Proteomic Characterization of Changes in Mouse Brain Cortex Protein Expression at Different Post-Mortem Intervals: A Preliminary Study for Forensic Biomarker Identification.

Accuracy in the evaluation of death-induced tissue degradation for thanato-chronological purposes is strictly dependent on the condition of the biological source as well as on the precision of post-mortem interval (PMI) estimation. Thus, the optimization of tissue handling and identification of sensitive post-mortem biomarkers could help establish a timeline for post-mortem events. To this aim, we investigated the proteome changes in cortex samples of 6-week-old female SAMR1 mice over a post-mortem time course.

Hallmarks for Thrombotic and Hemorrhagic Risks in Chronic Kidney Disease Patients.

Chronic kidney disease (CKD) is a global health issue causing a significant health burden. CKD patients develop thrombotic and hemorrhagic complications, and cardiovascular diseases are associated with increased hospitalization and mortality in this population. The hemostatic alterations are multifactorial in these patients; therefore, the results of different studies are varying and controversial.

Differential Regulation of Wingless-Wnt/c-Jun N-Terminal Kinase Crosstalk via Oxidative Eustress in Primary and Metastatic Colorectal Cancer Cells.

In the tumor microenvironment (TME), ROS production affects survival, progression, and therapy resistance in colorectal cancer (CRC). HO-mediated oxidative stress can modulate Wnt/β-catenin signaling and metabolic reprogramming of the TME. Currently, it is unclear how mild/moderate oxidative stress (eustress) modulates Wnt/β-catenin/APC and JNK signaling relationships in primary and metastatic CRC cells.

A Very Early Diagnosis of Complete Androgen Insensitivity Syndrome Due to a Novel Variant in the AR Gene: A Neonatal Case Study.

Androgen insensitivity syndrome (AIS) is one of the most common Disorders of Sexual Differentiation (DSDs). AIS is characterized by an X-linked recessive inheritance pattern associated with variants in the androgen receptor (AR) gene that affects the masculinization process in individuals with XY karyotype. Here, we report a neonatal case of a very early diagnosis of complete AIS due to a novel variant in the AR gene.

Subchronic Effects of Tetrachloroethylene on Two Freshwater Copepod Species: Implications for Groundwater Risk Assessment.

Aliphatic chlorinated hydrocarbons, notably tetrachloroethylene (also known as perchloroethylene [PCE]), are persistent, mobile, and toxic (PMT) and/or very persistent, mobile, and toxic (vPMT) groundwater pollutants, often exceeding safe drinking water thresholds. The present study delves into the groundwater risk assessment of PCE with a novel focus on the sensitivity of stygobitic species-organisms uniquely adapted to groundwater environments. Through a comparative analysis of the subchronic effects of PCE on the locomotion behavior of two copepod species, the stygobitic Moraria sp.

Banking of post-SMILE stromal lenticules for additive keratoplasty: A new challenge for eye banks?

Purpose: ReLEx (Refractive Lenticule Extraction) Small Incision Lenticule Extraction (SMILE), the second generation of ReLEx Femtosecond Lenticule Extraction (FLEx), is a minimally invasive, flapless procedure designed to treat refractive errors such as myopia, hyperopia, presbyopia, and astigmatism. This review aims to provide a comprehensive overview of the methods for preserving SMILE-derived lenticules and discusses their potential future applications.

Methods: A narrative literature review was conducted using PubMed, Scopus, and Web of Science databases, focusing on articles published up to January 2024 and available in English.

Chemical characteristics and sources apportionment of volatile organic compounds in the primary urban area of Shijiazhuang, North China Plain.

VOCs (Volatile organic compounds) exert a vital role in ozone and secondary organic aerosol production, necessitating investigations into their concentration, chemical characteristics, and source apportionment for the effective implementation of measures aimed at preventing and controlling atmospheric pollution. From July to October 2020, online monitoring was conducted in the main urban area of Shijiazhuang to collect data on VOCs and analyze their concentrations and reactivity. Additionally, the PMF (positive matrix factorization) method was utilized to identify the VOCs sources.

Sil1-deficient fibroblasts generate an aberrant extracellular matrix leading to tendon disorganisation in Marinesco-Sjögren syndrome.

