Trends in incidence and survival of childhood cancers in Khon Kaen, Thailand (2000-2019): a population-based Khon Kaen Cancer Registry study.

BACKGROUND: In Thailand, the national health care system and nationwide standard treatment protocols have evolved over time, potentially influencing the trends in the incidence and survival rates of childhood cancers. However, further investigations are required to comprehensively study these trends in Khon Kaen, Thailand. METHODS: Childhood cancer patients aged 0-14 years (n = 541) who were diagnosed with one of the five most common cancers between 2000 and 2019 from the population-based Khon Kaen Cancer Registry were enrolled. Descriptive statistics were used to analyse the demographic data, which are presented as numbers, percentages, means, and standard deviations. The trends in incidence between 2000 and 2019, including age-standardized incidence rates (ASRs) and annual percent changes (APCs), were analysed using the Joinpoint regression model. Survival analysis was performed for 5-year relative survival rates (RSRs) according to the Pohar Perme estimator and Kaplan-Meier survival curves. RESULTS: The ASRs of the overall top 5 childhood cancer groups were 67.96 and 106.12 per million person-years in 2000 and 2019, respectively. Overall, the APC significantly increased by 2.37% each year for both sexes. The overall 5-year RSRs were 60.5% for both sexes, 58.2% for males, and 63.9% for females. The highest 5-year RSR was for germ cell tumours (84.3%), whereas the lowest 5-year RSR was for neuroblastoma (29.1%). CONCLUSIONS: The incidence and survival rates of childhood cancers in Khon Kaen, Thailand, varied according to sex. The incidence trends increased over time, meanwhile, the relative survival rates rose to satisfactory levels and were comparable to those of other nations with similar financial status. The implementation of national health policies and adherence to national treatment guidelines have improved cancer diagnosis and treatment outcomes.

Clinical features and treatment outcomes of liver involvement in paediatric Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is the most common histiocytic disorder in children, and liver involvement in LCH is rare. This retrospective study reported the clinical features and prognosis of patients with hepatic LCH. Liver involvement was defined by histopathological findings, liver dysfunction or abnormalities, or ultrasound imaging. A total of 130 patients (14.5%) with hepatic LCH out of 899 in the LCH population were enrolled. Patients with liver involvement had greater frequencies of skin, lung, hearing system, and haematologic system involvement, and hemophagocytic lymphohistiocytosis (P<0.001, 0.001, 0.002, 0.009, and <0.001, respectively). Overall survival and progression-free survival were lower in LCH patients with liver involvement than in those without liver involvement (P<0.001 and <0.001). In patients with liver involvement, the overall survival (OS) and progression-free survival (PFS) rates were lower in patients with cholangitis than in those without cholangitis (P<0.020 and 0.030). For the treatment response, the response rate of hepatic LCH patients to initial first-line therapy (n=89) was 22.5%. However, there was no significant difference in the response rate or recurrence rate between patients who shifted from first-line treatment to second-line treatment (n=29) or to targeted therapy (n=13) (P=0.453 and 1.000). The response rate of hepatic LCH patients who received initial second-line therapy (n=13) was 38.5%. Two of these patients subsequently experienced bone recurrence. The response rate of hepatic LCH patients who received initial targeted therapy (n=16) was 75.0%. Three patients subsequently experienced recurrence, including 2 in the bone and 1 in the liver and skin. A total of 39.3% of patients who received second-line treatment had severe myelosuppression (grade III-IV), and 50.8% had varying degrees of gastrointestinal events, whereas there was no severe toxicity in patients who received first-line treatment and targeted therapy. Four patients underwent liver transplantation because of liver cirrhosis. The patients' liver disease improved within a follow-up period of 18-79 months. This study demonstrated that LCH with liver involvement, especially cholangitis, indicates a poor prognosis. Targeted therapy provides a good treatment response and less toxicity. However, it may relapse after withdrawal. Liver transplantation is still a reliable salvage option for patients with end-stage liver disease.

Age at death during the Covid-19 lockdown in French metropolitan regions: a non parametric quantile regression approach.

