Wnt/ß-Catenin-Activated Nonpilomatrical Carcinoma of the Skin: A Case Series.

Among skin epithelial tumors, recurrent mutations in the APC/CTNNB1 genes resulting in activation of the Wnt/ß-catenin pathway have been reported predominantly in neoplasms with matrical differentiation. In the present study, we describe the morphologic, immunohistochemical, and genetic features of 16 primary cutaneous carcinomas harboring mutations activating the Wnt/ß-catenin pathway without evidence of matrical differentiation, as well as 4 combined tumors in which a similar Wnt/ß-catenin-activated carcinoma component was associated with Merkel cell carcinoma (MCC) or pilomatrical carcinoma. Among the pure tumor cases, 6 of 16 patients were women with a median age of 80 years (range, 58-98 years). Tumors were located on the head and neck (n = 7, 44%), upper limb (n = 4, 25%), trunk (n = 3, 18%), and leg (n = 2, 13%). Metastatic spread was observed in 4 cases resulting in death from disease in 1 patient. Microscopically, all cases were poorly differentiated neoplasms infiltrating the dermis and/or subcutaneous tissue. In 13 cases, solid "squamoid" areas were associated with a basophilic component characterized by rosette/pseudoglandular formation resulting in a biphasic appearance. Three specimens consisted only of poorly differentiated carcinoma lacking rosette formation. Immunohistochemical studies showed frequent expression of EMA (100%), BerEP4 (100%), cytokeratin 7 (94%), chromogranin A (44%), synaptophysin (82%), and cytokeratin 20 (69%). Complete loss of Rb expression was observed in all but 1 case. Nuclear ß-catenin and CDX2 expressions were detected in all cases. Recurrent pathogenic somatic mutations were observed in APC (60%), CTNNB1 (40%), and RB1 (n = 47%). Global methylation analysis confirmed that cases with rosette formation constituted a homogeneous tumor group distinct from established skin tumor entities (pilomatrical carcinoma, MCC, and squamous cell carcinoma), although the 3 other cases lacking such morphologic features did not. In addition, we identified 4 combined neoplasms in which there was a component showing a similar poorly differentiated rosette-forming carcinoma demonstrating Rb loss and ß-catenin activation associated with either MCC (n = 3) or pilomatrical carcinoma (n = 1). In conclusion, we describe a distinctive neoplasm, for which we propose the term "Wnt/ß-catenin-activated rosette-forming carcinoma," morphologically characterized by the association of rosette formation, squamous and/or neuroendocrine differentiation, diffuse CDX2 expression, Rb loss, and mutations in CTNNB1/APC genes.

The SABER School Feeding policy tool: a 10-year analysis of its use by countries in developing policies for their national school meals programs.

Since its launch in 2011, 59 governments have used the World Bank's Systems Approach for Better Education Results (SABER) policy tool to design their national school-based health and nutrition programs. This tool guides governments to self-evaluate their education system policies against international benchmarks and identify actionable priorities to strengthen national programs. Thirty-two of the 49 countries in sub-Saharan Africa (65%) have undertaken a SABER review, and globally the approach has been adopted by 68% of the world's low-income countries and 54% of lower-middle-income countries. Analysis of 51 comparable SABER School Feeding surveys suggests that countries with longer established national school meals frameworks tend also to be more advanced in other policy areas, and vice versa. The SABER reviews consistently identify, perhaps predictably, that the weakest policy areas relate to program design, implementation and fiscal space. This analysis also found that the tool had an additional value in tracking the evolution of policies when implemented over several time points, and showed that policy areas become more advanced as national programs mature. These benefits of the tool are particularly relevant to the 98 countries that co-created the global School Meals Coalition in 2021. The Coalition member countries have the specific goal of enhancing coverage and support for the well-being of schoolchildren and adolescents affected by the school closures during the COVID-19 pandemic. The SABER tool has the demonstrated potential to implement, accelerate and track changes in school meals policy and, since it has been previously used by 74% (31/42) of low- and lower-middle-income countries in sub-Saharan Africa, is an already accepted element of the political economies of those countries and so has the potential to be deployed rapidly.

Reproducibility between preschool and school-age Social Responsiveness Scale forms in the Environmental influences on Child Health Outcomes program.

Evidence suggests core autism trait consistency in older children, but development of these traits is variable in early childhood. The Social Responsiveness Scale (SRS) measures autism-related traits and broader autism phenotype, with two age-dependent forms in childhood (preschool, 2.5-4.5 years; school age, 4-18 years). Score consistency has been observed within forms, though reliability across forms has not been evaluated. Using data from the Environmental Influences on Child Health Outcomes (ECHO) program (n = 853), preschool, and school-age SRS scores were collected via maternal report when children were an average of 3.0 and 5.8 years, respectively. We compared reproducibility of SRS total scores (T-scores) and agreement above a clinically meaningful cutoff (T-scores ≥ 60) and examined predictors of discordance in cutoff scores across forms. Participant scores across forms were similar (mean difference: 3.3 points; standard deviation: 7), though preschool scores were on average lower than school-age scores. Most children (88%) were classified below the cutoff on both forms, and overall concordance was high (92%). However, discordance was higher in cohorts following younger siblings of autistic children (16%). Proportions of children with an autism diagnoses were also higher among those with discordant scores (27%) than among those with concordant scores (4%). Our findings indicate SRS scores are broadly reproducible across preschool and school-age forms, particularly for capturing broader, nonclinical traits, but also suggest that greater variability of autism-related traits in preschool-age children may reduce reliability with later school-age scores for those in the clinical range.

