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Ovarian reserve tests are valuable for evaluation of female fertility, and to formulate appropriate treatment strategies for infertile women. Antral follicle count (AFC) and Anti-Mullerian hormone (AMH) are most reliable markers of ovarian reserve which are related inversely to age. There are many factors that affect ovarian reserve like race, ethnicity, fertility status, BMI or any chronic illness. We conducted this study to find outage specific nomograms for AMH and AFC among fertile and Infertile Indian women, to find out any variations between fertile and Infertile ovarian reserves at various centiles, to define the age cut-off of decline in AMH and AFC among fertile and Infertile Indian women and to find correlation between AMH and AFC. It was a prospective cross sectional single centre study conducted at a tertiary hospital of northern India from March 2017 to February 2022. Fertile healthy women were recruited from family planning clinic, oocyte donors and subfertile women from Gynaecology and ART clinic. AMH was done using ELISA, Beckmann Coulter Gen II assay and AFC was done using TVS with high frequency probe (9.0 MHZ, Voluson,S-6, GE Healthcare, USA) by trained personnel. R Statistical Programming Language was used for statistical modelling and visualization. Age-specific AFC centile chart and AMH centile chart were generated using GAMLSS (Generalized Additive Models for Location Scale and Shape) package available in R Statistical Computing Language. A Non-linear decline in ovarian reserves among fertile, while linear among infertile women was seen. Centiles defined for both groups with a faster decline in infertile women. Age cut off for decline in AMH and AFC in fertile women approximately 31 years using ROC analysis and Age cut off for decline in AMH and AFC in infertile women is approximately 34 years. There seems to be a good correlation between AFC and AMH. We need to counsel women to consider child bearing well before ovarian reserves decline (31–34 years). [ABSTRACT FROM AUTHOR]

Context: The kynurenine pathway generates metabolites integral to energy metabolism, neurotransmission, and immune function. Circulating kynurenine metabolites positively correlate with adiposity in children and adults, yet it is not known whether this relationship is present already at birth. Objective: In this prospective longitudinal study, we investigate the relationship between cord blood kynurenine metabolites and measures of adiposity from birth to 4.5 years. Methods: Liquid chromatography-tandem mass spectrometry was used to quantify cord blood kynurenine metabolites in 812 neonates from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) study. Fat percentage was measured by air displacement plethysmography and abdominal adipose tissue compartment volumes; superficial (sSAT) and deep subcutaneous (dSAT) and internal adipose tissue were quantified by magnetic resonance imaging at early infancy in a smaller subset of neonates, and again at 4 to 4.5 years of age. Results: Cord blood kynurenine metabolites appeared to be higher in female newborns, higher in Indian newborns compared with Chinese newborns, and higher in infants born by cesarean section compared with vaginal delivery. Kynurenine, xanthurenic acid, and quinolinic acid were positively associated with birthweight, but not with subsequent weight during infancy and childhood. Quinolinic acid was positively associated with sSAT at birth. Kynurenic acid and quinolinic acid were positively associated with fat percentage at 4 years. Conclusion: Several cord blood kynurenine metabolite concentrations were positively associated with birthweight, with higher kynurenic acid and quinolinic acid correlating to higher percentage body fat in childhood, suggesting these cord blood metabolites as biomarkers of early childhood adiposity. [ABSTRACT FROM AUTHOR]

Parental genes can influence the phenotype of their offspring through genomic-epigenomic interactions even without the direct inheritance of specific parental genotypes. Maternal genetic variations can affect the ovarian and intrauterine environments and potentially alter lactation behaviors, impacting offspring nutrition and health outcomes independently of the fetal genome. Similarly, paternal genetic changes can affect the endocrine system and vascular functions in the testes, influencing sperm quality and seminal fluid composition. These changes can initiate early epigenetic modifications in sperm, including alterations in microRNAs, tRNA-derived small RNAs (tsRNAs), and DNA methylation patterns. These epigenetic modifications might induce further changes in target organs of the offspring, leading to modified gene expression and phenotypic outcomes without transmitting the original parental genetic alterations. This review presents clinical evidence supporting this hypothesis and discusses the potential underlying molecular mechanisms. Parental gene-offspring epigenome-offspring phenotype interactions have been observed in neurocognitive disorders and cardio-renal diseases. [ABSTRACT FROM AUTHOR]

