Reductions in sustained prescription opioid use within the US between 2017 and 2021.

Over the last decade, various efforts have been made to curtail the opioid crisis. The impact of these efforts, since the onset of the COVID-19 pandemic, has not been well characterized. We sought to develop national estimates of the prevalence of sustained prescription opioid use for a time period spanning the COVID-19 pandemic (2017-2021).

Changes in Surgical Volume in Military Medical Treatment Facilities and Military Surgeon Clinical Combat Readiness During the COVID-19 Pandemic.

Mini-abstract In this retrospective study, we evaluated changes in measures of surgeon clinical combat readiness within the military health system during the COVID-19 pandemic. We found a 36% reduction in surgical knowledge and skills as compared to pre-COVID. Sizable reductions were encountered for surgery for colectomy (-50%) and aneurysm repair (-61%).

Spindle-slow oscillation coupling correlates with memory performance and connectivity changes in a hippocampal network after sleep.

After experiences are encoded, post-encoding reactivations during sleep have been proposed to mediate long-term memory consolidation. Spindle-slow oscillation coupling during NREM sleep is a candidate mechanism through which a hippocampal-cortical dialogue may strengthen a newly formed memory engram. Here, we investigated the role of fast spindle- and slow spindle-slow oscillation coupling in the consolidation of spatial memory in humans with a virtual watermaze task involving allocentric and egocentric learning strategies.

Longitudinal Assessment of Acute Concussion Outcomes Through SMS Text (ConText Study).

Objective: Mild traumatic brain injury (mTBI), or concussion, is a common health problem that has seen a recent increase in US adolescents. This study uses SMS text messaging (a mobile health [mHealth] tool) to report patient symptoms. We aim to better characterize mTBI recovery and hypothesize that this mHealth tool will have high retention rates and correlate with a conventional means of assessing symptoms, the Post-Concussion Symptom Inventory (PCSI).

Sleep Leads to Brain-Wide Neural Changes Independent of Allocentric and Egocentric Spatial Training in Humans and Rats.

Sleep is important for memory consolidation and systems consolidation in particular, which is thought to occur during sleep. While there has been a significant amount of research regarding the effect of sleep on behavior and certain mechanisms during sleep, evidence that sleep leads to consolidation across the system has been lacking until now. We investigated the role of sleep in the consolidation of spatial memory in both rats and humans using a watermaze task involving allocentric- and egocentric-based training.

Sacral anatomical interspace landmark for lumbar puncture in pregnancy: A randomized trial.

Objective: To determine whether the sacral anatomical interspace landmark (SAIL) technique is more accurate than the classic intercristal line (ICL) technique in pregnant patients and to assess the percentage of clinical determinations above the third lumbar vertebra.

Methods: In this prospective, randomized, open-label trial, there were 110 singleton pregnant patients with gestational age greater than 37 weeks included. Selection procedure was a convenience sample of pregnant patients who presented for office visits or vaginal or cesarean delivery between March 15 and July 31, 2018, at a single-center obstetric tertiary care university hospital.

Medical Updates and Appointment Confirmations: Pet Owners' Perceptions of Current Practices and Preferences.

Pet ownership is increasing, in large part due to the number of millennial pet owners. More pet owners as well as the advent of extensive veterinary care options have resulted in a substantial increase in veterinary care spending. Yet, regardless of client cohort or type of medical procedure performed, communication between clients and veterinarians continues to be a key component in patient care and client satisfaction.

Normal Range for Maternal Lactic Acid during Pregnancy and Labor: A Systematic Review and Meta-Analysis of Observational Studies.

Objective: This article systematically reviews the literature to establish the normal range of lactic acid in healthy pregnant women.

Study Design: Ovid MEDLINE, Embase.com, and Clinicaltrials.

Integrated Care Models: Optimizing Adult Ambulatory Care in Inflammatory Bowel Disease.

Background: Inflammatory bowel disease (IBD), including Crohn's disease and ulcerative colitis, is a chronic, complex and unpredictable disease affecting an increasing number of patients worldwide from a young age. Inflammatory bowel disease is associated with multiple comorbidities and complications, requiring ongoing preventative, acute and chronic care. The purpose of this article is to review the literature on outpatient care models used to treat adults with IBD and to gain insight on how to improve quality of care and reduce costs.

UK pet owners' use of the internet for online pet health information.

The internet has been found to be a popular source for human health information. However, there is a lack of information on pet owners' use of the internet to source pet health information and implications for the owner-veterinarian relationship. Therefore, the aim of this study was to address this gap in knowledge by focusing on UK pet owners' general use of the internet to find online pet health information and the impact of this behaviour on the owner-veterinarian relationship.

Patterns of Opioid Prescription and Use After Cesarean Delivery.

Objective: To define the amount of opioid analgesics prescribed and consumed after discharge after cesarean delivery.

Methods: We conducted a survey at six academic medical centers in the United States from September 2014 to March 2016. Women who had undergone a cesarean delivery were contacted by phone 2 weeks after discharge and participated in a structured interview about the opioid prescription they received on discharge and their oral opioid intake while at home.

Variants of the Morris water maze task to comparatively assess human and rodent place navigation.

Performance in the Morris water maze has been widely used in routine behavioural studies of rodents. Since the advent of computer-based virtual environments, adaptations of the water maze have become available for human research. Despite decades of comparative neuroscience, formal comparisons of human and animal place navigation performance are rare.

Memory and Spatial Cognition in Breast Cancer Patients Undergoing Adjuvant Endocrine Therapy.

Introduction: It is generally accepted that estrogens play a protective role in cognitive function. Therefore, it can be expected that subtotal estrogen deprivation following aromatase inhibition will alter cognitive performance.

