The Minnesota Critical Care Working Group 1: Monitoring and coordinating statewide critical care surge response in the COVID-19 pandemic, March 2020 through July 1, 2021.

Background: In response to the COVID-19 pandemic and as part of the statewide healthcare coalition response the Minnesota Critical Care Working Group (CCWG), composed of Interprofessional leaders from the state's nine largest health systems was established and entrusted to plan and coordinate critical care support for Minnesota from March 2020 through July1, 2021.

Research Question: Can a statewide Critical Care Working Group develop contingency and crisis level surge strategies and indicators in response to the COVID-19 pandemic while evolving into a highly collaborative team?

Study Design And Methods: CCWG members (Intensivists, ethicists, nurses, MDH and MHA leaders) met by audio video conferencing as often as daily assessing COVID and non-COVID hospitalization data, developed surge indicators reflecting contingency versus crisis conditions, and planned responses collaboratively. A foundation of collaboration and teamwork developed which facilitated an effective statewide response.

The Minnesota Critical Care Working Group 2: Crisis Conditions During the COVID-19 Pandemic, July 2021 through March 2022.

Background: The Minnesota Statewide Healthcare Coordination Center requested that the Minnesota Critical Care Working Group (CCWG) and Ethics Working Group (EWG), comprising interprofessional leaders from Minnesota's 9 largest health systems, plan and coordinate critical care operations during the COVID-19 pandemic, including the fall 2021 surge.

Research Question: Can a statewide working group collaboratively analyze real-time evidence to identify crisis conditions and to engage state leadership to implement care processes?

Study Design And Methods: The CCWG and EWG met via videoconferencing during the severe surge of fall 2021 to analyze evidence and plan for potential crisis care conditions. Five sources of evidence informed their actions: group consensus on operating conditions, federal teletracking data, the Medical Operations Coordination Center (MOCC) patient placement data, and 2 surveys created and distributed to hospitals and health care professionals.

Ocular involvement of oak processionary caterpillar hairs: Clinical outcome up to one year.

Purpose: To evaluate a consecutive series of patients that presented with ocular findings after contact with the oak processionary caterpillar (OPC) during an epidemic reproduction of the OPC in Germany in 2019 and to assess the 1-year outcome of those eyes with persisting OPC hairs in the cornea.

Methods: Retrospective analysis of 11 eyes (11 patients) that presented in June/July 2019 with acute ocular symptoms after outdoor activity or caterpillar nest removal. Evaluation of patients charts and slit-lamp images up to one year.

Can you be a peer if you don't share the same health or social conditions? A qualitative study on peer integration in a primary care setting.

Background: Peer support has been extensively studied in specific areas of community-based primary care such as mental health, substance use, HIV, homelessness, and Indigenous health. These programs are often built on the assumption that peers must share similar social identities or lived experiences of disease to be effective. However, it remains unclear how peers can be integrated in general primary care setting that serves people with a diversity of health conditions and social backgrounds.

Microvascular Density Analysis of Patients with Inactive Systemic Lupus Erythematosus-A Two-Year Follow-Up Optical Coherence Tomography Angiography Study.

This study aims to investigate the long-term effect of inactive systemic lupus erythematosus (SLE) on the retinal microcirculation measured via optical coherence tomography angiography (OCT-A). Twenty-four eyes of 24 patients with inactive SLE under hydroxychloroquine (HCQ) therapy were included. The OCT-A data (mainly vessel density (VD) and foveal avascular zone (FAZ) data of the superficial and of the deep capillary plexus (SCP, DCP) and the choriocapillaris (CC)) were analyzed and compared between the baseline examination (t) and 2 years later (t).

Reduced Retinal Blood Vessel Densities Measured by Optical Coherence Tomography Angiography in Keratoconus Patients Are Negatively Correlated with Keratoconus Severity.

Keratoconus (KC) is the most common corneal ectasia. Optical coherence tomography angiography (OCT-A) is a relatively new non-invasive imaging technique that allows the visualization and quantification of retinal and choriocapillary blood vessels. The aim of this study is to assess retinal and choriocapillary vessel density (VD) differences between KC patients and healthy controls and to investigate correlations between VD and KC severity.

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To investigate macular and peripapillary vascular density (VD) in patients with anorexia nervosa (AN) compared to healthy controls. :Whole face scans of the superficial and deep macular layers and whole face and peripapillary scans of the radial peripapillary capillaries (RPC) were obtained using optical coherence tomography angiography (OCTA, AngioVueR, Optovue) in ten patients with AN and ten age-matched controls.The primary objective was to determine whether there was a difference between the vessel density (VD) in the above areas in AN and controls.

