De Novo Pathogenic Variant Associated with Lethal Encephalocardiomyopathy-Case Report and Literature Review.

Pathogenic variants in , encoding dynamin-like protein-1 (DRP1), cause a lethal encephalopathy. DRP1 defective function results in altered mitochondrial networks, characterized by elongated/spaghetti-like, highly interconnected mitochondria. We validated in yeast the pathogenicity of a de novo variant identified by whole exome sequencing performed more than 10 years after the patient's death.

Regeneration of Vascular Endothelium in Different Large Vessels.

The regeneration of endothelial cells (ECs) lining arteries, veins, and large lymphatic vessels plays an important role in vascular pathology. To understand the mechanisms of atherogenesis, it is important to determine what happens during endothelial regeneration. A comparison of these processes in the above-mentioned vessels reveals both similarities and some significant differences.

Targeting Bacterial Cell Division with Benzodioxane-Benzamide FtsZ Inhibitors as a Novel Strategy to Fight Gram-Positive Ovococcal Pathogens.

The widespread emergence of antimicrobial resistance (AMR) is a serious threat to global public health and among Gram-positive cocci, constitutes a priority in the list of AMR-threatening pathogens. To counteract this fundamental problem, the bacterial cell division cycle and the crucial proteins involved in this process emerged as novel attractive targets. FtsZ is an essential cell division protein, and FtsZ inhibitors, especially the benzamide derivatives, have been exploited in the last decade.

Irisin and Metastatic Melanoma: Selective Anti-Invasiveness Activity in BRAF Wild-Type Cells.

Irisin is a newly discovered 12 kDa messenger protein involved in energy metabolism. Irisin affects signaling pathways in several types of cancer; however, the role of irisin in metastatic melanoma (MM) has not been described yet. We explored the biological effects of irisin in in vitro models of MM cells (HBL, LND1, Hmel1 and M3) capable of the oncogenic activation of BRAF.

Onvansertib and Navitoclax Combination as a New Therapeutic Option for Mucinous Ovarian Carcinoma.

Mucinous epithelial ovarian cancer (mEOC) is a rare subtype of epithelial ovarian cancer, characterized by poor responses to standard platinum-based chemotherapy. Polo-like kinase 1 (PLK1) is a key regulator of mitosis and cell cycle progression and its inhibition has been recently identified as a target in mEOC. In this study, we aimed to identify further therapeutic targets in mEOC using a CRISPR/Cas9 library targeting 3015 genes, with and without treatment with onvansertib, a PLK1 inhibitor.

Identification of Four New Mutations in the GLA Gene Associated with Anderson-Fabry Disease.

Anderson-Fabry disease is a hereditary, progressive, multisystemic lysosomal storage disorder caused by a functional deficiency of the enzyme α-galactosidase A (α-GalA). This defect is due to mutations in the gene, located in the long arm of the X chromosome (Xq21-22). Functional deficiency of the α-GalA enzyme leads to reduced degradation and accumulation of its substrates, predominantly globotriaosylceramide (Gb3), which accumulate in the lysosomes of numerous cell types, giving rise to the symptomatology.

The Role of Butirprost as an Adjuvant in Enhancing the Effect of Antibiotics in Patients Affected by Chronic Bacterial Prostatitis: A Randomized Prospective Trial.

Bacterial prostatitis (BP) is a common prostatic infection characterized by pain and urinary symptoms, often with negative bacterial cultures from prostatic secretions. It affects young and older men bimodally and impacts quality of life (QoL) significantly. : Treatment typically involves antibiotics, but a multimodal approach with additional nutraceuticals may enhance outcomes.

Health Risk Factors, Prevention, and Inequalities.

The powerful quote from Martin Luther King Jr [...

Is the Use of Tourniquets More Advantageous than Other Bleeding Control Techniques in Patients with Limb Hemorrhage? A Systematic Review and Meta-Analysis.

Trauma, particularly uncontrolled bleeding, is a major cause of death. Recent evidence-based guidelines recommend the use of a tourniquet when life-threating limb bleeding cannot be controlled with direct pressure. Prehospital hemorrhage management, according to the XABCDE protocol, emphasizes the critical role of tourniquets in controlling massive bleeding.

Tracheostomy Practice in the Italian Intensive Care Units: A Point-Prevalence Survey.

