Myositis/myasthenia gravis caused by immune checkpoint inhibition: A report of two cases and a brief review of the literature.

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapy by enhancing the ability of the immune system to combat malignancies. Nivolumab and cemiplimab, monoclonal antibodies targeting programmed cell death protein 1, have exhibited notable therapeutic efficacy; however, they are associated with immune-related adverse events (irAEs). The present study describes the cases of 2 patients, a 71-year-old male with metastatic esophageal adenocarcinoma and a 66-year-old female with metastatic squamous cell carcinoma who developed acute/subacute onset rapidly progressive myositis/myasthenia gravis (MG) following treatment with nivolumab and cemiplimab.

Reversion of metabolic dysfunction-associated steatohepatitis by skeletal muscle-directed FGF21 gene therapy.

The highly prevalent metabolic dysfunction-associated steatohepatitis (MASH) is associated with liver steatosis, inflammation, and hepatocyte injury, which can lead to fibrosis and may progress to hepatocellular carcinoma and death. New treatment modalities such as gene therapy may be transformative for MASH patients. Here, we describe that one-time intramuscular administration of adeno-associated viral vectors of serotype 1 (AAV1) encoding native fibroblast growth factor 21 (FGF21), a key metabolic regulator, resulted in sustained increased circulating levels of the factor, which mediated long-term (>1 year) MASH and hepatic fibrosis reversion and halted development of liver tumors in obese male and female mouse models.

Understanding Community-Specific Health Behaviors to Prevent Type 2 Diabetes and Depression in Rural Adolescents: A Qualitative Study.

Background: Type 2 diabetes (T2D) and depression co-occur, and rates are on the rise in adolescents, disproportionately affecting teenagers in rural communities and those who identify as members of historically disadvantaged racial/ethnic groups. Addressing the promotion of health behaviors is important for prevention of these comorbid health concerns; however, disparities in their prevalence highlight that a healthy lifestyle is not equally accessible for all individuals. Thus, holistic and multi-level approaches that address structural inequities, leverage cultural and family assets, and are effectively integrated into the community are critically needed.

Value contribution of etranacogene dezaparvovec gene therapy in moderately severe and severe haemophilia B through multi-criteria decision analysis.

Introduction: The value of gene therapies for haemophilia needs to be assessed holistically.

Aim: To determine the value of etranacogene dezaparvovec (ED) compared to current extended half-life (EHL) recombinant factors (rFIX), using multi-criteria decision analysis (MCDA).

Method: MCDA EVIDEM methodology adapted to orphan drugs was used, with nine quantitative criteria and four contextual criteria.

CD11b suppresses TLR7-driven inflammatory signaling to protect against lupus nephritis.

Lupus Nephritis (LN) is a severe complication of systemic lupus erythematosus (SLE) that affects kidney function. Here, we investigated the role of CD11b, a protein encoded by the gene, in the development of LN and its functional activation as a therapeutic strategy. Genetic coding variants of significantly increase the risk for SLE and LN by producing a less active CD11b and leading to elevated levels of type I interferon (IFN I).

The integrated genomic surveillance system of Andalusia (SIEGA) provides a One Health regional resource connected with the clinic.

The One Health approach, recognizing the interconnectedness of human, animal, and environmental health, has gained significance amid emerging zoonotic diseases and antibiotic resistance concerns. This paper aims to demonstrate the utility of a collaborative tool, the SIEGA, for monitoring infectious diseases across domains, fostering a comprehensive understanding of disease dynamics and risk factors, highlighting the pivotal role of One Health surveillance systems. Raw whole-genome sequencing is processed through different species-specific open software that additionally reports the presence of genes associated to anti-microbial resistances and virulence.

Rational Design and Evaluation of Photoactive Molecularly Imprinted Nanoparticles for Tetracycline Degradation Under Visible Light.