[Frequency and distribution of the active agent of intravitreal injections in German centers 2015-2021-An oregis study].

Introduction: Digitalization in medicine, especially the electronic documentation of patient data, is revolutionizing healthcare systems worldwide. The evaluation of real-world data collected under everyday conditions presents opportunities but also challenges. Electronic medical registries provide a means to compile extensive patient data for scientific inquiries.

Discovery of the Potent and Selective ATR Inhibitor Camonsertib (RP-3500).

ATR is a key kinase in the DNA-damage response (DDR) that is synthetic lethal with several other DDR proteins, making it an attractive target for the treatment of genetically selected solid tumors. Herein we describe the discovery of a novel ATR inhibitor guided by a pharmacophore model to position a key hydrogen bond. Optimization was driven by potency and selectivity over the related kinase mTOR, resulting in the identification of camonsertib (RP-3500) with high potency and excellent ADME properties.

Developing LHS scholars' competency around reducing burnout and moral injury.

Unlabelled: Despite the known benefits of supportive work environments for promoting patient quality and safety and healthcare worker retention, there is no clear mandate for improving work environments within Learning Health Systems (LHS) nor an LHS wellness competency. Striking rises in burnout levels among healthcare workers provide urgency for this topic.

Methods: We brought three experts on moral injury, burnout prevention, and ethics to a recurring, interactive LHS training program "Design Shop" session, harnessing scholars' ideas prior to the meeting.

Accuracy of Bruch's membrane opening minimum rim width and retinal nerve fiber layer thickness in glaucoma diagnosis depending on optic disc size.

Background/aim: The aim of this paper is to compare retinal nerve fiber layer thickness (RNFL) and Bruch's membrane opening-based minimum rim width (BMO-MRW) in terms of their performance in detecting early and moderate/advanced glaucoma using receiver operating characteristics (ROC) analysis and the classification using the 5th percentile as a cut-off.

Methods: One hundred eyes from 100 patients with early glaucoma (mean deviation (MD): < -5.0 dB) and 100 eyes from 100 patients with moderate/advanced glaucoma (MD: > -5.

Nanograms of SARS-CoV-2 spike protein delivered by exosomes induce potent neutralization of both delta and omicron variants.

Exosomes are emerging as potent and safe delivery carriers for use in vaccinology and therapeutics. A better vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is needed to provide improved, broader, longer lasting neutralization of SARS-CoV-2, a more robust T cell response, enable widespread global usage, and further enhance the safety profile of vaccines given the likelihood of repeated booster vaccinations. Here, we use Capricor's StealthXTM platform to engineer exosomes to express native SARS-CoV-2 spike Delta variant (STX-S) protein on the surface for the delivery of a protein-based vaccine for immunization against SARS-CoV-2 infection.

FURTHER EVIDENCE AGAINST BILATERAL MANIFESTATION OF COATS DISEASE IN OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF THE MACULA.

Purpose: Recent studies have questioned the traditional view, which regards Coats disease as a strictly unilateral entity. Applying optical coherence tomography angiography, this prospective, monocentric study investigates quantitative capillary changes of the macula associated with Coats disease.

Methods: Twenty-four eyes (4 untreated, 8 pre-treated) of 12 patients with stage 2 Coats disease (age range: 9-61 years) and 15 eyes of healthy, age-matched controls from the University of Muenster Medical Center, Germany received macular optical coherence tomography angiography measurements of the superficial, deep, and choriocapillary capillary plexus.

Exosome-Based Multivalent Vaccine: Achieving Potent Immunization, Broadened Reactivity, and Strong T-Cell Responses with Nanograms of Proteins.

Currently approved vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have focused solely on the spike protein to provide immunity. The first vaccines were developed rapidly using spike mRNA delivered by lipid nanoparticles but required ultralow-temperature storage and have had limited immunity against variations in spike. Subsequently, protein-based vaccines were developed, which offer broader immunity but require significant time for development and the use of an adjuvant to boost the immune response.

Sub-Retinal Injection of Human Lipofuscin in the Mouse - A Model of "Dry" Age-Related Macular Degeneration?

Lipofuscin (LF) accumulates during lifetime in the retinal pigment epithelium (RPE) and is thought to play a crucial role in intermediate and late age-related macular degeneration (AMD). In an attemt to simulate aged retina and to study response of retinal microglia and RPE cells to LF, we injected a suspension of LF into the subretinal space of adult mice. LF suspension was obtained from human donor eyes.

Long-Term Outcomes of Canaliculotomy with Silicone Tube Intubation in the Management of Canaliculitis.

