One-Pot Time-Induced Proteome Integral Solubility Alteration Assay for Automated and Sensitive Drug-Target Identification.

The proteome integral solubility alteration (PISA) assay is widely used for identifying drug targets, but it is labor-intensive and time-consuming and requires a substantial amount of biological sample. Aiming at enabling automation and greatly reducing the sample amount, we developed one-pot time-induced (OPTI)-PISA. Here, we demonstrate OPTI-PISA performance on identifying targets of multiple drugs in cell lysate and scaling down the sample amount to sub-microgram levels, making the PISA method suitable for NanoProteomics.

Vascular access devices and associated complications in paediatric critical care: A prospective cohort study.

Background: Though 60-80% of hospitalized patients have an intravascular device placed during hospitalization, there is a substantial risk of complication related to the placement, maintenance and removal of these devices. The objectives of this study were to describe vascular access device use, device complications and lumen dysfunction.

Methods: An observational cohort study was conducted over a 4.

Merging multi-omics with proteome integral solubility alteration unveils antibiotic mode of action.

Antimicrobial resistance is responsible for an alarming number of deaths, estimated at 5 million per year. To combat priority pathogens, like , the development of novel therapies is of utmost importance. Understanding the molecular alterations induced by medications is critical for the design of multi-targeting treatments capable of eradicating the infection and mitigating its pathogenicity.

Multifaceted Proteome Analysis at Solubility, Redox, and Expression Dimensions for Target Identification.

Multifaceted interrogation of the proteome deepens the system-wide understanding of biological systems; however, mapping the redox changes in the proteome has so far been significantly more challenging than expression and solubility/stability analyses. Here, the first high-throughput redox proteomics approach integrated with expression analysis (REX) is devised and combined with the Proteome Integral Solubility Alteration (PISA) assay. The whole PISA-REX experiment with up to four biological replicates can be multiplexed into a single tandem mass tag TMTpro set.

Gel-Assisted Proteome Position Integral Shift Assay Returns Molecular Weight to Shotgun Proteomics and Identifies Caspase 3 Substrates.

Here, we present a high-throughput virtual top-down proteomics approach that restores the molecular weight (MW) information in shotgun proteomics and demonstrates its utility in studying proteolytic events in programmed cell death. With gel-assisted proteome position integral shift (GAPPIS), we quantified over 7000 proteins in staurosporine-induced apoptotic HeLa cells and identified 84 proteins exhibiting in a statistically significant manner at least two of the following features: (i) a negative MW shift; (ii) an elevated ratio in a pair of a semitryptic and tryptic peptide, (iii) a negative shift in the standard deviation of MW estimated for different peptides, and (iv) a negative shift in skewness of the same data. Of these proteins, 58 molecules were previously unreported caspase 3 substrates.

Invasive Group A Streptococcal Infections in Pediatric Critical Care: A Retrospective Cohort Study.

Background And Objective: The reported rising global rates of invasive group A Streptococcus (iGAS) infection raise concern for disease related increase in critical illness and fatalities. An enhanced understanding of various presentations to health care and clinical course could improve early recognition and therapy in children with iGAS. The objective of this study was to describe the epidemiology of iGAS infections among children admitted to critical care.

A chemical inhibitor of IST1-CHMP1B interaction impairs endosomal recycling and induces noncanonical LC3 lipidation.

The endosomal sorting complex required for transport (ESCRT) machinery constitutes multisubunit protein complexes that play an essential role in membrane remodeling and trafficking. ESCRTs regulate a wide array of cellular processes, including cytokinetic abscission, cargo sorting into multivesicular bodies (MVBs), membrane repair, and autophagy. Given the versatile functionality of ESCRTs, and the intricate organizational structure of the ESCRT machinery, the targeted modulation of distinct ESCRT complexes is considerably challenging.

Dual molecule targeting HDAC6 leads to intratumoral CD4+ cytotoxic lymphocytes recruitment through MHC-II upregulation on lung cancer cells.

