Clinical evaluation of adults undergoing elective surgery utilizing intraoperative incisional wound irrigation (CLEAN Wound): protocol for a randomised controlled trial.

Introduction: In moderate to high-risk surgical procedures, 15-25% of patients develop a postoperative surgical site infection. Intraoperative incisional wound irrigation has the potential to reduce surgical site infections, and additional randomised controlled trials are required to provide evidence of effectiveness.

Methods And Analysis: This protocol describes a pragmatic, adaptive, participant and adjudicator-blinded trial at 13 sites in Canada in up to 2500 participants.

The clinical and biochemical spectrum of ectopic acromegaly.

Ectopic acromegaly is a rare condition caused by extrapituitary central or peripheral neuroendocrine tumours (NET) that hypersecrete GH or, more commonly, GHRH. It affects less than 1% of acromegaly patients and a misdiagnosis of classic acromegaly can lead to an inappropriate pituitary surgery. Four types of ectopic acromegaly have been described: 1) Central ectopic GH-secretion: Careful cross-sectional imaging is required to exclude ectopic pituitary adenomas.

Physiological Dynamics in the Upper Gastrointestinal Tract and the Development of Gastrointestinal Absorption Models for the Immediate-Release Oral Dosage Forms in Healthy Adult Human.

This review is a revisit of various oral drug absorption models developed in the past decades, focusing on how to incorporate the physiological dynamics in the upper gastrointestinal (GI) tract. For immediate-release oral drugs, GI absorption is a critical input of drug exposure and subsequent human body response, yet difficult to model largely due to the complex GI environment. One of the biggest hurdles lies at capturing the high within-subject variability (WSV) of bioavailability measures, which can be mechanistically explained by the GI physiological dynamics.

Stochastic Differential Equation-based Mixed Effects Model of the Fluid Volume in the Fasted Stomach in Healthy Adult Human.

The rate and extent of drug dissolution and absorption from a solid oral dosage form depend largely on the fluid volume along the gastrointestinal tract. Hence, a model built upon the gastric fluid volume profiles can help to predict drug dissolution and subsequent absorption. To capture the great inter- and intra-individual variability (IAV) of the gastric fluid volume in fasted human, a stochastic differential equation (SDE)-based mixed effects model was developed and compared with the ordinary differential equation (ODE)-based model.

In Vitro Predictive Dissolution Test Should Be Developed and Recommended as a Bioequivalence Standard for the Immediate-Release Solid Oral Dosage Forms of the Highly Variable Mycophenolate Mofetil.

The prodrug mycophenolate mofetil (MMF), which is presystemically hydrolyzed into the pharmacologically active compound mycophenolic acid (MPA), has been widely used for the prophylaxis of acute allograft rejection in solid organ transplantation. However, the huge variability in the plasma concentration level makes the development of MMF drug products difficult due to the great challenge of meeting the traditional bioequivalence (BE) limits. Numerous models have been developed in the past decade to explain the variability, with the emphasis on characterizing the enterohepatic circulation.

Proposing a "Brain Health Checkup (BHC)" as a Global Potential "Standard of Care" to Overcome Reward Dysregulation in Primary Care Medicine: Coupling Genetic Risk Testing and Induction of "Dopamine Homeostasis".

In 2021, over 100,000 people died prematurely from opioid overdoses. Neuropsychiatric and cognitive impairments are underreported comorbidities of reward dysregulation due to genetic antecedents and epigenetic insults. Recent genome-wide association studies involving millions of subjects revealed frequent comorbidity with substance use disorder (SUD) in a sizeable meta-analysis of depression.

Physiologically-Based Pharmacokinetic Modeling to Predict Methylphenidate Exposure Affected by Interplay Among Carboxylesterase 1 Pharmacogenetics, Drug-Drug Interactions, and Sex.

Background And Objective: The pharmacokinetics (PK) of methylphenidate (MPH) differ significantly among individuals. Carboxylesterase 1 (CES1) is the primary enzyme metabolizing MPH, and its function is affected by genetic variants, drug-drug interaction (DDI), and sex. The object of this study is to evaluate CES1 pharmacogenetics as related to MPH metabolism using human liver samples and develop a physiologically-based pharmacokinetic (PBPK) modeling approach to investigate the influence of CES1 genotypes and other factors on MPH PK.

Neurobiology and Spirituality in Addiction Recovery.

This commentary explores the neurobiology of spirituality and asks whether it is possible or desirable to apply genetic engineering to increase human spiritual and religious experience - (gene-spirituality) to deal better with the ever-increasing catastrophes that face humanity? Neurological connections between spirituality and reward genes, reward deficiencies (RDS) (hypodopaminergia), the mirror neuron system, and the default mode network are examined. Some interventions from addiction medicine that may be useful to enhance the neuro-spirituality connectome identified as a cornerstone of the Purpose and Meaning of Life as Reward (PMLR) are identified as reasonable targets for interventions to treat RDS and balance DMN activity.

The potential of psychedelic medicine - A personal account.

In 1965, I was training in clinical toxicology in the pharmacology department of the University of California San Francisco (UCSF) and living in the Haight Ashbury. I studied various psychedelics, including LSD, mescaline, and ibogaine, in human and animal models. The psychedelics were then being used as a therapeutic drug in clinical settings and researched as a potential antipersonnel agent by the U.

Efficacy of an eConsult service to cure hepatitis C in primary care.

In 2016, an eConsult service was developed within a safety net health system to expand access to hepatitis C (HCV) treatment in the primary care setting. The eConsult system provides individualized treatment recommendations from specially trained primary care pharmacists and primary care physicians to primary care providers with less experience in the rapidly changing treatment of HCV. Since its launch, this service has had a large impact in expanding care to a largely homeless and low-income urban population within our health system.