: A tracheostomy is a frequently performed surgical intervention in intensive care units (ICUs) for patients requiring prolonged mechanical ventilation. This procedure can offer significant benefits, including reduced sedation requirements, improved patient comfort, and enhanced airway management. However, it is also associated with various risks, and the absence of standardized clinical guidelines complicates its implementation.

Midline Anterior Neck Inclusion Cyst in a Pediatric Patient: A Case Report and Literature Review with a Dermatologic Perspective.

Midline Anterior Neck Inclusion Cysts (MANICs) are rare congenital anomalies caused by improper embryonic fusion. These superficial benign lesions typically appear yellowish and cystic without deeper anatomic connections. We describe an 11-month-old boy with a stable, asymptomatic, yellow, elastic cystic lesion on the midline of the anterior neck, measuring 4 mm and present since shortly after birth.

Serum Lipids Alterations in Patients Under Systemic JAK Inhibitors Treatments in Dermatology: Clinical Aspects and Management.

: Janus kinase inhibitors (JAKi) have significantly advanced the treatment of various dermatological conditions by modulating the JAK-STAT signalling pathway. While these inhibitors have proven effective, they also pose challenges due to associated increase in serum lipid levels and relative potential cardiovascular risks. This perspective work aims to discuss the implications of these lipid alterations proposing management strategies for patients with dermatological disorders under JAKi treatments.

De Novo Assembly of the Polyhydroxybutyrate (PHB) Producer Strain H1 Genome and Genomic Analysis of PHB Production Machinery.

Polyhydroxybutyrate (PHB) is a biodegradable natural polymer produced by different prokaryotes as a valuable carbon and energy storage compound. Its biosynthesis pathway requires the sole expression of the operon, although auxiliary genes play a role in controlling polymer accumulation, degradation, granule formation and stabilization. Due to its biodegradability, PHB is currently regarded as a promising alternative to synthetic plastics for industrial/biotechnological applications.

Prevalence of Hepatitis C Virus Among Hospitalized Patients in a Tertiary Hospital in Italy: The Basis for a National Screening Assessment Model?

Free-of-charge hepatitis C virus antibody (HCV Ab) screening in some key populations and in 1969-1989 birth cohorts have been funded in Italy as the first step in confirming diagnosis in individuals who may be unaware of their infection. The purpose of this study is to leverage existing in-hospital routine screening data to better understand the distribution of HCV. A retrospective study of hospitalized patients (PTs) tested for HCV Ab for 5 years (from January 2017 to December 2022) in San Raffaele hospital was conducted according to age categories: birth year group before 1947 (patients older than 76 years old), birth year group 1947-1968, birth year group 1969-1989, and two other groups with birth year groups 1990-2000 and 2001-2022 (with patients younger than 33 years old) using the TriNetX platform.

Hereditary Breast Cancer: Comprehensive Risk Assessment and Prevention Strategies.

Women carrying pathogenic/likely pathogenic (P/LP) variants in moderate- or high-penetrance genes have an increased risk of developing breast cancer. However, most P/LP variants associated with breast cancer risk show incomplete penetrance. Age, gender, family history, polygenic risk, lifestyle, reproductive, hormonal, and environmental factors can affect the expressivity and penetrance of the disease.

Relevance of Next-Generation Sequencing in the Diagnosis of Thalassemia and Hemoglobinopathies: The Experience of Four Italian Diagnostic Hubs.

Unlabelled: Thalassemias and hemoglobinopathies are among the most common genetic diseases worldwide and have a significant impact on public health. The decreasing cost of next-generation sequencing (NGS) has quickly enabled the development of new assays that allow for the simultaneous analysis of small nucleotide variants (SNVs) and copy number variants (CNVs) as deletions/duplications of α- and β-globin genes.

Background/objectives: This study highlighted the efficacy and rapid identification of all types of mutations in the α- and β-globin genes, including silent variants, using the Devyser Thalassemia NGS kit.

Remodeling of Mitochondria-Endoplasmic Reticulum Contact Sites Accompanies LUHMES Differentiation.

Neural progenitor cells (NPCs) are often used to study the subcellular mechanisms underlying differentiation into neurons in vitro. Works published to date have focused on the pathways that distinguish undifferentiated NPCs from mature neurons, neglecting the earlier and intermediate stages of this process. Current evidence suggests that mitochondria interaction with the ER is fundamental to a wide range of intracellular processes.

