Navigating triplet repeats sequencing: concepts, methodological challenges and perspective for Huntington's disease.

The accurate characterization of triplet repeats, especially the overrepresented CAG repeats, is increasingly relevant for several reasons. First, germline expansion of CAG repeats above a gene-specific threshold causes multiple neurodegenerative disorders; for instance, Huntington's disease (HD) is triggered by >36 CAG repeats in the huntingtin (HTT) gene. Second, extreme expansions up to 800 CAG repeats have been found in specific cell types affected by the disease.

When repetita no-longer iuvant: somatic instability of the CAG triplet in Huntington's disease.

Trinucleotide repeats in DNA exhibit a dual nature due to their inherent instability. While their rapid expansion can diversify gene expression during evolution, exceeding a certain threshold can lead to diseases such as Huntington's disease (HD), a neurodegenerative condition, triggered by >36 C-A-G repeats in exon 1 of the Huntingtin gene. Notably, the discovery of somatic instability (SI) of the tract allows these mutations, inherited from an affected parent, to further expand throughout the patient's lifetime, resulting in a mosaic brain with specific neurons exhibiting variable and often extreme CAG lengths, ultimately leading to their death.

Risk and protective factors for ASF in domestic pigs and wild boar in the EU, and mitigation measures for managing the disease in wild boar.

Five epidemiological aspects of ASF were evaluated using literature reviews, field studies, questionnaires and mathematical models. First, a literature review and a case-control study in commercial pig farms emphasised the importance of biosecurity and farming practices, including the spread of manure around farms and the use of bedding material as risk factors, while the use of insect nets was a protective factor. Second, although wild boar density is a relevant known factor, the statistical and mechanistic models did not show a clear and consistent effect of wild boar density on ASF epidemiology in the selected scenarios.

The protumorigenic enzyme GPAT2 inhibits arachidonic acid-triggered apoptosis in breast cancer.

Background: Cancer is a significant health challenge and the leading cause of mortality globally. Tumor cells use multiple mechanisms to acquire their distinctive capacity for uncontrolled proliferation, one of which is the evasion of apoptosis. It has been shown that in breast, colon, and liver cancer, evasion of apoptosis is associated with the overexpression of enzymes that metabolize arachidonic acid (AA) because free AA is a strong inducer of apoptosis.

Racism in Pediatric Serious Illness and Palliative Care: A Scoping Review of Qualitative Research.

Context: Racial disparities in health outcomes have historically impacted Black and Native American children with serious illness, yet little is known about how racism shapes the healthcare experiences of these families. To improve care experiences for this population, we must understand the myriad of ways that racism may impact their experiences with serious illness.

Objectives: 1) To assess the extent to which the experiences of Black and Native American families have been captured in existing serious illness and palliative care literature and 2) explore how experiences of racism uniquely impact this population.

Novel Genetic Variant in : Prenatal and Postnatal Neuroimaging Phenotype.

Objectives: To provide a comprehensive description of neuroradiologic findings in a patient with a probable pathogenic variant of , particularly in relation to pontine and cerebellar hypoplasia.

Methods: We first report prenatal and postnatal neuroradiologic phenotype of a female patient carrying a likely pathogenic variant and discuss its function.

Results: An ultrasound shows borderline ventriculomegaly, rotated cerebellar vermis, and dysgenetic corpus callosum.

Hereditary Amyloidosis: Insights Into a Fibrinogen A Variant Protein.

Amyloidosis are a group of diseases in which soluble proteins aggregate and deposit in fibrillar conformation extracellularly in tissues. The effectiveness of therapeutic strategies depends on the specific protein involved, being crucial to accurately determine its nature. Moreover, following the diagnosis, the search for the mutation within relatives allows the clinical advice.

Epidemiological analysis of African swine fever in the European Union during 2023.

In 2023, 14 Member States were affected by African swine fever (ASF), including Croatia and Sweden where ASF emerged (wild boar outbreaks only) and Greece where ASF re-emerged after being free since 2021. The number of ASF outbreaks among domestic pigs in the EU was five times higher than in 2022, reaching a similar magnitude to that in 2019. This was predominantly driven by the introduction and subsequent spread of ASF in Croatia and its resurgence in Romania, representing 96% of the EU outbreaks.

