Successful Use of Kidneys from a Deceased Donor with Active Herpes Zoster Infection.

Background: The limited donor pool and increasing recipient wait list require a reevaluation of kidney organ suitability for transplantation. Use of higher infectious risk organs that were previously discarded may help improve access to transplantation and reduce patient mortality without placing patients at a higher risk of poor posttransplant outcomes. There is very little data available regarding the safe use of kidney organs from deceased donors with varicella zoster virus infection at the time of organ retrieval.

COVID-19 Data Utilization in North Carolina: Qualitative Analysis of Stakeholder Experiences.

Background: As the world faced the pandemic caused by the novel coronavirus disease 2019 (COVID-19), medical professionals, technologists, community leaders, and policy makers sought to understand how best to leverage data for public health surveillance and community education. With this complex public health problem, North Carolinians relied on data from state, federal, and global health organizations to increase their understanding of the pandemic and guide decision-making.

Objective: We aimed to describe the role that stakeholders involved in COVID-19-related data played in managing the pandemic in North Carolina.

Chiral tridentate bis(oxazol-2-ylimino) isoindoline-based pincer ligands: isolation and characterization deligation from prepared Cd-ligand complexes.

The first isolation and structural characterization of a series of chiral trinitrogen 1,3-bis(4,5-dihydrooxazol-2-ylimino)isoindoline-based pincer ligands are reported. Cadmium complexes, isolated as Cd(L2X)2 where L2X is the deprotonated form of L2XH = 1,3-bis(4,5-dihydro-4-(R)-phenyloxazol-2-ylimino)-isoindoline ((R,R)-5H) or 1,3-bis(4,5-dihydro-4-(S)-iso-propyloxazol-2-ylimino)isoindoline ((S,S)-6H) were prepared in situ via traditional or microwave-based techniques with the latter being more efficient but less able to be scaled up at this time. Ligands (R,R)-5H and (S,S)-6H were isolated via deligation from their respective cadmium complexes using a thiol-based ligand exchange protocol.

Discovery of Arylsulfonamide Na1.7 Inhibitors: IVIVC, MPO Methods, and Optimization of Selectivity Profile.

The voltage-gated sodium channel Na1.7 continues to be a high-profile target for the treatment of various pain afflictions due to its strong human genetic validation. While isoform selective molecules have been discovered and advanced into the clinic, to date, this target has yet to bear fruit in the form of marketed therapeutics for the treatment of pain.

Na1.7 target modulation and efficacy can be measured in nonhuman primate assays.

Humans with loss-of-function mutations in the Na1.7 channel gene (SCN9A) show profound insensitivity to pain, whereas those with gain-of-function mutations can have inherited pain syndromes. Therefore, inhibition of the Na1.

Pharmacological Characterization of the Novel and Selective 7 Nicotinic Acetylcholine Receptor-Positive Allosteric Modulator BNC375.

Treatments for cognitive deficits associated with central nervous system (CNS) disorders such as Alzheimer disease and schizophrenia remain significant unmet medical needs that incur substantial pressure on the health care system. The 7 nicotinic acetylcholine receptor (nAChR) has garnered substantial attention as a target for cognitive deficits based on receptor localization, robust preclinical effects, genetics implicating its involvement in cognitive disorders, and encouraging, albeit mixed, clinical data with 7 nAChR orthosteric agonists. Importantly, previous orthosteric agonists at this receptor suffered from off-target activity, receptor desensitization, and an inverted U-shaped dose-effect curve in preclinical assays that limit their clinical utility.

Randomised controlled trial of a video intervention and behaviour contract to improve medication adherence after renal transplantation: the VECTOR study protocol.

Introduction: Non-adherence after kidney transplantation contributes to increased rejections, hospitalisations and healthcare expenditures. Although effective adherence interventions are sorely needed, increasing education and support to transplant recipients demands greater use of care providers' time and resources in a healthcare system that is stretched. The objective of this clinical trial is to determine the effectiveness of an electronically delivered video series and adherence behaviour contract on improving medication adherence to immunosuppressant medications.

Accessing Ambiphilic Phosphine Boronates through C-H Borylation by an Unforeseen Cationic Iridium Complex.

