Original Research: Improving Pain Assessment After Inpatient Orthopedic Surgery: A Comparison of Two Scales.

Purpose: In pain assessment, the commonly used Numeric Rating Scale (NRS) offers an incremental 0-to-10 range of response options. But this broad range often leads to discordant evaluations between nurses and their patients. This study aimed to compare the NRS to the three-category Interventional Pain Assessment (IPA) scale, validate the IPA scale in an inpatient setting, and determine RN and patient scale preferences.

Assessing pain management in total joint arthroplasty using the Detroit interventional pain assessment scale-A prospective cohort study.

Background: Total joint arthroplasty (TJA) is an effective treatment for end-stage osteoarthritis, but postoperative pain has been poorly managed. The purpose of this study was to (1) assess how much narcotic medication was prescribed after TJA; (2) assess if patients were satisfied with their pain management; (3) compare these same data between total hip arthroplasty (THA)/total knee arthroplasty (TKA); (4) compare these same data between preoperative opioid users/opioid-naïve patients.

Methods: An IRB-approved prospective study was conducted at a US academic joint replacement practice.

Evaluating Postoperative Pain Management Using the Detroit Interventional Pain Management Tool After Fracture Surgery: How Well Are We Really Doing?

Objectives: To assess patients' opioid prescription usage and pain management satisfaction after fracture surgery.

Design: An IRB-approved prospective prognostic cohort study for postoperative patients with fracture was conducted. Patients were evaluated by an independent observer at 2 weeks, 6 weeks, 3 months, and 6 months postoperatively where they were given Detroit Interventional Pain Assessment questionnaires regarding their postoperative pain and opioid usage.

Analyzing the Accuracy of Digital Sizing on Long-Leg Alignment X-rays by Using a 1-Inch Ball Bearing: A Cheap and Effective Method.

Background and objective Sizing on digital films is important for implants and planning deformity correction. CT is the most accurate digital measurement method. We use a 1-inch ball bearing (cost: $1) to size our long-leg standing films (LLSFs) when planning deformity correction.

Detroit Interventional Pain Assessment Scale: A Pain Score and Method for Measuring and Evaluating Post-Operative Pain Management-A Prospective Study.

: Orthopedic surgeons commonly prescribe opioids, surpassing all medical specialties. Our objective was to develop a pain management scale that captures medication use, patient-reported pain scores, and helps orthopedic surgeons evaluate their post-operative prescribing practice. : An IRB-approved prospective study followed 502 post-operative orthopedic surgery patients over a six-month period.

Neurofibromin 1 mutations impair the function of human induced pluripotent stem cell-derived microglia.

Neurofibromatosis type 1 (NF1) is an autosomal dominant condition caused by germline mutations in the neurofibromin 1 (NF1) gene. Children with NF1 are prone to the development of multiple nervous system abnormalities, including autism and brain tumors, which could reflect the effect of NF1 mutation on microglia function. Using heterozygous Nf1-mutant mice, we previously demonstrated that impaired purinergic signaling underlies deficits in microglia process extension and phagocytosis in situ.

Presence of Post-traumatic Limps in an Adult Population Diagnosed on a "Catwalk Video": A Comparative Study Between Healthcare and Nonhealthcare Individuals.

Background Walking is an everyday activity but also complex in nature. Gait disorders have the potential to drastically affect an individual's quality of life and their ability to be independent. The causes of gait disorders are numerous.

Using FastID to analyze complex SNP mixtures from indoor dust.

Forensically relevant single nucleotide polymorphisms (SNPs) can provide valuable supplemental information to short tandem repeats (STRs) for investigative leads, and genotyping can now be streamlined using massively parallel sequencing (MPS). Dust is an attractive evidence source, as it accumulates on undisturbed surfaces, often is overlooked by perpetrators, and contains sufficient human DNA for analysis. To assess whether SNPs genotyped from indoor dust using MPS could be used to detect known household occupants, 13 households were recruited and provided buccal samples from each occupant and dust from five predefined indoor locations.

Origin of Elevated S-Glutathionylated GAPDH in Chronic Neurodegenerative Diseases.

HO-oxidized glyceraldehyde-3-phosphate dehydrogenase (GAPDH) catalytic cysteine residues (C(SH) undergo rapid S-glutathionylation. Restoration of the enzyme activity is accomplished by thiol/disulfide S2 displacement (directly or enzymatically) forming glutathione disulfide (G(SS)G) and active enzyme, a process that should be facile as C(SH) reside on the subunit surface. As S-glutathionylated GAPDH accumulates following ischemic and/or oxidative stress, in vitro/silico approaches have been employed to address this paradox.

Upward propagation of gigantic jets revealed by 3D radio and optical mapping.

Occasionally, lightning will exit the top of a thunderstorm and connect to the lower edge of space, forming a gigantic jet. Here, we report on observations of a negative gigantic jet that transferred an extraordinary amount of charge between the troposphere and ionosphere (∼300 C). It occurred in unusual circumstances, emerging from an area of weak convection.

Robust Pharmacodynamic Effect of LY3202626, a Central Nervous System Penetrant, Low Dose BACE1 Inhibitor, in Humans and Nonclinical Species.

Background: The development of beta-site amyloid-beta precursor protein cleaving enzyme (BACE) 1 inhibitors for the treatment of Alzheimer's disease requires optimization of inhibitor potency, selectivity, and brain penetration. Moreover, there is a need for low-dose compounds since liver toxicity was found with some BACE inhibitors.

Objective: To determine whether the high potency and robust pharmacodynamic effect of the BACE inhibitor LY3202626 observed in nonclinical species translated to humans.

Discovery and Early Clinical Development of LY3202626, a Low-Dose, CNS-Penetrant BACE Inhibitor.

