Identification of LY3522348: A Highly Selective and Orally Efficacious Ketohexokinase Inhibitor.

The identification of clinical candidate LY3522348 (compound ) is described. LY3522348 is a highly selective, oral dual inhibitor of human ketohexokinase isoforms C and A (hKHK-C, hKHK-A). Optimization began with highly efficient ()-2-(2-methylazetidin-1-yl)-6-(1-pyrazol-4-yl)-4-(trifluoromethyl)nicotinonitrile ().

Continuous Thoracic Paravertebral Block to Treat Electrical Storm.

Continuous ganglion block is increasingly being used to help manage ventricular tachyarrhythmias. We present the cases of 2 patients in whom we used continuous left thoracic paravertebral block to achieve sympathetic denervation and improvement in drug-refractory ventricular tachyarrhythmias. Whether as destination therapy or bridging therapy, we conclude that the block is safe, improves patients' comfort, and is superior in several ways to stellate ganglion block and other single-injection techniques.

LC-MS/MS analysis of bisphenol S and five other bisphenols in total diet food samples.

It is already known that bisphenol S (BPS) has been used as a substitute for BPA in thermal papers in recent years. It is not clear, however, if BPS has also been used to replace BPA in can coatings as currently being speculated due to a lack of credible studies on migration of BPS from can coatings and occurrence data of BPS in foods. In this study, an LC-MS/MS method was developed for the analysis of BPS, along with several other bisphenols, and method detection limits for BPS varied from 0.

Non-inferiority trial of a pedal controlled injection device: a step toward enhancing patient safety and operator independence during neural blockade.

Background And Objectives: Limitations in manpower in health care facilities, both in civilian and military settings, can severely affect patient safety as well as overall outcomes. Regional anesthesia via neural blockade is an effective means of managing uncontrolled acute pain, which has been associated with cardiopulmonary, endocrine, immunologic, and hematologic derangement in addition to the development of potentially life-threatening coagulopathy. We have designed a remote-controlled injection device that may expedite the performance of regional nerve blocks in these situations.

The Evolution of Iliac Bone Graft Donor Site Analgesia in Cleft Patients: Transversus Abdominis Plane Block Is Safe and Efficacious.

Background: The transversus abdominis plane (TAP) block has been increasingly used as a means of abdominal wall analgesia. This study aims to determine if TAP block analgesia provides a benefit in cleft patients undergoing alveolar bone grafting with iliac crest cancellous bone graft.

Methods: Two groups of 20 consecutive patients undergoing alveolar bone grafting with iliac crest cancellous bone with either TAP block or indwelling catheter pain pump were examined in a retrospective fashion.

Comparison of single-injection ultrasound-guided approach versus multilevel landmark-based approach for thoracic paravertebral blockade for breast tumor resection: a retrospective analysis at a tertiary care teaching institution.

Background: The role of thoracic paravertebral blockade (TPVB) in decreasing opioid requirements in breast cancer surgery is well documented, and there is mounting evidence that this may improve survival and reduce the rate of malignancy recurrence following cancer-related mastectomy. We compared the two techniques currently in use at our institution, the anatomic landmark-guided (ALG) multilevel versus an ultrasound-guided (USG) single injection, to determine an optimal technique.

Methods: We retrospectively reviewed records of patients who received TPVB from January 2013 to December 2014.

Hemodynamic instability and Horner's syndrome following a labour lumbar neuraxial block: A warning sign of a potentially lethal event?

The development of Horner's syndrome during routine neuraxial anaesthesia suggests anatomic, technical or physiologic variance. Even more importantly, it warrants immediate cessation of the anaesthetic intervention.

Epidural Catheter Migration in a Patient with Severe Spinal Stenosis.

Establishment of appropriate neuraxial catheter positioning is typically a straightforward procedural undertaking. It can, however, lead to deception of even the most experienced clinician and occur despite the most meticulous attention to detail. Written and verbal consent were obtained from the patient to prepare, discuss, and publish this case report; we describe the occurrence of what we believe was the intraoperative migration of an epidural catheter in the setting of significant tissue changes resulting from a previous spinal fusion.

Data generated from three quantitative mass spectral methods for the analysis of trivalent influenza vaccine antigens are compared.

Herein we present the data necessary for generation of alternative means to produce equimolar mixtures of peptides ("Design and Expression of a QconCAT Protein to Validate Hi3 Protein Quantification of Influenza Vaccine Antigens" (D.G.S.

Design and expression of a QconCAT protein to validate Hi3 protein quantification of influenza vaccine antigens.

Unlabelled: Quantification of the antigens hemagglutinin and neuraminidase in influenza vaccines has been reported using an antibody-free liquid chromatography-mass spectrometry (LC-MS) based method known as MS(E) "Hi3". This approach is based on the average signal intensity of the three most intense tryptic peptides relative to a primary standard. This strategy assumes that the Hi3 signal responses are consistent for all proteins, and therefore comparable to a spiked reference for absolute quantification.

