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Mutations of the mitochondrial genome (mtDNA) cause a range of profoundly debilitating clinical conditions for which treatment options are very limited. Most mtDNA diseases show heteroplasmy – tissues express both wild-type and mutant mtDNA. While the level of heteroplasmy broadly correlates with disease severity, the relationships between specific mtDNA mutations, heteroplasmy, disease phenotype and severity are poorly understood. We have carried out extensive bioenergetic, metabolomic and RNAseq studies on heteroplasmic patient-derived cells carrying the most prevalent disease related mtDNA mutation, the m.3243 A > G. These studies reveal that the mutation promotes changes in metabolites which are associated with the upregulation of the PI3K-Akt-mTORC1 axis in patient-derived cells and tissues. Remarkably, pharmacological inhibition of PI3K, Akt, or mTORC1 reduced mtDNA mutant load and partially rescued cellular bioenergetic function. The PI3K-Akt-mTORC1 axis thus represents a potential therapeutic target that may benefit people suffering from the consequences of the m.3243 A > G mutation. Heteroplasmic mtDNA mutations cause disease in humans. Here, Chung et al find the PI3K-Akt-mTORC1 pathway constitutively activated in cells with the heteroplasmic m.3243 A > G mutation, and inhibition of the pathway cell autonomously reduces mutant mtDNA load and rescues mitochondrial bioenergetics.

A high-fat diet (HFD) during pregnancy promotes fat accumulation and reduces docosahexaenoic acid (DHA) levels in the liver of the offspring at postnatal ages, which can depend on fetal sex. However, the prenatal mechanisms behind these associations are still unclear. Thus, we analyzed if an HFD alters DHA content and the expression of molecules related to fatty acid (FA) metabolism in the fetal liver. Female C57BL/6 mice were fed a control diet or HFD for 4–6 weeks before pregnancy until the gestational day (GD) 17.5. A subgroup of each diet received DHA (100 mg/Kg) orally from GD 6.5 until 16.5. On GD 17.5, maternal livers, placentas, and livers from male and female fetuses were collected for FA profiling with gas-chromatography and gene expression of molecules related to FA metabolism using qPCR. PPAR-α protein expression was evaluated using Western blot. The gene expression of placental FA transporters was also assessed. An HFD increased eicosapentaenoic acid (EPA) and decreased DHA levels and protein expression of PPAR-α in the fetal livers of both sexes. DHA increased the gene expression of Ppara, Cpt1, and Acsl1 in the livers of female fetuses. Therefore, an HFD reduces DHA levels and PPAR-α, a master regulator of gene expression, in the fetal liver. In turn, the livers of female fetuses seem to be more sensitive to DHA action.

Mutations in mitochondrial DNA cause severe multisystem disease, frequently associated with muscle weakness. The m.3243A>G mutation is the major cause of Mitochondrial Encephalomyopathy Lactic Acidosis and Stroke Like episodes (MELAS). Experimental models that recapitulate the disease phenotype in vitro for disease modelling or drug screening are very limited. We have therefore generated hiPSC-derived muscle fibres with variable heteroplasmic mtDNA mutation load without significantly affecting muscle differentiation potential. The cells are excitable and show physiological characteristics of muscle fibres and show well organised myofibrillar structure. In cells carrying the m.3243A>G, the mitochondrial membrane potential and oxygen consumption were reduced in relation to the mutant load. We have shown through proteomic, phosphoproteomic, and metabolomic analyses that the m.3243A>G mutation variably affects the cell phenotype in relation to the mutant load. This variation is reflected by an increase in the NADH/NAD+ ratio, which in turns influences key nutrient-sensing pathways in the myofibres. This model enables detailed study of the impact of the mutation on cellular bioenergetics and on muscle physiology with the potential to provide a platform for drug screening.