Generation of human cerebral organoids with a structured outer subventricular zone.

Outer radial glia (oRG) emerge as cortical progenitor cells that support the development of an enlarged outer subventricular zone (oSVZ) and the expansion of the neocortex. The in vitro generation of oRG is essential to investigate the underlying mechanisms of human neocortical development and expansion. By activating the STAT3 signaling pathway using leukemia inhibitory factor (LIF), which is not expressed in guided cortical organoids, we define a cortical organoid differentiation method from human pluripotent stem cells (hPSCs) that recapitulates the expansion of a progenitor pool into the oSVZ.

Portal hypertension-like pattern in coronavirus disease 2019 acute respiratory distress syndrome.

Objectives: Although respiratory failure is the most common feature in coronavirus disease 2019 (COVID-19), abdominal organ involvement is likewise frequently observed. To investigate visceral and thoracic circulation and abdominal organ damage in COVID-19 patients.

Materials And Methods: A monocentric observational study was carried on.

Digitally enhanced hands-on surgical training (DEHST) enhances the performance during freehand nail distal interlocking.

Purpose: Freehand distal interlocking of intramedullary nails remains a challenging task. Recently, a new training device for digitally enhanced hands-on surgical training (DEHST) was introduced, potentially improving surgical skills needed for distal interlocking.

Aim: To evaluate whether training with DEHST enhances the performance of novices (first-year residents without surgical experience in freehand distal nail interlocking).

Comparison of first-tier whole-exome sequencing with a multi-step traditional approach for diagnosing paediatric outpatients: An Italian prospective study.

Background: The recent guidelines suggest the use of genome-wide analyses, such as whole exome sequencing (WES), at the beginning of the diagnostic approach for cases with suspected genetic conditions. However, in many realities it still provides for the execution of a multi-step pathway, thus requiring several genetic tests to end the so-called 'diagnostic odyssey'.

Methods: We reported the results of GENE Project (Genomic analysis Evaluation NEtwork): a multicentre prospective cohort study on 125 paediatric outpatients with a suspected genetic disease in which we performed first-tier trio-WES, including exome-based copy number variation analysis, in parallel to a 'traditional approach' of two/three sequential genetic tests.

The translational potential of cholesterol-based therapies for neurological disease.

Cholesterol is an important metabolite and membrane component and is enriched in the brain owing to its role in neuronal maturation and function. In the adult brain, cholesterol is produced locally, predominantly by astrocytes. When cholesterol has been used, recycled and catabolized, the derivatives are excreted across the blood-brain barrier.

Induced myocardial ischemia in candidates to liver transplantation without evidence of heart disease.

Background: Coronary artery disease (CAD) is associated with perioperative liver transplantation (LT) mortality. In absence of a defined risk algorithm, we aimed to test whether stress echocardiography and coronary computed tomography angiography (CCTA) could detect CAD in end-stage liver disease (ESLD) patients without previous evidence of heart disease.

Methods: LT candidates ≥30 years underwent a cardiovascular (CV) assessment through stress echocardiography.

Chronic cholesterol administration to the brain supports complete and long-lasting cognitive and motor amelioration in Huntington's disease.

Evidence that Huntington's disease (HD) is characterized by impaired cholesterol biosynthesis in the brain has led to strategies to increase its level in the brain of the rapidly progressing R6/2 mouse model, with a positive therapeutic outcome. Here we tested the long-term efficacy of chronic administration of cholesterol to the brain of the slowly progressing zQ175DN knock-in HD mice in preventing ("early treatment") or reversing ("late treatment") HD symptoms. To do this we used the most advanced formulation of cholesterol loaded brain-permeable nanoparticles (NPs), termed hybrid-g7-NPs-chol, which were injected intraperitoneally.

Microcephaly-associated protein WDR62 shuttles from the Golgi apparatus to the spindle poles in human neural progenitors.

WDR62 is a spindle pole-associated scaffold protein with pleiotropic functions. Recessive mutations in cause structural brain abnormalities and account for the second most common cause of autosomal recessive primary microcephaly (MCPH), indicating WDR62 as a critical hub for human brain development. Here, we investigated WDR62 function in corticogenesis through the analysis of a C-terminal truncating mutation (D955AfsX112).