Genetic Mapping of , a New Lethal Allele of .

The mutation was generated in a Flp/FRT EMS screen for conditional mutations that cause growth and developmental defects in a genetic background that blocks apoptosis. The mutations were conditional, based on the allele being present on the starting chromosome, and blocking canonical apoptosis in a homozygous state. The mosaic eyes exhibit defects in eye development including patches of rough eye and irregular surface structure.

Pain after oocyte retrieval in women with endometriosis undergoing fertility preservation or IVF.

Research Question: Do women with endometriosis undergoing oocyte retrieval for fertility preservation experience the same level of pain as women undergoing oocyte retrieval for IVF?

Design: This retrospective cohort study included 796 cycles in women with endometriosis undergoing oocyte retrieval for fertility preservation (n = 401) or IVF (n = 395) between January 2020 and October 2022. Post-operative pain assessments were compared between the two groups using a numeric rating scale (NRS).

Results: Women in the fertility preservation group were younger (32.

Ontogenetic Patterning of Human Subchondral Bone Microarchitecture in the Proximal Tibia.

High-resolution computed tomography images were acquired for 31 proximal human tibiae, age 8 to 37.5 years, from Norris Farms #36 cemetery site (A.D.

Unsupervised high-frequency smartphone-based cognitive assessments are reliable, valid, and feasible in older adults at risk for Alzheimer's disease.

Objective: Smartphones have the potential for capturing subtle changes in cognition that characterize preclinical Alzheimer's disease (AD) in older adults. The Ambulatory Research in Cognition (ARC) smartphone application is based on principles from ecological momentary assessment (EMA) and administers brief tests of associative memory, processing speed, and working memory up to 4 times per day over 7 consecutive days. ARC was designed to be administered unsupervised using participants' personal devices in their everyday environments.

Equitable Policies Need Equitable Practices: Alcohol- and Substance-Exposed Pregnancy as a Case Study.

There is clear need for more effective public health policies. Coupled with calls for more effective policies, increasing demand to address public health disparities experienced by systemically marginalized and historically oppressed groups emphasizes the long-standing need for policies that improve public health equity. Such need is highlighted when examining public health issues such as alcohol- and substance-exposed pregnancy (ASEP): Current policies are ineffective at reducing ASEP, and marginalized groups experience disproportionately lower benefits and higher negative consequences as a result of such policies.

Bridging the Technological Divide: Stigmas and Challenges With Technology in Digital Brain Health Studies of Older Adults.

The COVID-19 pandemic has increased adoption of remote assessments in clinical research. However, longstanding stereotypes persist regarding older adults' technology familiarity and their willingness to participate in technology-enabled remote studies. We examined the validity of these stereotypes using a novel technology familiarity assessment ( = 342) and with a critical evaluation of participation factors from an intensive smartphone study of cognition in older adults ( = 445).

Stimulation Duration in Patients with Early Oocyte Maturation Triggering Criteria Does Not Impact IVF-ICSI Outcomes.

Results from studies reporting the optimal stimulation duration of IVF-ICSI cycles are inconsistent. The aim of this study was to determine whether, in the presence of early ovulation-triggering criteria, prolonged ovarian stimulation modified the chances of a live birth. This cross-sectional study included 312 women presenting triggering criteria beginning from D8 of ovarian stimulation.

Impact of COVID-19 on hospital acquired infections.

While there are established and effective guidelines for prevention of hospital-acquired infections (HAIs), the impact of the COVID-19 pandemic on those implemented practices and policies have not been thoroughly investigated. This report examines the impact of COVID-19 on HAI rates at 2 hospitals within the same healthcare system. HAIs significantly increased during the COVID-19 pandemic which correlated with the use of overtime and agency nursing hours.

Implementation of a strategy for identification and monitoring of clinical outcome measures in a department of pharmacy.

Purpose: To describe a department of pharmacy strategy to identify and monitor outcome measures that represent the impact of clinical pharmacy services on patient outcomes.

Summary: Our department established the Clinical Impact Committee, with the goal of developing and maintaining an approach to demonstrate the impact of clinical pharmacists on patient care outcomes. We describe the committee's structure, aims, and key stakeholders, inclusive of both departmental leadership and clinical pharmacist representatives across service lines.

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.

Defining Target Engagement Required for Efficacy at the Retinoic Acid Receptor-Related Orphan Receptor C2 (RORγt).

The Th17 pathway has been implicated in autoimmune diseases. The retinoic acid receptor-related orphan receptor C2 (RORγt) is a master regulator of Th17 cells and controls the expression of IL-17A. RORγt is expressed primarily in IL-17A-producing lymphoid cells.

Direct Analysis from Phase-Separated Liquid Samples using ADE-OPI-MS: Applicability to High-Throughput Screening for Inhibitors of Diacylglycerol Acyltransferase 2.