The Evolution of an Innovative Community-Engaged Health Navigator Program to Address Social Determinants of Health.

Background: Health navigators and other types of community health workers (CHWs) have become recognized as essential components of quality care, and key for addressing health disparities owing to the complex health care services landscape presents almost insurmountable challenges for vulnerable individuals. Bernalillo County, New Mexico, has high rates of uninsurance, poverty, and food insecurity.

Objectives: The design of the Pathways to a Healthy Bernalillo County Program (BP) has evolved innovations that are unique in terms of program stability and security, expansive reach, and community capacity across six domains: sustainable public mechanism for program funding, involvement of community organizations in designing the program, expanded focus to address the broader social determinants of health with targeted outreach, an integrated, community-based implementation structure, an outcomes-based payment structure, and using an adaptive program design that actively incorporates navigators in the process.

Data set for mass spectrometric analysis of recombinant human serum albumin from various expression systems.

Human serum albumin (HSA) is a versatile and important protein for the pharmaceutical industry (Fanali et al., Mol. Aspects Med.

Treatment of acute flares of chronic pancreatitis pain with ultrasound guided transversus abdominis plane block: a novel application of a pain management technique in the acute care setting.

The use of transversus abdominis plane (TAP) block to provide either analgesia or anesthesia to the anterior abdominal wall is well described. The technique yields high analgesic effectiveness and is opioid sparing and potentially of long duration with reported analgesia lasting up to 36 hours. When compared to neuraxial analgesia, TAP blocks are associated with a lower incidence of hypotension and motor blockade.

Trial ultrasound-guided continuous left stellate ganglion blockade before surgical gangliolysis in a patient with a left ventricular assist device and intractable ventricular tachycardia: a pain control application to a complex hemodynamic condition.

Stellate ganglion blockade for cardiac dysrhythmia is a well-described technique but infrequently used to manage ventricular tachycardia (VT). In patients with left ventricular assist devices (LVADs), these dysrhythmias cause increased morbidity because of right ventricular dysfunction, and often severe discomfort. Continuous stellate ganglion blockade may yield valuable information on a diagnostic and therapeutic basis in preparation for definitive, permanent interventions.

Universal anti-neuraminidase antibody inhibiting all influenza A subtypes.

The only universally conserved sequence amongst all influenza A viral neuraminidase (NA) is located between amino acids 222-230 and plays crucial roles in viral replication. However, it remained unclear as to whether this universal epitope is exposed during the course of infection to allow binding and inhibition by antibodies. Using a monoclonal antibody (MAb) targeting this specific epitope, we demonstrated that all nine subtypes of NA were inhibited in vitro by the MAb.

A comparison of neon versus helium ion beam induced deposition via Monte Carlo simulations.

The ion beam induced nanoscale synthesis of PtCx (where x ∼ 5) using the trimethyl (methylcyclopentadienyl)platinum(IV) (MeCpPt(IV)Me3) precursor is investigated by performing Monte Carlo simulations of helium and neon ions. The helium beam leads to more lateral growth relative to the neon beam because of its larger interaction volume. The lateral growth of the nanopillars is dominated by molecules deposited via secondary electrons in both the simulations.

Building institutional capacity for diversity and inclusion in academic medicine.

Today, most agree that the health care system in the United States is in need of reform and that existing health disparities have huge implications for both that system and society as a whole. As a result, academic medicine has come to play a central role in addressing health disparities in a pluralistic society. Today, diversity is no longer a projection; it is a reality.

Simultaneous quantification of the viral antigens hemagglutinin and neuraminidase in influenza vaccines by LC-MSE.

Current methods for quality control of inactivated influenza vaccines prior to regulatory approval include determining the hemagglutinin (HA) content by single radial immunodiffusion (SRID), verifying neuraminidase (NA) enzymatic activity, and demonstrating that the levels of the contaminant protein ovalbumin are below a set threshold of 1 μg/dose. The SRID assays require the availability of strain-specific reference HA antigens and antibodies, the production of which is a potential rate-limiting step in vaccine development and release, particularly during a pandemic. Immune responses induced by neuraminidase also contribute to protection from infection; however, the amounts of NA antigen in influenza vaccines are currently not quantified or standardized.

Investigation of the differences in thermal stability of two recombinant human serum albumins with 1,2-dipalmitoyl-sn-glycero-3-phosphocholine liposomes by UV circular dichroism spectropolarimetry.

Previous studies have demonstrated that liposome-protein interactions can result in changes to the thermal stability of the protein. We utilized far-UV circular dichroism spectropolarimetry and fluorescence spectroscopy to investigate the interaction of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes with two recombinant human serum albumins (rHSA). We demonstrate that rHSA expressed in Oryza sativa (OsrHSA) has improved secondary structure thermal stability compared to rHSA expressed in Pichia pastoris (PprHSA).