Endocrinological features and epileptic encephalopathy in COX deficiency due to SCO1 mutations: case series and review of literature.

Context: Cytochrome C oxidase (COX) is the fourth component of the respiratory chain and is located within the internal membrane of mitochondria. COX deficiency causes an inherited mitochondrial disease with significant genetic and phenotypic heterogeneity. Four clinical subtypes have been identified, each with distinct phenotypes and genetic variants.

The Requirements of Managing Phase I Clinical Trials Risks: The British and Italian Case Studies.

Phase I clinical trials represent a critical point in drug development because the investigational medicinal product is being tested in humans for the first time. For this reason, it is essential to evaluate and identify the Maximum Tolerated Dose (MTD) and the safety of the new compound. To mitigate the possible risks associated with drug administration and treatment, the European Competent Authority issued various guidelines to provide provisions and harmonize risk management processes.

A novel bioinformatic method for the identification of antimicrobial peptides in metagenomes.

Aims: This study aimed to develop a new bioinformatic approach for the identification of novel antimicrobial peptides (AMPs), which did not depend on sequence similarity to known AMPs held within databases, but on structural mimicry of another antimicrobial compound, in this case an ultrashort, synthetic, cationic lipopeptide (C12-OOWW-NH2).

Methods And Results: When applied to a collection of metagenomic datasets, our outlined bioinformatic method successfully identified several short (8-10aa) functional AMPs, the activity of which was verified via disk diffusion and minimum inhibitory concentration assays against a panel of 12 bacterial strains. Some peptides had activity comparable to, or in some cases, greater than, those from published studies that identified AMPs using more conventional methods.

Ultrasound Patterns of Hepatocellular Carcinoma and Their Prognostic Impact: A Retrospective Study.

Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related death. Abdominal ultrasound (US) is by far the most widely used first-level exam for the diagnosis of HCC. We aimed to assess whether different ultrasound patterns were related to tumor prognosis.

SMARCE1-related meningiomas: A clear example of cancer predisposing syndrome.

We report the case of a 16-year-old girl presenting with spinal clear-cell multiple meningiomas (CCMs). In view of this presentation, we sequenced a bioinformatic panel of genes associated with susceptibility to meningioma, identifying a germline heterozygous variant in SMARCE1. Somatic DNA investigations in the CCM demonstrated the deletion of the wild-type allele (loss of heterozygosity, LOH), supporting the causative role of this variant.

FOXI3 pathogenic variants cause one form of craniofacial microsomia.

Craniofacial microsomia (CFM; also known as Goldenhar syndrome), is a craniofacial developmental disorder of variable expressivity and severity with a recognizable set of abnormalities. These birth defects are associated with structures derived from the first and second pharyngeal arches, can occur unilaterally and include ear dysplasia, microtia, preauricular tags and pits, facial asymmetry and other malformations. The inheritance pattern is controversial, and the molecular etiology of this syndrome is largely unknown.

US regulations to curb alleged cancer causes are ineffectual and compromised by scientific, constitutional and ethical violations.

The 1958 Delaney amendment to the Federal Food Drug and Cosmetics Act prohibited food additives causing cancer in animals by appropriate tests. Regulators responded by adopting chronic lifetime cancer tests in rodents, soon challenged as inappropriate, for they led to very inconsistent results depending on the subjective choice of animals, test design and conduct, and interpretive assumptions. Presently, decades of discussions and trials have come to conclude it is impossible to translate chronic animal data into verifiable prospects of cancer hazards and risks in humans.

Italian guidance on Dementia Day Care Centres: A position paper.

Dementia Day Care Centres (DDCCs) are defined as services providing care and rehabilitation to people with dementia associated with behavioural and psychological symptoms (BPSD) in a semi-residential setting. According to available evidence, DDCCs may decrease BPSD, depressive symptoms and caregiver burden. The present position paper reports a consensus of Italian experts of different disciplines regarding DDCCs and includes recommendations about architectural features, requirements of personnel, psychosocial interventions, management of psychoactive drug treatment, prevention and care of geriatric syndromes, and support to family caregivers.

High-precision anomalous dimension of three-dimensional percolation and spatial profile of the critical giant cluster.

In three-dimensional percolation, we apply and test the critical geometry approach for bounded critical phenomena based on the fractional Yamabe equation. The method predicts the functional shape of the order parameter profile ϕ, which is obtained by raising the solution of the Yamabe equation to the scaling dimension Δ_{ϕ}. The latter can be fixed from outcomes of numerical simulations, from which we obtain Δ_{ϕ}=0.

Pathophysiology and Therapy of High-Altitude Sickness: Practical Approach in Emergency and Critical Care.

High altitude can be a hostile environment and a paradigm of how environmental factors can determine illness when human biological adaptability is exceeded. This paper aims to provide a comprehensive review of high-altitude sickness, including its epidemiology, pathophysiology, and treatments. The first section of our work defines high altitude and considers the mechanisms of adaptation to it and the associated risk factors for low adaptability.

Carriers of Rare Variants Are at High Risk of Life-Threatening COVID-19.

