Early mobilization in coronavirus-19 patients treated with extracorporeal membrane oxygenation.

Background: Coronavirus disease 2019 (COVID-19) pneumonia can be associated with refractory respiratory failure requiring extracorporeal membrane oxygenation(ECMO). Although ECMO has helped many COVID patients, optimal management strategies for these patients remain unknown.

Methods: We conducted a retrospective review of all COVID patients requiring ECMO at our hospital.

An Interprofessional Approach to Mobilizing Patients With COVID-19 Receiving Extracorporeal Membrane Oxygenation.

Objective: To assess survival outcomes with the intervention of an interprofessional mobilization program for patients with COVID-19 who were receiving venovenous extracorporeal membrane oxygenation (VV-ECMO).

Design: Preintervention and postintervention retrospective cohort study.

Methods: Survival outcomes of nonmobilized, adult patients (n = 16) with COVID-19 who were receiving VV-ECMO (May 2020 through December 2020) were compared with those of 26 patients who received a mobility care plan (January 2021 through November 2021).

Blood Product Utilization in Patients With COVID-19 on ECMO.

Introduction: Although extracorporeal membrane oxygenation (ECMO) has been associated with improved outcomes in COVID patients with respiratory failure, data regarding the need for blood product utilization in this population is inadequate.

Methods: We conducted a retrospective review of all COVID patients requiring ECMO support at our facility. Patient demographics, co-morbidities, measures of acuity, and blood product utilization were identified.

Intermediate-term survival and functional outcomes of COVID-19 extracorporeal membrane oxygenation patients.

Background: Extracorporeal membrane oxygenation (ECMO) has been associated with acceptable short-term survival in patients with refractory respiratory failure secondary to coronavirus disease 2019 (COVID-19) pneumonia. Previous studies have demonstrated acceptable long-term outcomes in patients supported with ECMO for respiratory failure of other etiologies. However, long-term survival and functional outcomes in COVID ECMO patients remain unknown.

Sample Mass Estimate for the Use of Near-Infrared and Raman Spectroscopy to Monitor Content Uniformity in a Tablet Press Feed Frame of a Drug Product Continuous Manufacturing Process.

Recently, feed frame-based process analytical technology measurements used to assure product quality during continuous manufacturing processes have received significant attention. These measurements are able to accurately determine uniformity of the powder blend before compression, and in these applications, it is necessary to understand the interrogated sample volume per measurement. This understanding ensures that the blend measurement can be indicative of the uniformity of the final dosage form.

Characterization of Near-Infrared and Raman Spectroscopy for In-Line Monitoring of a Low-Drug Load Formulation in a Continuous Manufacturing Process.

Reflectance spectroscopy is an excellent candidate for process analytical technology (PAT) applications in continuous manufacturing of pharmaceutical tablets. Spectroscopic methods provide a real-time, nondestructive measurement of the active pharmaceutical ingredient (API) concentration in order to ensure product quality and uniformity. Of particular challenge is the powder blends with low drug loads (<5% w/w) where the measurement of the signal-to-noise and, in turn, precision limit the ability of the method.

Development of Near Infrared Spectroscopy-based Process Monitoring Methodology for Pharmaceutical Continuous Manufacturing Using an Offline Calibration Approach.

A near-infrared (NIR) calibration was developed using an efficient offline approach to enable a quantitative partial least-squares (PLS) chemometric model to measure and monitor the concentration of active pharmaceutical ingredients (API) in powder blends in the feed frame (FF) of a tablet press. The approach leveraged an offline "feed frame table," which was designed to mimic the full process from a NIR measurement perspective, thereby facilitating a more robust model by allowing more sources of variability to be included in the calibration by minimizing the consumption of API and other raw materials. The design of experiment (DOE) for the calibration was established by an initial risk assessment and included anticipated variability from factors related to formulation, process, environment, and instrumentation.

Kilogram-scale prexasertib monolactate monohydrate synthesis under continuous-flow CGMP conditions.

Advances in drug potency and tailored therapeutics are promoting pharmaceutical manufacturing to transition from a traditional batch paradigm to more flexible continuous processing. Here we report the development of a multistep continuous-flow CGMP (current good manufacturing practices) process that produced 24 kilograms of prexasertib monolactate monohydrate suitable for use in human clinical trials. Eight continuous unit operations were conducted to produce the target at roughly 3 kilograms per day using small continuous reactors, extractors, evaporators, crystallizers, and filters in laboratory fume hoods.

Investigation of the mechanism of racemization of litronesib in aqueous solution: unexpected base-catalyzed inversion of a fully substituted carbon chiral center.

