Differentiation of Human iPS Cells Into Sensory Neurons Exhibits Developmental Stage-Specific Cryopreservation Challenges.

Differentiation of human induced pluripotent stem cells (hiPSCs) generates cell phenotypes valuable for cell therapy and personalized medicine. Successful translation of these hiPSC-derived therapeutic products will rely upon effective cryopreservation at multiple stages of the manufacturing cycle. From the perspective of cryobiology, we attempted to understand how the challenge of cryopreservation evolves between cell phenotypes along an hiPSC-to-sensory neuron differentiation trajectory.

Chemically induced senescence in human stem cell-derived neurons promotes phenotypic presentation of neurodegeneration.

Modeling age-related neurodegenerative disorders with human stem cells are difficult due to the embryonic nature of stem cell-derived neurons. We developed a chemical cocktail to induce senescence of iPSC-derived neurons to address this challenge. We first screened small molecules that induce embryonic fibroblasts to exhibit features characteristic of aged fibroblasts.

Sustained inflammation, coagulation activation and elevated endothelin-1 levels without macrovascular dysfunction at 3 months after COVID-19.

Introduction: Endothelial damage and thrombosis caused by COVID-19 may imperil cardiovascular health. More than a year since the WHO declared COVID-19 pandemic, information on its effects beyond the acute phase is lacking. We investigate endothelial dysfunction, coagulation and inflammation, 3 months post-COVID-19.

A quiet extirpation of the breeding little auk Alle alle population in Iceland in the shadow of the famous cousin extermination.

The little auk Alle alle is an Arctic seabird breeding in the North Atlantic. Its southernmost breeding population in the Low Arctic occurred in Iceland but started to decline in numbers at the beginning of the 20th century ending in extirpation at the end of the same century. Climate warming has been blamed for the disappearance of this population.

Circular functional analysis of OCT data for precise identification of structural phenotypes in the eye.

Progressive optic neuropathies such as glaucoma are major causes of blindness globally. Multiple sources of subjectivity and analytical challenges are often encountered by clinicians in the process of early diagnosis and clinical management of these diseases. In glaucoma, the structural damage is often characterized by neuroretinal rim (NRR) thinning of the optic nerve head, and other clinical parameters.

Localized alopecia and suppression of hypothalamic-pituitary-adrenal (HPA) axis in dogs following treatment with difluprednate 0.05% ophthalmic emulsion (Durezol®).

Background: Despite the common use of topical ophthalmic corticosteroids in dogs, detailed reports on systemic and dermatologic adverse effects are limited.

Results: Nine purpose-bred research Beagles were treated with difluprednate 0.05% ophthalmic emulsion in one or both eyes 2-3 times daily.

P038 Ozanimod First-Dose Cardiac Effects in Patients with Moderately to Severely Active Ulcerative Colitis and Relapsing Multiple Sclerosis.

Background: Ozanimod, an oral sphingosine 1-phosphate (S1P) receptor modulator that selectively targets S1P1 and S1P5, is approved in the US for treating moderately to severely active ulcerative colitis (UC) and in multiple countries for treating relapsing forms of multiple sclerosis (MS). In a Phase 1 study of ozanimod in healthy participants, first-dose cardiac effects were mitigated with gradual dose escalation. Based on these results, an initial 7-day ozanimod dose escalation regimen was implemented in all Phase 2 and 3 UC and MS trials.

P037 Effect of Ozanimod Treatment and Discontinuation on Absolute Lymphocyte Count in Moderate-to-Severe Ulcerative Colitis: Results from a Phase 3 Trial.

Background: Ozanimod is an oral sphingosine 1-phosphate (S1P) receptor modulator selectively targeting S1P1 and S1P5, which reduces migration of lymphocytes involved in adaptive immunity from lymphoid tissues to blood and inflamed tissues while preserving components of the innate immune response. Ozanimod is approved in multiple countries for the treatment of relapsing forms of multiple sclerosis and in the US for the treatment of moderately-to-severely active ulcerative colitis (UC). The reduction of circulating lymphocytes is expected based on the mechanism of action of ozanimod and thought to be an important driver of efficacy.