The human cerebellum is increasingly recognized to be involved in nonmotor and higher-order cognitive functions. Yet, its ties with the entire cerebral cortex have not been holistically studied in a whole brain exploration with a unified analytical framework. Here, we characterized dissociable cortical-cerebellar structural covariation patterns based on regional gray matter volume (GMV) across the brain in n = 38,527 UK Biobank participants. Our results invigorate previous observations in that important shares of cortical-cerebellar structural covariation are described as 1) a dissociation between the higher-level cognitive system and lower-level sensorimotor system and 2) an anticorrelation between the visual-attention system and advanced associative networks within the cerebellum. We also discovered a novel pattern of ipsilateral, rather than contralateral, cerebral-cerebellar associations. Furthermore, phenome-wide association assays revealed key phenotypes, including cognitive phenotypes, lifestyle, physical properties, and blood assays, associated with each decomposed covariation pattern, helping to understand their real-world implications. This systems neuroscience view paves the way for future studies to explore the implications of these structural covariations, potentially illuminating new pathways in our understanding of neurological and cognitive disorders. NEW & NOTEWORTHY: Cerebellum's association with the entire cerebral cortex has not been holistically studied in a unified way. Here, we conjointly characterize the population-level cortical-cerebellar structural covariation patterns leveraging ∼40,000 UK Biobank participants whole brain structural scans and ∼1,000 phenotypes. We revitalize the previous hypothesis of an anticorrelation between the visual-attention system and advanced associative networks within the cerebellum. We also discovered a novel ipsilateral cerebral-cerebellar associations. Phenome-wide association (PheWAS) revealed real-world implications of the structural covariation patterns. [ABSTRACT FROM AUTHOR]

During the second-to-third trimester, the neuronal pathways of the fetal brain experience rapid development, resulting in the complex architecture of the interwired network at birth. While diffusion MRI-based tractography has been employed to study the prenatal development of structural connectivity network (SCN) in preterm neonatal and postmortem fetal brains, the in utero development of SCN in the normal fetal brain remains largely unknown. In this study, we utilized in utero dMRI data from human fetuses of both sexes between 26 and 38 gestational weeks to investigate the developmental trajectories of the fetal brain SCN, focusing on intrahemispheric connections. Our analysis revealed significant increases in global efficiency, mean local efficiency, and clustering coefficient, along with significant decrease in shortest path length, while small-worldness persisted during the studied period, revealing balanced network integration and segregation. Widespread short-ranged connectivity strengthened significantly. The nodal strength developed in a posterior-to-anterior and medial-to-lateral order, reflecting a spatiotemporal gradient in cortical network connectivity development. Moreover, we observed distinct lateralization patterns in the fetal brain SCN. Globally, there was a leftward lateralization in network efficiency, clustering coefficient, and small-worldness. The regional lateralization patterns in most language, motor, and visual-related areas were consistent with prior knowledge, except for Wernicke’s area, indicating lateralized brain wiring is an innate property of the human brain starting from the fetal period. Our findings provided a comprehensive view of the development of the fetal brain SCN and its lateralization, as a normative template that may be used to characterize atypical development. [ABSTRACT FROM AUTHOR]

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]

This article reports on a case of a 34-year-old male with type 1 diabetes who presented to the emergency department with abdominal pain. The patient was diagnosed with diabetic ketoacidosis (DKA) and was found to have intussusception, a rare condition in adults. The patient was treated with conservative measures and his DKA resolved after three days of treatment. The article discusses the potential for DKA complicated with intussusception to resolve without surgical intervention and highlights the importance of timely identification of intussusception in DKA patients. [Extracted from the article]

Purpose: To evaluate the association of body stature with ocular biometrics and refraction in preschool children. Methods: A cross-sectional, school-based study was conducted in Shenzhen, China. Preschool children aged 3 to 6 from 10 randomly-selected kindergartens were recruited. Ocular biometric parameters, including axial length (AL), anterior chamber depth (ACD), vitreous chamber depth (VCD), corneal radius curvature (CR), axial length to corneal radius ratio (AL-to-CR ratio) and lens thickness (LT) were measured using non-contact partial-coherence laser interferometry. Cycloplegic refractions were obtained by a desktop autorefractor. Body height and weight were measured using standard procedures. The association between body stature and ocular biometrics were analyzed with univariable and multivariable regression model. Results: A total of 373 preschoolers were included. AL, ACD, VCD, CR, and AL-to-CR ratio, were positively associated with height and weight (p < 0.05), whereas LT was negatively associated with height and weight (p < 0.01). No association was observed between stature and central cornea thickness and refraction. After adjusted for age and gender in a multivariable regression model, AL had positive associations with height (p < 0.01) and weight (p < 0.01). However, refraction had no significant association with stature parameters. Conclusion: Taller and heavier preschoolers had eyes with longer AL, deeper vitreous chamber, and flatter cornea. The significant associations between body stature and ocular biometric parameters reveal the driving influence of body development on the growth of eyeballs in preschoolers. [ABSTRACT FROM AUTHOR]

