Factors associated with poor intraoperative perfusion and postoperative complications in otolaryngological autologous tissue transfers: A single-centre retrospective observational study.

The purpose of this study was to identify haemodynamic factors that are associated with tissue hypoperfusion in flap/graft surgical patients that might be modified to reduce perioperative morbidity. We conducted a single-centre, retrospective, observational study of 1355 patients undergoing head and neck flap reconstructions. Logistic regression and chi-square analyses were employed to identify factors which signal perioperative complications.

NAD+ METABOLISM RESTRICTION BOOSTS HIGH-DOSE MELPHALAN EFFICACY IN PATIENTS WITH MULTIPLE MYELOMA.

Elevated levels of the nicotinamide adenine dinucleotide (NAD+)-generating enzyme nicotinamide phosphoribosyltransferase (NAMPT) are a common feature across numerous cancer types. Accordingly, we previously reported pervasive NAD+ dysregulation in Multiple Myeloma (MM) cells in association with upregulated NAMPT expression. Unfortunately, albeit being effective in preclinical models of cancer, NAMPT inhibition has proven ineffective in clinical trials due to the existence of alternative NAD+ production routes utilizing NAD+ precursors other than nicotinamide.

Phased array-based nonlinear wave mixing technique: Application to lack-of-fusion porosity characterization in additively manufactured metals.

The objective of this research is to demonstrate the effectiveness of a phased array-based nonlinear wave mixing technique to characterize internal, localized microscale damage in an additively manufactured (AM) component. By using phased arrays for the generation of the incident waves, it is possible to produce a nonlinear wave mixing scanning technique without the need for immersion or changing coupling conditions. The phased arrays can be configured to generate incident waves in multiple directions that meet the resonance conditions required for nonlinear wave mixing at a variety of internal locations.

Safety and efficacy of concomitant treatment with non-vitamin K antagonist oral anticoagulants and antiseizure medications: A propensity score matching cohort study.

Research on cerebrovascular events in atrial fibrillation (AF) patients taking non-vitamin K antagonist oral anticoagulants (NOACs) with antiseizure medications (ASMs) is limited, highlighting a significant gap in literature. We assessed thrombotic and hemorrhagic risks in patients on NOACs and ASMs versus those on NOACs or ASMs alone. We analyzed a retrospective cohort from five centers, including AF and epilepsy patients on both medications (n = 188), AF patients on NOACs (n = 298), and epilepsy patients on ASMs (n = 50), with a 3-year follow-up.

Macrophage migration inhibitory factor blockade reprograms macrophages and disrupts prosurvival signaling in acute myeloid leukemia.

The malignant microenvironment plays a major role in the development of resistance to therapies and the occurrence of relapses in acute myeloid leukemia (AML). We previously showed that interactions of AML blasts with bone marrow macrophages (MΦ) shift their polarization towards a protumoral (M2-like) phenotype, promoting drug resistance; we demonstrated that inhibiting the colony-stimulating factor-1 receptor (CSF1R) repolarizes MΦ towards an antitumoral (M1-like) phenotype and that other factors may be involved. We investigated here macrophage migration inhibitory factor (MIF) as a target in AML blast survival and protumoral interactions with MΦ.

Effect of anti-CGRP-targeted therapy on migraine aura: Results of an observational case series study.

Introduction: Limited clinical evidence is available regarding the potential effectiveness of anti-CGRP monoclonal antibodies for the preventive treatment of migraine with aura.

Aim Of The Study: This observational study involved a series of migraine patients affected by either migraine with or without aura, who were investigated for any changes in their frequencies and their migraine aura attack characteristics observed during treatment with anti-CGRP Mabs over a 1-year period.

Patients And Methods: Twelve migraine patients were included, seven of whom were treated with erenumab, 2 with fremanezumab, and 3 with galcanezumab.

Long-lasting effects of COVID-19 pandemic on hospitalizations and severity of bronchiolitis.

Bronchiolitis is a common cause of hospitalization in infants. The long-lasting impact of hygiene and social behavior changes during the pandemic on this disease is debated. We investigated the prevalence of hospitalized cases, clinical severity, and underlying risk factors before and during pandemic.

Gender-related stress factors and emotional perception in migraine: a structured online questionnaire in migraine patients and controls.

Background: While migraine is markedly prevalent in women, gender-related phenotype differences were rarely assessed. For this reason, we investigated, through a multicenter observational cross-sectional study, based on an online questionnaire, gender-related differences in stress factors, emotions, and pain perception in migraine patients and controls and their impact on migraine severity.

Methods: The study was designed as an online questionnaire.

Reliable prediction intervals with directly optimized inductive conformal regression for deep learning.

By generating prediction intervals (PIs) to quantify the uncertainty of each prediction in deep learning regression, the risk of wrong predictions can be effectively controlled. High-quality PIs need to be as narrow as possible, whilst covering a preset proportion of real labels. At present, many approaches to improve the quality of PIs can effectively reduce the width of PIs, but they do not ensure that enough real labels are captured.

Nicotinaldehyde, a Novel Precursor of NAD Biosynthesis, Abrogates the Anti-Cancer Activity of an NAD-Lowering Agent in Leukemia.

Targeting NAD depletion in cancer cells has emerged as an attractive therapeutic strategy for cancer treatment, based on the higher reliance of malignant vs. healthy cells on NAD to sustain their aberrant proliferation and altered metabolism. NAD depletion is exquisitely observed when NAMPT, a key enzyme for the biosynthesis of NAD, is inhibited.

Predictors of Post-induction Hypotension for Patients With Pulmonary Hypertension.

