Improving acute care outcome in internal medicine: the role of early stabilization and intermediate care unit.

The progressive reduction of acute care beds will necessitate hospital admission in medical settings solely for acutely ill patients requiring urgent organ support. Early stabilization of the acute condition, potentially through an appropriate treatment unit, may not only improve short-term patient outcomes but also reduce the length of hospital stay. To determine if stabilization of the acute condition in an intermediate care unit (IMCU) is associated with improved patient outcomes and reduced in-hospital stay.

Time Course of Reversal of Fentanyl-Induced Respiratory Depression in Healthy Subjects by Intramuscular Nalmefene and Intramuscular and Intranasal Naloxone.

The increase in opioid overdose deaths, particularly involving potent, long-acting synthetic opioids, has led to calls for stronger, longer-acting opioid-overdose-reversal agents. Using an opioid-induced respiratory depression model, we investigated the onset and time course of action of naloxone and a long-acting opioid antagonist, nalmefene, in reversing the effects of an ongoing intravenous fentanyl infusion over a period of up to 100 min. Healthy, moderately experienced opioid users received intramuscular (IM) nalmefene 1 mg, IM naloxone 2 mg, or intranasal (IN) naloxone 4 mg after fentanyl-induced respiratory depression was established based on reduction in respiratory minute volume (MV).

Evaluation of sunobinop for next-day residual effects in healthy participants.

Sunobinop is a novel, potent, selective partial agonist at nociceptin/orphanin FQ peptide (NOP) receptors. The primary objective of this randomized, double-blind, placebo-controlled study was to assess the next-day residual effects of an evening dose of sunobinop in healthy participants. Participants were randomized into 1 of 5 treatment sequences.

Transcriptional and epigenetic characterization of a new in vitro platform to model the formation of human pharyngeal endoderm.

Background: The Pharyngeal Endoderm (PE) is an extremely relevant developmental tissue, serving as the progenitor for the esophagus, parathyroids, thyroids, lungs, and thymus. While several studies have highlighted the importance of PE cells, a detailed transcriptional and epigenetic characterization of this important developmental stage is still missing, especially in humans, due to technical and ethical constraints pertaining to its early formation.

Results: Here we fill this knowledge gap by developing an in vitro protocol for the derivation of PE-like cells from human Embryonic Stem Cells (hESCs) and by providing an integrated multi-omics characterization.

Assessing triage efficiency in Italy: a comparative study using simulated cases among nurses.

Background: Emergency Departments (EDs) across Italy use different triage systems, which vary from region to region. This study aimed to assess whether nurses working in different EDs assign triage codes in a similar and standardized manner.

Methods: A multicenter observational simulation study involved the EDs of Bolzano Hospital, Merano Hospital, Pisa University Hospital, and Rovereto Hospital.

Universal Lynch Syndrome Screening in Colorectal Cancer: A 5-Year Experience of a Portuguese Pathology Department.

Lynch syndrome (LS) is a prevalent genetic condition associated with colorectal cancer (CRC). Accurate identification of LS patients is challenging, and a universal tumor screening approach has been recommended. We present the methodology and results of universal LS screening in our hospital's Pathology Department.

Muscle Dysmorphia in Gym-Going Men: The Role of Narcissism Vulnerability and Perfectionism.

Objective: Muscle dysmorphia (MD) refers to a pathological preoccupation with the idea that one's body is not lean and muscular enough. Literature suggests that vulnerable facet of narcissism and perfectionism are strongly related to the risk of developing MD symptoms. However, until now, there is a paucity of research exploring their relationship, which is the primary aim of this study.

Trauma Center model application in the University Hospital of Pisa: a single-center comparative study.

The Trauma Center, Hub, is a highly specialized hospital indicated for complex major trauma management after stabilization at a 1st level hospital, Spoke. Although in the United States this organization demonstrated its effectiveness in mortality, in the Italian context, data available are limited. On 30 September 2018, the University Hospital of Pisa formalized the introduction of the Trauma Center, optimizing Emergency Department (ED) organization to guarantee the highest standard of care.

Diagnosis of acute aortic syndromes with ultrasound and d-dimer: the PROFUNDUS study.

Background: In patients complaining common symptoms such as chest/abdominal/back pain or syncope, acute aortic syndromes (AAS) are rare underlying causes. AAS diagnosis requires urgent advanced aortic imaging (AAI), mostly computed tomography angiography. However, patient selection for AAI poses conflicting risks of misdiagnosis and overtesting.

Management of intra-abdominal infections: recommendations by the Italian council for the optimization of antimicrobial use.

Intra-abdominal infections (IAIs) are common surgical emergencies and are an important cause of morbidity and mortality in hospital settings, particularly if poorly managed. The cornerstones of effective IAIs management include early diagnosis, adequate source control, appropriate antimicrobial therapy, and early physiologic stabilization using intravenous fluids and vasopressor agents in critically ill patients. Adequate empiric antimicrobial therapy in patients with IAIs is of paramount importance because inappropriate antimicrobial therapy is associated with poor outcomes.

