Natural language processing to evaluate texting conversations between patients and healthcare providers during COVID-19 Home-Based Care in Rwanda at scale.

Community isolation of patients with communicable infectious diseases limits spread of pathogens but our understanding of isolated patients' needs and challenges is incomplete. Rwanda deployed a digital health service nationally to assist public health clinicians to remotely monitor and support SARS-CoV-2 cases via their mobile phones using daily interactive short message service (SMS) check-ins. We aimed to assess the texting patterns and communicated topics to better understand patient experiences.

CYP P450 and non-CYP P450 Drug Metabolizing Enzyme Families Exhibit Differential Sensitivities towards Proinflammatory Cytokine Modulation.

Compromised hepatic drug metabolism in response to proinflammatory cytokine release is primarily attributed to downregulation of cytochrome P450 (CYP) enzymes. However, whether inflammation also affects other phase I and phase II drug metabolizing enzymes (DMEs), such as the flavin monooxygenases (FMOs), carboxylesterases (CESs), and UDP glucuronosyltransferases (UGTs), remains unclear. This study aimed to decipher the impact of physiologically relevant concentrations of proinflammatory cytokines on expression and activity of phase I and phase II enzymes, to establish a hierarchy of their sensitivity as compared with the CYPs.

A very versatile molecular machine.

In this issue (J Bacteriol. 206: e0014024, https://doi.org/10.

Alopecia areata exhibits cutaneous and systemic OX40 activation across atopic backgrounds.

Background: Alopecia areata (AA) is a chronic, nonscarring hair-loss disorder associated with significant quality-of-life impairment and limited treatment options. AA has been recently linked to atopy and shown to exhibit both Th1- and Th2-driven inflammation. However, a comprehensive molecular and cellular characterization across blood and scalp compartments in both atopic and nonatopic patients is lacking.

CNS Viral Infections-What to Consider for Improving Drug Treatment: A Plea for Using Mathematical Modeling Approaches.

Neurotropic viruses may cause meningitis, myelitis, encephalitis, or meningoencephalitis. These inflammatory conditions of the central nervous system (CNS) may have serious and devastating consequences if not treated adequately. In this review, we first summarize how neurotropic viruses can enter the CNS by (1) crossing the blood-brain barrier or blood-cerebrospinal fluid barrier; (2) invading the nose via the olfactory route; or (3) invading the peripheral nervous system.

Ultrasound-mediated gene delivery specifically targets liver sinusoidal endothelial cells for sustained FVIII expression in hemophilia A mice.

The ability to target the native production site of factor VIII (FVIII)-liver sinusoidal endothelial cells (LSECs)-can improve the outcome of hemophilia A (HA) gene therapy. By testing a matrix of ultrasound-mediated gene delivery (UMGD) parameters for delivering a GFP plasmid into the livers of HA mice, we were able to define specific conditions for targeted gene delivery to different cell types in the liver. Subsequently, two conditions were selected for experiments to treat HA mice via UMGD of an endothelial-specific human FVIII plasmid: low energy (LE; 50 W/cm, 150 μs pulse duration) to predominantly target endothelial cells or high energy (HE; 110 W/cm, 150 μs pulse duration) to predominantly target hepatocytes.

Unraveling the Effects of Acute Inflammation on Pharmacokinetics: A Model-Based Analysis Focusing on Renal Glomerular Filtration Rate and Cytochrome P450 3A4-Mediated Metabolism.

Unlabelled: BACKGROUND AND OBJECTIVES: Acute inflammation caused by infections or sepsis can impact pharmacokinetics. We used a model-based analysis to evaluate the effect of acute inflammation as represented by interleukin-6 (IL-6) levels on drug clearance, focusing on renal glomerular filtration rate (GFR) and cytochrome P450 3A4 (CYP3A4)-mediated metabolism.

Methods: A physiologically based model incorporating renal and hepatic drug clearance was implemented.

The impact of genotype on phenoconversion by concomitant medication.

Pharmacogenetics-informed drug prescribing is increasingly applied in clinical practice. Typically, drug metabolizing phenotypes are determined based on genetic test results, whereupon dosage or drugs are adjusted. Drug-drug-interactions (DDIs) caused by concomitant medication can however cause mismatches between predicted and observed phenotypes (phenoconversion).

Mobile phone access and preferences among medical inpatients at an urban Canadian hospital for post-discharge planning: A pre-COVID-19 cross-sectional survey.

Background: Digital health interventions are increasingly used for patient care, yet little data is available on the phone access type and usage preferences amongst medical ward inpatients to inform the most appropriate digital interventions post-discharge.

Methods: To identify mobile phone ownership, internet access, and cellular use preferences among medical inpatients, we conducted a researcher-administered survey of patients admitted to five internal medicine units at Vancouver General Hospital (VGH) in January 2020. The survey was administered over 2 days separated by a 2-week period.

Rotary Nanomotors in the Rear View Mirror.

Rotation is part of our everyday lives. For most of human history, rotation was considered a uniquely human invention, something beyond the anatomical capabilities of organisms. In 1973, Howard Berg made the audacious proposal that the common gut bacterium swims by rotating helical flagellar filaments.

Adverse event reviews in healthcare: what matters to patients and their family? A qualitative study exploring the perspective of patients and family.

