Sacubitril/valsartan reduces proteasome activation and cardiomyocyte area in an experimental mouse model of hypertrophy.

Sacubitril/valsartan (Sac/Val) belongs to the group of angiotensin receptor-neprilysin inhibitors and has been used for the treatment of heart failure (HF) for several years. The mechanisms that mediate the beneficial effects of Sac/Val are not yet fully understood. In this study we investigated whether Sac/Val influences the two proteolytic systems, the ubiquitin-proteasome system (UPS) and the autophagy-lysosomal pathway (ALP), in a mouse model of pressure overload induced by transverse aortic constriction (TAC) and in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) treated with endothelin-1 (ET1) serving as a human cellular model of hypertrophy.

MRI Denoising Using Pixel-Wise Threshold Selection.

Magnetic resonance imaging (MRI) has emerged as a promising technique for non-invasive medical imaging. The primary challenge in MRI is the trade-off between image visual quality and acquisition time. Current MRI image denoising algorithms employ global thresholding to denoise the whole image, which leads to inadequate denoising or image distortion.

Efficient enzyme-free isolation of brain-derived extracellular vesicles.

Extracellular vesicles (EVs) have gained significant attention as pathology mediators and potential diagnostic tools for neurodegenerative diseases. However, isolation of brain-derived EVs (BDEVs) from tissue remains challenging, often involving enzymatic digestion steps that may compromise the integrity of EV proteins and overall functionality. Here, we describe that collagenase digestion, commonly used for BDEV isolation, produces undesired protein cleavage of EV-associated proteins in brain tissue homogenates and cell-derived EVs.

Development of Undergraduate Competencies in Caring for People Experiencing Homelessness.

Background: Nurses play a critical role in reducing health inequities in people experiencing homelessness (PEH), a key social determinant of health. Health disparities specific to PEH are exacerbated by numerous factors, including bias, stigma, and a lack of nursing competency in caring for PEH.

Purpose: The purpose of this study was to validate registered nurse key competencies; associated knowledge, skills, and attitudes; and concepts, content, and learning activities to serve as an educational framework in providing care for PEH.

Does adapting a self-report instrument to improve its cognitive accessibility for people with intellectual disability result in a better measure? - A cognitive interview study.

Background And Aims: We investigated whether improving the cognitive accessibility of a widely used self-report measure leads to better understanding and more accurate answers in a sample of adults with mild intellectual disability and borderline intellectual functioning.

Methods And Procedures: We undertook a series of cognitive interviews before and after adaptation of the instructions and selected items of an existing self-report measure of adaptive functioning. Interview results and participant feedback were supplemented with quantitative comparisons between participant and carer scores.

Discovery of Antimicrobial Peptides in Urinary Tract Infections.

Antimicrobial peptides (AMPs) play a pivotal role in the innate immune system as a frontline defense against microbial threats. AMPs can serve as biomarkers and alternative antibiotics, overcoming mortality related to multidrug-resistant pathogens in urinary tract infections (UTIs). While the relevance of AMPs in UTIs has been validated and AMP drugs approved by the US Food and Drug Administration are in clinical use, information about their modification status, regulation, and mechanism of action remains sparse.

Assay for Characterizing Adsorption-Properties of Surfaces (APS).

Analytes, from sample preparation, until entering an analytical instrument, are prone to adsorb to surfaces, driven by the chemical properties of the surface and the liquids they are dissolved in. This problem can be addressed with internal standards when a single or few known analytes are quantified that are usually not available in omics. However, minimal to no loss of analytes is the aim.

Cognitive Motor Dissociation in Disorders of Consciousness.

Background: Patients with brain injury who are unresponsive to commands may perform cognitive tasks that are detected on functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). This phenomenon, known as cognitive motor dissociation, has not been systematically studied in a large cohort of persons with disorders of consciousness.

Methods: In this prospective cohort study conducted at six international centers, we collected clinical, behavioral, and task-based fMRI and EEG data from a convenience sample of 353 adults with disorders of consciousness.

Multiomic profiling of medulloblastoma reveals subtype-specific targetable alterations at the proteome and N-glycan level.

Medulloblastomas (MBs) are malignant pediatric brain tumors that are molecularly and clinically heterogenous. The application of omics technologies-mainly studying nucleic acids-has significantly improved MB classification and stratification, but treatment options are still unsatisfactory. The proteome and their N-glycans hold the potential to discover clinically relevant phenotypes and targetable pathways.

Heart immunoengineering by lentiviral vector-mediated genetic modification during normothermic perfusion.

Heart transplantation is associated with major hurdles, including the limited number of available organs for transplantation, the risk of rejection due to genetic discrepancies, and the burden of immunosuppression. In this study, we demonstrated the feasibility of permanent genetic engineering of the heart during perfusion. Lentiviral vectors encoding for short hairpin RNAs targeting beta2-microglobulin (shβ2m) and class II transactivator (shCIITA) were delivered to the graft during two hours of normothermic EVHP.

