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Access to high-quality early music education programs may mitigate the effects of poverty on the hypothalamic-pituitary-adrenal (HPA) axis, but fundamental questions remain about the role of early educators in conveying these benefits. In the current study, we measured the basal or resting cortisol levels of 76 children (M[subscript age] = 4.17 years; 42% female) over the course of the school day while they attended a Head Start preschool that included early music education classes. The results of a series of hierarchical linear models (HLMs) indicated that child-directed music and movement activities during these classes were associated with lower levels of cortisol (relative to teacher-directed activities; B = -0.019, p = 0.013), as were higher quality teacher-child interactions (B = -0.018, p = 0.013); both associations were moderated by child age. We discuss the implications of these results for future educational neuroscience research that seeks to inform early education programs for young children placed at risk by poverty.

Abstract Background The COVID-19 pandemic negatively impacted tuberculosis (TB) treatment services, including directly observed therapy (DOT) programs used to promote medication adherence. We compared DOT adherence embedded in a research study before and after COVID-19 lockdowns in South Africa. Methods We analyzed data from 263 observational study participants undergoing drug susceptible (DS)-TB DOT between May 2017 to March 2022. Participants enrolled before October 2019 were considered ‘pre-COVID-19’ and those enrolled after September 2020 were considered ‘post-COVID-19 lockdown groups. Negative binomial regression models were used to compare DOT non-adherence rates between the two lockdown groups. We then conducted a sensitivity analysis which only included participants enrolled in the immediate period following the first COVID-19 lockdown. Results DOT non-adherence rate was higher in the post-COVID-19 lockdown group (aIRR = 1.42, 95% CI = 1.04–1.96; p = 0.028) compared to pre-COVID-19 lockdown period, adjusting for age, sex, employment status, household hunger, depression risk, and smoked substance use. DOT non-adherence was highest immediately following the initial lockdown (aIRR = 1.74, 95% CI = 1.17–2.67; p = 0.006). Conclusion The COVID-19 lockdowns adversely effected adherence to TB DOT in the period after lockdowns were lifted. The change in DOT adherence persisted even after adjusting for socioeconomic and behavioral variables. We need a better understanding of what treatment adherence barriers were exacerbated by COVID-19 lockdowns to improve outcomes in post-pandemic times. Trial registration ClinicalTrials.gov Registration Number: NCT02840877. Registered on 19 July 2016.

Far-Infrared Radiation (FIR) is emerging as a novel non-invasive tool for mitigating inflammation and oxidative stress, offering potential benefits for certain medical conditions such as cardiovascular disease and chronic inflammatory disorders. We previously demonstrated that the application of patch-based FIR therapy on human umbilical vein endothelial cells (HUVECs) reduced the expression of inflammatory biomarkers and the levels of reactive oxygen species (ROS). Several in vitro studies have shown the inhibitory effects of FIR therapy on cell growth in different cancer cells (including murine melanoma cells), mainly using the wound healing assay, without direct cell motility or tracking analysis. The main objective of the present study was to conduct an in-depth analysis of single-cell motility and tracking during the wound healing assay, using an innovative high-throughput technique in the human melanoma cell line M14/C2. This technique evaluates various motility descriptors, such as average velocity, average curvature, average turning angle, and diffusion coefficient. Our results demonstrated that patch-based FIR therapy did not impact cell proliferation and viability or the activation of mitogen-activated protein kinases (MAPKs) in the human melanoma cell line M14/C2. Moreover, no significant differences in cell motility and tracking were observed between control cells and patch-treated cells. Altogether, these findings confirm the beneficial effects of the in vitro application of patch-based FIR therapy in human melanoma cell lines, although such effects need to be confirmed in future in vivo studies.

Gynecomastia in adolescence is a benign condition that mostly disappears spontaneously within approximately two years from onset. When it is associated with hypogonadism, it may suggest a disorder of sexual differentiation. We report the case of a young man (18 years old) with gynecomastia associated with azoospermia, small testes, hyperestrogenism and hypergonadotropic hypogonadism. A karyotype 46,XX was found, and searching for SRY (sex-determining region Y) by fluorescence in situ hybridization (FISH) highlighted the presence of the gene on the terminal region of the short arm, with breakpoints likely in Xp22.3 and Yp11.3. Implications of testosterone replacement therapy with respect to sex differentiation disorder and to physical performance are discussed.

