Using 42 CFR part 2 revisions to integrate substance use disorder treatment information into electronic health records at a safety net health system.

Background: Regulations put in place to protect the privacy of individuals receiving substance use disorder (SUD) treatment have resulted in an unintended consequence of siloed SUD treatment and referral information outside of the integrated electronic health record (EHR). Recent revisions to these regulations have opened the door to data integration, which creates opportunities for enhanced patient care and more efficient workflows. We report on the experience of one safety-net hospital system integrating SUD treatment data into the EHR.

Dihydropyrmidine dehydrogenase from Escherichia coli: Transient state analysis reveals both reductive activation prior to turnover and diminished substrate effector roles relative to the mammalian form.

Dihydropyrimidine dehydrogenase (DPD) is an enzyme that uses an elaborate architecture to catalyze a simple net reaction: the reduction of the vinylic bond of uracil and thymine. Known DPDs have two active sites separated by approximately 60 Å. One active site has an FAD cofactor and binds NAD(P) and the other has an FMN cofactor and binds pyrimidines.

Fc-competent multispecific PDL-1/TIGIT/LAG-3 antibodies potentiate superior anti-tumor T cell response.

The landscape of current cancer immunotherapy is dominated by antibodies targeting PD-1/PD-L1 and CTLA-4 that have transformed cancer therapy, yet their efficacy is limited by primary and acquired resistance. The blockade of additional immune checkpoints, especially TIGIT and LAG-3, has been extensively explored, but so far only a LAG-3 antibody has been approved for combination with nivolumab to treat unresectable or metastatic melanoma. Here we report the development of a PDL1 × TIGIT bi-specific antibody (bsAb) GB265, a PDL1 × LAG3 bsAb GB266, and a PDL1 × TIGIT × LAG3 tri-specific antibody (tsAb) GB266T, all with intact Fc function.

A novel IgG Fc by computer-aided design enhances heavy-chain heterodimerization in bi- or trispecific antibodies.

The classical `knob-into-holes' (KIH) strategy (knob(T366Y)/hole (Y407T)) has successfully enhanced the heterodimerization of a bispecific antibody (BsAb) resulting in heterodimer formation up to 92% of protein A (ProA)-purified protein pool. However, it does not show high efficiency for every BsAb. KIH was initially applied to a CD20/CD3 BsAb.

PvdF of pyoverdin biosynthesis is a structurally unique N-formyltetrahydrofolate-dependent formyltransferase.

The hydroxyornithine transformylase from Pseudomonas aeruginosa is known by the gene name pvdF, and has been hypothesized to use N-formyltetrahydrofolate (N-fTHF) as a co-substrate formyl donor to convert N-hydroxyornithine (OHOrn) to N-formyl- N-hydroxyornithine (fOHOrn). PvdF is in the biosynthetic pathway for pyoverdin biosynthesis, a siderophore generated under iron-limiting conditions that has been linked to virulence, quorum sensing and biofilm formation. The structure of PvdF was determined by X-ray crystallography to 2.

The enzyme: Renalase.

Within the last two years catalytic substrates for renalase have been identified, some 10 years after its initial discovery. 2- and 6-dihydronicotinamide (2- and 6-DHNAD) isomers of β-NAD(P)H (4-dihydroNAD(P)) are rapidly oxidized by renalase to form β-NAD(P). The two electrons liberated are then passed to molecular oxygen by the renalase FAD cofactor forming hydrogen peroxide.

Ligand binding phenomena that pertain to the metabolic function of renalase.

Renalase catalyzes the oxidation of isomers of β-NAD(P)H that carry the hydride in the 2 or 6 positions of the nicotinamide base to form β-NAD(P). This activity is thought to alleviate inhibition of multiple β-NAD(P)-dependent enzymes of primary and secondary metabolism by these isomers. Here we present evidence for a variety of ligand binding phenomena relevant to the function of renalase.

Renalase does not catalyze the oxidation of catecholamines.

