DegraderTCM: A Computationally Sparing Approach for Predicting Ternary Degradation Complexes.

Proteolysis targeting chimeras (PROTACs or degraders) represent a novel therapeutic modality that has raised interest thanks to promising results and currently undergoing clinical testing. PROTACs induce the selective proteasomal degradation of undesired proteins by the formation of ternary complexes (TCs). Having knowledge of the 3D structure of TCs is crucial for the design of PROTAC drugs.

Accuracy of Two Continuous Glucose Monitoring Devices During Aerobic and High-Intensity Interval Training in Individuals with Type 1 Diabetes.

This study aimed to evaluate the accuracy of Dexcom G6 (DG6) and FreeStyle Libre-2 (FSL2) during aerobic training and high-intensity interval training (HIIT) in individuals with type 1 diabetes. Twenty-six males (mean age 29.3 ± 6.

Chamelogk: A Chromatographic Chameleonicity Quantifier to Design Orally Bioavailable Beyond-Rule-of-5 Drugs.

New chemical modalities in drug discovery include molecules belonging to the bRo5 chemical space. Because of their complex and flexible structure, bRo5 compounds often suffer from a poor solubility/permeability profile. Chameleonicity describes the capacity of a molecule to adapt to the environment through conformational changes; the design of molecular chameleons is a medicinal chemistry strategy simultaneously optimizing solubility and permeability.

In Silico Tools to Extract the Drug Design Information Content of Degradation Data: The Case of PROTACs Targeting the Androgen Receptor.

Proteolysis-Targeting Chimeras (PROTACs) have recently emerged as a promising technology in the drug discovery landscape. Large interest in the degradation of the androgen receptor (AR) as a new anti-prostatic cancer strategy has resulted in several papers focusing on PROTACs against AR. This study explores the potential of a few in silico tools to extract drug design information from AR degradation data in the format often reported in the literature.

Comparison of six microscopic methods and two operators for estimation of white and red blood cells in canine urine sediment.

Background: Little information is currently available about the analytical variability of urinalysis.

Objective: We aimed to compare results obtained by two operators using six microscopic methods in the quantification of urinary leukocytes (WBC) and erythrocytes (RBC).

Methods: Forty urine samples (10 mL) were centrifuged (450g, 5 minutes) and resuspended in 0.

Effect of Ethanol Consumption on the Accuracy of a Glucose Oxidase-Based Subcutaneous Glucose Sensor in Subjects with Type 1 Diabetes.

Continuous glucose monitors (CGM) have improved the management of patients with type 1 diabetes (T1D), with glucose oxidase (GOx)-based sensors being the most used. However, they are potentially subject to both electrochemical and enzymatic interferences, including those related to changes of pH. The objective of this study is to investigate the effect of ethanol, given as beer along with a mixed meal, on the accuracy of a commercial GOx-CGM.

Effect of meal composition and alcohol consumption on postprandial glucose concentration in subjects with type 1 diabetes: a randomized crossover trial.

Introduction: Meal composition is known to affect glycemic variability and glucose control in type 1 diabetes. The objective of this work was to evaluate the effect of high carbohydrate meals of different nutritional composition and alcohol on the postprandial glucose response in patients with type 1 diabetes.

Research Design And Methods: Twelve participants were recruited to this randomized crossover trial.

MiRNA 126 as a New Predictor Biomarker in Venous Thromboembolism of Persistent Residual Vein Obstruction: A Review of the Literature Plus a Pilot Study.

Venous thromboembolism (VTE) is the third most common cardiovascular disease. Interleukins (ILs) and micro-ribonucleic acids (miRNAs) have been proposed as molecules able to modulate endothelial inflammation and platelet hyperactivity. At present, no early biomarkers are available to predict the outcome of VTE.

Seasonal Local Models for Glucose Prediction in Type 1 Diabetes.

Linear empirical dynamic models have been widely used for blood glucose prediction and risks prevention in people with type 1 diabetes. More accurate blood glucose prediction models with longer prediction horizon (PH) are desirable to enable warnings to patients about imminent blood glucose changes with enough time to take corrective actions. In this study, a blood glucose prediction method is developed by integrating the predictions of a set of seasonal local models (each of them corresponding to different glucose profiles observed along historical data).

Study of abnormal adrenal receptors in subjects with ACTH-independent Cushing's syndrome and nodular adrenal hyperplasia.

Introduction: ACTH-independent Cushing's Syndrome (AICS) accounts for 15-20% of cases of Cushing's syndrome, with <1% due to abnormal receptors. Our aim is to study the presence of abnormal receptors in subjects diagnosed with AICS with nodular adrenal hyperplasia in a 14-year period (2002-2016), as well as its clinical-biological and evolutive characteristics.

Material And Methods: A multicentre descriptive study of a 15-case series of AICS with nodular adrenal hyperplasia (study period: 2002-2016).

Non-pharmacological management of gestational diabetes: The role of myo-inositol.

Gestational diabetes mellitus (GDM) is the most common metabolic disorder occurring in pregnancy. GDM plays an important role in the current diabetes epidemic: exposure to a high glycemic environment during the early stages of development increases the risk of the fetus to develop type two diabetes mellitus (T2DM) in adult life. Various cardiometabolic risk factors are linked to GDM.

Statements and Recommendations for Guided Bone Regeneration: Consensus Report of the Guided Bone Regeneration Symposium Held in Bologna, October 15 to 16, 2016.

