HSF1 Pathway Inhibitor Clinical Candidate (CCT361814/NXP800) Developed from a Phenotypic Screen as a Potential Treatment for Refractory Ovarian Cancer and Other Malignancies.

CCT251236 , a potent chemical probe, was previously developed from a cell-based phenotypic high-throughput screen (HTS) to discover inhibitors of transcription mediated by HSF1, a transcription factor that supports malignancy. Owing to its activity against models of refractory human ovarian cancer, was progressed into lead optimization. The reduction of P-glycoprotein efflux became a focus of early compound optimization; central ring halogen substitution was demonstrated by matched molecular pair analysis to be an effective strategy to mitigate this liability.

Survey on initial management of acute pancreatitis in Latin America.

Objective: The population of Latin America harbors the highest incidence of gallstones and acute biliary pancreatitis, yet little is known about the initial management of acute pancreatitis in this large geographic region.

Participants And Methods: We performed a post hoc analysis of responses from physicians based in Latin America to the international multidisciplinary survey on the initial management of acute pancreatitis. The questionnaire asked about management of patients during the first 72h after admission, related to fluid therapy, prescription of prophylactic antibiotics, feeding and nutrition, and timing of cholecystectomy.

Laminated holmium-166-containing electrospun bandages for use against skin cancer.

The number of non-melanoma skin cancer (NMSC) cases in the US will increase significantly over the next decade due to a rise in UV exposure. One of the treatment methods used to remove NMSC lesions is radiation therapy. The two types of radiation therapy used in the clinic are external beam therapy and brachytherapy.

Preparation and Optimization of an Ultraflexible Liposomal Gel for Lidocaine Transdermal Delivery.

The pain caused by lidocaine injections into the face prior to facial plastic surgeries intended to remove growths or tumorous lesions has been reported by many patients to be the worst part of these procedures. However, the lidocaine gels and creams currently on the market do not deliver an equal or better local anesthetic effect to replace these injections. To develop an alternative to the painful local anesthetic injection, we prepared ultraflexible liposomes using soy phosphatidylcholine, lidocaine, and different amounts of sodium cholate, a surfactant.

The Role of Bronchoscopy in the Management of Children With Cystic Fibrosis.

Background: Currently, no consensus guidelines recommend routine bronchoscopy procedure in cystic fibrosis (CF), as no evidence is available concerning its use as either a diagnostic or therapeutic tool. Its efficacy is controversial, and no randomized controlled prospective trials are available to check its effectiveness. The aims of the present study were to evaluate the effectiveness of bronchoscopy as a diagnostic/therapeutic tool in CF children and adolescents; and to verify the effect of serial bronchoscopy on lung disease progression in subjects with CF not responding to a single procedure.

Optimization of DOTAP/chol Cationic Lipid Nanoparticles for mRNA, pDNA, and Oligonucleotide Delivery.

Lipid nanoparticles (LNPs) can be used as delivery vehicles for nucleic acid biotherapeutics. In fact, LNPs are currently being used in the Pfizer/BioNTech and Moderna COVID-19 vaccines. Cationic LNPs composed of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP)/cholesterol (chol) LNPs have been classified as one of the most efficient gene delivery systems and are being tested in numerous clinical trials.

3D Printing and Dissolution Testing of Novel Capsule Shells for Use in Delivering Acetaminophen.

Individualized drug delivery improves drug efficacy and safety for patients. To implement individualized drug delivery, patient-specific tailored dosages produced on a small scale are needed. However, current pharmaceutical manufacturing is not suitable for personalized dosage forms.

Tirbanibulin: Topical Treatment for Actinic Keratosis.

We review here the pharmacology, pharmacokinetics, efficacy, dosage and administration, and place in therapy of tirbanibulin for the treatment of actinic keratosis (AK). A literature search using PubMed was conducted using the terms tirbanibulin (tirbanibulin) and actinic keratosis from September 2014 to February 2021. All English-language articles evaluating tirbanibulin were analyzed for this review.

Investigating the phosphinic acid tripeptide mimetic DG013A as a tool compound inhibitor of the M1-aminopeptidase ERAP1.

ERAP1 is a zinc-dependent M1-aminopeptidase that trims lipophilic amino acids from the N-terminus of peptides. Owing to its importance in the processing of antigens and regulation of the adaptive immune response, dysregulation of the highly polymorphic ERAP1 has been implicated in autoimmune disease and cancer. To test this hypothesis and establish the role of ERAP1 in these disease areas, high affinity, cell permeable and selective chemical probes are essential.

A Method for Liposome Co-encapsulation of Phenethyl Isothiocyanate and Cisplatin and Determining Its Toxicity Against Lung and Lung Cancer Cells.

Non-small cell lung cancer (NSCLC) is one of the leading causes of cancer-related deaths in the United States. It is extremely difficult to treat, and its survival rate is low. Today, the most effective treatments are still those that implement the platinum anticancer drug cisplatin (CDDP) in combination with other drugs.

Phenethyl Isothiocyanate-Containing Carbomer Gel for Use against Squamous Cell Carcinoma.

It is currently estimated that one in every five Americans will develop skin cancer during their lifetime. Squamous cell carcinoma (SCC) is a common type of skin cancer that can develop due to the skin's exposure to the sun. Herein, we prepared a topical gel containing 0.

Physicochemical Factors That Influence the Biocompatibility of Cationic Liposomes and Their Ability to Deliver DNA to the Nuclei of Ovarian Cancer SK-OV-3 Cells.

