A Hybrid Chart Review of Premature Coronary Artery Disease: An Opportunity to Improve Diagnostic Excellence and Management.

Background: Premature coronary artery disease (premCAD) and its risk factors may not always be diagnosed or treated optimally.

Objective: This study reviewed a sample of patients with premCAD within an integrated health care system to identify opportunities for improved diagnosis and care.

Design: Retrospective chart review.

Addressing the challenges restoring clinical services during the COVID-19 pandemic by harnessing the alignment of clinical and management leadership: an example from a large colorectal service.

Background: The COVID-19 pandemic has posed the greatest operational challenge to the English National Health Service since its inception. Elective surgical services have struggled due to the need to protect both staff and patients from viral exposure, and perioperative COVID-19 infection has been associated with significant excess mortality.

Interventions: In this brief report, we describe how through necessity, it has provided an opportunity to redesign services for the benefit of both patients and organisations, with attendant improvement in activity compared with prepandemic metrics.

Conserved multi-tissue transcriptomic adaptations to exercise training in humans and mice.

Physical activity is associated with beneficial adaptations in human and rodent metabolism. We studied over 50 complex traits before and after exercise intervention in middle-aged men and a panel of 100 diverse strains of female mice. Candidate gene analyses in three brain regions, muscle, liver, heart, and adipose tissue of mice indicate genetic drivers of clinically relevant traits, including volitional exercise volume, muscle metabolism, adiposity, and hepatic lipids.

Indole and azaindole halogenation catalyzed by the RebH enzyme variant 3-LSR utilizing co-purified reductase.

Biocatalytic C-H halogenation is becoming increasingly attractive due to excellent catalyst-controlled selectivity and environmentally benign reaction conditions. Significant efforts have been made on enzymatic halogenation of industrial arenes in a cost-effective manner. Here we report an unprecedented enzymatic halogenation of a panel of industrially important indole, azaindole and anthranilamide derivatives using a thermostable RebH variant without addition of any external flavin reductase enzyme.

Halogenation of Peptides and Proteins Using Engineered Tryptophan Halogenase Enzymes.

Halogenation of bioactive peptides via incorporation of non-natural amino acid derivatives during chemical synthesis is a common strategy to enhance functionality. Bacterial tyrptophan halogenases efficiently catalyze regiospecific halogenation of the free amino acid tryptophan, both in vitro and in vivo. Expansion of their substrate scope to peptides and proteins would facilitate highly-regulated post-synthesis/expression halogenation.

Predictors of Severe Acute Respiratory Syndrome Coronavirus 2 Infection Following High-Risk Exposure.

Background: Non-pharmaceutical interventions (NPIs) are recommended for COVID-19 prevention. However, the effectiveness of NPIs in preventing SARS-CoV-2 transmission remains poorly quantified.

Methods: We conducted a test-negative design case-control study enrolling cases (testing positive for SARS-CoV-2) and controls (testing negative) with molecular SARS-CoV-2 diagnostic test results reported to California Department of Public Health between 24 February-12 November, 2021.

A Slam-dependent hemophore contributes to heme acquisition in the bacterial pathogen Acinetobacter baumannii.

Nutrient acquisition systems are often crucial for pathogen growth and survival during infection, and represent attractive therapeutic targets. Here, we study the protein machinery required for heme uptake in the opportunistic pathogen Acinetobacter baumannii. We show that the hemO locus, which includes a gene encoding the heme-degrading enzyme, is required for high-affinity heme acquisition from hemoglobin and serum albumin.

Association between post-hospital clinic and telephone follow-up provider visits with 30-day readmission risk in an integrated health system.

Background: Follow-up visits with clinic providers after hospital discharge may not be feasible for some patients due to functional limitations, transportation challenges, need for physical distancing, or fear of exposure especially during the current COVID-19 pandemic.