Medical treatment with low ozone concentrations proved to exert therapeutic effects in various diseases by inducing a cytoprotective antioxidant response through the nuclear factor erythroid derived-like 2 (Nrf2) transcription factor pathway. Low ozone doses are increasingly administered to oncological patients as a complementary treatment to mitigate some adverse side-effects of antitumor treatments. However, a widespread concern exists about the possibility that the cytoprotective effect of Nrf2 activation may confer drug resistance to cancer cells or at least reduce the efficacy of antitumor agents. In this study, the effect of low ozone concentrations on tamoxifen-treated MCF7 human breast cancer cells has been investigated in vitro by histochemical and molecular techniques. Results demonstrated that cell viability, proliferation and migration were generally similar in tamoxifen-treated cells as in cells concomitantly treated with tamoxifen and ozone. Notably, low ozone concentrations were unable to overstimulate the antioxidant response through the Nfr2 pathway, thus excluding a possible ozone-driven cytoprotective effect that would lead to increased tumor cell survival during the antineoplastic treatment. These findings, though obtained in an in vitro model, support the hypothesis that low ozone concentrations do not interfere with the tamoxifen-induced effects on breast cancer cells.

Abstract Intermediate-depth seismicity is common in subducting slabs and the seismicity rate shows some statistically significant yet enigmatic global positive correlation with the maximal throw of outer-rise normal faults. Here, we have simulated the formation and subduction of outer-rise faults, using 2D thermomechanical numerical models of intra-oceanic subduction with coupled brittle-ductile damage of bending plates. We observed that outer-rise faults are formed episodically during slab segmentation and their maximal throw grows with time. When been subducted to intermediate depth, these faults are locally reactivated either by i) slab unbending/bending, simultaneous to the formation of new outer-rise faults or ii) episodic interplate coupling related to the rugged morphology of the faulted downgoing plate. Faults reactivation is concurrent with a local, transient deviatoric stress increase in intraslab domains among these structures. We suggest that slab domains affected by stress increase could be the appropriate location where potential brittle deformation can occur, generating intermediate-depth intraslab earthquakes, that are predominantly localized in heterogeneous regions of dense faulting formed within slab-segments boundaries. The temporal coincidence of stress growth at intermediate depths and throw-growth of, newly-formed, outer-rise faults at the surface may possibly explain the observed global positive correlation of intermediate-depth seismicity rate with maximal fault throw.

Resumo O envelhecimento da população mundial acirra as discussões sobre a inadequação das cidades às suas necessidades. A gratuidade no transporte público não basta para proporcionar maior inclusão da pessoa idosa. Este artigo visa apresentar reflexões acerca da efetividade do transporte público gratuito para a inclusão de pessoas idosas na cidade de São Paulo. Realizaram-se uma pesquisa qualitativa, exploratória, e um levantamento documental. Como resultado, sugerem-se itens complementares à implementação da gratuidade no transporte público para pessoas idosas, relativos a políticas públicas, infraestrutura, sistemas de transporte, educação e incorporação de tecnologias. Conclui-se que essas sugestões contribuem para a proposição de aspectos a serem endereçados em estudos futuros e no novo Marco Legal do Transporte Público Coletivo, visando a cidades mais inclusivas.

Abstract The increasing availability of experimental and computational protein structures entices their use for function prediction. Here we develop an automated procedure to identify enzymes involved in metabolic reactions by assessing substrate conformations docked to a library of protein structures. By screening AlphaFold-modeled vitamin B6-dependent enzymes, we find that a metric based on catalytically favorable conformations at the enzyme active site performs best (AUROC Score=0.84) in identifying genes associated with known reactions. Applying this procedure, we identify the mammalian gene encoding hydroxytrimethyllysine aldolase (HTMLA), the second enzyme of carnitine biosynthesis. Upon experimental validation, we find that the top-ranked candidates, serine hydroxymethyl transferase (SHMT) 1 and 2, catalyze the HTMLA reaction. However, a mouse protein absent in humans (threonine aldolase; Tha1) catalyzes the reaction more efficiently. Tha1 did not rank highest based on the AlphaFold model, but its rank improved to second place using the experimental crystal structure we determined at 2.26 Å resolution. Our findings suggest that humans have lost a gene involved in carnitine biosynthesis, with HTMLA activity of SHMT partially compensating for its function.