Purpose The purpose is to identify predictors of post-induction hypotension (PIH) during general anesthesia in a population of patients with varying degrees of pulmonary hypertension (PH). Methods This is a single-center, retrospective, observational study of perioperative data obtained via electronic health records from patients with PH undergoing surgery over a five-year period. Baseline patient characteristics, peri-induction management variables, and pre-induction mean arterial pressure (MAP) were statistically analyzed using Kruskal-Wallis rank sum tests, Pearson's chi-squared tests, and logistic regression analysis to identify risk factors for PIH.

Transport between im/mobile fractions shapes the speed and profile of cargo distribution in neurons.

Neuronal function requires continuous distribution of ion channels and other proteins throughout large cell morphologies. Protein distribution is complicated by immobilization of freely diffusing subunits such as on lipid rafts or in postsynaptic densities. Here, we infer rates of immobilization for the voltage-gated potassium channel Kv4.

Relapse rate in children with nephrotic syndrome during the SARS-CoV-2 pandemic.

Background: Viral upper respiratory tract infections trigger nephrotic syndrome relapses. Few data exist on the impact of the SARS-CoV-2 pandemic on the risk of relapse in children with idiopathic nephrotic syndrome (INS).

Methods: In a Belgian and Italian cohort of children with INS, we performed a retrospective analysis on the number and duration of relapses observed in 3 different periods in 2020: first COVID period, February 15-May 31; second COVID period, June 1-September 14; third COVID period, September 15-December 31.

Identification of new FK866 analogues with potent anticancer activity against pancreatic cancer.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal diseases for which chemotherapy has not been very successful yet. FK866 ((E)-N-(4-(1-benzoylpiperidin-4-yl)butyl)-3-(pyridin-3-yl)acrylamide) is a well-known NAMPT (nicotinamide phosphoribosyltransferase) inhibitor with anti-cancer activities, but it failed in phase II clinical trials. We found that FK866 shows anti-proliferative activity in three PDAC cell lines, as well as in Jurkat T-cell leukemia cells.

Gut microbiota severely hampers the efficacy of NAD-lowering therapy in leukemia.

Most cancer cells have high need for nicotinamide adenine dinucleotide (NAD) to sustain their survival. This led to the development of inhibitors of nicotinamide (NAM) phosphoribosyltransferase (NAMPT), the rate-limiting NAD biosynthesis enzyme from NAM. Such inhibitors kill cancer cells in preclinical studies but failed in clinical ones.

Immunological findings in patients with migraine and other primary headaches: a narrative review.

Experimental findings suggest an involvement of neuroinflammatory mechanisms in the pathophysiology of migraine. Specifically, preclinical models of migraine have emphasized the role of neuroinflammation following the activation of the trigeminal pathway at several peripheral and central sites including dural vessels, the trigeminal ganglion, and the trigeminal nucleus caudalis. The evidence of an induction of inflammatory events in migraine pathophysiological mechanisms has prompted researchers to investigate the human leukocyte antigen (HLA) phenotypes as well as cytokine genetic polymorphisms in order to verify their potential relationship with migraine risk and severity.

Validation of a Novel Wearable Multistream Data Acquisition and Analysis System for Ergonomic Studies.

Nowadays, the growing interest in gathering physiological data and human behavior in everyday life scenarios is paralleled by an increase in wireless devices recording brain and body signals. However, the technical issues that characterize these solutions often limit the full brain-related assessments in real-life scenarios. Here we introduce the Biohub platform, a hardware/software (HW/SW) integrated wearable system for multistream synchronized acquisitions.

Nonlinear ultrasonic technique for the characterization of microstructure in additive materials.

This study employs nonlinear ultrasonic techniques to track microstructural changes in additively manufactured metals. The second harmonic generation technique based on the transmission of Rayleigh surface waves is used to measure the acoustic nonlinearity parameter, β. Stainless steel specimens are made through three procedures: traditional wrought manufacturing, laser-powder bed fusion, and laser engineered net shaping.

Reactive oxygen/nitrogen species contribute substantially to the antileukemia effect of APO866, a NAD lowering agent.

APO866 is a small molecule drug that specifically inhibits nicotinamide phosphoribosyltransferase (NAMPT), a key enzyme involved in nicotinamide adenine dinucleotide (NAD) biosynthesis from the natural precursor nicotinamide. Although, the antitumor activity of APO866 on various types of cancer models has been reported, information regarding mechanisms by which APO866 exerts its cytotoxic effects is not well defined. Here we show that APO866 induces a strong, time-dependent increase in highly reactive ROS, nitric oxide, cytosolic/mitochondrial superoxide anions and hydrogen peroxide.

Molecular Approaches for the Treatment of Pompe Disease.

Glycogen storage disease type II (GSDII, Pompe disease) is a rare metabolic disorder caused by a deficiency of acid alpha-glucosidase (GAA), an enzyme localized within lysosomes that is solely responsible for glycogen degradation in this compartment. The manifestations of GSDII are heterogeneous but are classified as early or late onset. The natural course of early-onset Pompe disease (EOPD) is severe and rapidly fatal if left untreated.

Periostin Limits Tumor Response to VEGFA Inhibition.

Resistance to antiangiogenic drugs limits their applicability in cancer therapy. Here, we show that revascularization and progression of pancreatic neuroendocrine tumors (PNETs) under extended vascular-endothelial growth factor A (VEGFA) blockade are dependent on periostin (POSTN), a matricellular protein expressed by stromal cells. Genetic deletion of Postn in RIP1-Tag2 mice blunted tumor rebounds of M2-like macrophages and αSMA stromal cells in response to prolonged VEGFA inhibition and suppressed PNET revascularization and progression on therapy.

A melanin-mediated cancer immunotherapy patch.

Melanin is capable of transforming 99.9% of the absorbed sunlight energy into heat, reducing the risk of skin cancer. We here develop a melanin-mediated cancer immunotherapy strategy through a transdermal microneedle patch.