CRISPR/Cas9 Ribonucleoprotein Nucleofection for Genome Editing in Primary Human Keratinocytes: Knockouts, Deletions, and Homology-Directed Repair Mutagenesis.

Keratinocytes are the most abundant cell type in the human epidermis, the outermost layer of the skin. For years, primary human keratinocytes (HKs) have been used as a crucial tool for studying the pathogenesis of a wide range of skin-related diseases. To mimic the physiological and pathological behavior of human skin, organotypic 3D skin models can be generated by in vitro differentiation of HKs.

A Close Relationship Between Ultra-Processed Foods and Adiposity in Adults in Southern Italy.

Background/objectives: One of the main culprits of the obesity epidemic is the obesogenic food environment, which promotes the consumption of ultra-processed foods (UPFs) that are highly palatable, have low nutritional quality and a high caloric impact and are economical and ready to use. This monocentric retrospective study explored the association between UPFs, obesity and adiposity measurements among adults living with obesity in Southern Italy.

Methods: According to their Body Mass Index (BMI) values, 175 participants (63M) were recruited and stratified into three groups.

Safety and Effectiveness of a 4-Week Diet on Low-Carb Ready-to-Eat Ketogenic Products as Preoperative Care Treatment in Patients Scheduled for Metabolic and Bariatric Surgery.

Before metabolic and bariatric surgery (MBS), moderate weight loss and liver left lateral section (LLLS) volume reduction are desirable. Low-carb ketogenic diet-induced weight loss before MBS has been shown to have beneficial effects on the reduction in body weight (BW) and LLLS. However, the nutritional protocol of low-carb ketogenic diet may be hard to keep for prolonged periods due to the lack of sweet taste.

How to Manage a Neonate Born from a SARS-CoV-2-Positive Mother: A Narrative Review.

From 2020 to today, considerable knowledge on SARS-CoV-2 has been collected, even on pregnant women and their fetuses and newborns, and clinical guidelines have been written and implemented worldwide. Vaccination has considerably improved outcomes, but hesitancy amongst pregnant patients and the emergence of variants remain challenging, and SARS-CoV-2 positivity during pregnancy continues to be associated with an increased risk of maternal complications, premature delivery, and higher neonatal mortality and morbidity. A body of data now exists on the effect of SARS-CoV-2 during pregnancy on early neonatal outcomes, medical education in obstetrics and pediatrics, and longer-term developmental outcomes.

A CD Study of a Structure-Based Selection of -Heterocyclic Bis-Carbene Gold(I) Complexes as Potential Ligands of the G-Quadruplex-Forming Human Telomeric hTel23 Sequence.

Herein, we report the structure-based selection via molecular docking of four -heterocyclic bis-carbene gold(I) complexes, whose potential as ligands for the hTel23 G-quadruplex structure has been investigated using circular dichroism (CD) spectroscopy, CD melting, and polyacrylamide gel electrophoresis (PAGE). The complex containing a bis(1,2,3,4,6,7,8,9-octahydro-11-11-pyridazino[1,2-a]indazol-11-yl) scaffold induces a transition from the hybrid (3 + 1) topology to a prevalent parallel G-quadruplex conformation, whereas the complex featuring a bis(2-(2-acetamidoethyl)-3-imidazo[1,5-a]pyridin-3(2)-yl) moiety disrupted the original G-quadruplex structure. These results deserve particular attention in light of the recent findings on the pathological involvements of G-quadruplexes in neurodegenerative diseases.

Novel Approaches for the Early Detection of Glaucoma Using Artificial Intelligence.

Background: If left untreated, glaucoma-the second most common cause of blindness worldwide-causes irreversible visual loss due to a gradual neurodegeneration of the retinal ganglion cells. Conventional techniques for identifying glaucoma, like optical coherence tomography (OCT) and visual field exams, are frequently laborious and dependent on subjective interpretation. Through the fast and accurate analysis of massive amounts of imaging data, artificial intelligence (AI), in particular machine learning (ML) and deep learning (DL), has emerged as a promising method to improve the early detection and management of glaucoma.

Challenges and Considerations in Diagnosing and Managing p16+-Related Oropharyngeal Squamous Cell Carcinoma (OPSCC) with Neck Metastasis: Implications of p16 Positivity, Tobacco Exposure, and De-Escalation Strategies.

