Evaluating student understanding of pharmacodynamics core concepts.

Pharmacodynamics is an essential subdiscipline of pharmacology that underpins safe and effective prescribing and therapeutic decision-making, as well as drug discovery and development. The exponential increase in the number of therapeutic drugs has prompted members of the pharmacology educator community to question existing pharmacology curricula focused on individual drugs and move toward a curriculum focused on conceptual understanding. A first step towards conceptual understanding is to establish what students currently know about pharmacodynamic core concepts.

Jaccoud's Arthropathy Secondary to Leprosy.

Jaccoud's arthropathy is a deforming, non-erosive form of arthritis initially described in patients with rheumatic fever. However, it has been recently observed more frequently in those with systemic lupus erythematosus. Cases of Jaccoud's arthropathy have also been described to be associated with other conditions.

Death and survival of gut CD4 T cells following HIV-1 infection ex vivo.

The gastrointestinal tract is ground zero for the massive and sustained CD4 T cell depletion during acute HIV-1 infection. To date, the molecular mechanisms governing this fundamental pathogenic process remain unclear. HIV-1 infection in the gastrointestinal tract is associated with chronic inflammation due to a disrupted epithelial barrier that results in microbial translocation.

Inactivation of GSK3β by Ser phosphorylation prevents thymocyte necroptosis and impacts Tcr repertoire diversity.

The assembly of Tcrb and Tcra genes require double negative (DN) thymocytes to undergo multiple rounds of programmed DNA double-strand breaks (DSBs), followed by their efficient repair. However, mechanisms governing cell cycle checkpoints and specific survival pathways during the repair process remain unclear. Here, we report high-resolution scRNA-seq analyses of individually sorted mouse DN3 and DN4 thymocytes, which reveals a G2M cell cycle checkpoint, in addition to the known G1 checkpoint, during Tcrb and Tcra recombination.

A Lactobacillus consortium provides insights into the sleep-exercise-microbiome nexus in proof of concept studies of elite athletes and in the general population.

Background: The complex relationship among sleep, exercise, and the gut microbiome presents a unique opportunity to improve health and wellness. Here, we conducted the first large-scale investigation into the influence of a novel elite athlete-derived probiotic, consisting of a multi-strain Lactobacillus consortium, on sleep quality, exercise recovery, and gut microbiome composition in both elite athletes (n = 11) and the general population (n = 257).

Results: Our two-phase study design, which included an open-label study followed by a controlled longitudinal study in a professional soccer team, allowed us to identify key interactions between probiotics, the gut microbiome, and the host.

The antibacterial and antibiofilm role of cannabidiol against periodontopathogenic bacteria.

Aims: Bacterial resistance and systemic risks associated with periodontitis underscore the need for novel antimicrobial agents. Cannabis sativa is a promising source of antimicrobial molecules, and cannabidiol (CBD) attracts significant interest. This study evaluated the antibacterial and antibiofilm activity of CBD against periodontopathogens, and assessed its toxicity in vivo model.

Dr. Jekyll or Mr. Hyde: The multifaceted roles of miR-145-5p in human health and disease.

MicroRNAs (miRNAs) are classified as small, non-coding RNAs that play crucial roles in diverse biological processes, including cellular development, differentiation, growth, and metabolism. MiRNAs regulate gene expression by recognizing complementary sequences within messenger RNA (mRNA) molecules. Recent studies have revealed that miR-145-5p functions as a tumor suppressor in several cancers, including lung, liver, and breast cancers.

Incidence, Risk Factors, and Outcomes of BK Hemorrhagic Cystitis in Hematopoietic Stem Cell Transplantation From HLA-Matched and Haploidentical Donors With Post-Transplant Cyclophosphamide.

BK hemorrhagic cystitis (BK-HC) is a common complication following hematopoietic stem cell transplantation (HSCT), particularly when posttransplant cyclophosphamide (PTCy) is used as graft-versus-host disease (GVHD) prophylaxis. However, comparative studies of BK-HC incidence in matched sibling donors (MSD) and unrelated donors (MUD) often include small haploidentical (HAPLO) donor cohorts and usually lack detailed information on disease evolution, coinfections, management and impact on outcomes. This study aimed to evaluate the incidence, risk factors, and outcomes in patients with hematologic malignancies undergoing HSCT from MSD, MUD, HAPLO donors using PTCy as GVHD prophylaxis.