Methods: The aim of the study was to determine the effects of post-hospital clinic (POSH) and telephone (TPOSH) follow-up provider visits versus no visit on 30-day readmission. We used a retrospective cohort design based on data from 1/1/2017 to 12/31/2019 on adult patients (n = 213,513) discharged home from 15 Kaiser Permanente Southern California hospitals.

Engineered RebH Halogenase Variants Demonstrating a Specificity Switch from Tryptophan towards Novel Indole Compounds.

Activating industrially important aromatic hydrocarbons by installing halogen atoms is extremely important in organic synthesis and often improves the pharmacological properties of drug molecules. To this end, tryptophan halogenase enzymes are potentially valuable tools for regioselective halogenation of arenes, including various industrially important indole derivatives and similar scaffolds. Although endogenous enzymes show reasonable substrate scope towards indole compounds, their efficacy can often be improved by engineering.

Serological Profiling of Group A Streptococcus Infections in Acute Rheumatic Fever.

Rheumatic fever is a serious post-infectious sequela of group A Streptococcus (GAS). Prior GAS exposures were mapped in sera using a large panel of M-type specific peptides. Rheumatic fever patients had serological evidence of significantly more GAS exposures than matched controls suggesting immune priming by repeat infections contributes to pathogenesis.

Post-Visit Patient Understanding About Newly Prescribed Medications.

Background: Good patient understanding of basic medication-related information such as directions for use and side effects promotes medication adherence, but information is lacking about how well patients understand basic medication-related information after their office visits.

Objective: The purpose of this study is to investigate post-visit patient understanding about newly prescribed medications.

Design: Secondary mixed methods analysis comparing patient survey responses about newly prescribed medications to information conveyed by physicians during office visits (from audio recordings of office visits).

Employing standardized risk assessment in pretrial release decisions: Association with criminal justice outcomes and racial equity.

Objective: We examined efforts by a Mississippi court to base pretrial release decisions on risk assessment rather than primarily on bond.

Hypotheses: (a) Pretrial detention will be shorter than that associated with prevailing bond practices in the same counties. (b) Rearrest rates will be lower than a similar pretrial population in a nearby southern state.

Mitochondrial Dysfunction Is an Early Consequence of Partial or Complete Dystrophin Loss in Mice.

Duchenne muscular dystrophy (DMD) is characterized by rapid wasting of skeletal muscle. Mitochondrial dysfunction is a well-known pathological feature of DMD. However, whether mitochondrial dysfunction occurs before muscle fiber damage in DMD pathology is not well known.

The change of gravity vector induces short-term phosphoproteomic alterations in Arabidopsis.

Plants can sense the gravitational force. When plants perceive a change in this natural force, they tend to reorient their organs with respect to the direction of the gravity vector, i.e.

Early postoperative MRI and detection of residual adenoma after transsphenoidal pituitary surgery.

Objective: Current practice guidelines recommend delayed (≥ 3 months after operation) postoperative MRI after transsphenoidal surgery for pituitary adenomas, although this practice defers obtaining important information, such as the presence of a residual adenoma, that might influence patient management during the perioperative period. In this study, the authors compared detection of residual adenomas by means of early postoperative (EPO) MRI (< 48 hours postsurgery) with both surgeon intraoperative assessment and late postoperative (LPO) MRI at 3 months.

Methods: Adult patients who underwent microscopic transsphenoidal surgery for pituitary adenomas with MRI preoperatively, < 48 hours after the operation, 3 months postoperatively, and yearly for 4 years were included.

Systems immunology reveals a linked IgG3-C4 response in patients with acute rheumatic fever.

Acute rheumatic fever (ARF) and chronic rheumatic heart disease (RHD) are autoimmune sequelae of a Group A streptococcal infection with significant global mortality and poorly understood pathogenesis. Immunoglobulin and complement deposition were observed in ARF/RHD valve tissue over 50 years ago, yet contemporary investigations have been lacking. This study applied systems immunology to investigate the relationships between the complement system and immunoglobulin in ARF.

The impact of exercise on mitochondrial dynamics and the role of Drp1 in exercise performance and training adaptations in skeletal muscle.