This work presents the use of photoactive molecularly imprinted nanoparticles (MINs) to promote antibiotic degradation under visible light irradiation. Prototype MINs for the model antibiotic tetracycline (TC) were developed using molecular dynamics simulations to predict the TC-binding capacity of seven pre-polymerization mixtures. The studied formulations contained varying proportions of functional monomers with diverse physicochemical profiles, namely -isopropylacrylamide (NIPAM), --butylacrylamide (TBAM), acrylic acid (AA), and (-(3-aminopropyl)methacrylamide hydrochloride) (APMA) and a constant ratio of the cross-linker ,'-methylene-bis-acrylamide (BIS).

Quantitative assessment of the nanoanatomy of the contractile vacuole complex in .

uses various mechanisms to cope with osmotic fluctuations during infection, including the remodeling of organelles such as the contractile vacuole complex (CVC). Little is known about the morphological changes of the CVC during pulsation cycles occurring upon osmotic stress. Here, we investigated the structure-function relationship between the CVC and the flagellar pocket domain where fluid discharge takes place-the adhesion plaque-during the CVC pulsation cycle.

Structure-Activity Relationship of Pyrrolidine Pentamine Derivatives as Inhibitors of the Aminoglycoside 6'--Acetyltransferase Type Ib.

Resistance to amikacin and other major aminoglycosides is commonly due to enzymatic acetylation by the aminoglycoside 6'--acetyltransferase type I enzyme, of which type Ib [AAC(6')-Ib] is the most widespread among Gram-negative pathogens. Finding enzymatic inhibitors could be an effective way to overcome resistance and extend the useful life of amikacin. Small molecules possess multiple properties that make them attractive for drug development.

Molecular dynamics simulations in pre-polymerization mixtures for peptide recognition.

Context: Molecularly imprinted polymers (MIPs) have promising applications as synthetic antibodies for protein and peptide recognition. A critical aspect of MIP design is the selection of functional monomers and their adequate proportions to achieve materials with high recognition capacity toward their targets. To contribute to this goal, we calibrated a molecular dynamics protocol to reproduce the experimental trends in peptide recognition of 13 pre-polymerization mixtures reported in the literature for the peptide toxin melittin.

A summary of the main themes and findings presented at the ASM Intermountain Branch meeting (2024).

The annual meeting for the Intermountain Branch was held in April 2024 on the campus of Brigham Young University. There were 127 branch members from Utah, Idaho, and Nevada who attended the meeting and were composed of undergraduate students, graduate or medical students, and faculty. This report highlights the diversity of, and the emerging trends in, the research conducted by American Society for Microbiology members in the Intermountain Branch.

Chlorin e6-Conjugated Mesoporous Titania Nanorods as Potential Nanoplatform for Photo-Chemotherapy.

Photodynamic therapy (PDT) has developed as an efficient strategy for cancer treatment. PDT involves the production of reactive oxygen species (ROS) by light irradiation after activating a photosensitizer (PS) in the presence of O. PS-coupled nanomaterials offer additional advantages, as they can merge the effects of PDT with conventional enabling-combined photo-chemotherapeutics effects.

Type 1 diabetes in pediatrics during the COVID-19 pandemic: Time from symptom onset and forms of presentation at a referral hospital.

Introduction. The COVID-19 pandemic impacted on the health care of patients with type 1 diabetes mellitus (DM1). An increase in diabetic ketoacidosis (DKA) as a form of diagnosis was reported.

Hemophilia and hepatology, back to the future.

Years ago, patients with hemophilia were often cared for because of liver issues. The use of hemoderivatives in the 1970s and 1980s, and the natural history of chronic hepatitis B and C, led to a surge of patients with cirrhosis and related complications after two or three decades. It was not until the approval of entecavir and tenofovir (2005-2008) against the B virus, and of direct-acting antiviral agents (2015) against the C virus, that a truly effective treatment became available for liver disease.

Deciphering psilocybin: Cytotoxicity, anti-inflammatory effects, and mechanistic insights.