Objective: This study examined relationships of maternal pregnancy and postpartum diet quality with infant birth size and weight status indicators through 12 months and tested whether breastfeeding duration modifies these associations. Methods: In the Pregnancy Eating Attributes Study (PEAS), dietary intake was assessed six times in 458 mothers who were followed from early pregnancy through 12 months postpartum (2014–2018). Logistic and linear mixed models estimated relationships of pregnancy and postpartum diet quality (Healthy Eating Index [HEI]) with offspring who were large‐for‐gestational‐age (LGA) at birth, as well as BMI z score (BMIz) and weight‐for‐length z score (WFLz) at birth, 6 weeks, 6 months, and 12 months. Results: Pregnancy HEI was inversely related to LGA (odds ratio [OR] = 0.95, 95% CI: 0.92 to 0.98); HEI was also inversely related to WFLz (β = −0.01, 95% CI: −0.02 to −0.002) and BMIz (β = −0.009, 95% CI: −0.02 to −0.0009) from birth through 12 months. Postpartum HEI was inversely related to WFLz (β = −0.01, 95% CI: −0.02 to −0.0009) and BMIz (β = −0.008, 95% CI: −0.02 to 0.0007) in infants who were breastfed for at least 6 months, but not in those who were breastfed for a shorter duration. Conclusions: Maternal diet quality during pregnancy (and during postpartum in mothers who breastfed for a longer duration) was inversely related to LGA and weight status indicators from birth through 12 months. Increasing maternal diet quality may have use for promoting healthy infant weight development. [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]

Noonan, Costello and Cardio-facio-cutaneous syndromes belong to a group of disorders named RASopathies due to their common pathogenetic origin that lies on the Ras/MAPK signaling pathway. Genetics has eased, at least in part, the distinction of these entities as they are presented with overlapping clinical features which, sometimes, become more pronounced with age. Distinctive face, cardiac and skeletal defects are among the primary abnormalities seen in these patients. Skeletal dysmorphisms range from mild to severe and may include anterior chest wall anomalies, scoliosis, kyphosis, short stature, hand anomalies, muscle weakness, osteopenia or/and osteoporosis. Patients usually have increased serum concentrations of bone resorption markers, while markers of bone formation are within normal range. The causative molecular defects encompass the members of the Ras/MAPK/ERK pathway and the adjacent cascades, important for the maintenance of normal bone homeostasis. It has been suggested that modulation of the expression of specific molecules involved in the processes of bone remodeling may affect the osteogenic fate decision, potentially, bringing out new pharmaceutical targets. Currently, the laboratory imprint of bone metabolism on the clinical picture of the affected individuals is not clear, maybe due to the rarity of these syndromes, the small number of the recruited patients and the methods used for the description of their clinical and biochemical profiles. [ABSTRACT FROM AUTHOR]

Advances in functional MRI (fMRI) allow mapping an individual's brain function in vivo. Task fMRI can localize domain-specific regions of cognitive processing or functional regions of interest (fROIs) within an individual. Moreover, data from resting state (no task) fMRI can be used to define an individual's connectome, which can characterize that individual's functional organization via connectivity-based parcellations. However, can connectivity-based parcellations alone predict an individual's fROIs? Here, we describe an approach to compute individualized rs-fROIs (i.e., regions that correspond to given fROI constructed using only resting state data) for motor control, working memory, high-level vision, and language comprehension. The rs-fROIs were computed and validated using a large sample of young adults (n = 1,018) with resting state and task fMRI from the Human Connectome Project. First, resting state parcellations were defined across a sequence of resolutions from broadscale to fine-grained networks in a training group of 500 individuals. Second, 21 rs-fROIs were defined from the training group by identifying the rs network that most closely matched task-defined fROIs across all individuals. Third, the selectivity of rs-fROIs was investigated in a training set of the remaining 518 individuals. All computed rs-fROIs were indeed selective for their preferred category. Critically, the rsfROIs had higher selectivity than probabilistic atlas parcels for nearly all fROIs. In conclusion, we present a potential approach to define selective fROIs on an individual-level circumventing the need for multiple task-based localizers. [ABSTRACT FROM AUTHOR]

Background: Body composition (BC) is an important factor in determining the risk of type 2-diabetes and cardiovascular disease. Computed tomography (CT) is a useful imaging technique for studying BC, however manual segmentation of CT images is time-consuming and subjective. The purpose of this study is to develop and evaluate fully automated segmentation techniques applicable to a 3-slice CT imaging protocol, consisting of single slices at the level of the liver, abdomen, and thigh, allowing detailed analysis of numerous tissues and organs. Methods: The study used more than 4000 CT subjects acquired from the large-scale SCAPIS and IGT cohort to train and evaluate four convolutional neural network based architectures: ResUNET, UNET++, Ghost-UNET, and the proposed Ghost-UNET++. The segmentation techniques were developed and evaluated for automated segmentation of the liver, spleen, skeletal muscle, bone marrow, cortical bone, and various adipose tissue depots, including visceral (VAT), intraperitoneal (IPAT), retroperitoneal (RPAT), subcutaneous (SAT), deep (DSAT), and superficial SAT (SSAT), as well as intermuscular adipose tissue (IMAT). The models were trained and validated for each target using tenfold cross-validation and test sets. Results: The Dice scores on cross validation in SCAPIS were: ResUNET 0.964 (0.909–0.996), UNET++ 0.981 (0.927–0.996), Ghost-UNET 0.961 (0.904–0.991), and Ghost-UNET++ 0.968 (0.910–0.994). All four models showed relatively strong results, however UNET++ had the best performance overall. Ghost-UNET++ performed competitively compared to UNET++ and showed a more computationally efficient approach. Conclusion: Fully automated segmentation techniques can be successfully applied to a 3-slice CT imaging protocol to analyze multiple tissues and organs related to BC. The overall best performance was achieved by UNET++, against which Ghost-UNET++ showed competitive results based on a more computationally efficient approach. The use of fully automated segmentation methods can reduce analysis time and provide objective results in large-scale studies of BC. [ABSTRACT FROM AUTHOR]