Abstract Dulaglutide is a glucagon‐like peptide‐1 (GLP‐1) receptor agonist, which stimulates insulin release via activation of GLP‐1 receptors on pancreatic beta cells. We report the case of a 45‐year‐old woman with type 2 diabetes mellitus who started dulaglutide subcutaneously and developed, a few minutes after the fourth administration, a persistent itchy reaction at the injection site, followed, after two more administrations, by a diffuse itchy delayed urticaria‐like rash, healed in 7 days after drug interruption. Skin test performed after 3 months from the event demonstrated the culprit role of the drug. Given the limited evidence in literature, there is currently no standardised protocol for testing patients sensitised to one or more glucagon‐like peptide‐1 receptor agonists. Performing skin tests, especially intradermal tests, is pivotal to confirm the aetiological role of the drug in the suspected hypersensitivity reaction, and possibly to identify an alternative to be proposed before precluding the entire drug class. To the best of our knowledge, this is the first case of systemic hypersensitivity reaction to dulaglutide presenting as a delayed urticaria‐like rash and confirmed by positive skin test.

Background The mass vaccination campaign against COVID-19 has been commonly considered the best response to the global COVID-19 pandemic crisis. However, to assess its real-world overall effects, the best way can be the analysis of all-cause mortality by vaccination status. The UK is perhaps the only country which has made publicly available all-cause mortality data by vaccination status. Methods Data from April 2021 to May 2023 published by the UK Office for National Statistics (ONS) were retrospectively analyzed by age groups and vaccination status; the standardized mortality ratio (SMR) for all-cause and non-COVID-19 mortality was calculated against the corresponding unvaccinated groups. Results We found that across all age groups, all-cause mortality SMRs increased from a certain date, dependent on the age group. Across all age groups, all-cause mortality SMRs were initially much lower than 1. However, due to their increase, by a certain date for the 18-39, 80-89 and 90+ age groups they exceeded the reference value. For the other age groups, the date at which the SMR would reach 1 can be predicted, provided the trend is maintained. Non-COVID-19 SMRs’ trends were very similar. Their initial values much lower than 1 are suggestive of significant biases in the ONS dataset, leading to underestimate the risks for the vaccinated people, as it is implausible that COVID-19 vaccines protect against non-COVID-19 deaths. Conclusions The increase over time in all-cause death SMRs in vaccinated people compared to unvaccinated, and their excess from the reference values for certain age groups, should be carefully considered to understand the underlying factors. It would be desirable for other major countries to systematically collect all-cause mortality by vaccination status and, in the meantime, a moratorium on promoting mass vaccination campaigns should be implemented.

El estudio aborda la problemática de las formas de habitar en entornos ecológicos frágiles, como los son los oasis en los desiertos. Es así como el oasis de San Pedro de Atacama presenta en la actualidad una disminución de su área agrícola debido a la urbanización y el turismo, afectando la sostenibilidad de las prácticas tradicionales de cultivo y poniendo en riesgo el equilibrio ecológico y cultural de este paraje atacameño. El artículo expone estrategias sostenibles de diseño para el habitar contemporáneamente en entornos frágiles, examinando cualidades térmicas y estrategias de control climático aplicado al caso de la Casa Taller de Magdalena Gutiérrez, utilizando los principios de Lisa Heschong y Eva Horn, se incluye en esta revisión los modos de gestión climática de Reyner Banham. La metodología empleada combina un análisis arquitectónico y etnográfico, estructurado en tres etapas: selección de obras, construcción del marco conceptual, análisis y sistematización de la obra. Se utilizaron modelos, fotografías, mapas y esquemas para contrastar teorías y cualidades térmicas y culturales con evidencias de la obra. Los criterios de clasificación incluyeron la evaluación de características como el grado de privacidad de las áreas y recintos, ventilación, iluminación, aislamiento térmico y métodos de calefacción, se empleó una calificación binaria para la evaluación sistemática. Los resultados destacaron que la Casa Taller es manifestación del habitar poético en la exterioridad del desierto de Atacama, sugiriendo una vocación para actividades comunitarias. Las cualidades lumínicas revelaron un diseño estratégico que maximiza la luz natural controlada, utilizando aberturas y claraboyas. Se concluyó que la casa Taller representa una expresión del “Regionalismo Crítico revisitado”, en este enfoque, la relación "sitio-forma" es fundamental, equilibrando la técnica local con la cultural y el entorno natural. Esta obra ofrece un modelo sostenible para habitar en entornos frágiles, en el que se integra adecuadamente el diseño arquitectónico con las condiciones climáticas y culturales del lugar.

