Germline Variant Spectrum in Southern Italian High-Risk Hereditary Breast Cancer Patients: Insights from Multi-Gene Panel Testing.

Hereditary breast cancer accounts for 5-10% of all cases, with pathogenic variants in and other susceptibility genes playing a crucial role. This study elucidates the prevalence and spectrum of germline variants in 13 cancer predisposition genes among high-risk hereditary breast cancer patients from Southern Italy. We employed next-generation sequencing (NGS) to analyze 254 individuals selected through genetic counseling.

Editorial on the Special Issue "Genetic and Molecular Basis of Inherited Disorders".

This Special Issue of , titled "Genetic and Molecular Basis of Inherited Disorders", presents a collection of pioneering research articles that advance our understanding of the genetic mechanisms underlying various hereditary diseases. The studies employ cutting-edge genomic techniques, including next-generation sequencing and genome-wide association studies, to elucidate novel genetic variants and their functional implications. Key investigations span a diverse range of conditions, from congenital idiopathic nystagmus and hereditary hearing loss to familial hypercholesterolemia and rare cancer predisposition syndromes.

Lung Recruitment Before Surfactant Administration in Extremely Preterm Neonates: 2-Year Follow-Up of a Randomized Clinical Trial.

Importance: A multicenter randomized clinical trial (RCT) showed a lung recruitment maneuver using high-frequency oscillatory ventilation just before surfactant administration (ie, intubate-recruit-surfactant-extubate [IN-REC-SUR-E]) improved the efficacy of treatment compared with the standard intubate-surfactant-extubate (IN-SUR-E) technique without increasing the risk of adverse neonatal outcomes.

Objective: To examine follow-up outcomes at corrected postnatal age (cPNA) 2 years of preterm infants previously enrolled in an RCT and treated with IN-REC-SUR-E or IN-SUR-E in 35 tertiary neonatal intensive care units.

Design, Setting, And Participants: This was a follow-up study of infants recruited into the primary RCT from 2015 to 2018 at 35 tertiary neonatal intensive care units (NICUs) in Italy.

Metabolic drives affecting Th17/Treg gene expression changes and differentiation: impact on immune-microenvironment regulation.

The CD4 T-cell population plays a vital role in the adaptive immune system by coordinating the immune response against different pathogens. A significant transformation occurs in CD4 cells during an immune response, as they shift from a dormant state to an active state. This transformation leads to extensive proliferation, differentiation, and cytokine production, which contribute to regulating and coordinating the immune response.

RANBP1, a member of the nuclear-cytoplasmic trafficking-regulator complex, is the terminal-striking point of the SGK1-dependent Th17 pathological differentiation.

The Th17 arrangement is critical for orchestrating both innate and acquired immune responses. In this context, the serum and glucocorticoid regulated kinase 1 (SGK1) exerts a key role in the governance of IL-23R-dependent Th17 maturation, through the phosphorylation-dependent control of FOXO1 localization. Our previous work has shown that some of the SGK1-key functions are dependent on RAN-binding protein 1 (RANBP1), a terminal gene in the nuclear transport regulation.

Celecoxib, a Non-Steroidal Anti-Inflammatory Drug, Exerts a Toxic Effect on Human Melanoma Cells Grown as 2D and 3D Cell Cultures.

Cutaneous melanoma (CM) remains one of the leading causes of tumor mortality due to its high metastatic spread. CM growth is influenced by inflammation regulated by prostaglandins (PGs) whose synthesis is catalyzed by cyclooxygenases (COXs). COX inhibitors, including non-steroidal anti-inflammatory drugs (NSAIDs), can inhibit tumor development and growth.

Kinase Inhibitors in Genetic Diseases.

Over the years, several studies have shown that kinase-regulated signaling pathways are involved in the development of rare genetic diseases. The study of the mechanisms underlying the onset of these diseases has opened a possible way for the development of targeted therapies using particular kinase inhibitors. Some of these are currently used to treat other diseases, such as cancer.

The Variant p.Ala84Pro Is Causative of X-Linked Hypophosphatemic Rickets: Possible Relationship with Burosumab Swinging Response in Adults.

Loss of function mutations in the gene could determine X-linked dominant hypophosphatemia. This is the most common form of genetic rickets. It is characterized by renal phosphate wasting determining an increase in fibroblast growth factor 23 (FGF-23), growth retard, bone deformities and musculoskeletal manifestations.

RANBP1 (RAN Binding Protein 1): The Missing Genetic Piece in Cancer Pathophysiology and Other Complex Diseases.

RANBP1 encoded by or (Hpall Tiny Fragments Locus 9A), plays regulatory functions of the RAN-network, belonging to the RAS superfamily of small GTPases. Through this function, RANBP1 regulates the RANGAP1 activity and, thus, the fluctuations between GTP-RAN and GDP-RAN. In the light of this, RANBP1 take actions in maintaining the nucleus-cytoplasmic gradient, thus making nuclear import-export functional.

Germline Testing in a Cohort of Patients at High Risk of Hereditary Cancer Predisposition Syndromes: First Two-Year Results from South Italy.