BACKGROUND: Lockdowns have been implemented to limit the number of hospitalisations and deaths during the first wave of 2019 coronavirus disease. These measures may have affected differently death characteristics, such age and sex. France was one of the hardest hit countries in Europe with a decreasing east-west gradient in excess mortality. This study aimed at describing the evolution of age at death quantiles during the lockdown in spring 2020 (17 March-11 May 2020) in the French metropolitan regions focusing on 3 representatives of the epidemic variations in the country: Bretagne, Ile-de-France (IDF) and Bourgogne-Franche-Comté (BFC). METHODS: Data were extracted from the French public mortality database from 1 January 2011 to 31 August 2020. The age distribution of mortality observed during the lockdown period (based on each decile, plus quantiles 1, 5, 95 and 99) was compared with the expected one using Bayesian non-parametric quantile regression. RESULTS: During the lockdown, 5457, 5917 and 22 346 deaths were reported in Bretagne, BFC and IDF, respectively. An excess mortality from + 3% in Bretagne to + 102% in IDF was observed during lockdown compared to the 3 previous years. Lockdown led to an important increase in the first quantiles of age at death, irrespective of the region, while the increase was more gradual for older age groups. It corresponded to fewer young people, mainly males, dying during the lockdown, with an increase in the age at death in the first quantile of about 7 years across regions. In females, a less significant shift in the first quantiles and a greater heterogeneity between regions were shown. A greater shift was observed in eastern region and IDF, which may also represent excess mortality among the elderly. CONCLUSIONS: This study focused on the innovative outcome of the age distribution at death. It shows the first quantiles of age at death increased differentially according to sex during the lockdown period, overall shift seems to depend on prior epidemic intensity before lockdown and complements studies on excess mortality during lockdowns.

The role of healthcare providers and caregivers in monitoring critically ill children: a qualitative study in a tertiary hospital, southern Malawi.

BACKGROUND: Critically ill children require close monitoring to facilitate timely interventions throughout their hospitalisation. In low- and middle-income countries with a high disease burden, scarce paediatric critical care resources complicates effective monitoring. This study describes the monitoring practices for critically ill children in a paediatric high-dependency unit (HDU) in Malawi and examines factors affecting this vital process. METHODS: A formative qualitative study based on 21 in-depth interviews of healthcare providers (n = 12) and caregivers of critically ill children (n = 9) in the HDU along with structured observations of the monitoring process. Interviews were transcribed and translated for thematic content analysis. RESULTS: The monitoring of critically ill children admitted to the HDU was intermittent, using devices and through clinical observations. Healthcare providers prioritised the most critically ill children for more frequent monitoring. The ward layout, power outages, lack of human resources and limited familiarity with available monitoring devices, affected monitoring. Caregivers, who were present throughout admission, were involved informally in monitoring and flagging possible deterioration of their child to the healthcare staff. CONCLUSION: Barriers to the monitoring of critically ill children in the HDU were related to ward layout and infrastructure, availability of accurate monitoring devices and limited human resources. Potential interventions include training healthcare providers to prioritise the most critically ill children, allocate and effectively employ available devices, and supporting caregivers to play a more formal role in escalation.

Association between age, gender, and oral traumatic ulcerative lesions: a retrospective study.

BACKGROUND: Oral traumatic ulcerative lesions (OTUL) are commonly encountered in clinical practice, yet there is limited research on their clinical characteristics and traumatic etiological factors. This retrospective study aimed to analyze the age, gender, clinical characteristics, and traumatic etiological factors in a large cohort of patients with OTUL and provide valuable insights for dental clinicians to optimize patient care and prevention strategies. METHODS: A total of 1543 patients with OTUL were enrolled in this study. Age, gender, medical history, clinical characteristics and traumatic etiological factors were collected and analyzed. Logistic regression analysis was performed to determine the significance of age and gender as factors related to OTUL. RESULTS: The study revealed significant variations in clinical characteristics and traumatic etiological factors among different age groups and between genders. Logistic regression analysis demonstrated that both age and gender were significant factors related to OTUL. CONCLUSION: The clinical characteristics of OTUL and traumatic etiological factors appear to be significantly different according to age and gender. More targeted prevention strategies should be implemented for all age and gender groups.