Advances and Challenges in Pediatric Sepsis Diagnosis: Integrating Early Warning Scores and Biomarkers for Improved Prognosis.

Identifying and managing pediatric sepsis is a major research focus, yet early detection and risk assessment remain challenging. In its early stages, sepsis symptoms often mimic those of mild infections or chronic conditions, complicating timely diagnosis. Although various early warning scores exist, their effectiveness is limited, particularly in prehospital settings where accurate, rapid assessment is crucial.

Atypical Metastases from Prostate Cancer: Alpha-Methylacyl-Coenzyme A Racemase (AMACR) as a Potential Molecular Target in Prostate-Specific Membrane Antigen-Negative Prostate Adenocarcinoma.

Prostate cancer (PCa) is a high-prevalence disease usually characterized by metastatic spread to the pelvic lymph nodes and bones and the development of visceral metastases only in the late stages of disease. Positron Emission Tomography (PET) plays a key role in the detection of PCa metastases. Several PET radiotracers are used in PCa patients according to the stage and pathological features of the disease, in particular Ga/F-prostate-specific membrane antigen (PSMA) ligands.

Antimicrobial Resistance and Biofilm-Forming Ability in ESBL-Producing and Non-ESBL-Producing and Isolated from Canine Urinary Samples from Italy.

In dogs, bacterial urinary tract infections are a frequent cause of antimicrobial prescription, increasing the risk of selecting antibiotic-resistant bacteria. This study analyzed resistance patterns, the presence of extended-spectrum β-lactamases (ESBLs) and biofilm-forming capacity in and previously isolated from urine samples collected from 133 selected dogs admitted to the Veterinary Teaching Hospital of Milan, Italy, in 2021 and 2023. : The and isolates were bacteriologically and genetically analyzed.

Vascular Access Device Infections: Current Management Practices and the Role of Multidisciplinary Teams at a Large Hospital in Northern Italy.

: Vascular access device (VAD)-associated infections, including catheter-related (CRBSI) and catheter-associated bloodstream infections (CABSI), present significant challenges in patient care. While multidisciplinary VAD teams (VATs) are equipped with protocols for managing these infections, adherence to these guidelines in real-life practice is inconsistent. This study aims to evaluate the alignment between actual VAD infection management practices and VAT-recommended protocols.

The Erythrocyte Sedimentation Rate (ESR) in Veterinary Medicine: A Focused Review in Dogs and Cats.

The erythrocyte sedimentation rate (ESR) measures the rate at which erythrocytes aggregate and sediment in a fixed time in an anticoagulated blood tube and is expressed as a speed (mm/h). The ESR is still widely used in human medicine mainly as a modified or alternate method to the original Westergren. In veterinary medicine, it was employed in the 1940s-1960s after which it was gradually abandoned or rarely employed.

Current Enzooticity of and in Central and Southern Italy.

and are major parasitic nematodes of dogs. Many environmental and phenological changes have recently modified their geographic patterns in many countries; thus, this study has updated the distribution of and in dog populations of selected regions of Central and Southern Italy. Also, collateral data on other endoparasites affecting the study population have been collected.

Deep Learning-Based Glioma Segmentation of 2D Intraoperative Ultrasound Images: A Multicenter Study Using the Brain Tumor Intraoperative Ultrasound Database (BraTioUS).

Intraoperative ultrasound (ioUS) provides real-time imaging during neurosurgical procedures, with advantages such as portability and cost-effectiveness. Accurate tumor segmentation has the potential to substantially enhance the interpretability of ioUS images; however, its implementation is limited by persistent challenges, including noise, artifacts, and anatomical variability. This study aims to develop a convolutional neural network (CNN) model for glioma segmentation in ioUS images via a multicenter dataset.

Cardiac Exposure Related to Adjuvant Radiotherapy in Patients Affected by Thymoma: A Dosimetric Comparison of Photon or Proton Intensity-Modulated Therapy.

Background: Radiotherapy for thymoma is delivered post-operatively in selected cases. Given the particular location of the thymic bed and the excellent prognosis, late cardiac toxicities may be an issue. The purpose of this retrospective dosimetric study is to investigate whether intensity-modulated proton beam therapy (IMPT) compared to photon therapy could better spare cardiac substructures, given prespecified dose constraints.