The beta-site APP cleaving enzyme 1, known as BACE1, has been a widely pursued Alzheimer's disease drug target owing to its critical role in the production of amyloid-beta. We have previously reported the clinical development of LY2811376 and LY2886721. LY2811376 advanced to Phase I before development was terminated due to nonclinical retinal toxicity.

An alternate workflow for preparing Precision ID Ancestry and Identity Panel libraries for Illumina sequencing.

Single nucleotide polymorphisms (SNPs) are well-established for forensic applications. Although they are not compatible with existing criminal databases, they offer some advantages over short tandem repeat (STR) markers including smaller amplicons, no stutter artifacts, and biogeographic ancestry and phenotype predictions. The Precision ID NGS System, a commercial workflow by Thermo Fisher Scientific, offers a streamlined solution for genotyping forensically relevant SNPs using next-generation sequencing.

Preparation and biological evaluation of BACE1 inhibitors: Leveraging trans-cyclopropyl moieties as ligand efficient conformational constraints.

Inhibition of BACE1 has become an important strategy in the quest for disease modifying agents to slow the progression of Alzheimer's disease. We previously reported the fragment-based discovery of LY2811376, the first BACE1 inhibitor reported to demonstrate robust reduction of human CSF Aβ in a Phase I clinical trial. We also reported on the discovery of LY2886721, a potent BACE1 inhibitor that reached phase 2 clinical trials.

Single Fragment or Bulk Soil DNA Metabarcoding: Which is Better for Characterizing Biological Taxa Found in Surface Soils for Sample Separation?

In forensic geology casework, sample size typically limits routine characterization of material using bulk approaches. To address this, DNA-based characterization of biological taxa has received attention, as the taxa present can be useful for sample-to-sample comparisons and source attribution. In our initial work, low biodiversity was captured when DNA barcodes were Sanger-sequenced from plant and insect fragments isolated from 10 forensic-type surface soils.

Thunderstorm charge structures producing gigantic jets.

Gigantic jets are atmospheric electrical discharges that propagate from the top of thunderclouds to the lower ionosphere. They begin as lightning leaders inside the thundercloud, and the thundercloud charge structure primarily determines if the leader is able to escape upward and form a gigantic jet. No observationally verified studies have been reported on the thundercloud charge structures of the parent storms of gigantic jets.

Developing a globally applicable evidence-informed competency framework to support capacity strengthening in clinical research.

Capacity development for clinical research is held back by a lack of recognition for the skills acquired through involvement in clinical trials and in other varied types of global health research studies. Although some competency frameworks and associated recognised career pathways exist for different clinical research roles, they mostly apply to a single role or study setting. Our experience supports the need for an integrated approach, looking at the many roles in parallel and at all types of clinical research beyond trials.

How Well Do Inexpensive, Portable Pulse Oximeter Values Agree with Arterial Oxygenation Saturation in Acutely Ill Patients?

The purpose of this study was to examine the level of agreement between a portable SpO2 device and the clinical gold standard SaO2 in intermediate care patients.

Incorporating ethical principles into clinical research protocols: a tool for protocol writers and ethics committees.

A novel Protocol Ethics Tool Kit ('Ethics Tool Kit') has been developed by a multi-stakeholder group of the Multi-Regional Clinical Trials Center of Brigham and Women's Hospital and Harvard. The purpose of the Ethics Tool Kit is to facilitate effective recognition, consideration and deliberation of critical ethical issues in clinical trial protocols. The Ethics Tool Kit may be used by investigators and sponsors to develop a dedicated Ethics Section within a protocol to improve the consistency and transparency between clinical trial protocols and research ethics committee reviews.

Preparation and biological evaluation of conformationally constrained BACE1 inhibitors.

The BACE1 enzyme is a key target for Alzheimer's disease. During our BACE1 research efforts, fragment screening revealed that bicyclic thiazine 3 had low millimolar activity against BACE1. Analysis of the co-crystal structure of 3 suggested that potency could be increased through extension toward the S3 pocket and through conformational constraint of the thiazine core.

The potent BACE1 inhibitor LY2886721 elicits robust central Aβ pharmacodynamic responses in mice, dogs, and humans.

BACE1 is a key protease controlling the formation of amyloid β, a peptide hypothesized to play a significant role in the pathogenesis of Alzheimer's disease (AD). Therefore, the development of potent and selective inhibitors of BACE1 has been a focus of many drug discovery efforts in academia and industry. Herein, we report the nonclinical and early clinical development of LY2886721, a BACE1 active site inhibitor that reached phase 2 clinical trials in AD.

Robust central reduction of amyloid-β in humans with an orally available, non-peptidic β-secretase inhibitor.

According to the amyloid cascade hypothesis, cerebral deposition of amyloid-β peptide (Aβ) is critical for Alzheimer's disease (AD) pathogenesis. Aβ generation is initiated when β-secretase (BACE1) cleaves the amyloid precursor protein. For more than a decade, BACE1 has been a prime target for designing drugs to prevent or treat AD.

Neurotherapeutic and neuroprosthetic effects of implanted functional electrical stimulation for ambulation after incomplete spinal cord injury.

The purpose of this single-subject study was to determine the neurotherapeutic and neuroprosthetic effects of an implanted functional electrical stimulation (FES) system designed to facilitate walking in an individual with a longstanding motor and sensory incomplete spinal cord injury. An implanted pulse generator and eight intramuscular stimulating electrodes were installed unilaterally, activating weak or paralyzed hip flexors, hip and knee extensors, and ankle dorsiflexors during 36 sessions of gait training with FES. The neurotherapeutic effects were assessed by a comparison of pre- and posttraining volitional walking.