Pareto in Prison.

The Pareto principle is based on the concept that roughly 80% of outcomes are generated by 20% of inputs, efforts, or contributors within a group. Using a national sample of U.S.

Urinary excretion of gluten immunoreactive peptides as an indicator of gastrointestinal function after fasting and dietary provocation in healthy volunteers.

Introduction: Understanding intestinal permeability is paramount for elucidating gastrointestinal health and pathology. The size and nature of the molecule traversing the intestinal barrier offer crucial insights into various acute and chronic diseases, as well as the evolution of some conditions. This study aims to assess the urinary excretion kinetics of gluten immunogenic peptides (u-GIP), a unique class of dietary peptides detectable in urine, in volunteers under controlled dietary conditions.

Instability of the HLA-E peptidome of HIV presents a major barrier to therapeutic targeting.

Naturally occurring T cells that recognize microbial peptides via HLA-E, a nonpolymorphic HLA class Ib molecule, could provide the foundation for new universal immunotherapeutics. However, confidence in the biological relevance of putative ligands is crucial, given that the mechanisms by which pathogen-derived peptides can access the HLA-E presentation pathway are poorly understood. We systematically interrogated the HIV proteome using immunopeptidomic and bioinformatic approaches, coupled with biochemical and cellular assays.

Rapid Anti-tTG-IgA Screening Test for Early Diagnosis of Celiac Disease in Pediatric Populations.

A large number of patients with celiac disease (CD) remain undiagnosed because they do not fulfill the criteria for entry into the conventional diagnostic workflow. This study evaluated the clinical utility of anti-tissue transglutaminase IgA antibody lateral flow immunoassays (anti-tTG-IgA LFIA) in the undiagnosed-CD-based pediatric population and the impact of a gluten-free diet (GFD) on screening-detected CD. A total of 576 volunteers were tested for anti-tTG-IgA.

Effect of remdesivir on adverse kidney outcomes in hospitalized patients with COVID-19 and impaired kidney function.

Background: Chronic kidney disease (CKD) is an important risk factor for mortality from COVID-19. Remdesivir has been shown to shorten time to recovery in patients with severe COVID-19. However, exclusion of patients with severe kidney function impairment in clinical trials has led to concerns about kidney safety of remdesivir in patients with pre-existing kidney disease.

A Propensity Score-Matched Observational Study of Remdesivir in Patients with COVID-19 and Severe Kidney Disease.

Background: Remdesivir is not currently approved for patients with eGFR <30 ml/min per 1.73 m. We aimed to determine the safety of remdesivir in patients with kidney failure.

Cyclic Peptide-Gadolinium Nanocomplexes as siRNA Delivery Tools.

We have recently reported that a cyclic peptide containing five tryptophan, five arginine, and one cysteine amino acids [(WR)C], was able to produce peptide-capped gadolinium nanoparticles, [(WR)C]-GdNPs, in the range of 240 to 260 nm upon mixing with an aqueous solution of GdCl. Herein, we report [(WR)C]-GdNPs as an efficient siRNA delivery system. The peptide-based gadolinium nanoparticles (50 µM) did not exhibit significant cytotoxicity (~93% cell viability at 50 µM) in human leukemia T lymphoblast cells (CCRF-CEM) and triple-negative breast cancer cells (MDA-MB-231) after 48 h.

COVID-19 Survival and its impact on chronic kidney disease.

Up to 87% of patients hospitalized with coronavirus disease 2019 (COVID-19) experience chronic sequelae following infection. The long-term impact of COVID-19 infection on kidney function is largely unknown at this point in the COVID-19 pandemic. In this review, we highlight the current understanding of the pathophysiology of COVID-19-associated kidney injury and the impact COVID-19 may have on long-term kidney function.

ADMM approach for efficient iterative tomographic deconvolution reconstruction of 3D quantitative phase images.

Tomographic deconvolution phase microscopy (TDPM) is a promising approach for 3D quantitative imaging of phase objects such as biological cells and optical fibers. In the present work, the alternating direction method of multipliers (ADMM) is applied to TDPM to shorten its image acquisition and processing times while simultaneously improving its accuracy. ADMM-TDPM is used to optimize the image fidelity by minimizing Gaussian noise and by using total variation regularization with the constraints of nonnegativity and known zeros.

The Impact of Obesity on COVID-19 Disease Severity.

Introduction: Obesity has been declared a major risk factor for morbidity and mortality in COVID-19 patients. In this rapid review, we provide an overview of recently-published papers with clinical and epidemiological relevance on this topic.

Methods: As part of a weekly COVID-19 data mining meeting, we conducted a literature review regarding the role of obesity in COVID-19 outcomes, particularly in young patients with COVID-19.

Spontaneous drying of non-polar deep-cavity cavitand pockets in aqueous solution.

There are many open questions regarding the hydration of solvent-exposed non-polar tracts and pockets in proteins. Although water is predicted to de-wet purely repulsive surfaces and evacuate crevices, the extent of de-wetting is unclear when ubiquitous van der Waals interactions are in play. The structural simplicity of synthetic supramolecular hosts imbues them with considerable potential to address this issue.

Direct-acting antiviral therapy slows kidney function decline in patients with Hepatitis C virus infection and chronic kidney disease.

Hepatitis C virus (HCV) infection is common and can accelerate chronic kidney disease (CKD) progression. Direct-acting antiviral (DAA) therapies against hepatitis C have consistently shown rates of sustained viral remission. However, the effect on kidney function is unknown.