Background: A "mismatch" sequence of less prenatal weight gain and more postnatal weight gain may lead to ectopic lipid accumulation, and trigger the development of early adrenarche/pubarche and the activation of the gonadotropic axis resulting in early puberty and ending up in full-blown adolescent polycystic ovary syndrome (PCOS). In the present study, we assess whether a low-dose combination of generics that collectively reduce ectopic fat through different pathways can slow down the accelerated maturation in "mismatch" girls with early puberty. Methods: Randomized, placebo-controlled, multicenter, phase 2a, study in 64 girls [age, 8.0–9.5 years; birthweight (BW) for gestational age: −2.5 < Z-score <0, body mass index (BMI): 0 < Z-score < +2.5 and early progressive puberty (Tanner B2 at 7.7–9.3 years)]. Pharmacological intervention will be with a half-dose version of SPIOMET (mini-spiomet), a combination that reverts the PCOS phenotype in "mismatch" adolescents; mini-spiomet will contain spironolactone (25 mg/day, to raise brown adipose tissue activity), pioglitazone (3.75 mg/day, to raise adiponectin and insulin sensitivity), and metformin (425 mg/day, to raise AMPK activity and GDF15). Recruitment: 1 year; double-blind treatment: 1 year; open follow-up: 1 year; analyses and reporting: 1 year. Interventions: randomization (1:1) for placebo vs mini-spiomet. Primary outcome: annualized bone age advancement (0–1 year) by BoneXpert; secondary outcomes: insulin, IGF-I, high-molecular-weight adiponectin (HMW-adip), sex hormone binding globulin (SHBG), ultra-sensitive C-reactive protein (usCRP), androgens, luteinizing hormone (LH), follicle-stimulating hormone (FSH), oestradiol, growth-and-differentiation factor 15 (GDF15), C-X-C motif chemokine ligand-14 (CXCL14), safety parameters, and quantification of hepato-visceral fat. Discussion: The present study, if successful, may provide a first proof of the concept that the rapid maturation of girls with an upward mismatch between pre- and post-natal weight gain can be slowed down with a fixed low-dose combination of old and safe generics jointly targeting a reduction of ectopic fat without necessarily lowering body weight. Trial registration: EudraCT 2021-006766-21. Registered on May 30, 2022. [ABSTRACT FROM AUTHOR]

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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]

Context Rapid-onset obesity with central hypoventilation, hypothalamic dysfunction, and autonomic dysregulation with neural crest tumors (ROHHAD-NET) syndrome pathophysiology remains elusive. Acquired neuroimmunological dysfunction has been proposed as a possible pathogenetic pathway. Objective The aim of our study was to characterize lymphocyte subpopulations subsets in peripheral blood (PB) and to evaluate a panel of proinflammatory cytokines/chemokines in ROHHAD(NET) patients vs controls. Methods We included 11 ROHHAD(NET) patients, 7 ROHHAD and 4 ROHHAD-NET, selected by clinical criteria. Controls were 11 simple obese children, matched for age and sex. Flow cytometric analysis and enzyme-linked immunosorbent assay were performed on PB and serum samples of the 2 groups. Results Analysis revealed that T lymphocytes are significantly increased in ROHHAD(NET) patients (P =.04) with a prevalence of CD4-T cells (P =.03) and a lower number of activated CD8-T cells (P =.02). With regard to regulatory subset, patients displayed increased regulatory B cells (P =.05) and type-1 regulatory T cells (P =.03). With regard to CD8-T cells, a lower number of T effector memory was observed (P =.02). In contrast, among CD4-T cells, we found a higher number of T naive (P =.04) and T effector (P =.0008). Interleukin-8 (IL-8) levels and monocyte chemotactic protein-1 were increased in patients vs controls (P =.008 and P =.01, respectively). Furthermore, IL-8 levels were higher in the subgroup with neural tumor (P =.0058) (ROHHAD-NET) than in patients without neural tumor (ROHHAD). Soluble HLA-G was significantly lower in patients vs controls (P =.03). Conclusion Our findings contribute to support the hypothesis of immune dysregulation, which may underlie this complex, often fatal disease. Because ROHHAD(NET) syndrome is an ultra-rare disease, multicentric studies are needed to improve the effect of our data in the management of this condition. [ABSTRACT FROM AUTHOR]