The peripheral epigenome predicts white matter volume contingent on developmental stage: An ECHO study.

Epigenetic processes, including DNA methylation, are emerging as key areas of interest for their potential roles as biomarkers and contributors to the risk of neurodevelopmental, psychiatric, and other brain-based disorders. Despite this growing focus, there remains a notable gap in our understanding of how DNA methylation correlates with individual variations in brain function and structure. Additionally, the dynamics of these relationships during developmental periods, which are critical windows during which many disorders first appear, are still largely unexplored. The current study extends the field by examining if peripheral DNA methylation of myelination-related genes predicts white matter volume in a healthy pediatric population [N = 250; females = 113; age range 2 months-14 years; Mage = 5.14, SDage = 3.60]. We assessed if DNA methylation of 17 myelin-related genes predict white matter volume and if age moderates these relationships. Results highlight low variability in myelin-related epigenetic variance at birth, which rapidly increases non-linearly with age, and that DNA methylation, measured at both the level of a CpG site or gene, is highly predictive of white matter volume, in early childhood but not late childhood. These novel findings propel the field forward by establishing that DNA methylation of myelin-related genes from a peripheral tissue is a predictive marker of white matter volume in children and is influenced by developmental stage. The research underscores the significance of peripheral epigenetic patterns as a proxy for investigating the effects of environmental factors, behaviors, and disorders associated with white matter.

Influence of age and sex on the thickness of the radial artery wall.

OBJECTIVE: The aim of this study is to investigate whether there is a relationship between age or sex and the thickness of the radial artery wall. MATERIALS AND METHODS: We harvested human radial arteries from 48 cadavers (30 men and 18 women) in the anatomy laboratory. Histological sections of 3 µm thickness were prepared at the Laboratory of Anatomy and Pathological Cytology, mounted on slides, and stained with hematoxylin-phloxine-safran, Masson's trichrome, and orcein. The thickness of each radial artery wall (intima-media thickness) was measured using optical microscopy, and an average measurement was established among the three thicknesses (upper third, middle third, and lower third). STATISTICAL METHODS: Statistical analyses were performed using the R software. Means and standard deviations were utilized. A correlation analysis was also conducted to assess the relationship between radial artery wall thickness and subjects' age. RESULTS: On average, the thickness of the left radial artery wall and that of the right radial artery measured 282 (34) micrometers (µm). We found a correlation between radial artery wall thickness and age in both men (p < 0.001) and women (p < 0.001). CONCLUSIONS: In conclusion, this study elucidates that radial artery wall thickness is related to age and sex in its assessment.

Gut-resident microorganisms and their genes are associated with cognition and neuroanatomy in children.

Emerging evidence implicates gut microbial metabolism in neurodevelopmental disorders, but its influence on typical neurodevelopment has not been explored in detail. We investigated the relationship between the microbiome and neuroanatomy and cognition of 381 healthy children, demonstrating that differences in microbial taxa and genes are associated with overall cognitive function and the size of brain regions. Using a combination of statistical and machine learning models, we showed that species including Alistipes obesi, Blautia wexlerae, and Ruminococcus gnavus were enriched or depleted in children with higher cognitive function scores. Microbial metabolism of short-chain fatty acids was also associated with cognitive function. In addition, machine models were able to predict the volume of brain regions from microbial profiles, and taxa that were important in predicting cognitive function were also important for predicting individual brain regions and specific subscales of cognitive function. These findings provide potential biomarkers of neurocognitive development and may enable development of targets for early detection and intervention.

A positive consequence of the COVID-19 pandemic: how the counterfactual experience of school closures is accelerating a multisectoral response to the treatment of neglected tropical diseases.

Global access to deworming treatment is one of the public health success stories of low-income countries in the twenty-first century. Parasitic worm infections are among the most ubiquitous chronic infections of humans, and early success with mass treatment programmes for these infections was the key catalyst for the neglected tropical disease (NTD) agenda. Since the launch of the 'London Declaration' in 2012, school-based deworming programmes have become the world's largest public health interventions. WHO estimates that by 2020, some 3.3 billion school-based drug treatments had been delivered. The success of this approach was brought to a dramatic halt in April 2020 when schools were closed worldwide in response to the COVID-19 pandemic. These closures immediately excluded 1.5 billion children not only from access to education but also from all school-based health services, including deworming. WHO Pulse surveys in 2021 identified NTD treatment as among the most negatively affected health interventions worldwide, second only to mental health interventions. In reaction, governments created a global Coalition with the twin aims of reopening schools and of rebuilding more resilient school-based health systems. Today, some 86 countries, comprising more than half the world's population, are delivering on this response, and school-based coverage of some key school-based programmes exceeds those from January 2020. This paper explores how science, and a combination of new policy and epidemiological perspectives that began in the 1980s, led to the exceptional growth in school-based NTD programmes after 2012, and are again driving new momentum in response to the COVID-19 pandemic. This article is part of the theme issue 'Challenges and opportunities in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs'.

