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This study aimed to evaluate the frequency of sleep and eating problems in children with autism spectrum disorder (ASD), the factors associated with these problems, and the relationship with the risk of developing depression and anxiety in their parents. In the study, 156 children with ASD and their parents were included. The Brief Autism Mealtime Behavior Inventory (BAMBI), the Children's Sleep Habits Questionnaire (CSHQ), the Hospital Anxiety Depression Scale (HADS) were completed by the parents. The Childhood Autism Rating Scale (CARS) was administered by the researchers to evaluate the severity of ASD in children. The mean age of children was 8.08 ± 2.84, and 87.2% of the children were male. The mean score of CARS was 41.25 ± 6.16, the mean score of BAMBI was 45.67 ± 11.87, and the mean score of CSHQ was 51.67 ± 10.17. According to the CSHQ, 83.3% of the children had sleep problems. The response rate above the cut-off point in the HAD-A subscale was 59.6%, whereas it was 67.3% in the HAD-D subscale. There was a positive correlation between CARS and BAMBI, CSHQ, HAD-A, and HAD-D subscales. There was a positive correlation between BAMBI and CHSQ, HAD-A, and HAD-D subscales. There was a positive correlation between the CSHQ, HAD-A, and HAD-D subscales. There was a negative correlation between the age of the child with ASD, food refusal, and resistance to bedtime. As sleeping and eating problems affect a large portion of children diagnosed with ASD and their caregivers, large population-based studies evaluating both these problems must be designed and carried out to understand factors affecting the prevalence, development, and persistence of sleeping and eating problems and to determine interventions to reduce these issues.

Current evidence shows that early interventions in children with autism spectrum disorder (ASD) are more efficient and associated with better long-term outcomes. This also highlights the need for early recognition of children with ASD symptoms by family physicians and referral to child psychiatrists. This study aimed to evaluate how family physicians' knowledge about ASD is reflected in clinical practice by making a diagnostic evaluation of the cases referred with suspected ASD. The study included 149 cases that family physicians referred to child psychiatrists regarding the assessment for ASD. Diagnostic evaluation of the subjects was carried out using the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-5) criteria. Childhood Autism Rating Scale (CARS) and Autism Behavior Checklist (ABC) were used in the evaluation process. Denver II developmental screening inventory was used to evaluate all subjects under six. The mean age of all participants was 39.1 (±13.2) months, and in ASD cases, it was 34.6 (±7.8) months. Of all referred cases, 72,5% were diagnosed according to the DSM-5 criteria. The most common diagnoses were global developmental delay (28.9%), language disorder (15.4%), ASD (15.4%), and attention deficit hyperactivity disorder (8.7%), respectively. The most common reason for referral specified on the consultation note was delayed speech, with a rate of 87.2%. In addition, 148 (99.3%) of the symptoms noted on the referral note were clustered within the DSM-5 ASD A criteria and 19 (12.8%) within the ASD B criteria. Developmental delay was more prominent in cases with ASD when compared to those with global developmental delay and language disorder. The most common diagnosis was a global developmental delay in referred cases, and only some of the symptoms seen in ASD from the referral notes of family physicians stood out as the reason for referral. These results underline the necessity of continuing ASD training for family physicians.

Introduction: People experiencing unsheltered homelessness (PEUH) have higher disease burden yet limited access to healthcare. COVID-19 introduced even greater risk for PEUH aged 65+ years with an underlying chronic health condition and were temporarily housed in hotels/motels for Project RoomKey (PRK). This study aimed to characterize a PRK cohort who received primary care from a street medicine program. Methods: This observational case series study included a sample of 35 PRK participants receiving primary care from a street medicine team at a single site from July to September 2020. We used the HOUSED BEDS assessment tool for taking history on PEUH. Results: Participants were 63% male, 40% Hispanic/Latino/a, 40% white, 94% English-speaking, and 73% had chronic health conditions. Assessment revealed: average Homelessness (H) of 4 years; 76% had no prior social service Outreach (O); average Utilization (U) was 4 emergency department visits in prior 6-months; 68% received Salary (S) from government income; Food access or Eat (E) was commonly purchased (29%) or donated (26%); clean water to Drink (D) for 59% of participants; 86% had access to a Bathroom (B); Encampment (E) was varied and 38% reported safety concerns; Daily routine (D) showed 76% could access a telephone, 32% received social support from family; 79% reported past or current Substance use (S). No participants contracted COVID-19 during study period. Conclusions: This study describes health and demographic characteristics of PRK participants in Southern California. Findings inform policies to continue PRK that includes onsite healthcare such as via street medicine.