Objectives: Explore what 'good' patient and family involvement in healthcare adverse event reviews may involve.

Design: Data was collected using semi-structured telephone interviews. Interview transcripts were analysed using an inductive thematic approach.

A systematic review on disease-drug-drug interactions with immunomodulating drugs: A critical appraisal of risk assessment and drug labelling.

Aim: Use of immunomodulating therapeutics for immune-mediated inflammatory diseases may cause disease-drug-drug interactions (DDDIs) by reversing inflammation-driven alterations in the metabolic capacity of cytochrome P450 enzymes. European Medicine Agency (EMA) and US Food and Drug Administration (FDA) guidelines from 2007 recommend that the DDDI potential of therapeutic proteins should be assessed. This systematic analysis aimed to characterize the available DDDI trials with immunomodulatory drugs, experimental evidence for a DDDI risk and reported DDDI risk information in FDA/EMA approved drug labelling.

Transcutaneous ultrasound-mediated gene delivery into canine livers achieves therapeutic levels of factor VIII expression.

A safe, effective, and inclusive gene therapy will significantly benefit a large population of patients with hemophilia. We used a minimally invasive transcutaneous ultrasound-mediated gene delivery (UMGD) strategy combined with microbubbles (MBs) to enhance gene transfer into 4 canine livers. A mixture of high-expressing, liver-specific human factor VIII (hFVIII) plasmid and MBs was injected into the hepatic vein via balloon catheter under fluoroscopy guidance with simultaneous transcutaneous UMGD treatment targeting a specific liver lobe.

Howard Berg (1934-2021).

David Blair and Michael Manson commemorate the late Howard Berg, who studied, among other things, the biophysics of bacterial motion.

Extracellular matrix dysfunction in Sorsby patient-derived retinal pigment epithelium.

Sorsby Fundus Dystrophy (SFD) is a rare form of macular degeneration that is clinically similar to age-related macular degeneration (AMD), and a histologic hallmark of SFD is a thick layer of extracellular deposits beneath the retinal pigment epithelium (RPE). Previous studies of SFD patient-induced pluripotent stem cell (iPSC) derived RPE differ as to whether these cultures recapitulate this key clinical feature by forming increased drusenoid deposits. The primary purpose of this study is to examine whether SFD patient-derived iPSC-RPE form basal deposits similar to what is found in affected family member SFD globes and to determine whether SFD iPSC RPE may be more oxidatively stressed.

Mechanosensitive recruitment of stator units promotes binding of the response regulator CheY-P to the flagellar motor.

Reversible switching of the bacterial flagellar motor between clockwise (CW) and counterclockwise (CCW) rotation is necessary for chemotaxis, which enables cells to swim towards favorable chemical habitats. Increase in the viscous resistance to the rotation of the motor (mechanical load) inhibits switching. However, cells must maintain homeostasis in switching to navigate within environments of different viscosities.

Psychosocial considerations in the assessment of hand transplant candidates: A single-center experience and brief literature review.

Vascularized composite allograft, including hand transplantation (HT), has gained wider usage as a reconstructive treatment over the past 30 years. HT recipients face unique psychosocial challenges compared to their solid organ and/or bone marrow transplant counterparts. Accordingly, the psychosocial evaluation among HT candidates continues to evolve, leaving a lack of consensus as to the critical psychosocial domains and psychometric testing instruments to help evaluate individuals considering HT.

Distinct Effects of Inflammation on Cytochrome P450 Regulation and Drug Metabolism: Lessons from Experimental Models and a Potential Role for Pharmacogenetics.

Personalized medicine strives to optimize drug treatment for the individual patient by taking into account both genetic and non-genetic factors for drug response. Inflammation is one of the non-genetic factors that has been shown to greatly affect the metabolism of drugs-primarily through inhibition of cytochrome P450 (CYP450) drug-metabolizing enzymes-and hence contribute to the mismatch between the genotype predicted drug response and the actual phenotype, a phenomenon called phenoconversion. This review focuses on inflammation-induced drug metabolism alterations.

Howard Berg's Random Walk through Biology.

This minireview presents the career of biophysicist Howard Berg from his first interest in bacterial chemotaxis and motility through the present. After a summary of some of his early work, a series of reminiscences of students, postdocs, colleagues, and family members is presented. In sum, these recollections capture the effect that Howard's scientific life has had on the field of bacterial chemotaxis and motility and on the careers and lives of those who have interacted with him.

Phenoconversion of Cytochrome P450 Metabolism: A Systematic Review.

Phenoconversion is the mismatch between the individual's genotype-based prediction of drug metabolism and the true capacity to metabolize drugs due to nongenetic factors. While the concept of phenoconversion has been described in narrative reviews, no systematic review is available. A systematic review was conducted to investigate factors contributing to phenoconversion and the impact on cytochrome P450 metabolism.

Biphasic chemotaxis of to the microbiota metabolite indole.

Bacterial chemotaxis to prominent microbiota metabolites such as indole is important in the formation of microbial communities in the gastrointestinal (GI) tract. However, the basis of chemotaxis to indole is poorly understood. Here, we exposed to a range of indole concentrations and measured the dynamic responses of individual flagellar motors to determine the chemotaxis response.