A decade of clinical research has indicated psilocybin's effectiveness in treating various neuropsychiatric disorders, such as depression and substance abuse. The correlation between increased pro-inflammatory cytokines and the severity of neuropsychiatric symptoms, along with the known anti-inflammatory potential of some psychedelics, suggests an immunomodulatory role for psilocybin. This study aims to understand the mechanism of action of psilocybin by investigating the cytotoxic and immunomodulatory effects of psilocybin and psilocin on both resting and LPS-activated RAW 264.

Treatment of infantile-onset Pompe disease in a rat model with muscle-directed AAV gene therapy.

Objective: Pompe disease (PD) is caused by deficiency of the lysosomal enzyme acid α-glucosidase (GAA), leading to progressive glycogen accumulation and severe myopathy with progressive muscle weakness. In the Infantile-Onset PD (IOPD), death generally occurs <1 year of age. There is no cure for IOPD.

Neonatal SARS-CoV-2 immunoglobulin G antibodies at delivery and their impact on COVID-19.

Objective: To assess neonatal SARS-CoV-2 anti-spike IgG antibody levels after maternal mRNA COVID-19 vaccination and/or infection during pregnancy and evaluate their protective effect.

Methods: Prospective observational study, conducted from January 2021 to December 2022. Infants were tested for anti-spike IgG antibodies at birth and then every 3 months until disappearance of titer.

Short communication: Investigating optimal laboratory growth conditions of Gracilibacillus halotolerans in media supplemented with salt.

Gracilibacillus halotolerans, a new and relatively unstudied extremophile, extracted from the Great Salt Lake USA, survives in an extreme saline environment. Uncovering optimal laboratory growth conditions can be useful to improve treatment strategies against antibiotic resistance and biofilm formation. In the current study, G.

Design and Implementation of a Prototype Seismogeodetic System for Tectonic Monitoring.

This manuscript describes the design, development, and implementation of a prototype system based on seismogeodetic techniques, consisting of a low-cost MEMS seismometer/accelerometer, a biaxial inclinometer, a multi-frequency GNSS receiver, and a meteorological sensor, installed at the Doñana Biological Station (Huelva, Spain) that transmits multiparameter data in real and/or deferred time to the control center at the University of Cadiz. The main objective of this system is to know, detect, and monitor the tectonic activity in the Gulf of Cadiz region and adjacent areas in which important seismic events occur produced by the interaction of the Eurasian and African plates, in addition to the ability to integrate into a regional early warning system (EWS) to minimize the consequences of dangerous geological phenomena.

Arginine reprograms metabolism in liver cancer via RBM39.

Metabolic reprogramming is a hallmark of cancer. However, mechanisms underlying metabolic reprogramming and how altered metabolism in turn enhances tumorigenicity are poorly understood. Here, we report that arginine levels are elevated in murine and patient hepatocellular carcinoma (HCC), despite reduced expression of arginine synthesis genes.

Cell internalization kinetics and surface charge accessibility of surface-modified PAMAM dendrimers.

Surface-modified PAMAM dendrimers have important applications in drug delivery, yet a gap remains about the role that surface functionalization plays on their cell internalization capacity. We examined the cell internalization kinetics of PAMAM dendrimers that were surface-modified with acetyl, folate and poly(ethylene glycol), as model functional groups differing in size, charge, and chemical functionality. Dendrimers with 25% functionalization were internalized by HEK cells, but with slower rates and lower maximum uptakes than the native dendrimer between 1-6 h of incubation.

Recent Developments on Drivable Area Estimation: A Survey and a Functional Analysis.

Most advanced autonomous driving systems (ADS) today rely on the prior creation of high-definition maps (HD maps). This process is expensive and needs to be performed frequently to keep up with the changing conditions of the road environment. Creating accurate navigation maps online is an alternative to reduce the cost and broaden the current operational design domains (ODD) of modern ADS.

Schimke immuno-osseous dysplasia. A case report in Colombia.

Background: Schimke immune-osseous dysplasia (SIOD) is an ultra-rare multisystemic, monogenic, and autosomal recessive inherited disease caused by biallelic mutations in the gene. Approximately 100 cases have been reported worldwide. The disease is characterized by skeletal, renal, and immunological abnormalities.