Chikungunya chronic arthralgia: impact on general and mental health and absenteeism from work.

Background: This study investigated the self-rated general health, mental health, and work absenteeism among patients with laboratory-confirmed chikungunya.

Methods: Telephone interviews were conducted with 63 patients ≥22 months after infection.

Results: Patients who reported (N=42) or did not report (N=21) chronic arthralgia, defined by duration ≥90 days, had different frequencies for low scores for general health (68.

Association of Gut Microbiome and Dipeptidyl Peptidase 4 in Immune-Mediated Inflammatory Bowel Disease: A Rapid Literature Review.

Immune-mediated inflammatory diseases (IMIDs) are characterized by dysregulated immune responses and chronic tissue inflammation. In the setting of inflammatory bowel disease (IBD), dipeptidyl peptidase 4 (DPP4) and gut microorganisms have been proved to interplay, potentially influenced by dietary factors. This rapid review aimed to study the DPP4-gut microbiome link in IBD.

HIV-1 Tat Protein and Cigarette Smoke Mediated ADAM17 Upregulation Can Lead to Impaired Mucociliary Clearance.

Human immunodeficiency virus type-1 (HIV-1) associated comorbidities account for the majority of poor health outcomes in people living with HIV (PLWH) in the era of antiretroviral therapy. Lung-related comorbidities such as chronic obstructive pulmonary disease (COPD) and bacterial pneumonia are primarily responsible for increased morbidity and mortality in PLWH, even when compensated for smoking. Smokers and COPD patients demonstrate cilia shortening, attenuated ciliary beat frequency (CBF), dysfunctional ciliated cells along with goblet cell hyperplasia, and mucus hypersecretion.

Regulation of human interferon signaling by transposon exonization.

Innate immune signaling is essential for clearing pathogens and damaged cells and must be tightly regulated to avoid excessive inflammation or autoimmunity. Here, we found that the alternative splicing of exons derived from transposable elements is a key mechanism controlling immune signaling in human cells. By analyzing long-read transcriptome datasets, we identified numerous transposon exonization events predicted to generate functional protein variants of immune genes, including the type I interferon receptor IFNAR2.

Effectiveness of physiotherapy modalities on persisting dyspnoea in long COVID: A systematic review and meta-analysis.

Background: Dyspnoea is often found months and years later in the "long-covid" syndrome, impairing quality of life and further perpetuating anxiety and post-traumatic stress disorders. Physiotherapy was recommended as a treatment in long-covid, but there is still insufficient evidence on its effectiveness.

Methods: We conducted a systematic literature search on MEDLINE, PEDro, WOS, Scopus, VHL and the Cochrane Library until July 2023 (PROSPERO registration number: CRD42023427464).

Serum Neutrophil Biomarkers to Predict Crohn's Disease Progression and Infliximab Treatment Outcomes.

Background And Aims: Predicting the treatment outcomes of biological therapies is an unmet need in Crohn's Disease. In this study, we explored the potential of serum neutrophil-related biomarkers to predict infliximab therapeutic results and disease progression in Crohn's Disease patients, over a 2-year period, in a real-world setting.

Methods: The study included 100 asymptomatic Crohn's Disease patients in the IFX maintenance phase from the prospective, observational, multicenter DIRECT study.

Interplay of elasticity and flow velocity on gorgonian feeding and implications for bioinspired design.

Evidence shows that gorgonians are more resistant to ocean acidification and rising temperatures than hard corals and are vital to reef health and the reestablishment of disrupted coral reef communities. Gorgonian coral's resilience and its diversity of morphology and environment make it well-suited as a model organism for bioinspired design applied to particle capture. We focus on flow near the polyps, using an updated form of the immersed boundary method to model the fluid-structure interaction of the flexible polyps and the surrounding ocean water.

In vitro cytotoxicity assessment of different solvents used in pesticide dilution.