Background: Despite the current therapeutic treatments including surgery, chemotherapy, radiotherapy and more recently immunotherapy, the mortality rate of lung cancer stays high. Regarding lung cancer, epigenetic modifications altering cell cycle, angiogenesis and programmed cancer cell death are therapeutic targets to combine with immunotherapy to improve treatment success. In a recent study, we uncovered that a molecule called QAPHA ((E)-3-(5-((2-cyanoquinolin-4-yl)(methyl)amino)-2-methoxyphenyl)-N-hydroxyacrylamide) has a dual function as both a tubulin polymerization and HDAC inhibitors.

The carbon footprint of critical care: a systematic review.

Purpose: The provision of healthcare is a substantial global contributor to greenhouse gas (GHG) emissions. Several medical specialties and national health systems have begun evaluating their carbon emission contributions. The aim of this review is to summarise and describe the carbon footprint resulting from the provision of adult, paediatric and neonatal critical care.

Distinct molecular targets of ProEGCG from EGCG and superior inhibition of angiogenesis signaling pathways for treatment of endometriosis.

Endometriosis is a common chronic gynecological disease with endometrial cell implantation outside the uterus. Angiogenesis is a major pathophysiology in endometriosis. Our previous studies have demonstrated that the prodrug of gallate (ProEGCG) exhibits superior anti-endometriotic and anti-angiogenic effects compared to gallate (EGCG).

Furosemide in pediatric intensive care: a retrospective cohort analysis.

Introduction: Furosemide is the most commonly used medication in pediatric intensive care. Growing data indicates improved hemodynamic stability and efficacy of furosemide infusions compared to intermittent injections, thereby suggesting furosemide infusions might be considered as first line therapy in critically ill, paediatric patients. The objective of this study is to examine furosemide treatment as either continuous infusions or intermittent injections and subsequent patient outcomes.

Towards detection of structurally-diverse glycated epitopes in native proteins: Single-chain antibody directed to non-A1c epitope in human haemoglobin.

Over 500 million people worldwide are affected by diabetes mellitus, a chronic disease that leads to high blood glucose levels and causes severe side effects. The predominant biological marker for diagnosis of diabetes is glycated haemoglobin (GHb). In human blood the predominant reducing sugar, glucose, irreversibly conjugates onto accessible amine groups within Hb.

SARS-CoV-2 Infection in the Second Trimester of Pregnancy: A Case Report of Fetal Intraventricular Hemorrhage After Critical COVID-19 Infection and a Brief Review of the Literature.

More than three and a half years have passed since the start of the coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and there have been several studies in the literature about the different damage and symptom patterns related to the condition; particular attention has been paid to the transmission of the disease from pregnant mothers to fetus. In this report, we present the case of a 36-year-old patient with a history of two cesarean sections (CS), two miscarriages, and hypothyroidism on replacement therapy, who contracted COVID-19 during the 15th week of gestation. Ultrasound (US) examination at 22 weeks revealed regular fetal biometry and bilateral ventriculomegaly, highly suggestive of massive intracerebral hemorrhage.

Endometrial Osseous Metaplasia: An Hysteroscopic Incidental Finding - An Overview.

Endometrial osseous metaplasia (EOM) is an uncommon clinical entity with the presence of bone in the endometrium which requires clinical and therapeutic framework. It is also described by various other names such as endometrial ossification, ectopic intrauterine bone, and heterotopic intrauterine bone. Ossification could have various locations as the cervix the ovary, and the vagina.

Ultralight Ultrafast Enzymes.

Inorganic materials depleted of heavy stable isotopes are known to deviate strongly in some physicochemical properties from their isotopically natural counterparts. Here we explored for the first time the effect of simultaneous depletion of the heavy carbon, hydrogen, oxygen and nitrogen isotopes on the bacterium E. coli and the enzymes expressed in it.

Intrapartum ultrasound and mother acceptance: A study with informed consent and questionnaire.

Introduction: Intrapartum ultrasound (IU) is used in the delivery ward; even if IU monitors the labouring women, it could be perceived as a discomfort and even as an" obstetric violence", because it is a young technique, not often well "accepted". A group of clinicians aimed at obtain an informed consent from patients, prior to perform a translabial ultrasound (TU). The aim of this study was to evaluate the acceptance of both translabial and transabdominal IU.