Background The hypothalamic-pituitary-adrenal (HPA) axis is a major stress response system, and excessive HPA responses can impact major depressive disorder and suicide. We examined relationships between reported early-life adversity (ELA), recent-life stress (RLS), suicide, and corticotropin-releasing hormone (CRH), CRH binding protein, FK506-binding protein (FKBP5), glucocorticoid receptor (GR), and brain-derived neurotrophic factor (BDNF) in postmortem human prefrontal cortex (BA9), and anterior cingulate cortex (BA24). Methods Thirteen quadruplets, matched for sex, age, and postmortem interval and consisting of suicide decedents and healthy controls, were divided equally into those with and without ELA. ELA, RLS, and psychiatric diagnoses were determined by psychological autopsy. Protein levels were determined by western blots. Results There were no suicide- or ELA-related differences in CRH, CRH binding protein, GR, or FKBP5 in BA9 or BA24 and no interaction between suicide and ELA (P  > .05). For BDNF, there was an interaction between suicide and ELA in BA24; suicides without ELA had less BDNF than controls without ELA, and controls with ELA had less BDNF than controls without ELA. CRH in BA9 and FKBP5 in anterior cingulate cortex correlated negatively with RLS. Least Absolute Shrinkage and Selection Operator logistic regression with cross-validation found combining BDNF, GR, and FKBP5 BA24 levels predicted suicide, but ELA did not contribute. A calculated "suicide risk score" using these measures had 71% sensitivity and 71% specificity. Conclusion A dysregulated HPA axis is related to suicide but not with ELA. RLS was related to select HPA axis proteins in specific brain regions. BDNF appears to be dysregulated in a region-specific way with ELA and suicide. [ABSTRACT FROM AUTHOR]

Brain asymmetry, involving structural and functional differences between the two hemispheres, is a major organizational principle of the human brain. The structural and functional connectivity within each hemisphere defines the hemispheric network or connectome. Elucidating left-right differences of the hemispheric network provides opportunities for brain asymmetry exploration. This review examines the asymmetry in the hemispheric white matter and functional network to assess health and brain disorders. In this article, the brain asymmetry in structural and functional connectivity including network topologies of healthy individuals, involving brain cognitive systems and the development trend, is highlighted. Moreover, the abnormal asymmetry of the hemispheric network related to cognition changes in brain disorders, such as Alzheimer's disease, schizophrenia, autism spectrum disorder, attention deficit hyperactivity disorder, and bipolar disorder, is presented. This review suggests that the hemispheric network is highly conserved for measuring human brain asymmetries and has potential in the study of the cognitive system and brain disorders. [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]

Background: Locked‐in syndrome represents the most severe form of central pontine myelinolysis and varies in presentation from asymptomatic to fully developed locked‐in‐syndrome characterized by the combination of quadriplegia, loss of the ability to communicate except through the use of the eyes, and an inability to follow commands. Methods: We report a 10‐year‐old boy who developed a severe case of locked‐in syndrome after heart transplantation. Results: Patient had a spontaneous recovery, treated with supportive treatment and the improvement was detected with cessation of calcineurin inhibitor therapy by substituting with an mTOR inhibitor (sirolimus). No cases of locked‐in syndrome post‐heart transplant in pediatrics cases have been documented in the literature. Conclusion: Physicians should recognize a rapid progression of central pontine myelinolysis and locked‐in syndrome in the context of heart transplant and although several factors likely contributed to this outcome, adjustment of immunosuppression including by substituting tacrolimus with sirolimus could be effective. [ABSTRACT FROM AUTHOR]

Background Longitudinal assessment of the determinants of obesogenic growth trajectories in childhood can suggest appropriate developmental windows for intervention. Methods Latent class growth mixture modelling was used to identify body mass index (BMI) z-score trajectories from birth to age 6 years in 994 children from a prospective mother–offspring cohort (Chinese, Indian and Malay ethnicities) based in Singapore. We evaluated the early-life determinants of the trajectories as well as their associations with cardiometabolic risk markers at age 6 years. Results Five BMI z-score trajectory patterns were identified, three within the healthy weight range, alongside early-acceleration and late-acceleration obesogenic trajectories. The early-acceleration pattern was characterized by elevated fetal abdominal circumference growth velocity, BMI acceleration immediately after birth and crossing of the obesity threshold by age 2 years. The late-acceleration pattern had normal fetal growth and BMI acceleration after infancy, and approached the obesity threshold by age 6 years. Abdominal fat, liver fat, insulin resistance and odds of pre-hypertension/hypertension were elevated in both groups. Indian ethnicity, high pre-pregnancy BMI, high polygenic risk scores for obesity and shorter breastfeeding duration were common risk factors for both groups. Malay ethnicity and low maternal educational attainment were uniquely associated with early BMI acceleration, whereas nulliparity and obesogenic eating behaviours in early childhood were uniquely associated with late BMI acceleration. Conclusion BMI acceleration starting immediately after birth or after infancy were both linked to early cardiometabolic alterations. The determinants of these trajectories may be useful for developing early risk stratification and intervention approaches to counteract metabolic adversities linked to childhood obesity. [ABSTRACT FROM AUTHOR]