Background: Marinesco-Sjögren syndrome (MSS) is an autosomal recessive neuromuscular disorder that arises in early childhood and is characterized by congenital cataracts, myopathy associated with muscle weakness, and degeneration of Purkinje neurons leading to ataxia. About 60% of MSS patients have loss-of-function mutations in the SIL1 gene. Sil1 is an endoplasmic reticulum (ER) protein required for the release of ADP from the master chaperone Bip, which in turn will release the folded proteins.

Pediatric-onset Multiple Sclerosis treatment: a multicentre observational study comparing natalizumab with fingolimod.

Background: Pediatric-onset Multiple Sclerosis (POMS) patients show more inflammatory disease compared with adult-onset MS. However, highly effective treatments are limited with only fingolimod being approved in Italy and natalizumab prescribed as off-label treatment.

Objectives: to compare the efficacy of natalizumab versus fingolimod in POMS.

Comparative renal outcomes of matched cohorts of patients with type 2 diabetes receiving SGLT2 inhibitors or GLP-1 receptor agonists under routine care.

Aims/hypothesis: We compared the effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) on renal outcomes in individuals with type 2 diabetes, focusing on the changes in eGFR and albuminuria.

Methods: This was a multicentre retrospective observational study on new users of diabetes medications. Participant characteristics were assessed before and after propensity score matching.

Primary stability evaluation of different morse cone implants in low-density artificial bone blocks: A comparison between high-and low-speed drilling.

This study aimed to evaluate various biomechanical parameters associated with the primary stability of Maestro and Due Cone implants placed in low-density artificial bones, prepared using high-speed drilling with irrigation and low-speed drilling without irrigation. The insertion torque (IT), removal torque (RT), and implant stability quotient (ISQ) values were recorded for Maestro and Due Cone implants placed in low-density polyurethane blocks (10 and 20 pounds per cubic foot (PCF) with and without a cortical layer) prepared using high-speed and low-speed with or without irrigation using a saline solution, respectively. A three-way ANOVA model and Tukey's post-hoc test were conducted, presenting data as means and standard deviations.

Preconception carrier screening and preimplantation genetic testing in the infertility management.

Background: Genetic testing serves as a valuable element of reproductive care, applicable at various stages of the reproductive journey: (i) before pregnancy, when a couple's genetic reproductive risk can be evaluated; (ii) before embryo implantation, as part of in vitro fertilization (IVF) treatment, to ascertain several inherited or de novo genetic/chromosomal diseases of the embryo before transfer; (iii) during the prenatal period, to assess the genetic costitution of the fetus. Preconception carrier screening (CS) is a genetic test typically performed on couples planning a pregnancy. The primary purpose of CS is to identify couples at-risk of conceiving a child affected by a severe genetic disorder with autosomal recessive or X-linked inheritance.

Sublingually administered bacterial lysates: rationale, mechanisms of action and clinical outcomes.

This review discusses available evidence on the mechanisms of action of bacterial lysates, and the clinical effects of their sublingual administration. Bacterial lysates act through many immunological effects, including dendritic cell activation, modification of circulating lymphocyte subsets and antibody production. The production of salivary IgA was repeatedly shown to be induced by the sublingual administration of a prototype bacterial lysate containing soluble and corpuscular antigens.

EV20/Omomyc: A novel dual MYC/HER3 targeting immunoconjugate.

MYC is one of the most important therapeutic targets in human cancer. Many attempts have been made to develop small molecules that could be used to curb its activity in patients, but most failed to identify a suitable direct inhibitor. After years of preclinical characterization, a tissue-penetrating peptide MYC inhibitor, called Omomyc, has been recently successfully used in a Phase I dose escalation study in late-stage, all-comers solid tumour patients.

TAM-associated CASQ1 mutants diminish intracellular Ca content and interfere with regulation of SOCE.

Tubular aggregate myopathy (TAM) is a rare myopathy characterized by muscle weakness and myalgia. Muscle fibers from TAM patients show characteristic accumulation of membrane tubules that contain proteins from the sarcoplasmic reticulum (SR). Gain-of-function mutations in STIM1 and ORAI1, the key proteins participating in the Store-Operated Ca Entry (SOCE) mechanism, were identified in patients with TAM.