Ambiphilic molecules, which contain a Lewis base and Lewis acid, are of great interest based on their unique ability to activate small molecules. Phosphine boronates are one class of these substrates that have interesting catalytic activity. Direct access to these phosphine boronates is described through the iridium-catalyzed C-H borylation of phosphines.

C-reactive protein levels in acute respiratory exacerbations of cystic fibrosis.

C-reactive protein (CRP) levels increase in response to bacterial infection and have been used to guide the use of antibiotics. We assessed CRP levels in a cohort of patients with cystic fibrosis (CF) admitted to hospital with an exacerbation of their lung disease, requiring treatment with broad-spectrum antibiotics. In this group, most subjects had CRP levels of less than 20 mg/L, including patients who had pneumonia.

Role of magnesium supplementation in the treatment of depression: A randomized clinical trial.

Current treatment options for depression are limited by efficacy, cost, availability, side effects, and acceptability to patients. Several studies have looked at the association between magnesium and depression, yet its role in symptom management is unclear. The objective of this trial was to test whether supplementation with over-the-counter magnesium chloride improves symptoms of depression.

Primer for nutritionists: Managing the side effects of antidepressants.

Unlabelled: Depression is a chronic disease affecting a significant portion of the U.S.

Population: Due to the popularity of ADs most nutrition professionals working in the outpatient setting will encounter patients taking one of these medications.

Benzoxazolinone aryl sulfonamides as potent, selective Na1.7 inhibitors with in vivo efficacy in a preclinical pain model.

Studies on human genetics have suggested that inhibitors of the Na1.7 voltage-gated sodium channel hold considerable promise as therapies for the treatment of chronic pain syndromes. Herein, we report novel, peripherally-restricted benzoxazolinone aryl sulfonamides as potent Na1.

Discovery of selective, orally bioavailable, N-linked arylsulfonamide Na1.7 inhibitors with pain efficacy in mice.

The voltage-gated sodium channel Na1.7 is a genetically validated target for the treatment of pain with gain-of-function mutations in man eliciting a variety of painful disorders and loss-of-function mutations affording insensitivity to pain. Unfortunately, drugs thought to garner efficacy via Na1 inhibition have undesirable side effect profiles due to their lack of selectivity over channel isoforms.

Thiocyanate-Ligated Heterobimetallic {PtM} Lantern Complexes Including a Ferromagnetically Coupled 1D Coordination Polymer.

A series of heterobimetallic lantern complexes with the central unit {PtM(SAc)4(NCS)} have been prepared and thoroughly characterized. The {Na(15C5)}[PtM(SAc)4(NCS)] series, 1 (Co), 2 (Ni), 3 (Zn), are discrete compounds in the solid state, whereas the {Na(12C4)2)}[PtM(SAc)4(NCS)] series, 4 (Co), 5 (Ni), 6 (Zn), and 7 (Mn), are ion-separated species. Compound 7 is the first {PtMn} lantern of any bridging ligand (carboxylate, amide, etc.

Increases in intravenous magnesium use among hospitalized patients: an institution cross-sectional experience.

Background: Among hospitalized patients, indications for the measurement of magnesium levels and treatment of hypomagnesemia with intravenous magnesium are not well defined. Recently, there have been reports of worldwide shortages of intravenous magnesium sulphate.

Objective: To examine secular trends in the administration of intravenous magnesium on hospital wards at a tertiary care institution.

Synthesis of a phosphapyracene via metal-mediated cyclization: structural and reactivity effects of acenaphthene precursors.

Metal-mediated synthesis of a new heterocycle, 1-phenyl-phosphapyracene (Ph-4, Ph-PyraPhos), by tandem phosphination/cyclization of peri-substituted 5-bromo-6-chloromethylacenaphthene (3) was investigated for comparison to Pt-catalyzed formation of 1-phosphaacenaphthenes (2, AcePhos) from the analogous naphthalene precursor (1). Reaction of PH2Ph with , NaOSiMe3 and a Cu catalyst gave ; a Pt catalyst yielded PHPh(CH2Ar) (Ph-11, Ar = 5-Br-acenaphthyl). Deprotonation of a complex of this secondary phosphine, [Pt((R,R)-Me-DuPhos)(Ph)(PHPh(CH2Ar))][PF6] (17), generated the phosphido intermediate Pt((R,R)-Me-DuPhos)(Ph)(PPhCH2Ar) (Ph-8), which cyclized to give [Pt((R,R)-Me-DuPhos)(Ph)(Ph-PyraPhos)][PF6] (18).