Mutations of the mitochondrial genome (mtDNA) cause a range of profoundly debilitating clinical conditions for which treatment options are very limited. Most mtDNA diseases show heteroplasmy – tissues express both wild-type and mutant mtDNA. While the level of heteroplasmy broadly correlates with disease severity, the relationships between specific mtDNA mutations, heteroplasmy, disease phenotype and severity are poorly understood. We have carried out extensive bioenergetic, metabolomic and RNAseq studies on heteroplasmic patient derived cells carrying the most prevalent disease related mtDNA mutation, m.3243A>G. These studies reveal that the mutation promotes changes in metabolites which is associated with the upregulation of the PI3K-Akt-mTORC1 axis in patient-derived cells and tissues. Remarkably, pharmacological inhibition of PI3K, Akt, or mTORC1 activated mitophagy, reduced mtDNA mutant load and rescued cellular bioenergetic function. The rescue was prevented by inhibition of mitophagy. The PI3K-Akt-mTORC1 axis thus represents a potential therapeutic target that may benefit people suffering from the consequences of the m.3243A>G mutation.

The high-flow nasal cannula (HFNC) has become a widely used respiratory support system, which has proven to be effective in different populations. The facilitation of oral communication and feeding have been described as advantages of this support. Nevertheless, swallowing disorders associated with the use of HFNC have been postulated. However, such evidence is scattered in the literature, not systematically searched, and needs to be adequately summarised. This review aimed to explore the literature, to identify and map the evidence, regarding the frequency and methods of assessment of swallowing disorders in adult HFNC users, in both critical and non-critical units. A scoping review will be conducted. A systematic search in MEDLINE (Ovid), Embase (Ovid), CENTRAL, CINAHL (EBSCOhost), and other resources will be conducted. Primary studies, in any language or publication status, assessing the incidence of swallowing disorders in adults with HFNC support will be included. Two reviewers will independently select studies and extract data. Disagreements will be resolved by consensus or a third reviewer. The results will be reported narratively, using tables and figures to support them. Positive end-expiratory pressure generated in the airway by HFNC could impair the proper swallowing performance. Knowing the methodological characteristics, the instruments or scales used to assess the presence of dysphagia, and the results of the studies may contribute to considering swallowing assessment in this population on a routine basis, as well as to guide the conduct of new studies that may respond to less researched areas in this topic. Registration number: INPLASY2022110078.

Congenital hypothyroidism (CH) is a leading preventable cause of neurocognitive impairment. Its incidence appears to be rising in several countries. We analysed 27 years of newborn-screening data (1997–2023) from the largest Chilean screening centre, covering 3,225,216 newborns (51.1% of national births), to characterise temporal trends and potential drivers of CH incidence. Annual CH incidence was modelled with Prais–Winsten regression to correct for first-order autocorrelation; additional models assessed trends in gestational age, sex, biochemical markers, and aetiological subtypes. We identified 1550 CH cases, giving a mean incidence of 4.9 per 10,000 live births and a significant yearly increase of 0.067 per 10,000 (95 % CI 0.037–0.098; p < 0.001). Mild cases (confirmation TSH < 20 mU/L) rose (+0.89 percentage points per year; p = 0.002). The program’s recall was low (0.05%). Over time, screening and diagnostic TSH values declined, total and free T4 concentrations rose, gestational age at diagnosis fell, and a shift from thyroid ectopy toward hypoplasia emerged; no regional differences were detected. The sustained increase in CH incidence, alongside falling TSH thresholds and growing detection of in situ glands, suggests enhanced recognition of milder disease. Ongoing surveillance should integrate environmental, iodine-nutrition, and genetic factors to clarify the causes of this trend.

In this work, our research group developed usable low-cost superparamagnetic nanoparticles (Fe 3 O 4 @NTA) that behave as an excellent energetic material to accelerate the thermal decomposition of ammonium perchlorate (AP). As a synthetic strategy, magnetite nanoparticles (Fe 3 O 4 ) were coated with nitrilotriacetic acid (NTA) by a simple preparation method. Based on High-resolution transmission electron microscopy (HR-TEM) and vibrating sample magnetometer (VSM) results, Fe 3 O 4 @NTA presents a mean diameter of 7.4 nm and superparamagnetic behavior. Chemical characterization by Energy-dispersive X-ray spectroscopy (XPS), Fourier transform infrared (FT-IR), X-ray diffraction (XRD), and thermogravimetric analysis (TGA) provided enough evidence for the presence of a carboxylic acid group and magnetite in the sample. The Fe 3 O 4 @NTA catalyst diminishes AP high-temperature decomposition (HTD) to 342 °C and shows a low activation energy (98.02 kJ mol −1 ). In addition, after the burning rate test, it was observed that these resulting nanoparticles showed an adequate magnetic response against an external magnet. These results are promising for future research, as the opportunity opens to reuse this functional magnetic material in successive catalytic cycles, thus contributing soon to the recycling of raw materials necessary for interplanetary travel. Graphical abstract