Objective: To determine the effect of acupuncture in treating poor ovarian response (POR). Methods: We searched MEDLINE (via PubMed), EMBASE, Allied and Complementary Medicine Database, CNKI, CBM, VIP database, Wanfang Database, and relevant registration databases from inception to January 30, 2023. In this review, both Chinese and English peer-reviewed literature were included. Only randomized controlled trials (RCTs) using acupuncture as an intervention for POR patients undergoing in vitro fertilization were considered. Results: Seven clinical randomized controlled trials (RCTs) were eventually included for comparison (516 women). The quality of included studies was generally low or very low. For the meta-analysis, seven studies showed that compared with controlled ovarian hyperstimulation (COH) therapy, acupuncture combined with COH therapy could significantly increase the implantation rate (RR=2.13, 95%CI [1.08, 4.21], p=0.03), the number of oocytes retrieved (MD=1.02, 95%CI [0.72, 1.32], p<0.00001), the thickness of endometrium (MD=0.54, 95%CI [0.13, 0.96], p=0.01), and the antral follicle count (MD=1.52, 95%CI [1.08, 1.95], p<0.00001), reduce follicle-stimulating hormone (FSH) levels (MD=-1.52, 95%CI [-2.41, -0.62], p=0.0009) and improve estradiol (E2) levels (MD=1667.80, 95%CI [1578.29, 1757.31], p<0.00001). Besides, there were significant differences in the duration of Gn (MD=0.47, 95%CI [-0.00, 0.94], p=0.05) between the two groups. However, no statistical variation was observed in improving clinical pregnancy rate (CPR), fertilization rate, high-quality embryo rate, luteinizing hormone (LH) value, anti-mullerian hormone (AMH) value, or reducing the dose of gonadotropin (Gn) values between the acupuncture plus COH therapy group and the COH therapy group. Conclusion: Acupuncture combined with COH therapy is doubtful in improving the pregnancy outcome of POR patients. Secondly, acupuncture can also improve the sex hormone level of POR women, and improve ovarian function. Furthermore, more RCTs of acupuncture in POR are needed to be incorporated into future meta-analyses. [ABSTRACT FROM AUTHOR]

Background: A "mismatch" sequence of less prenatal weight gain and more postnatal weight gain may lead to ectopic lipid accumulation, and trigger the development of early adrenarche/pubarche and the activation of the gonadotropic axis resulting in early puberty and ending up in full-blown adolescent polycystic ovary syndrome (PCOS). In the present study, we assess whether a low-dose combination of generics that collectively reduce ectopic fat through different pathways can slow down the accelerated maturation in "mismatch" girls with early puberty. Methods: Randomized, placebo-controlled, multicenter, phase 2a, study in 64 girls [age, 8.0–9.3 years; birthweight (BW) for gestational age in lower tertile (−1.96< Z-score <−0.44), body mass index (BMI) in upper tertile (+0.44< Z-score < +1.96) and early progressive puberty (Tanner B2 at 7.7–9.0 years)]. Pharmacological intervention will be with a half-dose version of SPIOMET (mini-spiomet), a combination that reverts the PCOS phenotype in "mismatch" adolescents; mini-spiomet will contain spironolactone (25 mg/day, to raise brown adipose tissue activity), pioglitazone (3.75 mg/day, to raise adiponectin and insulin sensitivity), and metformin (425 mg/day, to raise AMPK activity and GDF15). Recruitment: 1 year; double-blind treatment: 1 year; open follow-up: 1 year; analyses and reporting: 1 year. Interventions: randomization (1:1) for placebo vs mini-spiomet. Primary outcome: annualized bone age advancement (0–1 year) by BoneXpert; secondary outcomes: insulin, IGF-I, high-molecular-weight adiponectin (HMW-adip), sex hormone binding globulin (SHBG), ultra-sensitive C-reactive protein (usCRP), androgens, luteinizing hormone (LH), follicle-stimulating hormone (FSH), oestradiol, growth-and-differentiation factor 15 (GDF15), C-X-C motif chemokine ligand-14 (CXCL14), safety parameters, and quantification of hepato-visceral fat. Discussion: The present study, if successful, may provide a first proof of the concept that the rapid maturation of girls with an upward mismatch between pre- and post-natal weight gain can be slowed down with a fixed low-dose combination of old and safe generics jointly targeting a reduction of ectopic fat without necessarily lowering body weight. Trial registration: EudraCT 2021-006766-21. Registered on May 30, 2022. [ABSTRACT FROM AUTHOR]

Uterine cervical Müllerian adenosarcoma (MA), a rare malignant tumor of the female reproductive organs, is composed of a benign epithelium and a lowgrade malignant stromal component. Because few studies have investigated the clinical management of MA, misdiagnosis often occur. Therefore, we proposed an optimal course of clinical management for patients with MA. MA is possibly a malignant transformation of the cystadenofibroma. In this study, we present a case of a 46-year-old woman who presented with symptoms of MA of the uterine cervix, such as metrorrhagia and a cyst in the cervical canals, after transvaginal excision of the left ovarian mucinous cystadenofibroma. [ABSTRACT FROM AUTHOR]