Prodrug Approach to Exploit (S)-Alanine Amide as Arginine Mimic Moiety in the Development of Protein Arginine Methyltransferase 4 Inhibitors.

Protein arginine methyltransferase (PRMT) 4 (also known as coactivator-associated arginine methyltransferase 1; CARM1) is involved in a variety of biological processes and is considered as an emerging target class in oncology and other diseases. A successful strategy to identify PRMT substrate-competitive inhibitors has been to exploit chemical scaffolds able to mimic the arginine substrate. (S)-Alanine amide moiety is a valuable arginine mimic for the development of potent and selective PRMT4 inhibitors; however, its high hydrophilicity led to derivatives with poor cellular outcomes.

Safety, Tolerability, and Pharmacokinetics of Single- and Multiple-Ascending Doses of Sunobinop in Healthy Participants.

Sunobinop is an investigational, potent, selective partial agonist at the nociceptin/orphanin FQ peptide receptor in vitro. Three phase 1 studies were conducted to evaluate the safety, tolerability, and pharmacokinetics (PK) of escalating single- and multiple-dose administration of sunobinop in healthy participants. Study 1 was a randomized, double-blind, placebo-controlled, single-ascending dose study.

Successes and challenges in the development of BD1-selective BET inhibitors: a patent review.

Introduction: Bromodomain and ExtraTerminal (BET) domain proteins are transcriptional cofactors that, recognizing acetylated lysines of histone and non-histone proteins, can modulate gene expression. The BET family consists of four members, each of which contains two bromodomains (BD1 and BD2) able to recognize the acetylated mark. Pan-BET inhibitors (BETi) have shown a promising anticancer potential in many clinical trials; however, their further development has been in part hampered by the side effects due to their lack of selectivity.

Autoimmune Hepatitis on a Living Liver Donor: An Unexpected Long-Term Complication.

In Western countries, deceased donor liver transplantation remains the standard of care for patients with end-stage liver disease. Living donor liver transplantation is a viable and feasible strategy for patients with end-stage liver disease designed to mitigate the deceased organ shortage. Donor safety is the primary concern because liver donors, ideally, should not have any complication.

Analyzing the shifting state of college sexual violence compelled disclosure policies: National trends, empirical findings, and implications.

Following federal and state law, institutions of higher education (IHE) have implemented mandatory reporting (MR) policies, requiring some employees to report sexual violence they learn about to university officials regardless of victim/survivor consent (i.e., compelled disclosure).

Universal mandatory reporting policies show null effects in a statewide college sample.

Objective: It is widely assumed that universal mandatory reporting policies (MRPs) for sexual misconduct are important for campus safety, but there is little evidence to support these assumptions.

Hypotheses: Given the exploratory nature of this research, no formal hypotheses were tested. We did not expect universal MRPs to be significantly associated with increased reporting or postreporting outcomes.

A combined approach of structure-based virtual screening and NMR to interrupt the PD-1/PD-L1 axis: Biphenyl-benzimidazole containing compounds as novel PD-L1 inhibitors.

Immunotherapy has emerged as a game-changing approach for cancer treatment. Although monoclonal antibodies (mAbs) targeting the programmed cell death protein 1/programmed cell death protein 1 ligand 1 (PD-1/PD-L1) axis have entered the market revolutionizing the treatment landscape of many cancer types, small molecules, although presenting several advantages including the possibility of oral administration and/or reduced costs, struggled to enter in clinical trials, suffering of water insolubility and/or inadequate potency compared with mAbs. Thus, the search for novel scaffolds for both the design of effective small molecules and possible synergistic strategies is an ongoing field of interest.

Mechanisms, pathways and strategies for rejuvenation through epigenetic reprogramming.

Over the past decade, there has been a dramatic increase in efforts to ameliorate aging and the diseases it causes, with transient expression of nuclear reprogramming factors recently emerging as an intriguing approach. Expression of these factors, either systemically or in a tissue-specific manner, has been shown to combat age-related deterioration in mouse and human model systems at the cellular, tissue and organismal level. Here we discuss the current state of epigenetic rejuvenation strategies via partial reprogramming in both mouse and human models.

Multi-centric study for development and validation of a CT head rule for mild traumatic brain injury in direct oral anticoagulants: the HERO-M nomogram.

Background: Nomograms are easy-to-handle clinical tools which can help in estimating the risk of adverse outcome in certain population. This multi-center study aims to create and validate a simple and usable clinical prediction nomogram for individual risk of post-traumatic Intracranial Hemorrhage (ICH) after Mild Traumatic Brain Injury (MTBI) in patients treated with Direct Oral Anticoagulants (DOACs).

Methods: From January 1, 2016 to December 31, 2019, all patients on DOACs evaluated for an MTBI in five Italian Emergency Departments were enrolled.

Monolayer platform to generate and purify primordial germ-like cells in vitro provides insights into human germline specification.

Generating primordial germ cell-like cells (PGCLCs) from human pluripotent stem cells (hPSCs) advances studies of human reproduction and development of infertility treatments, but often entails complex 3D aggregates. Here we develop a simplified, monolayer method to differentiate hPSCs into PGCs within 3.5 days.