The Rise of Fentanyl: Molecular Aspects and Forensic Investigations.

Fentanyl is a synthetic opioid widely used for its potent analgesic effects in chronic pain management and intraoperative anesthesia. However, its high potency, low cost, and accessibility have also made it a significant drug of abuse, contributing to the global opioid epidemic. This review aims to provide an in-depth analysis of fentanyl's medical applications, pharmacokinetics, metabolism, and pharmacogenetics while examining its adverse effects and forensic implications.

Combined Effect of tDCS and Motor or Cognitive Activity in Patients with Alzheimer's Disease: A Proof-of-Concept Pilot Study.

(1) Background: Alzheimer's disease (AD) accounts for 70% of dementia cases and with no effective pharmacological treatments, new rehabilitation methods are needed. Motor and cognitive activities and transcranial direct current stimulation (tDCS) have shown promise in stabilizing and enhancing cognitive functions. Objective: we want to investigate the effects of tDCS combined with motor or cognitive activity on cognitive functions in AD patients.

Efficacy and activity of treatments after progression from palbociclib plus endocrine therapy in patients with HR/HER2 metastatic breast cancer: a prospective, monocentric study.

Background: Breast cancer is the most frequent tumour worldwide, and the HR/HER2 subtype is the most common. For this tumour type, endocrine therapy (ET) is the mainstay of treatment. The association of ET and CDK4/6 inhibitors (CDK4/6i) represents the gold standard for first-line or second-line therapies.

The emergency department arrival mode and its relations to ED management and 30-day mortality in acute heart failure: an ancillary analysis from the EURODEM study.

Background: Acute heart failure patients are often encountered in emergency departments (ED) from 11% to 57% using emergency medical services (EMS). Our aim was to evaluate the association of EMS use with acute heart failure patients' ED management and short-term outcomes.

Methods: This was a sub-analysis of a European EURODEM study.

Investigating SARS-CoV-2 transmission among co-workers in a University of Northern Italy during COVID-19 pandemic: an observational study.

Background: This study aimed to investigate SARS-CoV-2 transmission among co-workers at the University of Genoa, Italy, during the second COVID-19 pandemic wave.

Methods: A cross-sectional study was carried out in October 2020 - March 2021: RT-PCR confirmed cases of COVID-19 notified to the Occupational Health Service were included in the analysis.

Results: Among the n = 201 notified cases, contact tracing of n = 53 individuals identified n = 346 close contacts.

Clinical and epidemiological characteristics of COVID-19 during the early phase of the SARS-CoV-2 pandemic: a cross-sectional study among medical school physicians and residents employed in a regional reference teaching hospital in Northern Italy.

Objectives: The aim of the study was to evaluate the clinical presentation and burden of SARS-CoV-2 infections among medical school physicians and residents, mainly young medical doctors. The awareness of COVID‑19 clinical manifestations can improve the early detection of mild cases, possibly reducing further transmission to colleagues and patients.

Material And Methods: The study was carried out in March-May 2020, involving medical school physicians in a teaching hospital in northern Italy, with a working population of 881 medical doctors.

Epidemiology, treatment and outcome of patients with lower respiratory tract infection presenting to emergency departments with dyspnoea (AANZDEM and EuroDEM studies).

Objective: Lower respiratory tract infection (LRTI) is a frequent cause of dyspnoea in EDs, and is associated with considerable morbidity and mortality. We described and compared the management of this disease in Europe and Oceania/South-East Asia (SEA) cohorts.

Methods: We conducted a prospective cohort study with three time points in Europe and Oceania/SEA.

Seasonal variations of patients presenting dyspnea to emergency departments in Europe: Results from the EURODEM Study.

Background/aim: To describe seasonal variations in epidemiology, management, and short-term outcomes of patients in Europe presenting to an emergency department (ED) with a main complaint of dyspnea.

Materials And Methods: Anobservational prospective cohort study was performed in 66 European EDs which included consecutive patients presenting to EDs with dyspnea as the main complaint during 3 72-h study periods. Data were collected on demographics, comorbidities, chronic treatment, prehospital treatment, mode of arrival of patient to ED, clinical signs at admission, treatment in the ED, ED diagnosis, discharge from ED, and in-hospital outcome.

Efficacy of food supplement Acidif plus® in the treatment of uncomplicated UTIs in women: a pilot observational study.