Adherence to low-dose methotrexate in children with juvenile idiopathic arthritis using a sensitive methotrexate assay.

BACKGROUND: Low-dose weekly methotrexate (MTX) is the mainstay of treatment in juvenile idiopathic arthritis. Unfortunately, a substantial part of patients has insufficient efficacy of MTX. A potential cause of this inadequate response is suboptimal drug adherence. The aim of this study was to assess MTX adherence in juvenile idiopathic arthritis patients by quantification of MTX concentrations in plasma. Secondly, the association between MTX concentrations and either self-reported adherence issues, or concomitant use of biologics was examined. METHODS: This was a retrospective, observational study using plasma samples from juvenile idiopathic arthritis patients. An ultrasensitive liquid chromatography-tandem mass spectrometry method was developed for quantification of MTX and its metabolite 7-hydroxy-MTX in plasma. The determined MTX plasma concentrations in juvenile idiopathic arthritis patients were compared with corresponding adherence limits, categorising them as either adherent or possibly non-adherent to MTX therapy. RESULTS: Plasma samples of 43 patients with juvenile idiopathic arthritis were analysed. Adherence to MTX in this population was 88% shortly after initiation of MTX therapy and decreased to 77% after one year of treatment. Teenagers were more at risk for non-adherence (p = 0.002). We could not find an association between MTX adherence with either self-reported adherence issues, nor with the use of concomitant biological treatment (p = 1.00 and p = 0.27, respectively; Fisher's Exact). CONCLUSIONS: Quantification of MTX in plasma is a feasible and objective method to assess adherence in patients using low-dose weekly MTX. In clinical practice, the use of this method could be a helpful tool for physicians to refute or support suspicion of non-adherence to MTX therapy.

Disease characteristics, effectiveness, and safety of vestronidase alfa for the treatment of patients with mucopolysaccharidosis VII in a novel, longitudinal, multicenter disease monitoring program.

BACKGROUND: Mucopolysaccharidosis VII (MPS VII) is an ultra-rare, autosomal recessive, debilitating, progressive lysosomal storage disease caused by reduced activity of ß-glucuronidase (GUS) enzyme. Vestronidase alfa (recombinant human GUS) intravenous enzyme replacement therapy is an approved treatment for patients with MPS VII. METHODS: This disease monitoring program (DMP) is an ongoing, multicenter observational study collecting standardized real-world data from patients with MPS VII (N ≈ 50 planned) treated with vestronidase alfa or any other management approach. Data are monitored and recorded in compliance with Good Clinical Practice guidelines and planned interim analyses of captured data are performed annually. Here we summarize the safety and efficacy outcomes as of 17 November 2022. RESULTS: As of the data cutoff date, 35 patients were enrolled: 28 in the Treated Group and seven in the Untreated Group. Mean (SD) age at MPS VII diagnosis was 4.5 (4.0) years (range, 0.0 to 12.4 years), and mean (SD) age at DMP enrollment was 13.9 (11.1) years (range, 1.5 to 50.2 years). Ten patients (29%) had a history of nonimmune hydrops fetalis. In the 23 patients who initiated treatment prior to DMP enrollment, substantial changes in mean excretion from initial baseline to DMP enrollment were observed for the three urinary glycosaminoglycans (uGAGs): dermatan sulfate (DS), -84%; chondroitin sulfate (CS), -55%; heparan sulfate (HS), -42%. Also in this group, mean reduction from initial baseline to months 6, 12, and 24 were maintained for uGAG DS (-84%, -87%, -89%, respectively), CS (-70%, -71%, -76%, respectively), and HS (+ 3%, -32%, and - 41%, respectively). All adverse events (AEs) were consistent with the known vestronidase alfa safety profile. No patients discontinued vestronidase alfa. One patient died. CONCLUSIONS: To date, the DMP has collected invaluable MPS VII disease characteristic data. The benefit-risk profile of vestronidase alfa remains unchanged and favorable for its use in the treatment of pediatric and adult patients with MPS VII. Reductions in DS and CS uGAG demonstrate effectiveness of vestronidase alfa to Month 24. Enrollment is ongoing.

