence that demonstrates a sex-specific pattern of association between prenatal maternal distress and pathways associated with risk for psychopathology including offspring hypothalamic pituitary adrenocortical (HPA) axis regulation, brain development, and negative emotionality. Prenatal maternal distress exerts sex-specific consequences on the fetus. These differences may contribute to the well-established sex differences in psychopathology and in particular to greater female vulnerability to develop internalizing problems. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor in response to the article "Central Pontine Myelinolysis Following Bone Marrow Transplantation Complicated by Severe Hepatic Veno-Occlusive Disease," published in previous issue.