Enhancing of cerebral Abeta clearance by modulation of ABC transporter expression: a review of experimental approaches.

Clearance of amyloid-beta (Aβ) from the brain is impaired in both early-onset and late-onset Alzheimer's disease (AD). Mechanisms for clearing cerebral Aβ include proteolytic degradation, antibody-mediated clearance, blood brain barrier and blood cerebrospinal fluid barrier efflux, glymphatic drainage, and perivascular drainage. ATP-binding cassette (ABC) transporters are membrane efflux pumps driven by ATP hydrolysis.

Biomarker evidence of early vision and rod energy-linked pathophysiology benefits from very low dose DMSO in 5xFAD mice.

Here, we test whether early visual and OCT rod energy-linked biomarkers indicating pathophysiology in nicotinamide nucleotide transhydrogenase (Nnt)-null 5xFAD mice also occur in Nnt-intact 5xFAD mice and whether these biomarkers can be pharmacologically treated. Four-month-old wild-type or 5xFAD C57BL/6 substrains with either a null (B6J) Nnt or intact Nnt gene (B6NTac) and 5xFAD B6J mice treated for one month with either R-carvedilol + vehicle or only vehicle (0.01% DMSO) were studied.

Antihypertensive prescription is associated with improved 30-day outcomes for discharged hypertensive emergency department patients.

Background: Hypertension (HTN) is common in discharged emergency department (ED) patients, yet the short-term outcomes of treating HTN at ED discharge are unclear. This study aimed to investigate whether emergency physician (EP) prescription of oral antihypertensive therapy at ED discharge for hypertensive patients is associated with a decreased 30-day risk of the severe adverse events (AEs), death, and revisits to the ED.

Methods: We conducted an observational cohort study assessing the 30-day outcomes of discharged ED patients with HTN, comparing outcomes based on whether antihypertensive therapy was prescribed.

Acetazolamide Challenge Changes Outer Retina Bioenergy-Linked and Anatomical OCT Biomarkers Depending on Mouse Strain.

Purpose: The purpose of this study was to test the hypothesis that optical coherence tomography (OCT) bioenergy-linked and anatomical biomarkers are responsive to an acetazolamide (ACZ) provocation.

Methods: C57BL/6J mice (B6J, a strain with relatively inefficient mitochondria) and 129S6/ev mice (S6, a strain with relatively efficient mitochondria) were given a single IP injection of ACZ (carbonic anhydrase inhibitor) or vehicle. In each mouse, the Mitochondrial Configuration within Photoreceptors based on the profile shape Aspect Ratio (MCP/AR) index was determined from the hyper-reflective band immediately posterior to the external limiting membrane (ELM).

Bile salt hydrolase acyltransferase activity expands bile acid diversity.

Bile acids (BAs) are steroid detergents in bile that contribute to the absorption of fats and fat-soluble vitamins while shaping the gut microbiome because of their antimicrobial properties. Here we identify the enzyme responsible for a mechanism of BA metabolism by the gut microbiota involving amino acid conjugation to the acyl-site of BAs, thus producing a diverse suite of microbially conjugated bile acids (MCBAs). We show that this transformation is mediated by acyltransferase activity of bile salt hydrolase (bile salt hydrolase/transferase, BSH/T).

Metabolomics: An Emerging "Omics" Platform for Systems Biology and Its Implications for Huntington Disease Research.

Huntington's disease (HD) is a progressive, fatal neurodegenerative disease characterized by motor, cognitive, and psychiatric symptoms. The precise mechanisms of HD progression are poorly understood; however, it is known that there is an expansion of the trinucleotide cytosine-adenine-guanine (CAG) repeat in the Huntingtin gene. Important new strategies are of paramount importance to identify early biomarkers with predictive value for intervening in disease progression at a stage when cellular dysfunction has not progressed irreversibly.

The longitudinal biochemical profiling of TBI in a drop weight model of TBI.

Traumatic brain injury (TBI) is a major cause of mortality and disability worldwide, particularly among individuals under the age of 45. It is a complex, and heterogeneous disease with a multifaceted pathophysiology that remains to be elucidated. Metabolomics has the potential to identify metabolic pathways and unique biochemical profiles associated with TBI.

Do multiple physiological OCT biomarkers indicate age-related decline in rod mitochondrial function in C57BL/6J mice?

Purpose: To test the hypothesis that rod photoreceptor mitochondria function progressively declines over time.

Methods: 2, 12, and 24 month-old dark- and light-adapted C57BL/6J (B6J) mice were examined by OCT. We measured (i) an index of mitochondrial configuration within photoreceptors measured from the profile shape aspect ratio (MCP/AR) of the hyperreflective band posterior to the external limiting membrane (ELM), (ii) a proxy for energy-dependent pH-triggered water removal, the thickness of the ELM-retinal pigment epithelium (ELM-RPE), and its correlate (iii) the hyporeflective band (HB) signal intensity at the photoreceptor tips.

Impact of Ambulatory Care Pharmacist-Led Management on Hemoglobin A1c Values among Patients with Uncontrolled Diabetes in a Primary Care Clinic vs Usual Care over Two Years.

Literature has shown the positive impact of ambulatory care pharmacists on diabetes management, yet additional research on clinical outcomes compared to traditional care models is warranted. The objective of this study is to evaluate the impact of an ambulatory care pharmacist on glycemic control over two years compared to patients who received usual care. This retrospective cohort study matched patients with a baseline hemoglobin A1c (HgbA1c) ≥8% managed by the ambulatory care pharmacist to patients who received usual care.