Maximizing diversity from a kinase screen: identification of novel and selective pan-Trk inhibitors for chronic pain.

We have identified several series of small molecule inhibitors of TrkA with unique binding modes. The starting leads were chosen to maximize the structural and binding mode diversity derived from a high throughput screen of our internal compound collection. These leads were optimized for potency and selectivity employing a structure based drug design approach adhering to the principles of ligand efficiency to maximize binding affinity without overly relying on lipophilic interactions.

Phosphine-directed C-H borylation reactions: facile and selective access to ambiphilic phosphine boronate esters.

Ambiphilic ligands have received considerable attention over the last two decades due to their unique reactivity as organocatalysts and ligands. The iridium-catalyzed C-H borylation of phosphines is described in which the phosphine is used as a directing group to provide selective formation of arylboronate esters with unique scaffolds of ambiphilic compounds. A variety of aryl and benzylic phosphines were subjected to the reaction conditions, selectively providing stable, isolable boronate esters upon protection of the phosphine as the borane complex.

Limits to intensified mycophenolate mofetil dosing in kidney transplantation.

Background: Studies have shown that achieving adequate exposure of mycophenolic acid (MPA) early post transplant is associated with less acute rejection in kidney recipients. Intensified dosing with the equivalent of mycophenolate mofetil (MMF) 3 g daily in tacrolimus-treated patients has been shown to increase exposure however about 15% remain below the lower therapeutic threshold of MPA area under the curve (AUC) of 30 mg · hr⁻¹ · L⁻¹ early post transplant. A post hoc analysis of this study showed that a target MPA AUC >40 mg · hr⁻¹ · L⁻¹ was most effective.

Generic immunosuppression in solid organ transplantation: a Canadian perspective.

The introduction of generic immunosuppressant medications may present an opportunity for cost savings in solid organ transplantation if equivalent clinical outcomes to the branded counterparts can be achieved. An interprofessional working group of the Canadian Society of Transplantation was established to develop recommendations on the use of generic immunosuppression in solid organ transplant recipients (SOTR) based on a review of the available data. Under current Health Canada licensing requirements, a demonstration of bioequivalence with the branded formulation in healthy volunteers allows for bridging of clinical data.

"I did what?" Zolpidem and the courts.

Zolpidem is a widely prescribed nonbenzodiazepine hypnotic medication available in the United States since 1992. Attention has been drawn recently to its potential to cause sleep-related, complex behaviors such as sleepwalking and sleep driving. These automatic behaviors have led to a deluge of legal claims.

Synthesis and characterization of an unsymmetrical cobalt(III) active site analogue of nitrile hydratase.

The design, synthesis, and characterization of an unsymmetrical diamidato-dithiol ligand (H(4) 1, where the hydrogen atoms represent deprotonatable amide and thiol protons) and its cobalt(III) complex, a synthetic analogue of the cobalt-containing nitrile hydratase enzyme family, are reported. The ligand was prepared in 24% yield from an overall eight-step synthetic pathway following a modified protocol established in our laboratory that includes two peptide couples using O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate as the coupling agent. The ligand and all precursors were characterized by NMR spectroscopy and elemental analysis.

Novel metal complexes containing a chiral trinitrogen isoindoline-based pincer ligand: in situ synthesis and structural characterization.

The first synthesis and characterization of metal coordinated complexes containing in situ prepared chiral trinitrogen 1,3-bis(4,5-dihydrooxazol-2-ylimino)isoindoline-based pincer ligands are reported. Two zinc complexes, isolated as Zn(L)(2), where L = 1,3-bis(4,5-dihydro-4-(R)-phenyloxazol-2-ylimino)isoindoline ((R,R)-5) or 1,3-bis(4,5-dihydro-4-(S)-iso-propyloxazol-2-ylimino)isoindoline ((S,S)-6), respectively, are reported. Complexes Zn((R,R)-5)(2) and Zn((S,S)-6)(2) were prepared in situ through the condensation of phthalonitrile with enantiopure 2-amino-4-(R)-phenyloxazoline ((R)-3) or 2-amino-4-(S)-iso-propyloxazoline ((S)-4) in the presence of ZnCl(2) at 80 °C in dry toluene over 3-4 days.