Evaluation of model performance to predict survival after transjugular intrahepatic portosystemic shunt placement.

Background/aims: The MELD score was developed to predict survival after transjugular intrahepatic portosystemic shunt (TIPS) placement. Given changes in practice patterns and development of new prognostic tools in cirrhosis, we aimed to evaluate common models to predict mortality after TIPS placement.

Methods: Analysis of consecutive patients who underwent TIPS placement for ascites or bleeding.

Protein Carbamylation in Chronic Kidney Disease and Dialysis.

Protein carbamylation is a nonenzymatic posttranslational protein modification that can be driven, in part, by exposure to urea's dissociation product, cyanate. In humans, when kidney function is impaired and urea accumulates, systemic protein carbamylation levels increase. Additional mediators of protein carbamylation have been identified including inflammation, diet, smoking, circulating free amino acid levels, and environmental exposures.

Autoimmune Kidney Diseases Associated with Chronic Viral Infections.

Autoimmune kidney diseases triggered by viruses are an important cause of kidney disease in patients affected by chronic viral infection. Hepatitis B virus (HBV) infection is associated with membranous nephropathy and polyarteritis nodosa. Hepatitis C virus (HCV) infection is a major cause of cryoglobulinemic glomerulonephritis.

RIPK1 is a critical modulator of both tonic and TLR-responsive inflammatory and cell death pathways in human macrophage differentiation.

In this study, we took advantage of human-induced pluripotent stem cells (hiPSC) and CRISPR/Cas9 technology to investigate the potential roles of RIPK1 in regulating hematopoiesis and macrophage differentiation, proinflammatory activation, and cell death pathways. Knock-out of RIPK1 in hiPSCs demonstrated that this protein is not required for erythro-myeloid differentiation. Using a well-established macrophage differentiation protocol, knock-out of RIPK1 did not block the differentiation of iPSC-derived macrophages, which displayed a similar phenotype to WT hiPSC-derived macrophages.

Mini viral RNAs act as innate immune agonists during influenza virus infection.

The molecular processes that determine the outcome of influenza virus infection in humans are multifactorial and involve a complex interplay between host, viral and bacterial factors. However, it is generally accepted that a strong innate immune dysregulation known as 'cytokine storm' contributes to the pathology of infections with the 1918 H1N1 pandemic or the highly pathogenic avian influenza viruses of the H5N1 subtype. The RNA sensor retinoic acid-inducible gene I (RIG-I) plays an important role in sensing viral infection and initiating a signalling cascade that leads to interferon expression.

Serum Angiopoietin-2 Predicts Mortality and Kidney Outcomes in Decompensated Cirrhosis.

Acute kidney injury in decompensated cirrhosis has limited therapeutic options, and novel mechanistic targets are urgently needed. Angiopoietin-2 is a context-specific antagonist of Tie2, a receptor that signals vascular quiescence. Considering the prominence of vascular destabilization in decompensated cirrhosis, we evaluated Angiopoietin-2 to predict clinical outcomes.

GABA is an inhibitory neurotransmitter in the neural circuit regulating metamorphosis in a marine snail.

The marine mud snail, Tritia (=Ilyanassa) obsoleta, displays a biphasic life cycle. During the initial phase of early development, embryos hatch from benthic egg capsules to become weakly swimming veliger larvae. In the second phase, adult T.

The PB2 Subunit of the Influenza A Virus RNA Polymerase Is Imported into the Mitochondrial Matrix.

Unlabelled: The polymerase basic 2 (PB2) subunit of the RNA polymerase complex of seasonal human influenza A viruses has been shown to localize to the mitochondria. Various roles, including the regulation of apoptosis and innate immune responses to viral infection, have been proposed for mitochondrial PB2. In particular, PB2 has been shown to inhibit interferon expression by associating with the mitochondrial antiviral signaling (MAVS) protein, which acts downstream of RIG-I and MDA-5 in the interferon induction pathway.

Small Airway Dysfunction and Abnormal Exercise Responses. A Study in Coal Miners.

Rationale: Coal mine dust exposure can cause symptoms and loss of lung function from multiple mechanisms, but the roles of each disease process are not fully understood.

Objectives: We investigated the implications of small airway dysfunction for exercise physiology among a group of workers exposed to coal mine dust.

Methods: Twenty coal miners performed spirometry, first breathing air and then helium-oxygen, single-breath diffusing capacity, and computerized chest tomography, and then completed cardiopulmonary exercise testing.

Micelle Structure and Hydrophobic Hydration.

Despite the ubiquity and utility of micelles self-assembled from aqueous surfactants, longstanding questions remain regarding their surface structure and interior hydration. Here we combine Raman spectroscopy with multivariate curve resolution (Raman-MCR) to probe the hydrophobic hydration of surfactants with various aliphatic chain lengths, and either anionic (carboxylate) or cationic (trimethylammonium) head groups, both below and above the critical micelle concentration. Our results reveal significant penetration of water into micelle interiors, well beyond the first few carbons adjacent to the headgroup.

Small airways involvement in coal mine dust lung disease.

Inhalation of coal mine dust results in a spectrum of symptoms, dysfunction, and pathological changes in the respiratory tract that collectively have been labeled coal mine dust lung disease. Recent reports from periodic health surveillance among underground and surface coal miners in the United States have demonstrated an increasing prevalence and severity of dust diseases, and have also documented that some miners experience rapid disease progression. The coal macule is an inflammatory lesion associated with deposited dust, and occurs in the region of the most distal conducting airways and proximal respiratory bronchioles.