P031 Impact of Prior Biologic Exposure on Response to Ozanimod for Moderate-to-Severe Ulcerative Colitis in the Phase 3 True North Study.

Background: Ozanimod, an oral sphingosine 1-phosphate (S1P) receptor modulator selectively targeting S1P1 and S1P5, demonstrated superior efficacy and safety vs placebo for up to 52 weeks in adults with moderately to severely active ulcerative colitis (UC) in a phase 3 study (True North). In this post-hoc analysis, we evaluated the impact of prior biologic exposure on response to ozanimod.

Methods: True North consisted of two cohorts.

Impact of comorbidity on renal cell carcinoma prognosis: a nationwide cohort study.

Background: Presence of comorbid diseases at time of cancer diagnosis may affect prognosis. We evaluated the impact of comorbidity on survival of patients diagnosed with renal cell carcinoma (RCC), overall and among younger (<70 years) and older (≥70 years) patients.

Methods: We established a nationwide register-based cohort of 7894 patients aged ≥18 years diagnosed with RCC in Denmark between 2006 and 2017.

Intranasal ketamine for acute cluster headache attacks-Results from a proof-of-concept open-label trial.

Objective: To investigate the safety and efficacy of intranasal ketamine for the treatment of a single cluster headache (CH) attack.

Background: Acute treatment options for patients with CH who have an insufficient response to oxygen and triptans are limited. Intranasal ketamine has anecdotally been successful in treating a CH attack.

Sustainable glycerol terpolycarbonates as temporary bioadhesives.

We describe the synthesis of poly(glycidyl acetate--glycidyl butyrate carbonate)s the terpolymerization of glycidyl acetate (GA), glycidyl butyrate (GB), and CO by a cobalt salen complex in high atom economy. These new non-cytotoxic polycarbonates are pressure-sensitive adhesives, and peel testing shows the adhesive strength ranges from Scotch-Tape® to hot-melt glues based on glycidyl butyrate content. The tunable adherence, benign degradation products, and facile application and removal suggest their utility as temporary adhesives, such as those used in biomedical applications or medical devices.

Implementation and Outcomes of a Maternal Smoking Cessation Program for a Multi-ethnic Cohort in California, USA, 2012-2019.

Smoking during pregnancy remains one of the most significant risk factors for poor birth outcomes. During 2012-2019, the Loma Linda University Health Comprehensive Tobacco Treatment Program (CTTP) used a multicomponent behavioral intervention for tobacco cessation for 1402 pregnant smokers with components of known efficacy (i.e.

Searching for diagnostic certainty, governing risk: Patients' ambivalent experiences of medical testing.

Diagnosis is pivotal to medicine's epistemic system: it serves to explain individual symptoms, classify them into recognizable conditions and determine their prognosis and treatment. Medical tests, or investigative procedures for detecting and monitoring disease, play a central role in diagnosis. While testing promises diagnostic certainty or a definitive risk assessment, it often produces uncertainties and new questions which call for yet further tests.

The Prevalence of Pathogenic or Likely Pathogenic Germline Variants in a Nationwide Cohort of Young Colorectal Cancer Patients Using a Panel of 18 Genes Associated with Colorectal Cancer.

Introduction: The prevalence of pathogenic or likely pathogenic germline variants (PGV) in colorectal cancer (CRC) in young patients is seen in approximately one in five patients, with the majority of cases having gene variants associated with Lynch syndrome (LS). The primary aim was to describe the prevalence of 18 genes, all associated with hereditary polyposis and CRC, in a nationwide population of young CRC (yCRC) patients, and outline disease characteristics in patients with or without germline variants.

Methods: We screened 98 patients aged 18-40 with CRC diagnosed in 2010-2013 for variants in , , , , , , , , , , , , , , , , and using Next Generation Sequencing.

Screening patients at admission to Copenhagen hospitals for carriage of resistant bacteria after contact with healthcare systems abroad, 2016-2019.