This study aimed to investigate the emotional and behavioral responses of children with neurodevelopmental disorders and their parents during the recent novel coronavirus disease (COVID-19) pandemic and the associated factors. Our study included 299 children and adolescents with neurodevelopmental disorders and 299 mothers or fathers. Participant groups were as follows: autism spectrum disorder (n = 131, 43.8%); intellectual disability (n = 103, 34.4%); specific learning disorder (n = 46, 15.4%); and communication disorder (n = 19, 6.4%). A data form was created to investigate the emotional, behavioral, sleep problems, and appetite changes of the cases, and it was adapted for online application and conveyed to the parents in the form of emails. Our study indicated that children and adolescents' emotional problems were 44.5%, behavioral problems 33.4%, sleep problems 65.2%, and appetite problems 32.4%. Irritability (35.5%), hyperactivity (37.8%), stereotyped behavior (29.8%), delayed sleep phase (51.5%) were the most common problems reported by the parents. The frequencies of emotional and behavioral problems in the ASD group were higher than in the other groups (p < 0.05). In addition, the Hospital Anxiety Depression Scale (HADS) was used to determine the parents' anxiety and depression symptoms. Mean HADS anxiety and depression scores of parents were 8.5 ± 4.3 and 7.8 ± 4.2, respectively. Our study demonstrated that the COVID-19 pandemic and lockdown negatively affected children with neurodevelopmental disorders and their parents in many areas. It is necessary that these children and their families are evaluated and supported by local professionals, as the ongoing pandemic can exacerbate the current challenges. The findings of our study reflect the early period of the pandemic. For this reason, longitudinal studies about the long-term consequences of the pandemic are needed.

ObjectiveTo identify differences in the transcriptomic profiles during placentation from pregnancies conceived spontaneously vs. those with infertility using non-in vitro fertilization (IVF) fertility treatment (NIFT) or IVF.DesignCohort study.SettingAcademic medical center.Patient(s)Women undergoing chorionic villus sampling at gestational age 11-13 weeks (n = 141), with pregnancies that were conceived spontaneously (n = 74), with NIFT (n = 33), or with IVF (n = 34), resulting in the delivery of viable offspring.Intervention(s)Collection of chorionic villus samples from women who conceived spontaneously, with NIFT, or with IVF for gene expression analysis using RNA sequencing.Main outcome measure(s)Baseline maternal, paternal, and fetal demographics, maternal medical conditions, pregnancy complications, and outcomes. Differential gene expression of first-trimester placenta.Result(s)There were few differences in the transcriptome of first-trimester placenta from NIFT, IVF, and spontaneous pregnancies. There was one protein-coding differentially expressed gene (DEG) between the spontaneous and infertility groups, CACNA1I, one protein-coding DEG between the spontaneous and IVF groups, CACNA1I, and five protein-coding DEGs between the NIFT and IVF groups, SLC18A2, CCL21, FXYD2, PAEP, and DNER.Conclusion(s)This is the first and largest study looking at transcriptomic profiles of first-trimester placenta demonstrating similar transcriptomic profiles in pregnancies conceived using NIFT or IVF and spontaneous conceptions. Gene expression differences found to be highest in the NIFT group suggest that the underlying infertility, in addition to treatment-related factors, may contribute to the observed gene expression profiles.

Summary: Background: Defining the presence of acute and chronic brain inflammation remains a challenge to clinicians due to the heterogeneity of clinical presentations and aetiologies. However, defining the presence of neuroinflammation, and monitoring the effects of therapy is important given its reversible and potentially damaging nature. We investigated the utility of CSF metabolites in the diagnosis of primary neuroinflammatory disorders such as encephalitis and explored the potential pathogenic role of inflammation in epilepsy. Methods: Cerebrospinal fluid (CSF) collected from 341 paediatric patients (169 males, median age 5.8 years, range 0.1–17.1) were examined. The patients were separated into a primary inflammatory disorder group (n = 90) and epilepsy group (n = 80), who were compared with three control groups including neurogenetic and structural (n = 76), neurodevelopmental disorders, psychiatric and functional neurological disorders (n = 63), and headache (n = 32). Findings: There were statistically significant increases of CSF neopterin, kynurenine, quinolinic acid and kynurenine/tryptophan ratio (KYN/TRP) in the inflammation group compared to all control groups (all p