Germline pathogenic variants (PVs) in oncogenes and tumour suppressor genes are responsible for 5 to 10% of all diagnosed cancers, which are commonly known as hereditary cancer predisposition syndromes (HCPS). A total of 104 individuals at high risk of HCPS were selected by genetic counselling for genetic testing in the past 2 years. Most of them were subjects having a personal and family history of breast cancer (BC) selected according to current established criteria.

Th17-Gene Expression Profile in Patients with Chronic Venous Disease and Venous Ulcers: Genetic Modulations and Preliminary Clinical Evidence.

Chronic venous disease is a condition globally widespread, resulting in a disabling pathological disorder. The CD4 + Th17+ (Cluster Differentiation 4) lymphocytes represent a regulative factor for innate immunity related to the development of complex diseases. Recently, these mechanisms have been associated with vascular disease.

Inadequate health-related quality of life assessment and reporting in phase III clinical trials of immune checkpoint inhibitors in solid cancers: A systematic review.

We systematically reviewed QoL assessment and reporting in RCTs of immune checkpoint inhibitors (ICIs) in solid cancers published between 2013 and 2021. None of the 106 eligible trials included QoL among primary endpoints. QoL results were non-disclosed in 83/106 (78.

A Familial Form of Epidermolysis Bullosa Simplex Associated with a Pathogenic Variant in .

Epidermolysis bullosa simplex is a disease that belongs to a group of genodermatoses characterised by the formation of superficial bullous lesions caused by minor mechanical trauma to the skin. The skin fragility observed in the EBS is mainly caused by pathogenic variants in the and genes that compromise the mechanical stability of epithelial cells. By performing DNA sequencing in a female patient with EBS, we found the pathogenic variant c.

A Novel Splicing Variant of in a Fetus with Achondrogenesis Type II: Interpretation of Pathogenicity of In-Frame Deletions.

Achondrogenesis type II (ACG2) is a lethal skeletal dysplasia caused by dominant pathogenic variants in . Most of the variants found in patients with ACG2 affect the glycine residue included in the Gly-X-Y tripeptide repeat that characterizes the type II collagen helix. In this study, we reported a case of a novel splicing variant of in a fetus with ACG2.

Case Report: Identification of a Novel Pathogenic Germline Variant in a Family With Li-Fraumeni Syndrome.

Li-Fraumeni syndrome (LFS) is an inherited autosomal dominant disease characterized by a predisposition to many cancers. Germline pathogenic variants in are primarily responsible for LFS. By performing a targeted sequencing panel in a proband with liver carcinoma having a deceased son affected by osteosarcoma, we found the novel heterozygous frameshift variant c.

Multimodal imaging of Hypotrichosis with juvenile macular dystrophy: a case report.

Background: To report the first Italian case of hypotrichosis with juvenile macular dystrophy complicated by macular neovascularization diagnosed through multimodal imaging.

Case Presentation: An 11-year-old boy was referred to our Institution for bilateral maculopathy of unknown origin. Multimodal imaging helps the diagnosis of Juvenile Macular Dystrophy with Hypotrichosis (HJMD).

Phantom Phone Signal: why it should be of interest for psychiatry.

Phantom Phone Signal (PPS) refers to the false perception of a mobile phone ringing, vibrating and blinking, when in fact it did not. A recent literature about PPS is growing, parallel to an increasing interest about its possible psychopathological implications. The present review aims to synthesize the current knowledge about the phenomenon, and to present a conceptual framework that integrates PPS as a putative index of psychopathology.

[Clinical pathway for the physician throughout social insurances : what is worth to know ?].

Medical practitioners are frequently confronted with social insurance as well as with their patients' health and safety issues. Through the journey of Pierre, an employee, victim of an accident at work, we propose to address some common problems by specifying certain aspects relating to the legal and administrative framework in order to better guide clinical practice on the means of intervention and their limits.

Emotional symptoms and their related factors in adolescents during the acute phase of Covid-19 outbreak in South Italy.

Background: Several studies have shown that during COVID-19 pandemic outbreak, emotional symptoms increased in the general population. Less is known about youths.

Methods: We surveyed a sample of Italian adolescents during the strictest quarantine period and assessed the effects of socio-demographic and psychological factors on current emotional symptoms.

Details of the Contents of Paranoid Thoughts in Help-Seeking Adolescents with Psychotic-Like Experiences and Continuity with Bullying and Victimization: A Pilot Study.

: Psychosis recognizes an interaction between biological and social environmental factors. Adversities are now recognized to be consistently associated with psychotic-like experiences (PLEs). The purpose of this study was to describe the contents of paranoid symptoms and to focus on their relationship with bullying and victimization in help-seeking adolescents.

7q35 Microdeletion and 15q13.3 and Xp22.33 Microduplications in a Patient with Severe Myoclonic Epilepsy, Microcephaly, Dysmorphisms, Severe Psychomotor Delay and Intellectual Disability.

Copy number variations (CNVs) play a key role in the pathogenesis of several diseases, including a wide range of neurodevelopmental disorders. Here, we describe the detection of three CNVs simultaneously in a female patient with evidence of severe myoclonic epilepsy, microcephaly, hypertelorism, dimorphisms as well as severe psychomotor delay and intellectual disability. Array-CGH analysis revealed a ∼240 kb microdeletion at the 7q35 inherited from her father, a ∼538 kb microduplication at the 15q13.