Background: Accurate assessment and evaluation of health interventions are crucial to evidence-based care. The use of outcome measures in neurosurgery grew with the introduction of the Glasgow Coma Scale. Since then, various outcome measures have appeared, some of which are disease-specific and others more generally. This article aims to address the most widely used outcome measures in three major neurosurgery subspecialties, "vascular, traumatic, and oncologic," focusing on the potential, advantages, and drawbacks of a unified approach to these outcome measures. Methods: A literature review search was conducted by using PubMed MEDLINE and Google scholar Databases. Data for the three most common outcome measures, The Modified Rankin Scale (mRS), The Glasgow Outcome Scale (GOS), and The Karnofsky Performance Scale (KPS), were extracted and analyzed. Results: The original objective of establishing a standardized, common language for the accurate categorization, quantification, and evaluation of patients' outcomes has been eroded. The KPS, in particular, may provide a common ground for initiating a unified approach to outcome measures. With clinical testing and modification, it may offer a simple, internationally standardized approach to outcome measures in neurosurgery and elsewhere. Based on our analysis, Karnofsky's Performance Scale may provide a basis of reaching a unified global outcome measure. Conclusion: Outcome measures in neurosurgery, including mRS, GOS, and KPS, are widely utilized assessment tools for patients' outcomes in various neurosurgical specialties. A unified global measure may offer solutions with ease of use and application; however, there are limitations. [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]

Introduction PEA POD™ air displacement plethysmography quickly and noninvasively estimates neonatal body fat percentage (BF%). Low PEA POD™ BF% predicts morbidity better than classification as small-for-gestational-age (SGA; <10th centile), but PEA PODs are not widely available. We examined whether skinfold measurements could effectively identify neonates at risk; comparing skinfold BF%, PEA POD™ BF% and birthweight centiles’ prediction of hypothermia – a marker of reduced in utero nutrition. Methods Neonates had customized birthweight centiles calculated, and BF% prospectively estimated by: (i) triceps and subscapular skinfolds using sex-specific equations; and (ii) PEA POD™. Medical record review identified hypothermic (<36.5 °C) episodes. Results 42/149 (28%) neonates had hypothermia. Skinfold BF%, with an area under the curve (AUC) of 0.66, predicted hypothermia as well as PEA POD™ BF% (AUC = 0.62) and birthweight centile (AUC = 0.61). Birthweight <10th centile demonstrated 11.9% sensitivity, 38.5% positive predictive value (PPV) and 92.5% specificity for hypothermia. At equal specificity, skinfold and PEA POD™ BF% more than doubled sensitivity (26.2%) and PPV increased to 57.9%. Conclusion Neonatal BF% performs better to predict neonatal hypothermia than birthweight centile, and may be a better measure of true fetal growth restriction. Estimation of neonatal BF% by skinfold measurements is an inexpensive alternative to PEA POD™. [ABSTRACT FROM AUTHOR]

The fetal brains experience rapid and complex development in utero during the second and third trimesters. In utero MRI of the fetal brain in this period enables us to quantify normal fetal brain development in the spatiotemporal domain. In this study, we established a high-quality spatiotemporal atlas between 23 and 38 weeks gestational age (GA) from 90 healthy Chinese human fetuses of both sexes using a pairwise and groupwise registration pipeline. We quantified the fetal cortical morphology indices and characterized their spatiotemporal developmental pattern. The cortical thickness exhibited a biphasic pattern that first increased and then decreased; the curvature fitted well into the Gompertz growth model; sulcal depth increased linearly, while surface area expanded exponentially. The cortical thickness and curvature trajectories consistently pointed to a characteristic time point around GA of 31 weeks. The characteristic GA and growth rate obtained from individual cortical regions suggested a central-to-peripheral developmental gradient, with the earliest development in the parietal lobe, and we also observed a superior-to-inferior gradient within the temporal lobe. These findings may be linked to biophysical events, such as dendritic arborization and thalamocortical fibers ingrowth. The proposed atlas was also compared with an existing fetal atlas from a white/mixed population. Finally, we examined the structural asymmetry of the fetal brains and found extensive asymmetry that dynamically changed with development. The current study depicted a comprehensive profile of fetal cortical development, and the established atlas could be used as a normative reference for neurodevelopmental and diagnostic purposes, especially in the Chinese population. [ABSTRACT FROM AUTHOR]

Stress following preterm birth can disrupt the emerging foundation of the neonatal brain. The current study examined how structural brain development is affected by a stressful early environment and whether changes in topological architecture at term-equivalent age could explain the increased vulnerability for behavioral symptoms during early childhood. Longitudinal changes in structural brain connectivity were quantified using diffusion-weighted imaging (DWI) and tractography in preterm born infants (gestational age, 28weeks), imaged at 30 and/or 40weeks of gestation (N= 145, 43.5% female). A global index of postnatal stress was determined based on the number of invasive procedures during hospitalization (e.g., heel lance). Higher stress levels impaired structural connectivity growth in a subnetwork of 48 connections (p = 0.003), including the amygdala, insula, hippocampus, and posterior cingulate cortex. Findings were replicated in an independent validation sample (N= 123, 39.8% female, n=91 with follow-up). Classifying infants into vulnerable and resilient based on having more or less internalizing symptoms at two to five years of age (n = 71) revealed lower connectivity in the hippocampus and amygdala for vulnerable relative to resilient infants (p,0.001). Our findings suggest that higher stress exposure during hospital admission is associated with slower growth of structural connectivity. The preservation of global connectivity of the amygdala and hippocampus might reflect a stress-buffering or resilience-enhancing factor against a stressful early environment and early-childhood internalizing symptoms. [ABSTRACT FROM AUTHOR]

