Discovery of Benzoylsulfonohydrazides as Potent Inhibitors of the Histone Acetyltransferase KAT6A.

A high-throughput screen for inhibitors of the histone acetyltransferase, KAT6A, led to identification of an aryl sulfonohydrazide derivative (CTX-0124143) that inhibited KAT6A with an IC of 1.0 μM. Elaboration of the structure-activity relationship and medicinal chemistry optimization led to the discovery of WM-8014 (), a highly potent inhibitor of KAT6A (IC = 0.

Bone Surface Micro-Topography at Craniofacial Entheses: Insights on Osteogenic Adaptation at Muscle Insertions.

Macroscopic details of the bone-muscle interface are represented by a mosaic of calcified features inclusive of fossae, tuberosities, crests, and ridges. These features are in part of an adaptive osteogenic response to dissipate forces of localized mechanical loading. In an osteoarchaeological or paleontological context, these features are interpreted as "musculoskeletal stress markers" to infer habitual behaviors.

Carbapenem-Resistant Pseudomonas aeruginosa at US Emerging Infections Program Sites, 2015.

Pseudomonas aeruginosa is intrinsically resistant to many antimicrobial drugs, making carbapenems crucial in clinical management. During July-October 2015 in the United States, we piloted laboratory-based surveillance for carbapenem-resistant P. aeruginosa (CRPA) at sentinel facilities in Georgia, New Mexico, Oregon, and Tennessee, and population-based surveillance in Monroe County, NY.

Antioxidant properties and potential mechanisms of hydrolyzed proteins and peptides from cereals.

Cereals like wheat, rice, corn, barley, rye, oat, and millet are staple foods in many regions around the world and contribute to more than half of human energy requirements. Scientific publications contain evidence showing that apart from energy, the regular consumption of whole grains is useful for the prevention of many chronic diseases associated with oxidative stress. Biological activities have mostly been attributed to the presence of glucans and polyphenols.

Unravelling the Single-Stranded DNA Virome of the New Zealand Blackfly.

Over the last decade, arthropods have been shown to harbour a rich diversity of viruses. Through viral metagenomics a large diversity of single-stranded (ss) DNA viruses have been identified. Here we examine the ssDNA virome of the hematophagous New Zealand blackfly using viral metagenomics.

Extraskeletal Calcifications in Hutchinson-Gilford Progeria Syndrome.

Purpose: Children with Hutchinson-Gilford progeria syndrome (HGPS), a rare premature aging disease, exhibit extraskeletal calcifications detected by radiographic analysis and on physical examination. The aim of this study was to describe the natural history and pathophysiology of these abnormal calcifications in HGPS, and to determine whether medications and/or supplements tested in clinical trials alter their development.

Methods: Children from two successive clinical trials administering 1) lonafarnib (n = 26) and 2) lonafarnib + pravastatin + zoledronic acid (n = 37) were studied at baseline (pre-therapy), one year on therapy, and at end-of-therapy (3.

Modeling Regional Transmission and Containment of a Healthcare-associated Multidrug-resistant Organism.

Background: The Centers for Disease Control and Prevention (CDC) recently published interim guidance for a public health response to contain novel or targeted multidrug-resistant organisms (MDROs). We assessed the impact of implementing the strategy in a US state using a mathematical model.

Methods: We used a deterministic compartmental model, parametrized via a novel analysis of carbapenem-resistant Enterobacteriaceae data reported to the National Healthcare Safety Network and patient transfer data from the Centers for Medicare and Medicaid Services.

Utilisation of hydrocarbons and production of surfactants by bacteria isolated from plant leaf surfaces.

Leaves are covered by a cuticle composed of long (C11-C20) and very-long chain hydrocarbons (>C20), e.g. alkanes, fatty acids, alcohols, aldehydes, ketones and esters.

Intraoral Digital Impression Technique for a Neonate With Bilateral Cleft Lip and Palate.

Objective: Dental casts are an important aspect in the treatment planning, documentation, and analysis of the dental arch forms of infants with cleft lip and palate (CLP). Impression taking in a neonate is a technique-sensitive procedure, which can result in foreign body dislodgement and carries a small risk of aspiration and airway obstruction. The advent of digital dental technologies and intraoral scanning may facilitate safer, more effective, and accurate impressions for CLP infants.

Assessment of the Silver Penetration and Distribution in Carious Lesions of Deciduous Teeth Treated with Silver Diamine Fluoride.

The aim of this study was to determine the effects of 38% silver diamine fluoride (SDF) on carious lesions of human deciduous teeth. Ten extracted deciduous incisors with caries were collected and treated with SDF. After the treatment, the teeth were sectioned through the center of the carious lesion.

Conjugal Transfer, Whole-Genome Sequencing, and Plasmid Analysis of Four -Bearing Isolates from U.S. Patients.

Four clinical isolates bearing gene-harboring plasmids were characterized. All isolates demonstrated the ability to transfer colistin resistance to ; plasmids were stable in conjugants after multiple passages on nonselective media. was located on an IncX4 ( = 3) or IncN ( = 1) plasmid.