The primary goal of high-throughput screening (HTS) is to rapidly survey a broad collection of compounds, numbering from tens of thousands to millions of members, and identify those that modulate the activity of a therapeutic target of interest. For nearly two decades, mass spectrometry has been used as a label-free, direct-detection method for HTS and is widely acknowledged as being less susceptible to interferences than traditional optical techniques. Despite these advantages, the throughput of conventional MS-based platforms like RapidFire or parallel LC-MS, which typically acquire data at speeds of 6-30 s/sample, can still be limiting for large HTS campaigns.

The Road to Recovery: A Pilot Study of Driving Behaviors Following Antibody-Mediated Encephalitis.

Safe driving requires integration of higher-order cognitive and motor functions, which are commonly compromised in patients with antibody-mediated encephalitis (AME) associated with N-methyl-D-aspartate receptors or leucine-rich glioma-inactivated 1 autoantibodies. How these deficits influence the return to safe driving is largely unknown. Recognizing this, we piloted non-invasive remote monitoring technology to longitudinally assess driving behaviors in recovering AME patients.

Recruitment of African American and Non-Hispanic White Older Adults for Alzheimer Disease Research Via Traditional and Social Media: a Case Study.

The increasing prevalence of Alzheimer disease (AD), higher risk among certain ethnoracial groups, and lack of effective therapies highlights the need to recruit and enroll diverse populations in prospective, observational studies and clinical trials. However, there is little known about the effectiveness of traditional media vs. social media outreach on recruitment in aging study studies.

Interpretation of Cytochrome P-450 Inhibition and Induction Effects From Clinical Data: Current Standards and Recommendations for Implementation.

Agents that modify cytochrome P-450 (CYP) enzyme activity are characterized as strong, moderate, or weak inhibitors or inducers based on the magnitude of their impact on substrate exposure in clinical studies. Criteria for these classifications are simple and semiquantitative. However, assignment of a given agent to a CYP inhibitor or inducer category is often complicated by limitations of the published data, inconsistent study findings, and other factors.

Healthcare system strategy for seasonal influenza implementation plan.

Healthcare systems are expanding, no longer bound by county, state or country, thus necessitating the importance of consistent and standardized guidelines for the management and control of communicable diseases, including influenza. As a healthcare system consisting of diverse facilities with a focus not only on safe patient care but also patient satisfaction, there was a clear need for a multifaceted approach to manage influenza across the system. This resulted in the development of a strategic plan for decision-making, depiction of data and dissemination of information at both a system- and local facility-level.

A Systematic Review Examining Associations between Cardiovascular Conditions and Driving Outcomes among Older Drivers.

There is a vast literature on stroke as a cardiovascular disease and driving outcomes, however little is known about other cardiovascular conditions and driving. The purpose of this review is to examine the literature for studies assessing the effect of non-stroke, vascular conditions on daily driving, reported crash risk and driving decline in older adult drivers as captured by naturalistic methodologies. A systematic review of Embase, Ovid and Scopus Plus examined articles on driving and vascular conditions among older adults.

Depression is Associated with Tau and Not Amyloid Positron Emission Tomography in Cognitively Normal Adults.

Background: Depression is also common with older age. Alzheimer's disease (AD) studies suggest that both cerebrospinal fluid and positron emission tomography (PET) amyloid biomarkers are associated with more depressive symptoms in cognitively normal older adults. The recent availability of tau radiotracers offers the ability to examine in vivo tauopathy.

Evaluation of Genotypic Antiviral Resistance Testing as an Alternative to Phenotypic Testing in a Patient with DOCK8 Deficiency and Severe HSV-1 Disease.

Antiviral resistance frequently complicates the treatment of herpes simplex virus (HSV) infections in immunocompromised patients. Here we present the case of an adolescent boy with dedicator of cytokinesis 8 (DOCK8) deficiency, who experienced recurrent infections with resistant HSV-1. We used both phenotypic and genotypic methodologies to characterize the resistance profile of HSV-1 in the patient and conclude that genotypic testing outperformed phenotypic testing.

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.

Petroleum hydrocarbons in semipermeable membrane devices deployed in the Northern Gulf of Mexico and Florida keys following the Deepwater Horizon incident.

The Deepwater Horizon (DWH) oil spill from April to July of 2010 contaminated Gulf of Mexico waters through release of an estimated 4.1 × 10 barrels of oil. Beginning in June of 2010, semipermeable membrane devices (SPMDs) were deployed near areas with sensitive marine habitats (Alabama Alps and Western Shelf) potentially exposed to that oil.

Data warehouse strategies and the modern anatomic pathology laboratory: Quality management, patient safety, and pathology productivity issues and opportunities.

Application of lean process management strategies to process improvement in clinical and anatomic pathology laboratories afford opportunities to enhance workflow process to lower costs and simultaneously to improve patient safety. Bar-codes are now employed in most modern anatomic pathology laboratories to track specimens from the clinicians' office or the operating room all through the continuum of service to specimen disposal. In order to enhance patient safety and workload optimization strategies, novel computer hardware and software assets are being developed to enable monitoring, analysis, and improvement of specimen workflow and diagnostic accuracy.