Coupling cellular drug-target engagement to downstream pharmacology with CeTEAM.

Cellular target engagement technologies enable quantification of intracellular drug binding; however, simultaneous assessment of drug-associated phenotypes has proven challenging. Here, we present cellular target engagement by accumulation of mutant as a platform that can concomitantly evaluate drug-target interactions and phenotypic responses using conditionally stabilized drug biosensors. We observe that drug-responsive proteotypes are prevalent among reported mutants of known drug targets.

Mechanical power is associated with cardiac output and pulmonary blood flow in an experimental acute respiratory distress syndrome in pigs.

Background: Despite being essential in patients with acute respiratory distress syndrome (ARDS), mechanical ventilation (MV) may cause lung injury and hemodynamic instability. Mechanical power (MP) may describe the net injurious effects of MV, but whether it reflects the hemodynamic effects of MV is currently unclear. We hypothesized that MP is also associated with cardiac output (CO) and pulmonary blood flow (PBF).

Mechanical Power Correlates With Lung Inflammation Assessed by Positron-Emission Tomography in Experimental Acute Lung Injury in Pigs.

Mechanical ventilation (MV) may initiate or worsen lung injury, so-called ventilator-induced lung injury (VILI). Although different mechanisms of VILI have been identified, research mainly focused on single ventilator parameters. The mechanical power (MP) summarizes the potentially damaging effects of different parameters in one single variable and has been shown to be associated with lung damage.

Silencing the spindle assembly checkpoint: Let's play Polo!

Silencing of the spindle assembly checkpoint involves two protein phosphatases, PP1 and PP2A-B56, that are thought to extinguish checkpoint signaling through dephosphorylation of a checkpoint scaffold at kinetochores. In this issue, Cordeiro et al. (2020.

Killing two birds with one stone: how budding yeast Mps1 controls chromosome segregation and spindle assembly checkpoint through phosphorylation of a single kinetochore protein.

During mitosis, the identical sister chromatids of each chromosome must attach through their kinetochores to microtubules emanating from opposite spindle poles. This process, referred to as chromosome biorientation, is essential for equal partitioning of the genetic information to the two daughter cells. Defects in chromosome biorientation can give rise to aneuploidy, a hallmark of cancer and genetic diseases.

A common molecular mechanism underlies the role of Mps1 in chromosome biorientation and the spindle assembly checkpoint.

The Mps1 kinase corrects improper kinetochore-microtubule attachments, thereby ensuring chromosome biorientation. Yet, its critical phosphorylation targets in this process remain largely elusive. Mps1 also controls the spindle assembly checkpoint (SAC), which halts chromosome segregation until biorientation is attained.

One-Pot Synthesis of Biocompatible Silver Nanoparticle Composites from Cellulose and Keratin: Characterization and Antimicrobial Activity.

A novel, simple method was developed to synthesize biocompatible composites containing 50% cellulose (CEL) and 50% keratin (KER) and silver in the form of either ionic (Ag) or Ag nanoparticles (AgNPs or AgNPs). In this method, butylmethylimmidazolium chloride ([BMImCl]), a simple ionic liquid, was used as the sole solvent and silver chloride was added to the [BMImCl] solution of [CEL+KER] during the dissolution process. The silver in the composites can be maintained as ionic silver (Ag) or completely converted to metallic silver (Ag) by reducing it with NaBH.

Synthesis, structure and antimicrobial property of green composites from cellulose, wool, hair and chicken feather.

Novel composites between cellulose (CEL) and keratin (KER) from three different sources (wool, hair and chicken feather) were successfully synthesized in a simple one-step process in which butylmethylimidazolium chloride (BMIm(+)Cl(-)), an ionic liquid, was used as the sole solvent. The method is green and recyclable because [BMIm(+)Cl(-)] used was recovered for reuse. Spectroscopy (FTIR, XRD) and imaging (SEM) results confirm that CEL and KER remain chemically intact and homogeneously distributed in the composites.

Severely increased risk of amyotrophic lateral sclerosis among Italian professional football players.

The cause of amyotrophic lateral sclerosis (ALS) is still unknown. A possible relationship between ALS and sport participation has been supposed, but never definitely demonstrated. We studied a cohort of 7325 male professional football players engaged by a football team from the Italian First or Second Division in the period 1970-2001.

Selected food intake and risk of endometriosis.

Background: To offer data on the relationship between diet and risk of pelvic endometriosis, we analysed data collected in the framework of two case-control studies.

Methods: Data from two case-control studies conducted in Northern Italy between 1984 and 1999 were combined. Cases were 504 women aged < 65 years (median age 33 years, range 20-65) with a laparoscopically confirmed diagnosis of endometriosis, admitted to a network of obstetrics and gynaecology departments in Milan, Brescia and Pavia.

Risk factors for different histological types of ovarian cancer.