Evaluation of Interprofessional Quality Improvement Interventions Led by an Ambulatory Care Pharmacist on Adherence to a Controlled Substance Agreement Policy.

A controlled substance agreement (CSA) is a risk mitigation strategy for patients managed on controlled substance medications such as opioids and benzodiazepines. Limited literature exists to describe the role of the clinic pharmacy team to promote adherence to CSA monitoring parameters. The objective of this study is to evaluate the impact of interprofessional educational and clinical interventions led by an ambulatory care pharmacist on adherence to monitoring parameters within a CSA policy.

Emergency department use of an electronic differential diagnosis generator in the evaluation of critically ill patients.

Background: Accurate diagnosis is an essential component of managing critically ill emergency department (ED) patients. Electronic diagnosis generators (EDGs) are software tools which assist clinicians in their diagnosis generation; however, they have not been evaluated for use for critical ED patients. We aimed to evaluate the use of an EDG for this population to determine its impact on diagnosis generation and diagnostic testing.

Risk Factors for Coated Midline Catheter-Related Thrombosis: A Secondary Analysis of Existing Trial Data.

Midline catheter-related thrombosis (MCRT) is a high-stakes complication. The authors aimed to explore risk factors for the development of symptomatic MCRT, including patient, procedure, catheter, and vein characteristics. This study performed an analysis of existing trial data that compared MCRT in 2 MCs with differing antithrombotic properties.

Three-year Follow-up of a Single Incision Sling Procedure Performed Under Local Anesthesia in an Office Setting.

Objective: To assess the 3-year success of placing a single-incision midurethral sling (SIMS) using the Dynamic Intraoperative Standing Sling Technique (DISST) in an office setting under local anesthesia.

Methods: This is a prospective case series of 20 women who underwent in-office SIMS procedure by the DISST from July 2019 to February 2020. This is an extension of our pilot study (11) and all 20 patients were evaluated at a mean follow-up of 34.

Urinary Cytokines as Potential Biomarkers of Mild Cognitive Impairment and Alzheimer's Disease: A Pilot Study.

Background: Alzheimer's disease (AD) is the most common form of dementia, accounting for 80% of all cases. Mild cognitive impairment (MCI) is a transitional state between normal aging and AD. Early detection is crucial, as irreversible brain damage occurs before symptoms manifest.

Pre-estrus progesterone does not affect post-estrus luminal metabolome in cross-bred beef cows.

In Brief: The concentration of progesterone through the estrous cycle modulates uterine function to affect the luminal metabolome. This paper reports that the dynamic changes in the bovine uterine luminal metabolome during diestrus are independent of the concentration of progesterone in the previous cycle.

Abstract: In cattle, the concentration of sex steroids modulates uterine function, which is reflected in the composition of the luminal metabolome.

Effect of Instrumented Spine Surgery on Length of Stay.

Introduction: Total joint arthroplasty studies have identified that surgeries that take place later in the week have a longer length of stay compared with those earlier in the week. This has not been demonstrated in studies focused on anterior cervical diskectomy and fusions or minimally invasive lumbar laminectomies. All-inclusive instrumented spine surgeries, however, have not been analyzed.

Association of Metabolomic Biomarkers with Sleeve Gastrectomy Weight Loss Outcomes.

This prospective observational study aimed to evaluate the association of metabolomic alterations with weight loss outcomes following sleeve gastrectomy (SG). We evaluated the metabolomic profile of serum and feces prior to SG and three months post-SG, along with weight loss outcomes in 45 adults with obesity. The percent total weight loss for the highest versus the lowest weight loss tertiles (T3 vs.

Fetal effects of mild maternal COVID-19 infection: metabolomic profiling of cord blood.

Introduction: The impact of maternal coronavirus disease 2019 (COVID-19) infection on fetal health remains to be precisely characterized.

Objectives: Using metabolomic profiling of newborn umbilical cord blood, we aimed to investigate the potential fetal biological consequences of maternal COVID-19 infection.

Methods: Cord blood plasma samples from 23 mild COVID-19 cases (mother infected/newborn negative) and 23 gestational age-matched controls were analyzed using nuclear magnetic spectroscopy and liquid chromatography coupled with mass spectrometry.

Nasopharyngeal rapid diagnostic testing to reduce unnecessary antibiotic use and individualize management of acute otitis media.

Background: Acute otitis media (AOM) is the most common indication for antibiotics in children. The associated organism can influence the likelihood of antibiotic benefit and optimal treatment. Nasopharyngeal polymerase chain reaction can effectively exclude the presence of organisms in middle-ear fluid.

Multiple Bioenergy-Linked OCT Biomarkers Suggest Greater-Than-Normal Rod Mitochondria Activity Early in Experimental Alzheimer's Disease.

Purpose: In Alzheimer's disease, central brain neurons show evidence for early hyperactivity. It is unclear if this occurs in the retina, another disease target. Here, we tested for imaging biomarker manifestation of prodromal hyperactivity in rod mitochondria in vivo in experimental Alzheimer's disease.

A Comparison of Prehospital Pediatric Analgesic Use of Ketamine and Opioids.

Objective/introduction: Ketamine is an opioid-alternative used for analgesia in the prehospital setting. There are knowledge gaps regarding its use during emergency medical services (EMS) encounters for pediatric patients. Our objective was to compare pain reduction, adverse events, and prehospital deaths between ketamine and opioids when used for analgesia administered by any route among pediatric patients.