Access to early diagnosis for attention-deficit/hyperactivity disorder among children and adolescents in Mexico City at specialized mental health services.

BACKGROUND: In Mexico, this pioneering research was undertaken to assess the accessibility of timely diagnosis of Dyads [Children and adolescents with Attention Deficit Hyperactivity Disorder (ADHD) and their primary caregivers] at specialized mental health services. The study was conducted in two phases. The first phase involved designing an "Access Pathway" aimed to identify barriers and facilitators for ADHD diagnosis; several barriers, with only the teacher being identified as a facilitator. In the second phase, the study aimed to determine the time taken for dyads, to obtain a timely diagnosis at each stage of the Access Pathway. As well as identify any disparities based on gender and socioeconomic factors that might affect the age at which children can access a timely diagnosis. METHOD: In a retrospective cohort study, 177 dyads participated. To collect data, the Acceda Survey was used, based on the robust Conceptual Model Levesque, 2013. The survey consisted of 48 questions that were both dichotomous and polytomous allowing the creation of an Access Pathway that included five stages: the age of perception, the age of search, the age of first contact with a mental health professional, the age of arrival at the host hospital, and the age of diagnosis. The data was meticulously analyzed using a comprehensive descriptive approach and a nonparametric multivariate approach by sex, followed by post-hoc Mann-Whitney's U tests. Demographic factors were evaluated using univariable and multivariable Cox regression analyses. RESULTS: 71% of dyads experienced a late, significantly late, or highly late diagnosis of ADHD. Girls were detected one year later than boys. Both boys and girls took a year to seek specialized mental health care and an additional year to receive a formal specialized diagnosis. Children with more siblings had longer delays in diagnosis, while caregivers with formal employment were found to help obtain timely diagnoses. CONCLUSIONS: Our findings suggest starting the Access Pathway where signs and symptoms of ADHD are detected, particularly at school, to prevent children from suffering consequences. Mental health school-based service models have been successfully tested in other latitudes, making them a viable option to shorten the time to obtain a timely diagnosis.

Epigenetics of the non-coding RNA nc886 across blood, adipose tissue and skeletal muscle in offspring exposed to diabetes in pregnancy.

BACKGROUND: Diabetes in pregnancy is associated with increased risk of long-term metabolic disease in the offspring, potentially mediated by in utero epigenetic variation. Previously, we identified multiple differentially methylated single CpG sites in offspring of women with gestational diabetes mellitus (GDM), but whether stretches of differentially methylated regions (DMRs) can also be identified in adolescent GDM offspring is unknown. Here, we investigate which DNA regions in adolescent offspring are differentially methylated in blood by exposure to diabetes in pregnancy. The secondary aim was to characterize the RNA expression of the identified DMR, which contained the nc886 non-coding RNA. METHODS: To identify DMRs, we employed the bump hunter method in samples from young (9-16 yr, n = 92) offspring of women with GDM (O-GDM) and control offspring (n = 94). Validation by pyrosequencing was performed in an adult offspring cohort (age 28-33 years) consisting of O-GDM (n = 82), offspring exposed to maternal type 1 diabetes (O-T1D, n = 67) and control offspring (O-BP, n = 57). RNA-expression was measured using RT-qPCR in subcutaneous adipose tissue and skeletal muscle. RESULTS: One significant DMR represented by 10 CpGs with a bimodal methylation pattern was identified, located in the nc886/VTRNA2-1 non-coding RNA gene. Low methylation status across all CpGs of the nc886 in the young offspring was associated with maternal GDM. While low methylation degree in adult offspring in blood, adipose tissue, and skeletal muscle was not associated with maternal GDM, adipose tissue nc886 expression was increased in O-GDM compared to O-BP, but not in O-T1D. In addition, adipose tissue nc886 expression levels were positively associated with maternal pre-pregnancy BMI (p = 0.006), but not with the offspring's own adiposity. CONCLUSIONS: Our results highlight that nc886 is a metastable epiallele, whose methylation in young offspring is negatively correlated with maternal obesity and GDM status. The physiological effect of nc886 may be more important in adipose tissue than in skeletal muscle. Further research should aim to investigate how nc886 regulation in adipose tissue by exposure to GDM may contribute to development of metabolic disease.