Landscape evolution models (LEMs) are prime tools for simulating the evolution of source-to-sink systems through ranges of spatial and temporal scales. A plethora of various empirical laws have been successfully applied to describe the different parts of these systems: fluvial erosion, sediment transport and deposition, hillslope diffusion, or hydrology. Numerical frameworks exist to facilitate the combination of different subsets of laws, mostly by superposing grids of fluxes calculated independently. However, the exercise becomes increasingly challenging when the different laws are inter-connected: for example when a lake breaks the upstream–downstream continuum in the amount of sediment and water it receives and transmits; or when erosional efficiency depends on the lithological composition of the sediment flux. In this contribution, we present a method mixing the advantages of cellular automata and graph theory to address such cases. We demonstrate how the former ensure interoperability of the different fluxes (e.g. water, fluvial sediments, hillslope sediments) independently of the process law implemented in the model, while the latter offers a wide range of tools to process numerical landscapes, including landscapes with closed basins. We provide three scenarios largely benefiting from our method: (i) one where lake systems are primary controls on landscape evolution, (ii) one where sediment provenance is closely monitored through the stratigraphy and (iii) one where heterogeneous provenance influences fluvial incision dynamically. We finally outline the way forward to make this method more generic and flexible.

HEV mainly enters animal and human hosts through the orofecal route, which presents a critical health concern alongside the associated environmental variable. Among products of animal origin, milk (both ovine and bovine) can harbor HEV RNA, which can potentially be transmitted to consumers. In this study, a total of 220 raw ovine milk samples were collected from Apennine breed subjects farmed (transhumance method) in three different Italian provinces, L’Aquila, Pescara, and Teramo, located in the Abruzzo region (Central Italy). All the specimens were screened using one-step real-time RT-qPCR and nested RT-PCR assays. Among them, 5/220 or 2.27% harbored HEV RNA fragments belonging to the ORF1 and ORF2 codifying regions of the genotype 3c. The average viral amount discovered was 102 GE/mL. These subjects represented 2/57 or 3.51% of the Pescara herd, and 3/105 or 2.86% of the Teramo herd. Although HEV RNA was discovered in sheep fecal samples, the original data obtained in the present study represent the first HEV RNA detection in ovine raw milk from Italy.

Adipose tissue-derived adult stem (ADAS) cells and extracellular vesicle (EV) therapy offer promising avenues for treating neurodegenerative diseases due to their accessibility and potential for autologous cell transplantation. However, the clinical application of ADAS cells or EVs is limited by the challenge of precisely identifying them in specific regions of interest. This study compares two superparamagnetic iron oxide nanoparticles, differing mainly in size, to determine their efficacy for allowing non-invasive ADAS tracking via MRI/MPI and indirect labeling of EVs. We compared a USPIO (about 5 nm) with an SPIO (Resovist®, about 70 nm). A physicochemical characterization of nanoparticles was conducted using DLS, TEM, MRI, and MPI. ADAS cells were labeled with the two nanoparticles, and their viability was assessed via MTT assay. MRI detected labeled cells, while TEM and Prussian Blue staining were employed to confirm cell uptake. The results revealed that Resovist® exhibited higher transversal relaxivity value than USPIO and, consequently, allows for detection with higher sensitivity by MRI. A 200 µgFe/mL concentration was identified as optimal for ADAS labeling. MPI detected only Resovist®. The findings suggest that Resovist® may offer enhanced detection of ADAS cells and EVs, making it suitable for multimodal imaging. Preliminary results obtained by extracting EVs from ADAS cells labeled with Resovist® indicate that EVs retain the nanoparticles, paving the way to an efficient and multimodal detection of EVs.

This article explores the critical role of education in promoting sustainable development in the Maldives context. It presents the outcomes of a small-scale project, Playing with Solar, implemented in a small island school in collaboration with the island community. Because of the environmental and educational principles embedded in this project, it is presented as one that prioritizes sustainable development, actively engages with the community, and aligns with the key competencies underpinning the Maldives National Curriculum Framework. The Playing with Solar project is an example of transformative pedagogy aligned with sustainable development. By promoting problem-based learning, the project shows how key competencies and pedagogical principles can be operationalized in line with National Curriculum Framework syllabi that promote interdisciplinary learning, in contrast to textbook-based, transmission models of teaching.