This article overviews my recent acceptance of a Lifetime Achievement Award from Sapienza University of Rome, in which I discussed three decades of my work on the right brain in development, psychopathogenesis, and psychotherapy. In the following, I offer current brain laterality and hemispheric asymmetry research indicating that right brain emotional and relational processes operate beneath conscious awareness not only in early human development, but over the lifespan. I discuss recent interdisciplinary studies on the central role of ultrarapid right brain-to-right brain intersubjective communications of face, voice, and gesture and the implicit regulation of emotion in nonverbal attachment dynamics. Special emphasis is on the fundamental psychobiological process of interpersonal synchrony, and on the evolutionary mechanism of attachment, the interactive regulation of biological synchrony within and between organisms. I then present some clinical applications, suggesting that effective therapeutic work with "primitive" nonverbal emotional attachment dynamics focuses not on conscious verbal insight but on the formation of an unconscious emotion-communicating and regulating bond within the therapeutic relationship. Lastly, I review recent hyperscanning research of the patient's and therapist's brains during a face-to-face, emotionally focused psychotherapy session that supports the right brain-to-right brain communication model. I end suggesting that the right brain is dominant in both short-term symptom-reducing and long-term growth-promoting deep psychotherapy. [ABSTRACT FROM AUTHOR]

Background: Selecting an appropriate and personalized Gn starting dose (GSD) is an essential procedure for determining the quality and quantity of oocytes in the controlled ovarian stimulation (COS) process of the in-vitro fertilization (IVF) treatment cycle. The current approach for determining the GSD is mainly based on the experience of a clinician, lacking unified and scientific standards. This study aims to establish a prediction model of GSD, based on which good COS outcomes can be achieved with the influencing factors comprehensively evaluated quantitatively.Material and Methods: We collected a total of 1555 patients undergoing the first oocytes retrieving cycle and conducted correlation analysis to find the significant factors related to the GSD. Two GSD models are built based on two popular machine learning approaches, and the one with better model performance is selected as the final model. Finally, clinical application and validation were conducted to verify the effectiveness of the proposed model.Results: (1) Age, duration of infertility, type of infertility, body mass index (BMI), antral follicle count (AFC), basal follicle stimulating hormone (bFSH), estradiol (E2), luteinizing hormone (LH), anti-Müllerian hormone (AMH) and COS treatment regimen were closely related to the GSD (P < 0.05). (2) The selected model has good modeling performance in terms of both root mean square error (RMSE) (29.87 ~ 34.21) and regression coefficient R (0.947 ~ 0.953). (3) A comprehensive evaluation of influencing factors for GSD is conducted and shows that the top four most significant factors are age, AMH, AFC, and BMI. (4) The proposed GSD can approximate the actual value well in the clinical application, with the mean absolute error of only 11.26 units, and the recommended results can prompt the number of oocytes retrieved (NOR) close to the optimal number.Conclusion: Modeling the GSD value with machine learning approaches is feasible and effective, and the proposed model has good clinical application for determining the GSD in the IVF treatment cycle. [ABSTRACT FROM AUTHOR]

Background: Identifying blood-based DNA methylation patterns is a minimally invasive way to detect biomarkers in predicting age, characteristics of certain diseases and conditions, as well as responses to immunotherapies. As microarray platforms continue to evolve and increase the scope of CpGs measured, new discoveries based on the most recent platform version and how they compare to available data from the previous versions of the platform are unknown. The neutrophil dexamethasone methylation index (NDMI 850) is a blood-based DNA methylation biomarker built on the Illumina MethylationEPIC (850K) array that measures epigenetic responses to dexamethasone (DEX), a synthetic glucocorticoid often administered for inflammation. Here, we compare the NDMI 850 to one we built using data from the Illumina Methylation 450K (NDMI 450). Results: The NDMI 450 consisted of 22 loci, 15 of which were present on the NDMI 850. In adult whole blood samples, the linear composite scores from NDMI 450 and NDMI 850 were highly correlated and had equivalent predictive accuracy for detecting DEX exposure among adult glioma patients and non-glioma adult controls. However, the NDMI 450 scores of newborn cord blood were significantly lower than NDMI 850 in samples measured with both assays. Conclusions: We developed an algorithm that reproduces the DNA methylation glucocorticoid response score using 450K data, increasing the accessibility for researchers to assess this biomarker in archived or publicly available datasets that use the 450K version of the Illumina BeadChip array. However, the NDMI850 and NDMI450 do not give similar results in cord blood, and due to data availability limitations, results from sample types of newborn cord blood should be interpreted with care. [ABSTRACT FROM AUTHOR]

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