A proposed simplified definition of metabolic syndrome in children and adolescents: a global perspective.

Metabolic syndrome (MetS) is becoming prevalent in the pediatric population. The existing pediatric MetS definitions (e.g., the International Diabetes Federation (IDF) definition and the modified National Cholesterol Education Program (NCEP) definition) involve complex cut-offs, precluding fast risk assessment in clinical practice.We proposed a simplified definition for assessing MetS risk in youths aged 6-17 years, and compared its performance with two existing widely used pediatric definitions (the IDF definition, and the NCEP definition) in 10 pediatric populations from 9 countries globally (n = 19,426) using the receiver operating characteristic (ROC) curve analyses. In general, the total MetS prevalence of 6.2% based on the simplified definition was roughly halfway between that of 4.2% and 7.7% estimated from the IDF and NCEP definitions, respectively. The ROC curve analyses showed a good agreement between the simplified definition and two existing definitions: the total area under the curve (95% confidence interval) of the proposed simplified definition for identifying MetS risk achieved 0.91 (0.89-0.92) and 0.79 (0.78-0.81) when using the IDF or NCEP definition as the gold standard, respectively.The proposed simplified definition may be useful for pediatricians to quickly identify MetS risk and cardiometabolic risk factors (CMRFs) clustering in clinical practice, and allow direct comparison of pediatric MetS prevalence across different populations, facilitating consistent pediatric MetS risk monitoring and the development of evidence-based pediatric MetS prevention strategies globally.

Phenotypic variability and management of patients with mosaic monosomy X and Y chromosome material: a case series.

BACKGROUND: we aim to discuss the origin and the differences of the phenotypic features and the management care of rare form of disorder of sex development due to Mosaic monosomy X and Y chromosome materiel. METHODS: We report our experience with patients harboring mosaic monosomy X and Y chromosome material diagnosed by blood cells karyotypes and cared for in our department from 2005 to 2022. RESULTS: We have included five infants in our study. The current average age was 8 years. In four cases, the diagnosis was still after born and it was at the age of 15 years in one case. Physical examination revealed a variable degree of virilization, ranging from a normal male phallus with unilateral ectopic gonad to ambiguous with a genital tubercle and bilateral not palpable gonads in four cases and normal female external genitalia in patient 5. Karyotype found 45, X/46, XY mosaicism in patient 1 and 2 and 45, X/46, X, der (Y) mosaicism in patient 3, 4 and 5. Three cases were assigned to male gender and two cases were assigned to female. After radiologic and histologic exploration, four patients had been explored by laparoscopy to perform gonadectomy in two cases and Mullerian derivative resection in the other. Urethroplasty was done in two cases of posterior hypospadias. Gender identity was concordant with the sex of assignment at birth in only 3 cases. CONCLUSION: Because of the phenotypic heterogeneity of this sexual disorders and the variability of its management care, then the decision should rely on a multidisciplinary team approach.

Cognitive, social, and mental health functions of refugee children - screening and supportive actions at school: a study protocol.

BACKGROUND: Despite a world-leading educational system, an achievement gap in educational outcomes exists between children of refugee background and native-born peers in Finland. To offer targeted support for children at schools, we need to be able to reliably assess and understand the interplay of the aspects of children's cognitive, social, and mental health functions that may explain the underachievement of refugee children. This study tests a novel research-based, universally applicable screening battery for evaluating cognitive, social, and mental health functioning of children at schools and planning supportive actions. It aims to answer research questions about a) the cognitive, social, and mental health functioning of refugee children compared with non-refugee immigrant and native-born children, b) the interplay of these different functions among refugee and other children, c) whether implementing a screening battery can inform schools in planning supportive actions for (refugee) children, and d) whether such supportive actions result in improvements in cognitive, social, and mental health functioning. METHODS: Four hundred fifty children aged 10-12 will be recruited from primary schools, including 150 children of refugee background, 150 of non-refugee immigrant background, and 150 native-born Finnish children. A screening battery including tasks and questionnaires on different aspects of cognitive, social, and mental health functioning will be used to assess the children in their classrooms at the start and end of a school year. Supporting information will also be collected from parents and teachers. The information gathered will be collated into class-level feedback reports for teachers and, with parental permission, individualized reports for multiprofessional student welfare bodies, for informing supportive actions. Correlational and latent profile analyses, ANOVAs, and linear regression will be used to answer the research questions. DISCUSSION: This study will help clarify how the interplay of cognitive, social, and mental health factors may explain underachievement at school among refugee children. It will provide evidence about the extent to which a standardized screening battery could be helpful in informing and planning supportive actions for children at schools, and whether such supportive actions can lead to positive cognitive, social, or mental health outcomes. TRIAL REGISTRATION: The study will be preregistered on the Open Science Framework.