Cationic liposomes composed of 3-[N-(N',N'-dimethylaminoethane)-carbamoyl] cholesterol (DC-chol) and dioleoylphosphatidylethanolamine (DOPE) have previously been shown to have applications in gene delivery. Our study aims to explore the effects of inclusion of polyethylene glycol (PEG) and using different molar ratios of DC-chol/DOPE on size, zeta potential, cytotoxicity and DNA delivery of DC-chol/DOPE liposomes. Our results show that PEGylation reduces the cytotoxicity of DC-chol/DOPE liposomes, and, furthermore, PEGylated liposome-DNA lipoplexes are smaller in size and more uniform in size distribution than those that are not PEGylated.

The Mediterranean Athlete's Nutrition: Are Protein Supplements Necessary?

(1) Background: It is recommended that an athlete, in order to ensure correct nutrition and performance, should consume between 1.2 and 2.0 g/kg/day of protein, while the daily recommended protein intake for a non-athlete is 0.

Vascular and metabolic risk factor differences prior to dementia diagnosis: a multidatabase case-control study using European electronic health records.

Objective: The objective of the study is to compare body mass index (BMI), systolic/diastolic blood pressure (SBP/DBP) and serum total cholesterol levels between dementia cases and controls at multiple time intervals prior to dementia onset, and to test time interval as a modifying factor for these associations.

Design: Case-control study.

Setting: Six European electronic health records databases.

Echocardiographic two-dimensional speckle tracking identifies acute regional myocardial edema and sub-acute fibrosis in pediatric focal myocarditis with normal ejection fraction: comparison with cardiac magnetic resonance.

The aim here was to describe the role of speckle tracking echocardiography (STE), in identifying impairment in systolic function in children and adolescents with focal myocarditis and without reduction in ejection fraction. We describe data from 33 pediatric patients (age 4-17 years) admitted for focal myocarditis, confirmed by cardiac magnetic resonance (CMR), and without impaired ejection fraction and/or wall motion abnormalities. All children underwent Doppler echocardiography examination with analysis of global (G) and segmental longitudinal strain (LS) and CMR for the quantification of edema and myocardial fibrosis.

Corifollitropin alfa for poor responders patients, a prospective randomized study.

Background: Poor ovarian response remains one of the biggest challenges for reproductive endocrinologists. The introduction of corifollitropin alpha (CFA) offered an alternative option to other gonadotropins for its longer half-life, its more rapid achievement of the threshold and higher FSH levels. We compared two different protocols with CFA, a long agonist and a short antagonist, and a no-CFA protocol.

Treatment pathway analysis of newly diagnosed dementia patients in four electronic health record databases in Europe.

Purpose: Real-world studies to describe the use of first, second and third line therapies for the management and symptomatic treatment of dementia are lacking. This retrospective cohort study describes the first-, second- and third-line therapies used for the management and symptomatic treatment of dementia, and in particular Alzheimer's Disease.

Methods: Medical records of patients with newly diagnosed dementia between 1997 and 2017 were collected using four databases from the UK, Denmark, Italy and the Netherlands.

Evidence of impaired longitudinal strain in pre-Fontan palliation in functional single left ventricle.

Background: We evaluated two-dimensional speckle-tracking echocardiography longitudinal strain (L2DSE) in functionally single left ventricles (LV).

Methods: We retrospectively analyzed 21 patients with functionally single LV. We divided patients into two groups according to pre-Fontan cardiac catheterization data: group 1, adequate data for Fontan procedure and group 2, inadequate data.

Non-alcoholic fatty liver disease and risk of incident acute myocardial infarction and stroke: findings from matched cohort study of 18 million European adults.

Objective: To estimate the risk of acute myocardial infarction (AMI) or stroke in adults with non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH).

Design: Matched cohort study.

Setting: Population based, electronic primary healthcare databases before 31 December 2015 from four European countries: Italy (n=1 542 672), Netherlands (n=2 225 925), Spain (n=5 488 397), and UK (n=12 695 046).

Measuring the Effectiveness of Safety Warnings on the Risk of Stroke in Older Antipsychotic Users: A Nationwide Cohort Study in Two Large Electronic Medical Records Databases in the United Kingdom and Italy.

Introduction: Safety warnings relating to antipsychotic-associated stroke among older persons in the UK and Italy were issued. However, the impact of these safety warnings on stroke risk has not been measured to date.

Objective: The aim of this study was to measure the change in stroke incidence after two safety warnings in both the UK and Italy.

Dual-source computed tomography coronary artery imaging in children.

Computed tomography (CT) has a well-established diagnostic role in the assessment of coronary arteries in adults. However, its application in a pediatric setting is still limited and often impaired by several technical issues, such as high heart rates, poor patient cooperation, and radiation dose exposure. Nonetheless, CT is becoming crucial in the noninvasive approach of children affected by coronary abnormalities and congenital heart disease.

Risks and clinical predictors of cirrhosis and hepatocellular carcinoma diagnoses in adults with diagnosed NAFLD: real-world study of 18 million patients in four European cohorts.

Background: Non-alcoholic fatty liver disease (NAFLD) is a common condition that progresses in some patients to steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC). Here we used healthcare records of 18 million adults to estimate risk of acquiring advanced liver disease diagnoses in patients with NAFLD or NASH compared to individually matched controls.

Methods: Data were extracted from four European primary care databases representing the UK, Netherlands, Italy and Spain.