Background: Urinary tract infections (UTIs) are among the most common bacterial infection diagnosed in women. The standard therapy is represented by short course of anti-microbial treatment to eradicate causative pathogens. However, due to antibiotic treatment, normal microbiota of the gastrointestinal tract is at risk of depletion and prolonged use of antibiotics can lead to the development of resistant strains.

Selective inhibition of Ph-positive ALL cell growth through kinase-dependent and -independent effects by CDK6-specific PROTACs.

Expression of the cell cycle regulatory gene CDK6 is required for Philadelphia-positive (Ph+) acute lymphoblastic leukemia (ALL) cell growth, whereas expression of the closely related CDK4 protein is dispensable. Moreover, CDK6 silencing is more effective than treatment with the dual CDK4/6 inhibitor palbociclib in suppressing Ph+ ALL in mice, suggesting that the growth-promoting effects of CDK6 are, in part, kinase-independent in Ph+ ALL. Accordingly, we developed CDK4/6-targeted proteolysis-targeting chimeras (PROTACs) that inhibit CDK6 enzymatic activity in vitro, promote the rapid and preferential degradation of CDK6 over CDK4 in Ph+ ALL cells, and markedly suppress S-phase cells concomitant with inhibition of CDK6-regulated phospho-RB and FOXM1 expression.

Treatment and outcome of adult patients with acute asthma in emergency departments in Australasia, South East Asia and Europe: Are guidelines followed? AANZDEM/EuroDEM study.

Objective: Asthma exacerbations are common presentations to ED. Key guideline recommendations for management include administration of inhaled bronchodilators, systemic corticosteroids and titrated oxygen therapy. Our aim was to compare management and outcomes between patients treated for asthma in Europe (EUR) and South East Asia/Australasia (SEA) and compliance with international guidelines.

Epidemiology of patients presenting with dyspnea to emergency departments in Europe and the Asia-Pacific region.

Objective: The primary objective of this study was to describe the epidemiology and management of dyspneic patients presenting to emergency departments (EDs) in an international patient population. Our secondary objective was to compare the EURODEM and AANZDEM patient populations.

Patients And Methods: An observational prospective cohort study was carried out in Europe and the Asia-Pacific region.

Continent-wide decoupling of Y-chromosomal genetic variation from language and geography in native South Americans.

Numerous studies of human populations in Europe and Asia have revealed a concordance between their extant genetic structure and the prevailing regional pattern of geography and language. For native South Americans, however, such evidence has been lacking so far. Therefore, we examined the relationship between Y-chromosomal genotype on the one hand, and male geographic origin and linguistic affiliation on the other, in the largest study of South American natives to date in terms of sampled individuals and populations.

[State of emergency plans for massive influx of injured (PEMAF) in Italian hospitals. Pilot study].

Aim of this study is to assess the level of implementation of plans for the massive influx of injured (PEMAF) in Italian hospitals. An anonymous questionnaire was administered to a sample of 100 hospitals selected through the network of the Italian Society of Emergency Medicine (SIMEU). Each answer of the questionnaire was assigned a score, then reported on a scale of compliance (maximum 65 points, threshold 35 points).

Quality in emergency departments: a study on 3,285,440 admissions.

Introduction: A multi-centre study has been conducted, during 2005, by means of a questionnaire posted on the Italian Society of Emergency Medicine (SIMEU) web page. Our intention was to carry out an organisational and functional analysis of Italian Emergency Departments (ED) in order to pick out some macro-indicators of the activities performed. Participation was good, in that 69 ED (3,285,440 admissions to emergency services) responded to the questionnaire.

Multiple genetic lesions in solid tumors: relevance to diagnosis, prognosis, and molecular mechanisms.

In recent years, significant progress has been made in identifying characteristic chromosomal and molecular rearrangements associated with several solid tumors. Most solid tumors studied have been found to be characterized by recurrent chromosomal abnormalities that are specific to histologic types. We have studied primary specimens of malignant melanoma, gastrointestinal cancer, renal carcinoma, lung and ovarian cancer, by cytogenetic and molecular means, and we discuss the genetic alterations found.

Beta-endorphins ACTH and cortisol in CSF and plasma of HIV infected patients.