Objective: Mitochondria are organelles primarily responsible for energy production, and recent evidence indicates that alterations in size, shape, location, and quantity occur in response to fluctuations in energy supply and demand. We tested the impact of acute and chronic exercise on mitochondrial dynamics signaling and determined the impact of the mitochondrial fission regulator Dynamin related protein (Drp)1 on exercise performance and muscle adaptations to training.

Methods: Wildtype and muscle-specific Drp1 heterozygote (mDrp1) mice, as well as dysglycemic (DG) and healthy normoglycemic men (control) performed acute and chronic exercise.

Anaesthetic management of cardiac phaeochromocytoma: A case series.

Introduction: Primary cardiac phaeochromocytoma is uncommon, with few anaesthetists encountering this rare pathology in clinical practice. Further, there is little information available on the detailed intraoperative and postoperative haemodynamics and principles of the anaesthetic management of this condition.

Presentation Of Case: We present a retrospective, single-centre case series of four patients with cardiac phaeochromocytoma who presented for surgical excision.

Forward and reverse mutations in stages of cancer development.

Background: Massive occurrences of interstitial loss of heterozygosity (LOH) likely resulting from gene conversions were found by us in different cancers as a type of single-nucleotide variations (SNVs), comparable in abundance to the commonly investigated gain of heterozygosity (GOH) type of SNVs, raising the question of the relationships between these two opposing types of cancer mutations.

Methods: In the present study, SNVs in 12 tetra sample and 17 trio sample sets from four cancer types along with copy number variations (CNVs) were analyzed by AluScan sequencing, comparing tumor with white blood cells as well as tissues vicinal to the tumor. Four published "nontumor"-tumor metastasis trios and 246 pan-cancer pairs analyzed by whole-genome sequencing (WGS) and 67 trios by whole-exome sequencing (WES) were also examined.

Gabrb2-knockout mice displayed schizophrenia-like and comorbid phenotypes with interneuron-astrocyte-microglia dysregulation.

Intronic polymorphisms of the GABA receptor β subunit gene (GABRB2) under adaptive evolution were associated with schizophrenia and reduced expression, especially of the long isoform which differs in electrophysiological properties from the short isoform. The present study was directed to examining the gene dosage effects of Gabrb2 in knockout mice of both heterozygous (HT) and homozygous (KO) genotypes with respect to possible schizophrenia-like and comorbid phenotypes. The KO mice, and HT mice to a lesser extent, were found to display prepulse inhibition (PPI) deficit, locomotor hyperactivity, stereotypy, sociability impairments, spatial-working and spatial-reference memory deficits, reduced depression and anxiety, and accelerated pentylenetetrazol (PTZ)-induced seizure.

A randomized controlled trial of an automated telephone intervention to improve blood pressure control.

The objective of this study was to evaluate the effectiveness of a telephonic outreach program to improve blood pressure (BP) control among patients with hypertension. The authors identified adults 18 years and older with uncontrolled BP within the previous 12 months. Patients received either an automated telephone call advising them to have a walk-in BP check (n=31,619) or usual care (n=33,154).

Dynamic vascular changes following intravenous antibiotics in patients with cystic fibrosis.

Background: Adults with cystic fibrosis (CF) have altered large artery haemodynamics which is associated with a persisting systemic inflammatory state. We hypothesized that a short-term intervention favorably influencing the inflammatory status may modify their haemodynamic state.

Methods: Adult patients with CF were studied immediately preceding and following 2 weeks of intravenous antibiotics.

Comparing the intended consequences of three theories of evaluation.

This paper compares selected evaluation theories (Practical Participatory Evaluation, Values-Engaged Evaluation, Emergent Realist Evaluation) on the basis of their stated consequences. The discussion follows Mark's (2008) framework for research on evaluation and uses Miller's (2010) criteria of discernible impact and reproducibility in order to delineate the theories. The research on evaluation outcomes shows that some of the claims made by each evaluation theory are supported with evidence, but many substantial claims remain untested.