"The Strange Case of Dr Pump and Mr Acardiac": The Twin Reversed Arterial Perfusion (TRAP) Sequence in Two Monochorionic Monoamniotic (MCMA) Twin Pregnancies-Diagnosis, Prognosis and Management: Review of Literature.

The Twin Reversed Arterial Perfusion (TRAP) Sequence is an extremely rare complication of monochorionic twin pregnancies, with one severely malformed twin (the "acardiac") lacking autonomous placental blood supply and being perfused by the co-twin (the "pump"), through arterio-arterial (and sometimes also veno-venous) vascular anastomoses located on the placental surface. The prognosis is poor: mortality is 100% in the acardiac twin because of its severe malformations and about 50-55% in the pump twin, mainly due to heart failure and prematurity. So, the goal of perinatal management of the TRAP twin pregnancy is to deliver a healthy and near-term pump twin without heart failure or fetal hydrops.

Cornual Pregnancy.

Cornual pregnancy (CP) is a subtype of ectopic pregnancy that is implanted in the interstitial segment of the fallopian tube which is defined as the tubal section crossing uterine muscular tissue. Widely recognized risk factors for CP are endometriosis, uterine leiomyomata, or pelvic inflammatory disease; all these diseases can cause tubal anatomic changes and consequently alter embryo physiological implant process. Many treatment options are available for this condition each one must be tailored according to patient and operating scenario.

Pregnancy by Oocyte Donation: Reviewing Fetal-Maternal Risks and Complications.

Oocyte donation (OD) has greatly improved over the last three decades, becoming a preferred practice of assisted reproductive technology (ART) for infertile women wishing for motherhood. Through OD, indeed, it has become possible to overcome the physiological limitation due to the ovarian reserve (OR) exhaustion as well as the poor gamete reliability which parallels the increasing age of women. However, despite the great scientific contribution related to the success of OD in the field of infertility, this practice seems to be associated with a higher rate of major risky events during pregnancy as recurrent miscarriage, infections and placental diseases including gestational hypertension, pre-eclampsia and post-partum hemorrhage, as well as several maternal-fetal complications due to gametes manipulation and immune system interaction.

Assessment of climate impact on grape productivity: A new application for bioclimatic indices in Italy.

Italy is a world leader for viticulture and wine business with an export valued 7 billion of euros in 2021, and wine being the second most exported product within the national agri-food sector. However, these figures might be threatened by climate change and winegrowers call for more reliable local information on future impacts of climate change on viticulture. The study aims to understand the impact of climate on wine production in Italy using grape productivity data and bioclimatic indices.

A Study of Repair Mortars for Restoration of Wall Painted Plasters in a Hypogeum Rock-Cut Church of Matera (Southern Italy).

Several lime mortars for the repair of painted plasters of the rock-cut church of Ss. Pietro and Paolo in Matera were studied. They were designed taking into account both aesthetic criteria that need to be fulfilled in the field of paintings restoration, and physical-mechanical compatibility with the original materials on site, i.

Office intrauterine morcellation for retained products of conception.

Objective: Proposing hysteroscopic morcellation (HM) as a surgical-therapeutic approach in the treatment of retained products of conception (RPOC) to prevent intrauterine adhesions (IUAs).

Design: Prospective analysis.

Setting: A teaching and university hospital.

Thrombosed Arteriovenous Malformation of Umbilical Cord.

Background: Arteriovenous malformation of umbilical cord is an extremely rare congenital malformation. Causes of this condition are unknown. AVM of umbilical cord can cause significant complications in the developing fetus.

Proteome integral solubility alteration high-throughput proteomics assay identifies Collectin-12 as a non-apoptotic microglial caspase-3 substrate.

Caspases are a family of proteins mostly known for their role in the activation of the apoptotic pathway leading to cell death. In the last decade, caspases have been found to fulfill other tasks regulating the cell phenotype independently to cell death. Microglia are the immune cells of the brain responsible for the maintenance of physiological brain functions but can also be involved in disease progression when overactivated.