Interactions between HPA (Hypothalamic-pituitary-axis) and immune system seem to involve the EPO (endogenous opioid peptides) system, as shown by some recent findings. Possible relationships between beta-endorphin (beta-End) synthesis and severity rate of immunodeficiency have been studied in 48 HIV Ab positive patients, at different stages of infection. A statistically significant decrease in the beta-End synthesis was observed in these patients, as compared to a control group of 19 healthy subjects, but this decrease was not related to the CD4+T lymphocytes number.

Cytogenetic, molecular and phenotypic characterization of the newly established renal carcinoma cell line KJ29. Evidence of translocations for chromosomes 1 and 3.

The established non papillary human renal carcinoma cell line (RCC) KJ29 was submitted to a multiparametric characterization to evaluate its potential use for in vitro and in vivo studies. The cell line grows in vitro as monolayer as well as cell suspension. Cytogenetic analysis has shown a modal chromosome number of 50 with some marker chromosomes, including rearrangements of chromosomes 1 and 3.

Evolutionary conservation of the EPS8 gene and its mapping to human chromosome 12q23-q24.

We have previously isolated the coding sequence for a novel substrate for tyrosine kinases, eps8, from NIH3T3 fibroblasts. Eps8 was phosphorylated in vivo by several receptor tyrosine kinases (RTKs) and, upon overexpression, was able to enhance EGFR-mediated mitogenic signaling in NIH3T3 cells. To gain understanding of eps8 function as well as its role in normal and neoplastic proliferation, we cloned the human eps8 coding sequence and studied expression of the human RNA and protein, evolutionary conservation, and chromosomal location.

Chromosome locations of human EMX and OTX genes.

We have determined the chromosomal localization of four human homeobox-containing genes, EMX1, EMX2, OTX1, and OTX2, related to Drosophila genes expressed in the developing head of the fly. Murine homologs of these genes are expressed in specific nested domains in the developing rostral brain of midgestation embryos. DNAs from a panel of 19 rodent-human hybrids, each carrying one or a few human chromosomes such that most human chromosome regions were represented, were tested for the presence of the four gene loci by filter hybridization to radiolabeled probes.

[Insulin resistance in obese and non-obese patients with polycystic ovary syndrome. Possible role in the pathogenesis of the disease].

The pathogenesis of Polycystic Ovary Syndrome (PCOs) is not well known till now. Previous reports indicated an hyperinsulinemia and insulin resistance in obese and non obese PCOs. However the role of hyperinsulinemia in PCOs pathogenesis is not completely understood.

Genetic alteration in gastrointestinal cancer. A molecular and cytogenetic study.

We examined 16 cases of gastrointestinal cancer, of which 11 were from the colon, 1 from the rectum, and 4 of gastric origin, cytogenetically for expression and for loss of heterozygosity (LOH) on chromosome 18 using Deleted Colon Cancer (DCC) gene. LOH on chromosome 18 with DCC probe was detected in 7 out of 11 cases of colon, in 4 out of 4 cases of gastric and in 1 case of rectum cancer. In all gastrointestinal tumors the expression of DCC gene was absent, while it was present in normal tissue.

Highly efficient elimination of Philadelphia leukemic cells by exposure to bcr/abl antisense oligodeoxynucleotides combined with mafosfamide.

Synthetic oligodeoxynucleotides complementary to the break-point junction of bcr-abl transcripts selectively inhibit the proliferation of Philadelphia-positive leukemic cells, but residual leukemic cells persist in antisense oligodeoxynucleotides-treated cultures. Cyclophosphamide derivatives such as mafosfamide and 4-hydroperoxycyclophosphamide are used at high doses for purging of Philadelphia leukemic cells from marrows but such treatment can be associated with delayed engraftment and prolonged cytopenias. To develop a more effective procedure that might optimize the killing of leukemia cells and the sparing of normal hematopoietic progenitor cells, a 1:1 mixture of Philadelphia leukemic cells and normal bone marrow cells was exposed to a combination of a low dose of mafosfamide and bcr-abl antisense oligodeoxynucleotides and assayed for growth ability in clonogenic assays and in immunodeficient mice.

[Syndrome X and surgical stress. A clinical case].

The syndrome X is a clinical disease characterised by anginous pain with the absence of significant and angiographically visible stenosis of the coronary tree. D. P.