Various histological types of ovarian cancer may develop from different etiological aspects. Data separated by histological subtypes collected in the framework of a large case-control study on ovarian cancer conducted in Italy were analyzed. The cases were women below the age of 75 years, admitted to a network of hospitals in Milan.

Moderate alcohol drinking and risk of preterm birth.

Objective: We have analysed the association between alcohol drinking before and during the three trimesters of pregnancy and risk of preterm birth of babies with normal weight for gestational age or with low weight for gestational age (SGA).

Design: Case-control study.

Setting: General and university hospitals in Italy.

Diet and risk of seromucinous benign ovarian cysts.

Objective: To analyze the relation between selected dietary indicators and the risk of seromucinous benign ovarian cysts.

Study Design: We used data from a case-control study on risk factors for benign ovarian cysts conducted in Italy between 1984 and 1994. Cases included 225 women with a histologically confirmed diagnosis of benign seromucinous ovarian neoplasm dating back no more than 2 years.

Maternal and paternal smoking and pregnancy-induced hypertension.

Objective: Smoking has been suggested to reduce the risk of pregnancy-induced hypertension (PIH). We have analyzed the association between smoking and risk of PIH using data from a case-control study conducted in Italy.

Study Design: Cases were 215 women who gave birth on randomly selected days at a network of obstetric departments and with a diagnosis of PIH, i.

Oral contraceptives and risk of gestational trophoblastic disease.

Clinical reports suggested that the use of oral contraceptives (OC) after a molar pregnancy may increase the risk of persistent throphoblastic disease. However, few epidemiologic studies have analyzed the effect of OC use on the risk of developing gestational trophoblastic disease (GTD). To give further information, we have analyzed data from a case-control study on risk factors for GTD.

Risk factors for endometrial hyperplasia: results from a case-control study.

We analyzed epidemiologic characteristics of women at risk for endometrial hyperplasia (EH), using data from a case-control study. One hundred twenty nine women aged 35-73 (median 51 years) with histologically confirmed complex endometrial hyperplasia without atypies identified at the University of Milan during the period 1990-99 were examined. Controls were 258 non hysterectomized women aged 36-74 (median 52 years), admitted to a network of hospitals covering the same area where cases had been identified for conditions other than gynecological, malignant, or hormone-related.

Time since last birth and the risk of ovarian cancer.

Objectives: While parity is a protective factor in ovarian cancer, the role of time factors of pregnancy and birth is still controversial. We considered therefore the role of birth timing in the risk in ovarian cancer from a large case-control study.

Methods: Cases were 971 women (age range 22-74 years, median age 54) with histologically confirmed, incident epithelial ovarian cancer, interviewed between 1983 and 1991 in a network of hospitals in Milan, Italy.

Creatine as nutritional supplementation and medicinal product.

Because of assumed ergogenic effects, the creatine administration has become popular practice among subjects participating in different sports. Appropriate creatine monohydrate dosage may be considered a medicinal product since, in accordance with the Council Directive 65/65/EEC, any substance which may be administered with a view to restoring, correcting or modifying physiological functions in humans beings is considered a medicinal product. Thus, quality, efficacy and safety must characterise the substance.

Dietary factors and risk of spontaneous abortion.

Objective: This study examines the association between dietary habits and risk of spontaneous abortion.

Design: Hospital-based case-control study.

Setting: Obstetric hospitals in Milan, Italy.

Selected food intake and risk of multiple pregnancies.

In order to explore the association between multiple birth risk and diet, data were analysed from a case-control study on risk factors for multiple births conducted in Italy between 1988 and 1998. A total of 185 cases (median age 30 years) were interviewed: 36 women delivered monozygotic and 149 delivered spontaneous dizygotic multiple births. The control group comprised 498 women who gave birth at term (>37 weeks gestation) to healthy infants on randomly selected days at the same clinic.

Influence of menstrual and reproductive factors on ovarian cancer risk in women with and without family history of breast or ovarian cancer.

Background: As women with a family history of ovarian and/or breast cancer possibly inherit genetic changes that alter their risk of ovarian cancer, other established risk factors for ovarian cancer may influence the risk differently in women with and without a family history of the disease.

Methods: Case-control study conducted between 1983 and 1991 in Northern Italy. Cases were 971 women, under 75 years, with incident, histologically confirmed epithelial ovarian cancer, and controls were 2758 women, under 75 years, admitted to hospitals for non-malignant, non-hormone-related conditions, who had not undergone bilateral oophorectomy.

Risk factors for urinary incontinence in women.

Objectives: To review the epidemiological evidence on risk factors for urinary incontinence (UI) in women.

Methods: Using Medline and a manual search we identified the main papers published in English up to 1998.

Results: There is consistent evidence that the frequency of UI increases with age, but there is little information on the frequency of different types of UI in different age groups.