As a rare and often misdiagnosed disease of the lacrimal apparatus, only limited data exist on long-term outcomes of surgical methods for the treatment of primary canaliculitis. The aim of this study was to evaluate canaliculotomy with silicone tube intubation (STI) as a surgical procedure for canaliculitis in a long-term follow-up setting. A total of 25 eyes of 25 patients with canaliculitis treated with canaliculotomy and STI at the University of Muenster Medical Center, Germany, from 2015 to 2021 were included in this study.

Identification of , an Orally Bioavailable Compound that Inhibits the DNA Polymerase Activity of Polθ.

DNA polymerase theta (Polθ) is an attractive synthetic lethal target for drug discovery, predicted to be efficacious against breast and ovarian cancers harboring BRCA-mutant alleles. Here, we describe our hit-to-lead efforts in search of a selective inhibitor of human Polθ (encoded by POLQ). A high-throughput screening campaign of 350,000 compounds identified an 11 micromolar hit, giving rise to the N2-substituted fused pyrazolo series, which was validated by biophysical methods.

Primary Optic Disc Tumors - Case Series and Literature Overview.

Purpose: Primary optic disc tumors are often a challenge for ophthalmologists. They have very different appearances, and many primary optic disc tumors are associated with syndromic diseases (especially phakomatoses). Because of the rarity of primary optic disc tumors, classification and assessment are often difficult.

Discovery of an Orally Bioavailable and Selective PKMYT1 Inhibitor, RP-6306.

PKMYT1 is a regulator of CDK1 phosphorylation and is a compelling therapeutic target for the treatment of certain types of DNA damage response cancers due to its established synthetic lethal relationship with amplification. To date, no selective inhibitors have been reported for this kinase that would allow for investigation of the pharmacological role of PKMYT1. To address this need compound was identified as a weak PKMYT1 inhibitor.

SALUS-a non-inferiority trial to compare self-tonometry in glaucoma patients with regular inpatient intraocular pressure controls: study design and set-up.

Purpose: The SALUS study aims to improve the healthcare situation for glaucoma patients in Germany. In order to detect diurnal intraocular pressure (IOP) fluctuations, inpatient monitoring of IOP in an eye hospital for a minimum of 24 h is the current standard. SALUS assesses the benefits of a new form of outpatient care, where IOP can be measured by the patients themselves at home using a self-tonometer.

CCNE1 amplification is synthetic lethal with PKMYT1 kinase inhibition.

Amplification of the CCNE1 locus on chromosome 19q12 is prevalent in multiple tumour types, particularly in high-grade serous ovarian cancer, uterine tumours and gastro-oesophageal cancers, where high cyclin E levels are associated with genome instability, whole-genome doubling and resistance to cytotoxic and targeted therapies. To uncover therapeutic targets for tumours with CCNE1 amplification, we undertook genome-scale CRISPR-Cas9-based synthetic lethality screens in cellular models of CCNE1 amplification. Here we report that increasing CCNE1 dosage engenders a vulnerability to the inhibition of the PKMYT1 kinase, a negative regulator of CDK1.

[Corneal epithelial thickness in keratoconus patients compared to healthy controls].

Background: In keratoconus (KC) a progressive deformation and thinning of the cornea occurs. In contrast to Scheimpflug-based examinations, optical coherence tomography (OCT) can precisely measure the corneal layers separately, allowing separate analyses of corneal epithelial and corneal stromal thicknesses.

Aim Of This Work: The aim of this work was to analyze the corneal epithelial thickness measured by optical coherence tomography (OCT) in patients with KC in comparison to the corneal epithelial thickness in healthy subjects.

Compromised Integrity, Burnout, and Intent to Leave the Job in Critical Care Nurses and Physicians.

Unlabelled: To describe relationships between compromised integrity (CI), burnout, and intent-to-leave (ITL) practice in critical care (CC) and noncritical care (non-CC) nurses and physicians.

Design: CC nurses (RNs) and physicians (MDs) from the American Medical Association Coping with COVID survey were matched by gender, race, years in practice, and role with non-CC clinicians to determine likelihood of ITL in relation to burnout and CI.

Setting: U.

RP-3500: A Novel, Potent, and Selective ATR Inhibitor that is Effective in Preclinical Models as a Monotherapy and in Combination with PARP Inhibitors.

Ataxia telangiectasia and Rad3-related (ATR) kinase protects genome integrity during DNA replication. RP-3500 is a novel, orally bioavailable clinical-stage ATR kinase inhibitor (NCT04497116). RP-3500 is highly potent with IC values of 1.