A healthcare claims analysis to identify and characterize patients with suspected X-Linked Myotubular Myopathy (XLMTM) in the Brazilian Healthcare System.

BACKGROUND: X-linked myotubular myopathy (XLMTM) is a rare, life-threatening congenital disease, which is not well-defined. To our knowledge, no studies characterizing the XLMTM disease burden have been conducted in Brazil. We identified and described patients with suspected XLMTM using administrative claims data from the Brazilian public healthcare system. METHODS: Data from 2015 to 2019 were extracted from the DATASUS database. As no XLMTM-specific ICD-10 code was available, a stepwise algorithm was applied to identify patients with suspected XLMTM by selecting male patients with a congenital myopathies code (G71.2), aged < 18 years at index date (first claim of G71.2), with an associated diagnostic procedure (muscle biopsy/genetic test) and without spinal muscular atrophy or Duchenne muscular dystrophy. We attempted to identify patients with suspected severe XLMTM based on use of both respiratory and feeding support, which are nearly universal in the care of XLMTM patients. Analyses were performed for the overall cohort and stratified by age at index date < 5 years old and ≥ 5 years old. RESULTS: Of 173 patients with suspected XLMTM identified, 39% were < 5 years old at index date. Nearly all (N = 166) patients (96%) were diagnosed by muscle biopsy (91% of patients < 5 years old and 99% of patients ≥ 5 years old), six (3.5%) were diagnosed by clinical evaluation (8% of patients < 5 years old and 1% of patients ≥ 5 years old), and one was diagnosed by a genetic test. Most patients lived in Brasilia (n = 55), São Paulo (n = 33) and Minas Gerais (n = 27). More than 85% of patients < 5 years old and approximately 75% of patients ≥ 5 years old had physiotherapy at the index date. In both age groups, nearly 50% of patients required hospitalization at some point and 25% required mobility support. Respiratory and feeding support were required for 3% and 12% of patients, respectively, suggesting that between 5 and 21 patients may have had severe XLMTM. CONCLUSION: In this real-world study, genetic testing for XLMTM appears to be underutilized in Brazil and may contribute to underdiagnosis of the disease. Access to diagnosis and care is limited outside of specific regions with specialized clinics and hospitals. Substantial use of healthcare resources included hospitalization, physiotherapy, mobility support, and, to a lesser extent, feeding support and respiratory support.

Diagnostic value of cytokines in severe childhood Mycoplasma pneumoniae pneumonia combined with Adenovirus infection.

BACKGROUND: To explore the alterations of inflammatory markers and immune-related cytokines in children infected with Mycoplasma pneumoniae (MP) combined with Adenovirus (ADV). METHODS: The study population consisted of 201 children with MPP, and they were grouped according to whether they were coinfected with ADV infection and critically ill. Additionally, comparative analyses were performed. The diagnostic value of different indicators and combined indicators for SMPP combined with ADV was assessed using ROC curves. RESULTS: There was no difference between group A1 and group A2, group B1 and group B2 in terms of age, gender, duration of hospitalisation and fever. The levels of calcitoninogen(PCT), lactate dehydrogenase concentration(LDH), interleukin(IL)-6, IL-8, IL-10, IL-4, IL-12P70, and IFN-γ in group A were higher than group B. The severe group (A1, B1) was significantly higher than the mild group (A2, B2) in terms of D-dimer, CRP, PCT, LDH, IL-6, IL-8, IL-10, IL-17a and number of patients with pleural effusion, solid lung changes. Among the individual indexes of D-dimer, CRP, N%,LDH, and PCT, the AUC of the combined test was 0.977, which was higher than that of the individual indicators. Among IL-6, IL-8, IL-10, and IL-17a, the AUC of the combined assay was 0.802, which was higher than that of the individual indicators. CONCLUSION: MP combined with ADV infection was associated with increased expression levels of IL-6, IL-8, IL-10, IL-4, IL-12P70, IFN-γ, and LDH. IL-6, IL-8, IL-10, IL-17a, LDH, PCT, CRP, and D-dimer could be used as predictors of SMPP and the combined test can improve the diagnostic value.

