Direct Heterocycle C-H Alkenylation via Dual Catalysis Using a Palladacycle Precatalyst: Multifactor Optimization and Scope Exploration Enabled by High-Throughput Experimentation.

One of the major challenges in developing catalytic methods for C-C bond formation is the identification of generally applicable reaction conditions, particularly if multiple substrate structural classes are involved. Pd-catalyzed direct arylation reactions are powerful transformations that enable direct functionalization of C-H bonds; however, the corresponding direct alkenylation reactions, using vinyl (pseudo) halide electrophiles, are less well developed. Inspired by process development efforts toward , an investigational active pharmaceutical ingredient, we report that a Pd(II) palladacycle derived from tri--butylphosphine and Pd(OAc) is an effective single-component precatalyst for a variety of direct alkenylation reactions.

Basic statistics: A research primer for low- and middle-income countries.

Statistics can be used to describe data or make inferences about populations using samples. Median values (the 50th percentile) better represent central tendency of data samples than means (averages), particularly when data have extreme values. Errors resulting from use of inferential statistics when using classical hypothesis testing include type I (finding a difference between groups when one does not exist) and type II (failure to find a true difference) errors.

Evaluation of dexmedetomidine withdrawal in critically ill adults.

Background: Dexmedetomidine (DEX) withdrawal syndrome has been reported in the pediatric population, but literature describing DEX withdrawal in critically ill adults is limited. The purpose of this study was to determine the incidence of DEX withdrawal in adult patients and to identify factors associated with DEX withdrawal syndrome.

Methods: A retrospective chart review was performed in the adult intensive care units of two tertiary medical centers.

Resistance to Second-Generation HIV-1 Maturation Inhibitors.

A betulinic acid-based compound, bevirimat (BVM), inhibits HIV-1 maturation by blocking a late step in protease-mediated Gag processing: the cleavage of the capsid-spacer peptide 1 (CA-SP1) intermediate to mature CA. Previous studies showed that mutations conferring resistance to BVM cluster around the CA-SP1 cleavage site. Single amino acid polymorphisms in the SP1 region of Gag and the C terminus of CA reduced HIV-1 susceptibility to BVM, leading to the discontinuation of BVM's clinical development.

μImpact of a nursing-driven sedation protocol with criteria for infusion initiation in the surgical intensive care unit.

Purpose: Analgesia and sedation protocols (ASPs) reduce duration of mechanical ventilation (MV) in the medical intensive care unit (ICU), but data in the surgical ICU (SICU) are limited. The objective of this study was to determine the impact of a nursing-driven ASP with criteria for infusion initiation in the SICU.

Materials And Methods: A single-center, retrospective study compared ventilator-free days at day 28 from start of MV (VFD28) before and after ASP implementation.

Prospective Observational Evaluation of Sedation and Pain Management Guideline Adherence Across New Jersey Intensive Care Units.

Background: The practice guidelines for the management of pain, agitation, and delirium (PAD) from the Society of Critical Care Medicine shifted from primarily focusing on the treatment of anxiety in 2002 to the treatment of pain in 2013.

Objective: This prospective, observational, multicenter study aimed to assess the degree of practice adherence to the PAD guidelines for ventilated patients in New Jersey intensive care units (ICUs).

Methods: Pharmacist investigators at 8 centers designated 4 days at least 10 days apart to evaluate all patients on mechanical ventilation.

Case Reports of Aripiprazole Causing False-Positive Urine Amphetamine Drug Screens in Children.

Urine drug screens (UDSs) are used to identify the presence of certain medications. One limitation of UDSs is the potential for false-positive results caused by cross-reactivity with other substances. Amphetamines have an extensive list of cross-reacting medications.

Conformationally constrained functional peptide monolayers for the controlled display of bioactive carbohydrate ligands.

In this study, we employed thiolated peptides of the conformationally constrained, strongly helicogenic α-aminoisobutyric acid (Aib) residue to prepare self-assembled monolayers (SAMs) on gold surfaces. Electrochemistry and infrared reflection absorption spectroscopy support the formation of very well packed Aib-peptide SAMs. The immobilized peptides retain their helical structure, and the resulting SAMs are stabilized by a network of intermolecular H bonds involving the NH groups adjacent to the Au surface.

Biofunctional paper via the covalent modification of cellulose.

Paper-based analytical devices are the subject of growing interest for the development of low-cost point-of-care diagnostics, environmental monitoring technologies, and research tools for limited-resource settings. However, there are limited chemistries available for the conjugation of biomolecules to cellulose for use in biomedical applications. Herein, divinyl sulfone (DVS) chemistry was demonstrated to immobilize small molecules, proteins, and DNA covalently onto the hydroxyl groups of cellulose membranes through nucleophilic addition.

An organophosphonate strategy for functionalizing silicon photonic biosensors.

Silicon photonic microring resonators have established their potential for label-free and low-cost biosensing applications. However, the long-term performance of this optical sensing platform requires robust surface modification and biofunctionalization. Herein, we demonstrate a conjugation strategy based on an organophosphonate surface coating and vinyl sulfone linker to biofunctionalize silicon resonators for biomolecular sensing.

gem-Dimethyl 4-pentenyl glycosides: novel glycosylating agents and anomeric protecting groups.

Two classes of gem-dimethyl 4-n-pentenyl glycosides (i.e., C2-series and C3-series) have been prepared and studied in both the glycosylation and hydrolysis manifolds utilizing NBS as the sole stoichiometric activator.

Adenosine A1 antagonism attenuates beta-adrenergic-resistant sudden hypoxic cardiac insufficiency.

Objectives: In states such as hypoxia, shock, and cardiac arrest, compromised systemic oxygenation or perfusion appears to induce cardiac insufficiency that can be resistant to beta-adrenergic drugs. Elevated levels of adenosine may mediate such beta-adrenergic-resistant cardiac insufficiency via the adenosine A(1) receptor (A(1)AdoR). The objective of this study was to test the hypothesis that selective A(1)AdoR antagonism attenuates hypoxic cardiac insufficiency more efficaciously than beta(1)-adrenergic agonism or nonselective adenosine antagonism.

Adenosine A1 antagonism attenuates atropine-resistant hypoxic bradycardia in rats.

Objectives: To test the following hypotheses: Hypoxia induces bradycardia and hemodynamic compromise that are resistant to atropine but responsive to selective antagonism of the adenosine A1 receptor (A1AdoR). The mechanism for such attenuation is independent of the vagus nerve.

Methods: Ten minutes after sham or actual bilateral cervical vagotomy, paralyzed ventilated rats were made hypoxic (5% fractional inspired oxygen, continued until death).

De novo design of biomimetic antimicrobial polymers.

The design of polymers and oligomers that mimic the complex structures and remarkable biological properties of proteins is an important endeavor with both fundamental and practical implications. Recently, a number of nonnatural peptides with designed sequences have been elaborated to provide biologically active structures; in particular, facially amphiphilic peptides built from beta-amino acids have been shown to mimic both the structures as well as the biological function of natural antimicrobial peptides such as magainins and cecropins. However, these natural peptides as well as their beta-peptide analogues are expensive to prepare and difficult to produce on a large scale, limiting their potential use to certain pharmaceutical applications.