Summary: Background: Epileptic (previously infantile) spasms is the most common epileptic encephalopathy occurring during infancy and is frequently associated with abnormal neurodevelopmental outcomes. Epileptic spasms have a diverse range of known (genetic, structural) and unknown aetiologies. High dose corticosteroid treatment for 4 weeks often induces remission of spasms, although the mechanism of action of corticosteroid is unclear. Animal models of epileptic spasms have shown decreased brain kynurenic acid, which is increased after treatment with the ketogenic diet. We quantified kynurenine pathway metabolites in the cerebrospinal fluid (CSF) of infants with epileptic spasms and explored clinical correlations. Methods: A panel of nine metabolites in the kynurenine pathway (tryptophan, kynurenine, kynurenic acid, 3-hydroxykynurenine, xanthurenic acid, anthranilic acid, 3-hydroxyanthranilic acid, quinolinic acid, and picolinic acid) were measured using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). CSF collected from paediatric patients less than 3 years of age with epileptic spasms (n=34, 19 males, mean age 0.85, median 0.6, range 0.3–3 yrs) were compared with other epilepsy syndromes (n=26, 9 males, mean age 1.44, median 1.45, range 0.3–3 yrs), other non-inflammatory neurological diseases (OND) (n=29, 18 males, mean age 1.47, median 1.6, range 0.1–2.9 yrs) and inflammatory neurological controls (n=12, 4 males, mean age 1.80, median 1.80, range 0.8–2.5 yrs). Findings: There was a statistically significant decrease of CSF kynurenic acid in patients with epileptic spasms compared to OND (p

Objective: Maternal obesity increases the incidence of excess adiposity in newborns, resulting in lifelong diabetes risk. Elevated intrauterine fetal adiposity has been attributed to maternal hyperglycemia; however, this hypothesis does not account for the increased adiposity seen in newborns of mothers with obesity who have euglycemia. We aimed to explore the placental response to maternal hyperinsulinemia and the effect of insulin-like growth factor 2 (IGF-2) in promoting fetal adiposity by increasing storage and availability of nutrients to the fetus. Methods: We used placental villous explants and isolated trophoblasts from normal weight and obese women to assess the effect of insulin and IGF-2 on triglyceride content and insulin receptor signaling. Stable isotope tracer methods were used ex vivo to determine effect of hormone treatment on de novo lipogenesis (DNL), fatty acid uptake, fatty acid oxidation, and esterification in the placenta. Results: Here we show that placentae from euglycemic women with normal weight and obesity both have abundant insulin receptor. Placental depth and triglyceride were greater in women with obesity compared with normal weight women. In syncytialized placental trophoblasts and villous explants, insulin and IGF-2 activate insulin receptor, induce expression of lipogenic transcription factor SREBP-1 (sterol regulatory element-binding protein 1), and stimulate triglyceride accumulation. We demonstrate elevated triglyceride is attributable to increased esterification of fatty acids, without contribution from DNL and without an acceleration of fatty acid uptake. Conclusions: Our work reveals that obesity-driven aberrations in maternal metabolism, such as hyperinsulinemia, alter placental metabolism in euglycemic conditions, and may explain the higher prevalence of excess adiposity in the newborns of obese women.

Additive manufacturing (3D printing) and computer-aided design (CAD) still have limited uptake in biomedical and bioengineering research and education, despite the significant potential of these technologies. The utility of organ-scale 3D-printed models of living structures is widely appreciated, while the workflows for microscopy data translation into tactile accessible replicas are not well developed yet. Here, we demonstrate an accessible and reproducible CAD-based methodology for generating 3D-printed scalable models of human cells cultured in vitro and imaged using conventional scanning confocal microscopy with fused deposition modeling (FDM) 3D printing. We termed this technology CiTo-3DP (Cells-in-Touch for 3D Printing). As a proof-of-concept, we created dismountable CiTo-3DP models of human epithelial, mesenchymal, and neural cells by using selectively stained nuclei and cytoskeletal components. We also provide educational and research context for the presented cellular models. In the future, the CiTo-3DP approach can be adapted to different imaging and 3D printing modalities and comprehensively present various cell types, subcellular structures, and extracellular matrices. The resulting CAD and 3D printed models could be used for a broad spectrum of education and research applications.

Cells in many tissues fuse into syncytia acquiring new functions. By investigating whether physical remodelling promotes differentiation, here, the authors show that plasma membrane diminution post-fusion causes transient nutrient stress that inhibits YAP1 activity and may reduce proliferation-promoting transcription.