It is widely accepted that the function of human renalase is to oxidize catecholamines in blood. However, this belief is based on experiments that did not account for slow, facile catecholamine autoxidation reactions. Recent evidence has shown that renalase has substrates with which it reacts rapidly.

Bacterial Renalase: Structure and Kinetics of an Enzyme with 2- and 6-Dihydro-β-NAD(P) Oxidase Activity from Pseudomonas phaseolicola.

Despite a lack of convincing in vitro evidence and a number of sound refutations, it is widely accepted that renalase is an enzyme unique to animals that catalyzes the oxidative degradation of catecholamines in blood in order to lower vascular tone. Very recently, we identified isomers of β-NAD(P)H as substrates for renalase (Beaupre, B. A.

Metabolic function for human renalase: oxidation of isomeric forms of β-NAD(P)H that are inhibitory to primary metabolism.

Renalase is a recently identified flavoprotein that has been associated with numerous physiological maladies. There remains a prevailing belief that renalase functions as a hormone, imparting an influence on vascular tone and heart rate by oxidizing circulating catecholamines, chiefly epinephrine. This activity, however, has not been convincingly demonstrated in vitro, nor has the stoichiometry of this transformation been shown.

Kinetics and equilibria of the reductive and oxidative half-reactions of human renalase with α-NADPH.

Renalase is a recently discovered flavoprotein that has been reported to be a hormone produced by the kidney to down-modulate blood pressure and heart rate. The consensus belief has been that renalase oxidizes circulating catecholamine neurotransmitters thereby attenuating vascular tone. However, a convincing in vitro demonstration of this activity has not been made.

Renalase is an α-NAD(P)H oxidase/anomerase.

Renalase is a protein hormone secreted into the blood by the kidney that is reported to lower blood pressure and slow heart rate. Since its discovery in 2005, renalase has been the subject of conjecture pertaining to its catalytic function. While it has been widely reported that renalase is the third monoamine oxidase (monoamine oxidase C) that oxidizes circulating catecholamines such as epinephrine, there has been no convincing demonstration of this catalysis in vitro.

A risk-based food inspection program.

The inspection of food facilities is a crucial public service designed to prevent foodborne illnesses among retail food consumers. To enhance the existing food inspection process in San Bernardino County, California, a risk-based food inspection program and assessment instrument has been developed and proposed. A literature review and interviews with health professionals were conducted to establish a baseline understanding of various inspection procedures currently being employed throughout the nation.

A systematic program to enhance clinician group skills in an inpatient psychiatric hospital.

This article describes the collaborative effort of a team of discipline directors, administrators, and academicians to create a systematic program to enhance the group competencies of a large clinical staff working at a state hospital. The effects of the program were tested by a quasi-experimental field study. Quantitative measures of group process provided limited support for program effectiveness.

Evaluating the effectiveness of child and adolescent group treatment: a meta-analytic review.

Utilizing 56 outcome studies published between 1974 and 1997, this meta-analysis specifically examines the effect of group treatment with children and adolescents (ages 4-18). Various types of group treatment were assessed, including preventative programs, psychotherapy, counseling, guidance, and training groups. Results indicate that group treatment was significantly more effective for children than wait-list and placebo control groups (effect size = .

Memory, repression, and child sexual abuse: forensic implications for the mental health professional.

Childhood sexual abuse is prevalent in our society today. Over the last 30 years, mental health professionals have become increasingly involved in the assessment and treatment of adults who were sexually abused as children. The emergence of the phenomenon of recovered memories has divided both families and mental health professionals.

Factors associated with successful autologous blood donation for elective surgery.

Not all donors can donate the number of autologous blood units requested by their physicians before surgery, and donors are more frequently unsuccessful as more units are requested. Therefore, 368 autologous blood donors who were requested to donate 4 or more units during the 6-week period before surgery at one community blood center were studied. More men were able to donate 4 units with no deferrals for anemia than were women (86% [181 of 211] compared to 42% [48 of 115], P less than 0.

Pentachlorophenol toxicokinetics after intravenous and oral administration to rat.