3,3'-Disubstituted 5,5'-Bi(1,2,4-triazine) Derivatives with Potent in Vitro and in Vivo Antimalarial Activity.

A series of 3,3'-disubstituted 5,5'-bi(1,2,4-triazine) derivatives was synthesized and screened against the erythrocytic stage of Plasmodium falciparum 3D7 line. The most potent dimer, 6k, with an IC (50% inhibitory concentration) of 0.008 μM, had high in vitro potency against P.

CRISPR-Cas9 interrogation of a putative fetal globin repressor in human erythroid cells.

Sickle Cell Disease and ß-thalassemia, which are caused by defective or deficient adult ß-globin (HBB) respectively, are the most common serious genetic blood diseases in the world. Persistent expression of the fetal ß-like globin, also known as 𝛾-globin, can ameliorate both disorders by serving in place of the adult ß-globin as a part of the fetal hemoglobin tetramer (HbF). Here we use CRISPR-Cas9 gene editing to explore a potential 𝛾-globin silencer region upstream of the δ-globin gene identified by comparison of naturally-occurring deletion mutations associated with up-regulated 𝛾-globin.

Bone marrow transplantation for adolescents and young adults with sickle cell disease: Results of a prospective multicenter pilot study.

We conducted a multicenter pilot investigation of the safety and feasibility of bone marrow transplantation (BMT) in adults with severe sickle cell disease (SCD) (NCT 01565616) using a reduced toxicity preparative regimen of busulfan (13.2 mg/kg), fludarabine (175 mg/m ) and thymoglobulin (6 mg/kg) and cyclosporine or tacrolimus and methotrexate for graft-vs-host disease (GVHD) prophylaxis. Twenty-two patients (median age 22 years; range 17-36) were enrolled at eight centers.

D3T acts as a pro-oxidant in a cell culture model of diabetes-induced peripheral neuropathy.

Diabetes mellitus is one of the most common chronic diseases in the United States and peripheral neuropathy (PN) affects at least 50% of diabetic patients. Medications available for patients ameliorate symptoms (pain), but do not protect against cellular damage and come with severe side effects, leading to discontinued use. Our research group uses differentiated SH-SY5Y cells treated with advanced glycation end products (AGE) as a model to mimic diabetic conditions and to study the mechanisms of oxidative stress mediated cell damage and antioxidant protection.

Safety, tolerability, and pharmacology of AB928, a novel dual adenosine receptor antagonist, in a randomized, phase 1 study in healthy volunteers.

Adenosine suppresses antitumor immune responses via A and A receptors expressed on intratumoral immune cells. This effect is mediated by increased cyclic adenosine 5'-monophosphate (AMP) levels and phosphorylation of cyclic AMP response element binding protein (CREB). We conducted a phase 1, placebo-controlled, single-ascending-dose (SAD) and multiple-ascending-dose (MAD) study to assess the safety, tolerability, pharmacokinetics (PK), including food effect (FE), and pharmacodynamics (PD) of oral AB928, a novel dual AR/AR antagonist, in healthy volunteers.

The impact of standardized protocol implementation for surgical damage control and temporary abdominal closure after emergent laparotomy.

Background: To standardize care and promote early fascial closure among patients undergoing emergent laparotomy and temporary abdominal closure (TAC), we developed a protocol addressing patient selection, operative technique, resuscitation strategies, and critical care provisions. We hypothesized that primary fascial closure rates would increase following protocol implementation with no difference in complication rates.

Study Design: We performed a retrospective cohort analysis of 138 adult trauma and emergency general surgery patients who underwent emergent laparotomy and TAC, comparing protocol patients (n = 60) to recent historic controls (n = 78) who would have met protocol inclusion criteria.

Incidence of adverse events attributable to bupivacaine liposome injectable suspension or plain bupivacaine for postoperative pain in pediatric surgical patients: A retrospective matched cohort analysis.

Background: Surgical wound infiltration with local anesthetics is common as part of multimodal analgesia and enhanced recovery pathways in pediatric surgical patients. Liposomal bupivacaine can provide up to 92 hours of pain relief, and was approved by the U.S Food and Drug Administration for local infiltration in adults.

Rat behavior and dopamine release are modulated by conspecific distress.

Rats exhibit 'empathy' making them a model to understand the neural underpinnings of such behavior. We show data consistent with these findings, but also that behavior and dopamine (DA) release reflects subjective rather than objective evaluation of appetitive and aversive events that occur to another. We recorded DA release in two paradigms: one that involved cues predictive of unavoidable shock to the conspecific and another that allowed the rat to refrain from reward when there were harmful consequences to the conspecific.

Associations of lifestyle and vascular risk factors with Alzheimer's brain biomarker changes during middle age: a 3-year longitudinal study in the broader New York City area.

Objective: To investigate the associations between lifestyle and vascular risk factors and changes in Alzheimer's disease (AD) biomarkers (beta-amyloid load via C-PiB PET, glucose metabolism via F-FDG PET and neurodegeneration via structural MRI) and global cognition in middle-aged asymptomatic participants at risk for AD.

Design: Prospective, longitudinal.

Setting: The study was conducted at New York University Langone/Weill Cornell Medical Centres in New York City.