Thrombosis of small and large vessels is reported as a key player in COVID-19 severity. However, host genetic determinants of this susceptibility are still unclear. Congenital Thrombotic Thrombocytopenic Purpura is a severe autosomal recessive disorder characterized by uncleaved ultra-large vWF and thrombotic microangiopathy, frequently triggered by infections.

ECHOPAEDIA: Echography in Paediatric Patients in the Age of Coronavirus Disease 2019: Utility of Lung Ultrasound and Chest X-Ray in Diagnosis of Community-Acquired Pneumonia and Severe Acute Respiratory Syndrome Coronavirus 2 Pneumonia.

Background: In recent years, lung ultrasound (LUS) has spread to emergency departments and clinical practise gaining great support, especially in time of pandemic, but only a few studies have been done on children. The aim of the present study is to compare the diagnostic accuracy of LUS (using Soldati LUS score) and that of chest X-ray (CXR) in CAP and COVID-19 pneumonia in paediatric patients. Secondary objective of the study is to examine the association between LUS score and disease severity.

Magnetization profiles at the upper critical dimension as solutions of the integer Yamabe problem.

We study the connection between the magnetization profiles of models described by a scalar field with marginal interaction term in a bounded domain and the solutions of the so-called Yamabe problem in the same domain, which amounts to finding a metric having constant curvature. Taking the slab as a reference domain, we first study the magnetization profiles at the upper critical dimensions d=3, 4, 6 for different (scale-invariant) boundary conditions. By studying the saddle-point equations for the magnetization, we find general formulas in terms of Weierstrass elliptic functions, extending exact results known in literature and finding ones for the case of percolation.

The EU chemicals strategy for sustainability: in support of the BfR position.

The EU chemicals strategy for sustainability (CSS) asserts that both human health and the environment are presently threatened and that further regulation is necessary. In a recent Guest Editorial, members of the German competent authority for risk assessment, the BfR, raised concerns about the scientific justification for this strategy. The complexity and interdependence of the networks of regulation of chemical substances have ensured that public health and wellbeing in the EU have continuously improved.

Survey of diagnostic and typing capacity for enterovirus infection in Italy and identification of two echovirus 30 outbreaks.

Background: Enterovirus infections can cause a variety of illnesses, ranging from asymptomatic infections to severe illness and death.

Aim: To support polio eradication activities, in February 2019, the WHO Regional Reference Laboratory for polio in Italy, at the National Institute of Public Health (Istituto Superiore di Sanità), promoted an investigation on non-polio enterovirus laboratory capacity, with the support of the Italian Ministry of Health. The aim was to collect data on the assays used routinely for diagnostic purposes and to characterize enterovirus outbreaks strains by sequence analysis of the Viral Protein 1 region.

A New Lung Ultrasound Protocol Able to Predict Worsening in Patients Affected by Severe Acute Respiratory Syndrome Coronavirus 2 Pneumonia.

Objectives: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can generate severe pneumonia associated with high mortality. A bedside lung ultrasound (LUS) examination has been shown to have a potential role in this setting. The purpose of this study was to evaluate the potential prognostic value of a new LUS protocol (evaluation of 14 anatomic landmarks, with graded scores of 0-3) in patients with SARS-CoV-2 pneumonia and the association of LUS patterns with clinical or laboratory findings.

Identification, molecular characterization and segregation analysis of a variant pre-mutation allele in a three-generation Italian family.

DM1 is an autosomal dominant multisystemic disease caused by an unstable CTG repeat expansion in the 3'-untranslated region (UTR) of the gene. The complex variant expanded the alleles containing CAG, CCG, CTC and/or GGC interruptions repetition sequences have been reported in 3-8% of DM1 patients. To date, very few information is available about the frequency and clinical consequences of pre-mutated variant allele.

Human exposure to synthetic endocrine disrupting chemicals (S-EDCs) is generally negligible as compared to natural compounds with higher or comparable endocrine activity. How to evaluate the risk of the S-EDCs?

Theoretically, both synthetic endocrine-disrupting chemicals (S-EDCs) and natural (exogenous and endogenous) endocrine-disrupting chemicals (N-EDCs) can interact with endocrine receptors and disturb hormonal balance. However, compared to endogenous hormones, S-EDCs are only weak partial agonists with receptor affinities several orders of magnitude lower than S-EDCs. Thus, to elicit observable effects, S-EDCs require considerably higher concentrations to attain sufficient receptor occupancy or to displace natural hormones and other endogenous ligands.

Human exposure to synthetic endocrine disrupting chemicals (S-EDCs) is generally negligible as compared to natural compounds with higher or comparable endocrine activity: how to evaluate the risk of the S-EDCs?

Theoretically, both synthetic endocrine disrupting chemicals (S-EDCs) and natural (exogenous and endogenous) endocrine disrupting chemicals (N-EDCs) can interact with endocrine receptors and disturb hormonal balance. However, compared to endogenous hormones, S-EDCs are only weak partial agonists with receptor affinities several orders of magnitude lower. Thus, to elicit observable effects, S-EDCs require considerably higher concentrations to attain sufficient receptor occupancy or to displace natural hormones and other endogenous ligands.