Small All-Range Lidar for Asteroid and Comet Core Missions.

We report the development of a new type of space lidar specifically designed for missions to small planetary bodies for both topographic mapping and support of sample collection or landing. The instrument is designed to have a wide dynamic range with several operation modes for different mission phases. The laser transmitter consists of a fiber laser that is intensity modulated with a return-to-zero pseudo-noise (RZPN) code.

High Genetic Addiction Risk Score (GARS) in Chronically Prescribed Severe Chronic Opioid Probands Attending Multi-pain Clinics: an Open Clinical Pilot Trial.

Millions of Americans experience pain daily. In 2017, opioid overdose claimed 64,000 lives increasing to 84,000 lives in 2020, resulting in a decrease in national life expectancy. Chronic opioid use results in dependency, drug tolerance, neuroadaptation, hyperalgesia, potential addictive behaviors, or Reward Deficiency Syndrome (RDS) caused by a hypodopaminergia.

Improving naltrexone compliance and outcomes with putative pro- dopamine regulator KB220, compared to treatment as usual.

A recent analysis from Stanford University suggested that without any changes in currently available treatment, prevention, and public health approaches, we should expect to have 510,000 deaths from prescription opioids and street heroin from 2016 to 2025 in the US. In a recent review, Mayo Clinic Proceedings (October 2019), Gold and colleagues at Mayo Clinic reviewed the available medications used in opioid use disorders and concluded that in private and community practice adherence is more important as a limiting factor to retention, relapse, and repeat overdose. It is agreed that the primary utilization of known opioid agonists like methadone, buprenorphine and naloxone combinations, while useful as a way of reducing societal harm, is limited by 50% of more discontinuing treatment within 6 months, their diversion, and addiction liability.

Characterization of the cellular transport mechanisms for the anti-cachexia candidate compound TCMCB07.

Background: Cachexia is a debilitating, life-threatening condition whose pathology includes reduced food intake accompanied by hypermetabolism, leading to a catabolic state. The hypothalamic melanocortin system is a critical regulator of metabolic rate with effects being mediated through the melanocortin-4 receptor (MC4R). MC4R activation is also critical to the initiation and maintenance of cachexia.

Pharmacokinetics of gemcitabine and its amino acid ester prodrug following intravenous and oral administrations in mice.

Gemcitabine is an intravenously administered anti-cancer nucleoside analogue. Systemic exposure following oral administration of gemcitabine is limited by extensive first-pass metabolism via cytidine deaminase (CDA) and potentially by saturation of nucleoside transporter-mediated intestinal uptake. An amino acid ester prodrug of gemcitabine, 5'-l-valyl-gemcitabine (V-Gem), was previously shown to be a substrate of the intestinally expressed peptide transporter 1 (PEPT1) and stable against CDA-mediated metabolism.

Optical characterization of laser retroreflector arrays for lunar landers.

The Laser Retroreflector Array for Lunar Landers (LRALL) is a small optical instrument designed to provide a target for precision laser ranging from a spacecraft in lunar orbit, enabling geolocation of the lander and its instrument suite and establishing a fiducial maker on the lunar surface. Here we describe the optical performance of LRALL at visible and near-infrared wavelengths. Individual corner cube reflectors (CCRs) within LRALL were tested for surface flatness and dihedral angle values.

Chemoproteomic Identification of Serine Hydrolase RBBP9 as a Valacyclovir-Activating Enzyme.

Prodrug discovery and development in the pharmaceutical industry have been hampered by a lack of knowledge of prodrug activation pathways. Such knowledge would minimize the risks of prodrug failure by enabling proper selection of preclinical animal models, prediction of pharmacogenomic variability, and identification of drug-drug interactions. Technologies for annotation of activating enzymes have not kept pace with the growing need.

[Ectopic hyperparathyroidism. Detection of mediastinal localization].

The ectopic parathyroid tissue is a frequent cause of recurrent hyperparathyroidism (HPT), accounting 16% in primary HPT and 14% in secondary cases. Although intrathoracic ectopic glands represent 25-35% of all ectopic cases, only 2% requires thoracic surgery. The aim of this study is to report a case series of patients with ectopic mediastinal HPT treated by thoracic approach in a private institution in Argentina.

Bacterial Interactions as Detected by Pooled Antibiotic Susceptibility Testing (P-AST) in Polymicrobial Urine Specimens.

Introduction: Antimicrobial susceptibility is well characterized in monomicrobial infections, but bacterial species often coexist with other bacterial species. Antimicrobial susceptibility is often tested against single bacterial isolates; this approach ignores interactions between cohabiting bacteria that could impact susceptibility. Here, we use Pooled Antibiotic Susceptibility Testing to compare antimicrobial susceptibility patterns exhibited by polymicrobial and monomicrobial urine specimens obtained from patients with urinary tract infection symptoms.

Small and lightweight laser retro-reflector arrays for lunar landers.

A set of small and lightweight laser retro-reflector arrays (LRAs) was fabricated and tested for use on lunar landers under NASA's Commercial Lunar Payload Service program. Each array contains eight 1.27-cm-diameter corner cube retro-reflectors mounted on a dome-shaped aluminum structure.

Multiplex PCR Based Urinary Tract Infection (UTI) Analysis Compared to Traditional Urine Culture in Identifying Significant Pathogens in Symptomatic Patients.

Objective: To evaluate whether multiplex PCR-based molecular testing is noninferior to urine culture for detection of bacterial infections in symptomatic patients.

Methods: Retrospective record review of 582 consecutive elderly patients presenting with symptoms of lower urinary tract infection (UTI) was conducted. All patients had traditional urine cultures and PCR molecular testing run in parallel.