Introduction: In the past 10 years, long-term studies have demonstrated that guided bone regeneration (GBR) is a successful and reliable technique for vertical and horizontal ridge augmentation, but strict and rigorous protocols must be adopted.

Material And Methods: Because no reports have yet been published with statements and clinical recommendations for GBR, a closed meeting of all authors was organized to discuss this matter during a GBR symposium held in Bologna (Italy) in October 2016. The authors focused on the findings of systematic and narrative reviews, prepared before the meeting, covering aspects of the clinical management of GBR techniques.

Analyzing and Reanalyzing the Genome: Findings from the MedSeq Project.

Although genome sequencing is increasingly available in clinical and research settings, many questions remain about the interpretation of sequencing data. In the MedSeq Project, we explored how much effort is required to evaluate and report on more than 4,500 genes reportedly associated with monogenic conditions, as well as pharmacogenomic (PGx) markers, blood antigen serotyping, and polygenic risk scores in 100 individuals (50 with cardiomyopathy and 50 healthy) randomized to the sequencing arm. We defined the quality thresholds for determining the need for Sanger confirmation.

The XPF-ERCC1 Complex Is Essential for Genome Stability and Is Involved in the Mechanism of Gene Targeting in .

The XPF-ERCC1 complex, a highly conserved structure-specific endonuclease, functions in multiple DNA repair pathways that are pivotal for maintaining genome stability, including nucleotide excision repair, interstrand crosslink repair, and homologous recombination. XPF-ERCC1 incises double-stranded DNA at double-strand/single-strand junctions, making it an ideal enzyme for processing DNA structures that contain partially unwound strands. Here, we have examined the role of the XPF-ERCC1 complex in the model bryophyte which exhibits uniquely high gene targeting frequencies.

Polycystic Ovary Syndrome: Implication for Drug Metabolism on Assisted Reproductive Techniques-A Literature Review.

Polycystic ovary syndrome (PCOS) affects 6-10% of women and could be considered one of the most common endocrine alterations in women of reproductive age. The syndrome is characterized by several hormonal and metabolic alterations, including insulin resistance and hyperandrogenism, which play a severe detrimental role in the patient's fertility. We aimed to offer an overview about drug metabolism in the PCOS population.

Surgical Treatment of a High-Flow Femoro-Femoral Arteriovenous Fistula in an Intravenous Drug Abuser.

Background: We report the surgical treatment of a high-flow femoro-femoral arteriovenous fistula (AVF), a rare complication of intravenous drug abuse.

Methods: A 36-year-old woman with history of intravenous heroin and cocaine abuse presented with right lower limb edema, inguinal bruit, and heart failure. Duplex ultrasound examination (DUS) and computed tomography angiography showed a large, high-flow AVF involving the common femoral vein and the superficial femoral artery, which is associated with thrombosis of the great saphenous vein and an important inflammation in the right groin, without active bleeding.

Plasma Insulin Levels and Hypoglycemia Affect Subcutaneous Interstitial Glucose Concentration.

Background: Continuous glucose monitoring (CGM) accuracy during hypoglycemia is suboptimal. This might be partly explained by insulin or hypoglycemia-induced changes in the plasma interstitial subcutaneous (SC) fluid glucose gradient. The aim of the present study was to assess the role of plasma insulin (PI) and hypoglycemia itself in the plasma and interstitial SC fluid glucose concentration in patients with type 1 diabetes mellitus.

Extensive Assessment of Blood Glucose Monitoring During Postprandial Period and Its Impact on Closed-Loop Performance.

Background: Closed-loop (CL) systems aims to outperform usual treatments in blood glucose control and continuous glucose monitors (CGM) are a key component in such systems. Meals represents one of the main disturbances in blood glucose control, and postprandial period (PP) is a challenging situation for both CL system and CGM accuracy.

Methods: We performed an extensive analysis of sensor's performance by numerical accuracy and precision during PP, as well as its influence in blood glucose control under CL therapy.

Closed-Loop Control of Postprandial Glycemia Using an Insulin-on-Board Limitation Through Continuous Action on Glucose Target.

Background: Postprandial (PP) control remains a challenge for closed-loop (CL) systems. Few studies with inconsistent results have systematically investigated the PP period.

Objective: To compare a new CL algorithm with current pump therapy (open loop [OL]) in the PP glucose control in type 1 diabetes (T1D) subjects.

Endoscopic Ultrasonography May Select Subjects Having Asymptomatic Chronic Pancreatic Hyperenzymemia Who Require a Stricter Follow-up.

Objectives: We have previously shown that at least 50% of patients with asymptomatic chronic pancreatic hyperenzymemia (ACPH) may develop morphological pancreatic alterations. Endoscopic ultrasonography (EUS) may detect small lesions, and its sensitivity seems to be higher than other imaging techniques. The aim of this study was to evaluate whether EUS may modify the management of patients having ACPH.

Peroxisome Proliferator-Activated Receptor Modulation during Metabolic Diseases and Cancers: Master and Minions.

The prevalence of obesity and metabolic diseases (such as type 2 diabetes mellitus, dyslipidaemia, and cardiovascular diseases) has increased in the last decade, in both industrialized and developing countries. This also coincided with our observation of a similar increase in the prevalence of cancers. The aetiology of these diseases is very complex and involves genetic, nutritional, and environmental factors.

Vitamin B12 among Vegetarians: Status, Assessment and Supplementation.

Cobalamin is an essential molecule for humans. It acts as a cofactor in one-carbon transfers through methylation and molecular rearrangement. These functions take place in fatty acid, amino acid and nucleic acid metabolic pathways.