Mechanobiological Strategies to Enhance Ovine () Adipose-Derived Stem Cells Tendon Plasticity for Regenerative Medicine and Tissue Engineering Applications.

Adipose-derived stem cells (ADSCs) hold promise for tendon repair, even if their tenogenic plasticity and underlying mechanisms remain only partially understood, particularly in cells derived from the ovine animal model. This study aimed to characterize oADSCs during in vitro expansion to validate their phenotypic properties pre-transplantation. Moreover, their tenogenic potential was assessed using two in vitro-validated approaches: (1) teno-inductive conditioned media (CM) derived from a co-culture between ovine amniotic stem cells and fetal tendon explants, and (2) short- (48 h) and long-term (14 days) seeding on highly aligned PLGA (ha-PLGA) electrospun scaffold.

DNA Damage Response in Early Breast Cancer: A Phase III Cohort in the Phobos Study.

We assessed the impact of DNA damage response and repair (DDR) biomarker expressions in 222 node-positive early breast cancer (BC) patients from a previous Phase III GOIM 9902 trial of adjuvant taxanes. At a median follow-up of 64 months, the original study showed no disease-free survival (DFS) or overall survival (OS) differences with the addition of docetaxel (D) to epirubicine-cyclophosphamide (EC). Immunohistochemistry was employed to assess the expression of DDR phosphoproteins (pATM, pATR, pCHK1, γH2AX, pRPA32, and pWEE1) in tumor tissue, and their association with clinical outcomes was evaluated through the Cox elastic net model.

Clinical characteristics and treatment approach of established New-Onset status epilepticus (eNOSE): A Real-World multicenter experience.

Introduction: Status Epilepticus (SE) can occur in patients without a previous epilepsy diagnosis, a condition identified as "new-onset status epilepticus" (NOSE). Treatment with benzodiazepine may fail in NOSE termination, requiring anti-seizure medication (ASM) employment. The term "established NOSE" (eNOSE) is generally employed in this context.

Acinetobacter baumannii OmpA-like porins: functional characterization of bacterial physiology, antibiotic-resistance, and virulence.

Acinetobacter baumannii is a critical opportunistic pathogen associated with nosocomial infections. The high rates of antibiotic-resistance acquisition make most antibiotics ineffective. Thus, new medical countermeasures are urgently needed.

Design, Synthesis, and Anti-Prostate Cancer Potential of 2-(4-Nitrobenzyl) Malonates In Vitro and DAL Acute Oral Toxicity Assessment In Vivo.

New 4-nitrobenzyl derivatives were designed and synthesised by nucleophilic substitution reactions of 4-nitrobenzyl bromide with malonic acid and its derivatives. The synthesised molecules were characterised using mass analysis and spectroscopic techniques and tested for their antioxidant properties using various methods, such as nitric oxide, DPPH, and hydrogen peroxide radical scavenging methods. The anti-inflammatory activities of the molecules were assessed using RBC membrane stabilisation and albumin denaturation methods.

Mitochondria can substitute for parvalbumin to lower cytosolic calcium levels in the murine fast skeletal muscle.

Aim: Parvalbumin (PV) is a primary calcium buffer in mouse fast skeletal muscle fibers. Previous work showed that PV ablation has a limited impact on cytosolic Ca ([Ca]) transients and contractile response, while it enhances mitochondrial density and mitochondrial matrix-free calcium concentration ([Ca]). Here, we aimed to quantitatively test the hypothesis that mitochondria act to compensate for PV deficiency.

Advanced medullary thyroid carcinoma uncovered by persistently elevated procalcitonin in a patient with COVID-19.

Summary: We report the case of an 88-year-old man hospitalized for COVID-19 with persistently very high procalcitonin (proCt) levels despite infection resolution. Since proCt is an adjunct tumor marker in the diagnosis of medullary thyroid carcinoma (MTC), serum calcitonin (Ct) was also measured showing very high levels. Computed tomography (CT) scan showed the presence of a thyroid mass and neck ultrasound revealed a solid isoechoic, inhomogeneous, 50 mm nodule in the right thyroid lobe, extended into the mediastinum.