Novel 14q32.2 paternal deletion encompassing the whole DLK1 gene associated with Temple syndrome.

BACKGROUND: Temple syndrome (TS14) is a rare imprinting disorder caused by maternal UPD14, imprinting defects or paternal microdeletions which lead to an increase in the maternal expressed genes and a silencing the paternally expressed genes in the 14q32 imprinted domain. Classical TS14 phenotypic features include pre- and postnatal short stature, small hands and feet, muscular hypotonia, motor delay, feeding difficulties, weight gain, premature puberty along and precocious puberty. METHODS: An exon array comparative genomic hybridization was performed on a patient affected by psychomotor and language delay, muscular hypotonia, relative macrocephaly, and small hand and feet at two years old. At 6 years of age, the proband presented with precocious thelarche. Genes dosage and methylation within the 14q32 region were analyzed by MS-MLPA. Bisulfite PCR and pyrosequencing were employed to quantification methylation at the four known imprinted differentially methylated regions (DMR) within the 14q32 domain: DLK1 DMR, IG-DMR, MEG3 DMR and MEG8 DMR. RESULTS: The patient had inherited a 69 Kb deletion, encompassing the entire DLK1 gene, on the paternal allele. Relative hypermethylation of the two maternally methylated intervals, DLK1 and MEG8 DMRs, was observed along with normal methylation level at IG-DMR and MEG3 DMR, resulting in a phenotype consistent with TS14. Additional family members with the deletion showed modest methylation changes at both the DLK1 and MEG8 DMRs consistent with parental transmission. CONCLUSION: We describe a girl with clinical presentation suggestive of Temple syndrome resulting from a small paternal 14q32 deletion that led to DLK1 whole-gene deletion, as well as hypermethylation of the maternally methylated DLK1-DMR.

Mothers' evaluations of fathers' contributions to raising children with autism spectrum disorder in the United Arab Emirates.

BACKGROUND: Autism spectrum disorder (ASD) is a lifelong neurological condition which results in social skill deficits, communication difficulties, and restrictive and repetitive behaviour. The difficulties associated with parenting children with ASD have been studied extensively, mainly from the perspectives of mothers. The extent of involvement of fathers in the raising of children with ASD has received limited scholarly attention, especially in non-Western contexts such as the United Arab Emirates. OBJECTIVES: This study asked mothers to evaluate the involvement of fathers in the development of children with ASD. METHODS: In all, 240 mothers completed the Fathers' Involvement in Development and Rehabilitation Scale, designed based on a review of literature on the construct of involvement, namely attitude, participation in training, and support domains. The data were subjected to computation of mean scores, multivariate analysis of variance, hierarchical regression, and moderation analyses. RESULTS: The results suggested that fathers held positive attitudes and provided substantial support to their children with ASD. However, mothers were ambivalent regarding the participation of fathers in training to support the development of their children. Differences were also observed between participants according to marital status, location, child gender, and ASD severity. CONCLUSION: Recommendations for targeted training for fathers and other study implications are discussed.

It provides families with other avenues for treatment when there are no other options Surgeons' perspectives of being part of a precision medicine trial for poor prognosis paediatric cancer patients: A short report.