1. The toxicokinetics of pentachlorophenol (PCP) were studied in rats. Doses of 2.

Colon-specific delivery of dexamethasone from a glucoside prodrug in the guinea pig.

Dexamethasone-beta-D-glucoside is a potential prodrug for colonic delivery of the antiinflammatory agent, dexamethasone. The ability of this prodrug to deliver dexamethasone selectively to the colon depends not only on its being slowly absorbed from the alimentary canal, but also on its having chemical and enzymatic stability in the stomach and small intestine. Once reaching the large bowel, it should be quantitatively hydrolyzed to release the active agent.

Alloimmunization in sickle cell anemia and transfusion of racially unmatched blood.

Transfusion therapy for sickle cell anemia is limited by the development of antibodies to foreign red cells. To evaluate the frequency and risk factors associated with such alloimmunization, we determined the transfusion history, red-cell phenotype, and development of alloantibodies in 107 black patients with sickle cell anemia who received transfusions. We compared the results with those from similar studies in 51 black patients with sickle cell disease who had not received transfusions and in 19 nonblack patients who received transfusions for other forms of chronic anemia.

Moderate and severe reactions during autologous blood donations are no more frequent than during homologous blood donations.

Because autologous donation is permitted for donors who do not meet homologous blood donation standards, referring physicians and blood center personnel may be concerned about autologous donor reactions. Small studies have determined that mild reactions do not occur more frequently, but the incidence of rarer, more serious, moderate and severe reactions is unknown. We therefore studied the frequency of reactions during 10,200 autologous and 219,307 concurrent homologous donations at four blood centers.

Safety and use of autologous blood donation during the third trimester of pregnancy.

To examine autologous blood donation during the third trimester of pregnancy, records of 272 blood donors who donated by standard procedures were reviewed. The incidence of vasovagal reactions at autologous donation was 2.1% (7/341) versus 1.

Metabolic studies on phencyclidine: characterization of a phencyclidine iminium ion metabolite.

Studies on the metabolic bioactivation of the psychotomimetic amine phencyclidine have been pursued through the characterization of a new metabolite which is formed via initial cytochrome P-450 catalyzed oxidation of the parent drug to the corresponding iminium species. CI mass spectrometric and diode array UV and 1H NMR spectral analyses provided evidence for the conjugated amino enone compound, 1-(1-phenylcyclohexyl)-2,3-dihydro-4-pyridone. Confirmation of the proposed structure was achieved by comparing the 1H NMR and high-resolution EI mass spectral properties of the metabolic isolate with the corresponding spectra of an authentic synthetic sample.

Cation-exchange high-performance liquid chromatography assay for the nigrostriatal toxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and its monoamine oxidase B generated metabolites in brain tissues.

This paper describes a sensitive (1 pmol/mg tissue) and selective bioanalytical method for the quantitative estimation of the nigrostriatal toxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its monoamine oxidase B generated metabolites, the 1-methyl-4-phenyl-2,3-dihydropyridinium species MPDP+ and the 1-methyl-4-phenylpyridinium species MPP+. The method is based on initial separation of the analytes after treatment of brain tissue homogenates with 5% trichloroacetic acid. The soluble fraction is analyzed directly by cation-exchange high-performance liquid chromatography employing a diode array UV detector.

Phencyclidine iminium ion. NADPH-dependent metabolism, covalent binding to macromolecules, and inactivation of cytochrome(s) P-450.

The phencyclidine iminium ion (PCP-Im+), a potentially reactive 2,3,4,5-tetrahydropyridinium species, is formed by the cytochrome(s) P-450-catalyzed alpha-carbon oxidation of phencyclidine (PCP), a commonly abused psychotomimetic agent. Incubation of PCP-Im+ with liver microsomes obtained from phenobarbital-induced rabbits resulted in over 50% loss of microsomal N-demethylase activity and 30% reduction in cytochrome(s) P-450 content. These effects were concentration-dependent, irreversible, and exhibited pseudo-first order kinetics, characteristics of a mechanism-based enzyme inactivation process.