At-home dried blood spot (DBS) collection to increase population heterogeneity representation in pediatric research: An ECHO study.

Self-collection of dried blood samples (DBS) in the participant's home provides an alternative to university/hospital visits for research and has the potential to improve the representation of population heterogeneity in research. This study aimed to assess the feasibility of guardian and/or self-DBS collection in healthy youth in the lab and home. Guardians/youth [N = 140; females = 63; M age = 8.73, SD age = 3.56] who enrolled in a longitudinal study of typical development were asked during a lab visit to provide a DBS. Upon providing a sample, the participants were asked if they would be willing to self-collect in the home and return the sample via the post office. Of those asked to provide a sample in the lab, 82% consented and 18% declined, with a significant difference in age but no significant difference in sex, ethnicity, race, or family income. Of those who provided a sample in the lab, 75% were willing to self-collect DBS in the home, with no significant difference in demographic variables between them. We report a quality assessment and DNA extraction results from a subset of samples. The results demonstrate a high feasibility of DBS collection from healthy youth for research purposes both in the laboratory and in the home across different demographic variables. Developmental researchers should consider including this approach in their studies to increase population heterogeneity representation.

Building on a decade of progress in water, sanitation and hygiene to control, eliminate and eradicate neglected tropical diseases.

Water, sanitation and hygiene (WASH) are essential for the control and elimination of neglected tropical diseases (NTDs). The forthcoming NTD road map 'Ending the neglect to attain the Sustainable Development Goals: a road map for neglected tropical diseases 2021-2030' encourages cross-sectoral collaboration and includes cross-cutting targets on WASH. This commentary reflects on collaborative efforts between the NTD and WASH sectors over the past years and encourages strengthened partnerships to support the new road map and achieve the 2030 agenda ambition of leaving no one behind.

Neonatal mortality in East Africa and West Africa: a geographic analysis of district-level demographic and health survey data.

Under-five child mortality declined 47% since 2000 following the implementation of the United Nation's (UN) Millennium Development Goals. To further reduce under-five child mortality, the UN's Sustainable Development Goals (SDGs) will focus on interventions to address neonatal mortality, a major contributor of under-five mortality. The African region has the highest neonatal mortality rate (28.0 per 1000 live births), followed by that of the Eastern Mediterranean (26.6) and South-East Asia (24.3). This study used the Demographic and Health Survey Birth Recode data (http://dhsprogram.com/data/File-Types-and-Names.cfm) to identify high-risk districts and countries for neonatal mortality in two sub-regions of Africa - East Africa and West Africa. Geographically weighted Poisson regression models were estimated to capture the spatially varying relationships between neonatal mortality and dimensions of potential need i) care around the time of delivery, ii) maternal education, and iii) women's empowerment. In East Africa, neonatal mortality was significantly associated with home births, mothers without an education and mothers whose husbands decided on contraceptive practices, controlling for rural residency. In West Africa, neonatal mortality was also significantly associated with home births, mothers with a primary education and mothers who did not want or plan their last child. Importantly, neonatal mortality associated with home deliveries were explained by maternal exposure to unprotected water sources in East Africa and older maternal age and female sex of infants in West Africa. Future SDG-interventions may target these dimensions of need in priority high-risk districts and countries, to further reduce the burden of neonatal mortality in Africa.

Dysgeusia following consumption of pine nuts: more than 3000 cases in France.

INTRODUCTION: In March 2008, French poison centres (PCs) recorded the first calls reporting persistent bitterness following the ingestion of pine nuts. METHODS: The French toxic exposure surveillance system (French-Tess) was searched and a descriptive analysis of cases was performed on data recorded from 13 March 2008 to 31 January 2010. RESULTS: Some 3111 cases of bitterness were reported to PCs. The number of cases rose sharply from May 2009 to reach a peak in August 2009 with 697 cases. The median time to onset of dysgeusia was 24 hours and it lasted less than 14 days in 95% of cases. Raw as well as cooked or processed pine nuts were implicated. DISCUSSION: The delayed onset and persistence of dysgeusia suggest that the toxin may act via an unknown toxic mechanism on the receptor. The aetiological agent could be an unidentified toxin present in some varieties of non-edible pine nuts. CONCLUSION: The high incidence of the event and the lack of understanding of the nature of the toxin and its pathophysiological mechanism require continued monitoring of poison cases, botanical and biochemical analysis, and experimental studies.