Mitosis inhibitor (R)-litronesib (LY2523355) is a 1,3,4-thiadiazoline-bearing phenyl and N-(2-ethylamino)ethanesulfonamido-methyl substituents on tetrahedral C5. Chiral instability has been observed at pH 6 and above with the rate of racemization increasing with pH. A positively charged trigonal intermediate is inferred from the fact that p-methoxy substituent on the phenyl accelerated racemization, whereas a p-trifluoromethyl substituent had the opposite effect.

On-column nitrosation of amines observed in liquid chromatography impurity separations employing ammonium hydroxide and acetonitrile as mobile phase.

The availability of high performance liquid chromatography (HPLC) columns capable of operation at pH values up to 12 has allowed a greater selectivity space to be explored for method development in pharmaceutical analysis. Ammonium hydroxide is of particular value in the mobile phase because it is compatible with direct interfacing to electrospray mass spectrometers. This paper reports an unexpected N-nitrosation reaction that occurs with analytes containing primary and secondary amines when ammonium hydroxide is used to achieve the high pH and acetonitrile is used as the organic modifier.

Civil commitment for substance use disorder patients under the Florida Marchman Act: demographics and outcomes in the private clinical setting.

The Florida Marchman Act, a statutory process for civil commitment of persons with substance use disorders. The paper describes the various methods by which the Act may be employed, and examines the demographics and outcomes of 100 patients admitted to a private treatment setting pursuant to Marchman Act authority.

A systematic approach to development of liquid chromatographic impurity methods for pharmaceutical analysis.

A strategy for developing chromatographic methods designed to determine impurities and degradation products in active pharmaceutical ingredients and drug products is presented. Selectivity is achieved by evaluating a chromatographic space comprised of 12 stationary/mobile phase combinations. Stationary phases predicted to be orthogonal based on their hydrophobic subtraction model parameters used.

Mechanotransduction and anoikis: death and the homeless cell.

Developed organs display strict spatial organization of differentiated cells which is required for proper organ function. One important device that prevents tissue disorganization is the death of cells that lose anchorage to their native matrix, a signal that indicates potential loss of proper tissue context. Termed anoikis (Greek for Homelessness), this form of cell death is a specialized form of apoptosis.

An analysis of the results from Two-Generation Reproduction Toxicity Studies to assess the value of mating animals of the second (F1) generation for the detection of adverse treatment-related effects on reproductive performance.

The need to routinely perform a two-generation study to assess reproductive performance is under debate. This review has analysed the results from 22 consecutive Two-Generation Reproduction Toxicity Studies performed within our laboratories, to determine the value of mating each generation in the detection of treatment-related effects on reproductive performance. The chemicals included 13 agrochemicals, 5 industrial chemicals and 4 food additives.

HIV-1 Tat activates dual Nox pathways leading to independent activation of ERK and JNK MAP kinases.

Human immunodeficiency virus, type 1 Tat is known to exert pleiotropic effects on the vascular endothelium through mitogen-activated protein (MAP) kinases, although the signaling pathways leading to MAP kinase activation are incompletely understood. We focused on proximal pathways potentially governing downstream MAP kinase activity by Tat. Within 2 min, Tat activated both Ras and Rho GTPases in endothelial cells, leading to ERK phosphorylation by 10 min.

p66Shc mediates anoikis through RhoA.

Detachment of parenchymal cells from a solid matrix switches contextual cues from survival to death during anoikis. Marked shape changes accompany detachment and are thought to trigger cell death, although a working model to explain the coordination of attachment sensation, shape change, and cell fate is elusive. The constitutive form of the adapter Shc, p52Shc, confers survival properties, whereas the longer p66Shc signals death through association with cytochrome c.

Treatment for attorneys with substance related and co-occurring psychiatric disorders: demographics and outcomes.

The following paper is the result of a retrospective study of clinical case files of legal professionals treated for substance-related and co-occurring psychiatric disorders at a recovery center specializing in the care of impaired professionals. Attorneys traditionally differ from healthcare professionals in two important ways: first, they prematurely leave treatment in greater numbers, and second, they suffer a higher incidence of co-occurring psychiatric disorders. Sixty percent of the attorneys presented with concurrent psychiatric conditions (Axis I and Axis II), compared to 46% of their healthcare colleagues.

Ornithine decarboxylase promotes catalysis by binding the carboxylate in a buried pocket containing phenylalanine 397.

Ornithine decarboxylase (ODC) is a pyridoxal 5'-phosphate (PLP) dependent enzyme that catalyzes the decarboxylation of l-Orn to putrescine, a rate-limiting step in the formation of polyamines. The X-ray crystal structures of ODC, complexed to several ligands, support a model where the substrate is oriented with the carboxyl-leaving group buried on the re face of the PLP cofactor. This binding site is composed of hydrophobic and electron-rich residues, in which Phe-397 is predicted to form a close contact.