Background: The incidence of patients showing neck metastasis and no obvious primary tumor at the initial diagnostic evaluation or neck cancer of unknown primary (NCUP) is rising. It is estimated that a relevant part of these tumors arises in the tonsillar crypts or base of the tongue and are p16+-related. However, today, the detection rate of the primary tumor is suboptimal.

Efficacy and Safety of Keratosept Eye Drops in Patients with Punctate Keratitis: Clinical and Microbiological Evaluation on 50 Eyes.

We evaluated the efficacy and safety of eye drops with antiseptic and re-epithelizing properties (Keratosept, Bruschettini, Genova, Italy) on 50 eyes affected by punctate keratitis of suspected microbial origin. A biomicroscopic examination, fluorescein dye staining test (Fluotest), tear break-up time test (TBUT), and the ocular surface disease Index (OSDI) questionnaire were used to assess treatment efficacy. Treatment success was defined as a negative Fluotest and an OSDI score <12 on the 15th day of treatment.

Urinary Tract Infections in Kidney Transplant Patients: An Open Challenge-Update on Epidemiology, Risk Factors and Management.

Urinary tract infections are one of the main complications in kidney transplant patients, with a significant impact on graft function and survival. In fact, it is estimated that up to 74% of kidney transplant patients experience at least one episode of UTIs in the first year after transplantation, with an increased risk of graft loss and an increased risk of mortality. Several risk factors have been identified, such as female gender, old age, diabetes mellitus, immunosuppression, pre-transplant UTIs, urinary tract abnormalities, and prolonged dialysis.

Silibinin-Loaded Amphiphilic PLGA-Poloxamer Nanoparticles: Physicochemical Characterization, Release Kinetics, and Bioactivity Evaluation in Lung Cancer Cells.

Despite its potential against several carcinomas, the pharmacological efficacy of silibinin (SLB) is hampered by poor solubility, absorption, and oral bioavailability. To face these issues, we developed polylactic-co-glycolic acid (PLGA) nanoparticles (NPs) coated with hydrophilic polyethene oxide (PEO) for controlled and targeted SLB delivery. NPs were produced at two different SLB loadings and presented a spherical shape with smooth surfaces and stable size in water and cell culture medium.

Investigation of the Mechanism of Action of AMPs from Amphibians to Identify Bacterial Protein Targets for Therapeutic Applications.

Antimicrobial peptides (AMPs) from amphibians represent a promising source of novel antibacterial agents due to their potent and broad-spectrum antimicrobial activity, which positions them as valid alternatives to conventional antibiotics. This review provides a comprehensive analysis of the mechanisms through which amphibian-derived AMPs exert their effects against bacterial pathogens. We focus on the identification of bacterial protein targets implicated in the action of these peptides and on biological processes altered by the effect of AMPs.

Treatment of Carbapenem-Resistant in Real Life (T-ACI): A Prospective Single-Center Observational Study.

Carbapenem-resistant (CRAB) poses significant challenges in healthcare due to its multidrug resistance and high mortality rates among critically ill patients. We enrolled 45 patients. Cefiderocol was administered to 40% of patients, often (38.

Hereditary Neuromuscular Disorders in Reproductive Medicine.

Neuromuscular disorders (NMDs) encompass a broad range of hereditary and acquired conditions that affect motor units, significantly impacting patients' quality of life and reproductive health. This narrative review aims to explore in detail the reproductive challenges associated with major hereditary NMDs, including Charcot-Marie-Tooth disease (CMT), dystrophinopathies, Myotonic Dystrophy (DM), Facioscapulohumeral Muscular Dystrophy (FSHD), Spinal Muscular Atrophy (SMA), Limb-Girdle Muscular Dystrophy (LGMD), and Amyotrophic Lateral Sclerosis (ALS). Specifically, it discusses the stages of diagnosis and genetic testing, recurrence risk estimation, options for preimplantation genetic testing (PGT) and prenatal diagnosis (PND), the reciprocal influence between pregnancy and disease, potential obstetric complications, and risks to the newborn.

Editorial: Genetics and Genomics of Polyploid Plants.

Polyploidy, the condition of having more than two complete sets of chromosomes, is a widespread and influential phenomenon in the plant kingdom [...