Objectives: Patients having previous contact with healthcare systems abroad are routinely screened for resistant bacteria on admission to hospitals in Copenhagen. This study aimed to present carriage prevalence and geographical risk stratification, as well as phenotypic and genotypic characterisation of resistant isolates.

Methods: This study included screening samples analysed at one department of clinical microbiology in Copenhagen from 2016-2019.

Treatment with senicapoc, a K 3.1 channel blocker, alleviates hypoxaemia in a mouse model of acute respiratory distress syndrome.

Background And Purpose: Acute respiratory distress syndrome (ARDS) is characterized by pulmonary oedema and severe hypoxaemia. We investigated whether genetic deficit or blockade of calcium-activated potassium (K 3.1) channels would counteract pulmonary oedema and hypoxaemia in ventilator-induced lung injury, an experimental model for ARDS.

Barriers to Abortion in the Autonomy-Based Danish Legal Model.

In 2016, the Committee on Economic, Social and Cultural Rights adopted General Comment 22 on the right to sexual and reproductive health, which affirmed that states are obliged to adopt "appropriate legislative measures" to achieve the full realization of sexual and reproductive health and rights. It affirmed that the right to sexual and reproductive health is an integral part of the right to health and recognizes abortion services as a component part of the right to health. While a liberal legislation is in itself a step towards the realization of this obligation, in this article we explore a number of potential barriers to abortion access in an autonomy-based legal model using the Danish legal model as the case study.

Germline variants in DNA repair genes are associated with young-onset head and neck cancer.

The genetic predisposition to head and neck carcinomas (HNSCC) and how the known risk factors (papillomavirus infection, alcohol, and tobacco consumption) contribute to the early-onset disease are barely explored. Although HNSCC at early onset is rare, its frequency is increasing in recent years. Germline and somatic variants were assessed to build a comprehensive genetic influence pattern in HNSCC predisposition and patient outcome.

Ozanimod as Induction and Maintenance Therapy for Ulcerative Colitis.

Background: Ozanimod, a selective sphingosine-1-phosphate receptor modulator, is under investigation for the treatment of inflammatory bowel disease.

Methods: We conducted a phase 3, multicenter, randomized, double-blind, placebo-controlled trial of ozanimod as induction and maintenance therapy in patients with moderately to severely active ulcerative colitis. In the 10-week induction period, patients in cohort 1 were assigned to receive oral ozanimod hydrochloride at a dose of 1 mg (equivalent to 0.

Possible misinterpretation of penicillin susceptibility in Staphylococcus aureus blood isolate due to in vitro loss of the blaZ gene.

We describe a case of recurrent catheter-related blood stream infections (BSI) with Staphylococcus aureus, in which the first isolate tested susceptible to penicillin, while subsequent isolates were resistant. Phenotypic susceptibility correlated with the absence/presence of the blaZ gene. The in vitro stability of penicillin resistance was investigated by subculturing single colonies.

A prospective investigation of developmental trajectories of psychosocial adjustment in adolescents facing a chronic condition - study protocol of an observational, multi-center study.

Background: Relatively little is known about protective factors and the emergence and maintenance of positive outcomes in the field of adolescents with chronic conditions. Therefore, the primary aim of the study is to acquire a deeper understanding of the dynamic process of resilience factors, coping strategies and psychosocial adjustment of adolescents living with chronic conditions.

Methods/design: We plan to consecutively recruit N = 450 adolescents (12-21 years) from three German patient registries for chronic conditions (type 1 diabetes, cystic fibrosis, or juvenile idiopathic arthritis).

North Atlantic winter cyclones starve seabirds.

Each winter, the North Atlantic Ocean is the stage for numerous cyclones, the most severe ones leading to seabird mass-mortality events called "winter wrecks." During these, thousands of emaciated seabird carcasses are washed ashore along European and North American coasts. Winter cyclones can therefore shape seabird population dynamics by affecting survival rates as well as the body condition of surviving individuals and thus their future reproduction.