Epidemiologic Trends In Children With Toxicologic Exposures Requiring Intensive Care Before and During the COVID-19 Pandemic.

Objective: Pediatric poison exposures are a common reason for pediatric intensive care unit (PICU) -admission. The purpose of this study was to examine the exposure trends and patient outcomes in 2018-2019 compared with 2020-2021 amidst the COVID-19 pandemic.

Methods: This was a retrospective cohort study of patients 18 years of age or younger with a suspected toxicologic exposure from January 2018 to March 2021.

Proteomic analysis of the urothelial cancer landscape.

Urothelial bladder cancer (UC) has a wide tumor biological spectrum with challenging prognostic stratification and relevant therapy-associated morbidity. Most molecular classifications relate only indirectly to the therapeutically relevant protein level. We improve the pre-analytics of clinical samples for proteome analyses and characterize a cohort of 434 samples with 242 tumors and 192 paired normal mucosae covering the full range of UC.

Cystatin C loaded in brain-derived extracellular vesicles rescues synapses after ischemic insult in vitro and in vivo.

Synaptic loss is an early event in the penumbra area after an ischemic stroke. Promoting synaptic preservation in this area would likely improve functional neurological recovery. We aimed to detect proteins involved in endogenous protection mechanisms of synapses in the penumbra after stroke and to analyse potential beneficial effects of these candidates for a prospective stroke treatment.

HERC5 downregulation in non-small cell lung cancer is associated with altered energy metabolism and metastasis.

Background: Metastasis is the leading cause of cancer-related death in non-small cell lung cancer (NSCLC) patients. We previously showed that low HERC5 expression predicts early tumor dissemination and a dismal prognosis in NSCLC patients. Here, we performed functional studies to unravel the mechanism underlying the "metastasis-suppressor" effect of HERC5, with a focus on mitochondrial metabolism pathways.

Pulsatility analysis of the circle of Willis.

Purpose: To evaluate the phenomenological significance of cerebral blood pulsatility imaging in aging research.

Methods: N = 38 subjects from 20 to 72 years of age (24 females) were imaged with ultrafast MRI with a sampling rate of 100 ms and simultaneous acquisition of pulse oximetry data. Of these, 28 subjects had acceptable MRI and pulse data, with 16 subjects between 20 and 28 years of age, and 12 subjects between 61 and 72 years of age.

Improvement of palliative care for people with intellectual disabilities: A multi-site evaluation.

Background: To improve the quality of palliative care, six evidence-based tools were implemented in 10 care services specialised in care for people with intellectual disabilities. Contextual differences were taken into account by using a participatory action research approach.

Method: The RE-AIM framework (Reach, Effectiveness, Adoption, Implementation and Maintenance) structured the evaluation.

Patient-Caregiver Dyads & End-of-Life Care: Caregiver Personality Disrupts Gender-Based Norms.

Context: Gender and personality may individually impact end-of-life care. Men often receive more aggressive treatments than women near death, and personality - particularly openness - may be associated with increased care utilization when it diverges from traditional treatment norms. However, research has not examined the interaction of these variables in a dyadic context.

Temporal change of DNA methylation subclasses between matched newly diagnosed and recurrent glioblastoma.

The longitudinal transition of phenotypes is pivotal in glioblastoma treatment resistance and DNA methylation emerged as an important tool for classifying glioblastoma phenotypes. We aimed to characterize DNA methylation subclass heterogeneity during progression and assess its clinical impact. Matched tissues from 47 glioblastoma patients were subjected to DNA methylation profiling, including CpG-site alterations, tissue and serum deconvolution, mass spectrometry, and immunoassay.

Spontaneous Pituitary Neoplasm in Two Female Geriatric Southern Giant Pouched Rats ().

Southern giant pouched rats () are a small muroid species native to the sub-Saharan Africa. Their exceptionally developed olfactory system, trainability, and relatively small size makes them useful working animals for various applications in humanitarian work. At our institution, a breeding colony of Southern giant pouched rats is maintained to study their physiology and utility as scent detectors.

Fatty acid synthesis suppresses dietary polyunsaturated fatty acid use.

Dietary polyunsaturated fatty acids (PUFA) are increasingly recognized for their health benefits, whereas a high production of endogenous fatty acids - a process called de novo lipogenesis (DNL) - is closely linked to metabolic diseases. Determinants of PUFA incorporation into complex lipids are insufficiently understood and may influence the onset and progression of metabolic diseases. Here we show that fatty acid synthase (FASN), the key enzyme of DNL, critically determines the use of dietary PUFA in mice and humans.

Integrated proteomics spotlight the proteasome as a therapeutic vulnerability in embryonal tumors with multilayered rosettes.

Background: Embryonal tumors with multilayered rosettes (ETMR) are rare malignant embryonal brain tumors. The prognosis of ETMR is poor and novel therapeutic approaches are desperately needed. Comprehension of ETMR tumor biology is currently based on only few previous molecular studies, which mainly focused on the analyses of nucleic acids.