ICOSLG Is Associated with Anti-PD-1 and Concomitant Antihistamine Treatment Response in Advanced Melanoma.

We previously demonstrated that patients with metastatic unresectable stage IIIb-IV melanoma receiving cetirizine (a second-generation H1 antagonist antihistamine) premedication with immunotherapy had better outcomes than those not receiving cetirizine. In this retrospective study, we searched for a gene signature potentially predictive of the response to the addition of cetirizine to checkpoint inhibition (nivolumab or pembrolizumab with or without previous ipilimumab). Transcriptomic analysis showed that inducible T cell costimulator ligand (ICOSLG) expression directly correlated with the disease control rate (DCR) when detected with a loading value > 0.

How Does Physical Activity Modulate Hormone Responses?

Physical activity highly impacts the neuroendocrine system and hormonal secretion. Numerous variables, both those related to the individual, including genetics, age, sex, biological rhythms, nutritional status, level of training, intake of drugs or supplements, and previous or current pathologies, and those related to the physical activity in terms of type, intensity, and duration of exercise, or environmental conditions can shape the hormonal response to physical exercise. The aim of this review is to provide an overview of the effects of physical exercise on hormonal levels in the human body, focusing on changes in concentrations of hormones such as cortisol, testosterone, and insulin in response to different types and intensities of physical activity.

Immunohistochemical Investigation of Cyclooxygenase-2 Expression in Rabbit Uterine Adenocarcinoma and the Potential Use of COX-2 Inhibitors in Cancer Therapy.

Cyclooxygenase-2 (COX-2) is overexpressed in many human and animal cancers. Selective COX-2 inhibitors have shown antitumoral effects in tumors with a high expression of COX-2. This study evaluates (1) the expression of COX-2 in rabbit uterine adenocarcinomas, (2) the correlation between immunophenotypic expression and histopathological changes, and (3) the post-surgery response to therapy with COX-2 inhibitors.

Severe Obesity Defined by Percentiles of WHO and Cardiometabolic Risk in Youth with Obesity.

The pediatric definition of severe obesity (OB) depends on the body mass index (BMI) references. We evaluated different BMI-derived metrics of the World Health Organization (WHO) system to define which cut-off is associated with the highest cardiometabolic risk (CMR); In this multicentric study, data were retrieved for 3727 youths (1937 boys; 2225 children, 1502 adolescents). OB was defined as BMI > 97th percentile (BMI), severe OB was defined as BMI > 99th percentile (BMI), BMI ≥ 120% of the 97th percentile (120% BMI), or BMI Z-score > 3 (WHO tables), or BMI ≥ the International Obesity Task Force (IOTF) value crossing a BMI of 35 kg/m at the age of 18 (IOTF).

Relationship Between Loss of Y Chromosome and Urologic Cancers: New Future Perspectives.

The Y chromosome (ChrY) is essential for male sex determination and spermatogenesis. However, recent studies have revealed its broader role in various physiological processes and disease susceptibility, including cancer. A comprehensive literature review was conducted using databases like MEDLINE, Scopus, Web of Science, and Google Scholar.

Biphenotypic Sinonasal Sarcoma: Literature Review of a Peculiar Pathological Entity-The Neurosurgical Point of View.

Background: Biphenotypic sinonasal sarcoma (BSNS) is a low-grade tumor of the sinonasal tract with frequent extension to the orbit and skull base. Due to its rare incidence and recent histopathological and molecular characterization, little data are available in regard to its natural history, treatment and surveillance protocol.

Methods: A comprehensive literature review in Embase online electronic databases on BSNS was made.

Muscle Proteome Analysis of Facioscapulohumeral Dystrophy Patients Reveals a Metabolic Rewiring Promoting Oxidative/Reductive Stress Contributing to the Loss of Muscle Function.

Facioscapulohumeral muscular dystrophy (FSHD) is caused by the epigenetic de-repression of the double homeobox 4 (DUX4) gene, leading to asymmetric muscle weakness and atrophy that begins in the facial and scapular muscles and progresses to the lower limbs. This incurable condition can severely impair muscle function, ultimately resulting in a loss of ambulation. A thorough analysis of molecular factors associated with the varying degrees of muscle impairment in FSHD is still lacking.