Background: HE is a neuropsychiatric complication of liver disease characterized by systemic elevation in ammonia and proinflammatory cytokines. These neurotoxins cross the blood-brain barrier and cause neuroinflammation, which can activate the kynurenine pathway (KP). This results in dysregulated production of neuroactive KP metabolites, such as quinolinic acid, which is known to cause astrocyte and neuronal death. Our aim was to compare KP activity between patients with covert HE (CHE), patients without encephalopathic cirrhosis (NHE), and healthy controls (HCs). Methods: This was a single-center prospective cohort study conducted between 2018 and 2021 at St Vincent's Hospital, Sydney. Overall, 13 patients with CHE, 10 patients with NHE, and 12 with HC were recruited. Patients with cirrhosis were diagnosed with CHE if they scored ≤−4 on the Psychometric Hepatic Encephalopathy Score. KP metabolite levels were quantified on plasma samples via HPLC and gas chromatography/mass spectrometry. One-way Kruskal-Wallis test was used to compare the expression levels of KP enzymes. Results: KP was highly activated in patients with cirrhosis, demonstrated by higher levels of activity in the rate-limiting enzymes, indoleamine 2,3-dioxygenase, and tryptophan-2,3-dioxygenase in both CHE (65.04±20.72, p =0.003) and patients with NHE (64.85±22.10, p =0.015) compared to HC (40.95±7.301). Higher quinolinic acid concentrations were demonstrated in CHE (3726 nM±3385, p <0.001) and patients with NHE (1788 nM±632.3, p =0.032) compared to HC (624 nM±457). KP activation was positively correlated with inflammatory marker C-reactive protein in patients with CHE (Rs=0.721, p ≤0.01). Conclusions: KP is highly activated in patients with CHE, resulting in heightened production of neurotoxic metabolites. Dysregulation of the pathway is demonstrable in patients who do not yet show clinical signs of neurocognitive impairment. Therapeutic agents that modulate KP activity may be able to alleviate symptoms of patients with CHE. [ABSTRACT FROM AUTHOR]

Abstract Background The treatment with short-acting beta-2 agonists (SABA) alone is no longer recommended due to safety issues. Instead, the current Global Initiative for Asthma (GINA) Report recommends the use of the combination of inhaled corticosteroids (ICS) with the rapid/long-acting beta-2 agonist formoterol, although the use in steps 1 and 2 is still off-label in the EU and in many countries. It is important to understand clinicians’ knowledge and opinions on the issue with the ultimate goal to encourage the implementation of the new approach in clinical practice. Methods We performed an international survey, directed to pulmonologists interested in the management of patients with asthma. Results Most participants reported that SABA alone should not be used in GINA Step 1 asthma treatment. As-needed low-dose ICS/formoterol combination to patients in step 1, and as-needed low-dose ICS/formoterol as reliever therapy in any step were found to be of current use prescribed in their real-life settings. SABA alone was still prescribed to a proportion of patients, although the pulmonologists’ opinion was that it should no longer be used. Conclusions Most specialists are up to date and understand the relevance of the changes in GINA reports from 2019. Nevertheless, dissemination and implementation of GINA novel management strategy is still needed.

BackgroundMultiple testing to understand global changes in gene expression based on genetic and epigenetic modifications is evolving. Chorionic villi, obtained for prenatal testing, is limited, but can be used to understand ongoing human pregnancies. However, optimal storage, processing and utilization of CVS for multiple platform testing have not been established.ResultsLeftover CVS samples were flash-frozen or preserved in RNAlater. Modifications to standard isolation kits were performed to isolate quality DNA and RNA from samples as small as 2-5 mg. RNAlater samples had significantly higher RNA yields and quality and were successfully used in microarray and RNA-sequencing (RNA-seq). RNA-seq libraries generated using 200 versus 800-ng RNA showed similar biological coefficients of variation. RNAlater samples had lower DNA yields and quality, which improved by heating the elution buffer to 70 °C. Purification of DNA was not necessary for bisulfite-conversion and genome-wide methylation profiling. CVS cells were propagated and continue to express genes found in freshly isolated chorionic villi.ConclusionsCVS samples preserved in RNAlater are superior. Our optimized techniques provide specimens for genetic, epigenetic and gene expression studies from a single small sample which can be used to develop diagnostics and treatments using a systems biology approach in the prenatal period. © 2016 John Wiley & Sons, Ltd.

Collagen materials are widely applied in medicine due to optimal handling characteristics, biocompatibility, controlled biodegradation, the ability to form complexes with drugs and facilitate regeneration. Researchers from Sechenov University developed, studied in experiments and introduced into medicine a variety of materials based on collagen — a protein of connective tissue. At the same time, new collagen materials were launched into clinical practice abroad. In this review of Russian and world literature, we described how scientific and applied studies of collagen materials developed over time and tried to illustrate the current state and trends of collagen application for a variety of medical purposes — from hemostatic sponges to tissue-engineered constructs. The range of available collagen-based medical products and the emergence of new collagen materials indicate the keen interest in this biomaterial from the medical community and the potential of future discoveries.