Methods: In a cross-sectional study we investigated 80 postmenopausal women with breast cancer.

Characterizing Aging, Mild Cognitive Impairment, and Dementia with Blood-Based Biomarkers and Neuropsychology.

Background: Current treatment in Alzheimer's disease (AD) is initiated at a stage where the brain already has irreversible structural deteriorations. Therefore, the concept of treatment prior to obvious cognitive deficits has become widely accepted, and simple biochemical tests to discriminate normal aging from prodromal or demented stages are now common practice.

Objective: The objective of the study was the differentiation of controls, mild cognitive impairment (MCI) and AD patients by novel blood-based assays in combination with neuropsychological tests.

Quantitative high-throughput gene expression profiling of human striatal development to screen stem cell-derived medium spiny neurons.

A systematic characterization of the spatio-temporal gene expression during human neurodevelopment is essential to understand brain function in both physiological and pathological conditions. In recent years, stem cell technology has provided an in vitro tool to recapitulate human development, permitting also the generation of human models for many diseases. The correct differentiation of human pluripotent stem cell (hPSC) into specific cell types should be evaluated by comparison with specific cells/tissue profiles from the equivalent adult in vivo organ.

Polyglutamine- and temperature-dependent conformational rigidity in mutant huntingtin revealed by immunoassays and circular dichroism spectroscopy.

Background: In Huntington's disease, expansion of a CAG triplet repeat occurs in exon 1 of the huntingtin gene (HTT), resulting in a protein bearing>35 polyglutamine residues whose N-terminal fragments display a high propensity to misfold and aggregate. Recent data demonstrate that polyglutamine expansion results in conformational changes in the huntingtin protein (HTT), which likely influence its biological and biophysical properties. Developing assays to characterize and measure these conformational changes in isolated proteins and biological samples would advance the testing of novel therapeutic approaches aimed at correcting mutant HTT misfolding.

Discovery of novel non-carboxylic acid 5-amino-4-cyanopyrazole derivatives as potent and highly selective LPA1R antagonists.

High throughput screening (HTS) of our chemical library identified 3-alkylamino-2-aryl-5H-imidazo[1,2,b]pyrazol-7-carbonitrile 1 as a potent antagonist of the LPA1 receptor (LPA1R). Further evaluation of this class of compounds indicated that LPA1R antagonist activity originated from the degradation of the parent molecule in DMSO during the assay conditions. Here, we describe the isolation and characterization of the degradation products and their LPA1R antagonist activity.

Ageing and spatial reversal learning in humans: findings from a virtual water maze.

Deterioration in spatial memory with normal ageing is well accepted. Animal research has shown spatial reversal learning to be most vulnerable to pathological changes in the brain, but this has never been tested in humans. We studied ninety participants (52% females, 20-80 yrs) in a virtual water maze with a reversal learning procedure.

Discovery of N-[4-[6-tert-butyl-5-methoxy-8-(6-methoxy-2-oxo-1H-pyridin-3-yl)-3-quinolyl]phenyl]methanesulfonamide (RG7109), a potent inhibitor of the hepatitis C virus NS5B polymerase.

In the past few years, there have been many advances in the efforts to cure patients with hepatitis C virus (HCV). The ultimate goal of these efforts is to develop a combination therapy consisting of only direct-antiviral agents (DAAs). In this paper, we discuss our efforts that led to the identification of a bicyclic template with potent activity against the NS5B polymerase, a critical enzyme on the life cycle of HCV.

Discovery of a novel series of potent non-nucleoside inhibitors of hepatitis C virus NS5B.

Hepatitis C virus (HCV) is a major global public health problem. While the current standard of care, a direct-acting antiviral (DAA) protease inhibitor taken in combination with pegylated interferon and ribavirin, represents a major advancement in recent years, an unmet medical need still exists for treatment modalities that improve upon both efficacy and tolerability. Toward those ends, much effort has continued to focus on the discovery of new DAAs, with the ultimate goal to provide interferon-free combinations.

De novo fragment design: a medicinal chemistry approach to fragment-based lead generation.

The use of fragments with low binding affinity for their targets as starting points has received much attention recently. Screening of fragment libraries has been the most common method to find attractive starting points. Herein, we describe a unique, alternative approach to generating fragment leads.

Pyrrolopyrazines as selective spleen tyrosine kinase inhibitors.

We describe the discovery of several pyrrolopyrazines as potent and selective Syk inhibitors and the efforts that eventually led to the desired improvements in physicochemical properties and human whole blood potencies. Ultimately, our mouse model revealed unexpected toxicity that precluded us from further advancing this series.

Frataxin deficiency leads to defects in expression of antioxidants and Nrf2 expression in dorsal root ganglia of the Friedreich's ataxia YG8R mouse model.

Aims: Oxidative stress is thought to be involved in Friedreich's ataxia (FRDA), yet it has not been demonstrated in the target neurons that are first to degenerate. Using the YG8R mouse model of FRDA, microarray and neuritic growth experiments were carried out in the dorsal root ganglion (DRG), the primary site of neurodegeneration in this disease.

Results: YG8R hemizygous mice exhibited defects in movement, and DRG neurites had growth defects.

Mitochondrial dysfunction in Pten haplo-insufficient mice with social deficits and repetitive behavior: interplay between Pten and p53.

Etiology of aberrant social behavior consistently points to a strong polygenetic component involved in fundamental developmental pathways, with the potential of being enhanced by defects in bioenergetics. To this end, the occurrence of social deficits and mitochondrial outcomes were evaluated in conditional Pten (Phosphatase and tensin homolog) haplo-insufficient mice, in which only one allele was selectively knocked-out in neural tissues. Pten mutations have been linked to Alzheimer's disease and syndromic autism spectrum disorders, among others.