IntroductionThe high-flow nasal cannula (HFNC) has become a widely used respiratory support system, which has proven to be effective in different populations. The facilitation of oral communication and feeding have been described as advantages of this support. Nevertheless, swallowing disorders associated with the use of HFNC have been postulated. However, such evidence is scattered in the literature, not systematically searched, and needs to be adequately summarised. This review aimed to explore the literature, to identify and map the evidence, regarding the frequency and methods of assessment of swallowing disorders in adult HFNC users, in both critical and non-critical units.Materials and methodsA scoping review will be conducted. A systematic search in MEDLINE (Ovid), Embase (Ovid), CENTRAL, CINAHL (EBSCOhost), and other resources will be conducted. Primary studies, in any language or publication status, assessing the incidence of swallowing disorders in adults with HFNC support will be included. Two reviewers will independently select studies and extract data. Disagreements will be resolved by consensus or a third reviewer. The results will be reported narratively, using tables and figures to support them.DiscussionPositive end-expiratory pressure generated in the airway by HFNC could impair the proper swallowing performance. Knowing the methodological characteristics, the instruments or scales used to assess the presence of dysphagia, and the results of the studies may contribute to considering swallowing assessment in this population on a routine basis, as well as to guide the conduct of new studies that may respond to less researched areas in this topic.RegistrationRegistration number: INPLASY2022110078.

El trabajo que aquí se presenta da cuenta de los resultados obtenidos luego de la implementación de un proyecto de Metodología A+S que la Universidad Católica Silva Henríquez llevó a cabo en conjunto con el colegio municipal Los Bosquinos de Maipú. El objetivo principal de este trabajo fue evaluar el impacto de esta experiencia en el desarrollo de la producción de textos narrativos en el aula de historia, geografía y ciencias sociales mediante un trabajo interdisciplinario. Desde la perspectiva didáctica, se desarrolló un módulo didáctico que se sustenta en la escritura por proyectos desde un enfoque procesual. El estudio, de tipo preexperimental con análisis cuantitativo, considera la revisión textual—por parte de tres jueces expertos—de los cuentos realizados por 32 estudiantes de séptimo básico. Los resultados dan cuenta de una mejora considerable en la calidad de los textos narrativos, con énfasis en la competencia discursiva. Por su parte, se destaca el valor que esta experiencia de A+S representó no solo para la institución de educación superior, sino también para el socio comunitario.

El trabajo que aquí se presenta da cuenta de los resultados obtenidos luego de la implementación de un proyecto de Metodología A+S que la Universidad Católica Silva Henríquez llevó a cabo en conjunto con el colegio municipal Los Bosquinos de Maipú. El objetivo principal de este trabajo fue evaluar el impacto de esta experiencia en el desarrollo de la producción de textos narrativos en el aula de historia, geografía y ciencias sociales mediante un trabajo interdisciplinario. Desde la perspectiva didáctica, se desarrolló un módulo didáctico que se sustenta en la escritura por proyectos desde un enfoque procesual. El estudio, de tipo preexperimental con análisis cuantitativo, considera la revisión textual—por parte de tres jueces expertos—de los cuentos realizados por 32 estudiantes de séptimo básico. Los resultados dan cuenta de una mejora considerable en la calidad de los textos narrativos, con énfasis en la competencia discursiva. Por su parte, se destaca el valor que esta experiencia de A+S representó no solo para la institución de educación superior, sino también para el socio comunitario.