OBJECTIVE: Precision medicine is transforming cancer treatment, yet the perspectives of surgeons who often play a critical role in the delivery of precision medicine remain understudied. METHODS: We conducted semi-structured interviews with 13 surgeons involved in a precision medicine trial for children with poor prognosis cancer. We explored knowledge of genetics, confidence with somatic and germline results, ratings of benefit to stakeholders and willingness to undertake surgical procedures. RESULTS: Surgeons generally had positive attitudes towards precision medicine but expressed concerns about families' unrealistic expectations, mixed opinions on the benefits and the use of research-only biopsies. Most surgeons rated their genetics knowledge as 'good' (69%) and felt 'very confident' in identifying genetic specialists (66%), but 'not confident' (66.6%) in making treatment recommendations. Surgeons' willingness to undertake a procedure was influenced by potential patient benefit. CONCLUSIONS: Our findings support the need for more workforce and training support for surgeons to fully engage with precision medicine.

Adolescents with orofacial clefts: understanding their experiences.

OBJECTIVE: To understand the experience of young people with orofacial clefts regarding life as an adolescent. METHODS: Descriptive, qualitative study, developed in a Brazilian public and tertiary hospital, a reference center in the care of patients with craniofacial anomalies and related syndromes, between February and April 2019. The sample was defined by theoretical saturation. The following inclusion criteria were established: age between ten and 19 years old and having previously operated on orofacial cleft (lip and/or palate). Individuals with fissure associated with syndromes or other malformations were excluded. Data collection was performed through semi-structured interviews, which were audio recorded and transcribed in full. The trigger element was: how has it been for you to experience your adolescence? For the construction of the results, content analysis was used in the thematic modality. RESULTS: Seventeen adolescents participated. From the speeches, three categories were revealed: interacting socially, feeling supported, and experiencing and facing prejudice. CONCLUSIONS: The biopsychosocial and conflicting complexity that adolescents with orofacial clefts experience was noticed, as well as the importance of receiving support and establishing modalities of situational coping.

Visual scanning of social stimuli in preterm and autism spectrum disorder children.

OBJECTIVE: To evaluate the pattern of eye-gaze of preterm (PT), autism spectrum disorder (ASD) and neurotypical (Ty) children. METHODS: A cross-sectional study with eight preterm (born with ≤2000 g weight), nine ASD and five Ty male children, between six and nine years old, was performed. The eye gaze was evaluated presenting a board with a couple in social interaction, and a video with four children playing with blocks, projected in a screen computer, successively, evaluating the time that the children looked at each stimulus. RESULTS: Although all the groups focus on the central social figure with no significant differences, ASD presented significant differences in time fixation of the objects (p=0.021), while premature children fixated more time in the central social interaction than in the whole scene than typical children. CONCLUSIONS: Although this study found noteworthy differences in the eye-gaze patterns among the three groups, additional research with a more extensive participant pool is necessary to validate these preliminary results.

Trends in mortality rates and correlations between intracranial injuries and external causes: A Japanese population study.

The age-standardized incidence of head trauma in 2016 was 369 per 100,000 people worldwide. The Western Pacific region, including Japan, had the highest incidence. This study aimed to extract ICD-10 code data for intracranial injury (S06) and external causes of morbidity and mortality (V01-Y89), analyze their characteristics and interrelationships, and contribute to these diseases' prevention, treatment, and prognosis. The number of deaths according to injury type and external cause type of intracranial injury published by the Japanese government was statistically analyzed using JoinPoint, and univariate distribution and multivariate correlation were conducted using JMP Software. From 1999-2021, there was a downward trend in the number of deaths because of intracranial injuries: mortality from intracranial injuries was higher among those aged ≥65 years. Conversely, mortality from intracranial injuries was lower among those aged ≤14 years. Among deaths from intracranial injury, mortality from diffuse brain injury and traumatic subdural hemorrhage was more common. Among deaths from external causes of intracranial injury, mortality from falls, transport accidents, and other unforeseen accidents was more common. Mortality because of intracranial injuries increased significantly during the 2011 Great East Japan Earthquake. For some age groups and sexes, there were significant inverse correlations of mortality with traumatic subdural hemorrhage and traumatic subarachnoid hemorrhage for transport accidents, intentional self-harm and assault, and diffuse brain injury and focal brain injury for falls. We believe that the data presented in this study will be useful for preventing and treating intracranial injuries and for developing administrative measures to reduce intracranial injuries.