Pesticides are diluted in products called solvents for spraying fields and for cell viability studies. This study aimed to determine whether pesticide solvents can alter the toxicity of endosulfan and Vero cell viability. Thus, the cytotoxicity of some diluents commonly used in pesticide solutions was evaluated by the neutral red incorporation technique and cell growth.

Antitumoral action of carvedilol-a repositioning study of the drug incorporated into mesoporous silica MCM-41.

We have studied repositioning of carvedilol (an antihypertensive drug) incorporated into MCM-41 mesoporous silica. The repositioning proposes a reduction in the slow pace of discovery of new drugs, as well as toxicological safety and a significant reduction in high research costs, making it an attractive strategy for researchers and large pharmaceutical companies. We obtained MCM-41 bysynthesis and functionalized it by post-synthesis grafting with aminopropyltriethoxysilane (APTES) only or with folic acid (FA), which gave MCM-41-APTES and MCM-41-APTES-FA, respectively.

Takayasu's arteritis associated with tuberculosis: a retrospective study.

Background: Takayasu arteritis (TA) and tuberculosis (TB) share similar histopathological and immunological characteristics. Studies comparing patients with TA with or without active or latent TB infection (LTBI) have revealed some differences in clinical and angiographic profiles. Patient with TA and history of TB exhibited more constitutional symptoms and structural damage to the aorta.

Vaccination coverage, hesitancy and associated factors: a household survey of a cohort of children born in 2017 and 2018 in urban areas of state capital cities in the Brazilian Northeast.

Objective: To estimate vaccination coverage and analyze sociodemographic factors associated with non-vaccination in children born in 2017 and 2018 in the state capitals of Northeast Brazil.

Methods: A household survey using cluster sampling was conducted from 2020-2022 to estimate vaccination coverage and hesitancy. Factors associated with non-vaccination were analyzed using logistic regression to calculate Odds Ratios (OR) and their Confidence Intervals (95%CI).

Synthesis of dumbbell-like heteronanostructures encapsulated in ferritin protein: Towards multifunctional protein based opto-magnetic nanomaterials for biomedical theranostic.

Dumbbell-like hetero nanostructures based on gold and iron oxides is a promising material for biomedical applications, useful as versatile theranostic agents due the synergistic effect of their optical and magnetic properties. However, achieving precise control on their morphology, size dispersion, colloidal stability, biocompatibility and cell targeting remains as a current challenge. In this study, we address this challenge by employing biomimetic routes, using ferritin protein nanocages as template for these nanoparticles' synthesis.

Fruit Peel: Bioactive Composition as Determined by Distinct Harvest Seasons and In Vitro Anti-Cancer Activity.

Jaboticaba () is a recognizable and unique crop from Brazil. The fruit's byproducts are currently being studied, given their bioactive composition and promising anti-cancer potential. It is not evident, however, if different harvesting seasons can modify the chemical profile and antioxidant capacity of jaboticaba fruit fractions.

Slow dissociation kinetics of fentanyls and nitazenes correlates with reduced sensitivity to naloxone reversal at the μ-opioid receptor.

Background And Purpose: Fentanyls and nitazenes are μ-opioid receptor agonists responsible for a large number of opioid overdose deaths. Here, we determined the potency, dissociation kinetics and antagonism by naloxone at the μ receptor of several fentanyl and nitazene analogues, compared to morphine and DAMGO.

Experimental Approach: In vitro assays of G protein activation and signalling and arrestin recruitment were performed.

Gastric Bleeding in Stem Cell Transplantation: A Focus on Gastric Vascular Ectasia Under Post-Transplant Cyclophosphamide, Sirolimus, and Mycophenolate Mofetil Prophylaxis.

Gastrointestinal bleeding (GIB) is a serious complication following allogeneic hematopoietic stem cell transplantation (HSCT), with limited data on its incidence and characteristics, particularly for upper gastrointestinal bleeding (UGIB) of gastric origin. We aimed to evaluate the incidence, clinical, endoscopic, and histopathologic features, and outcomes of UGIB, with a focus on gastric vascular ectasias (GVEs) in patients undergoing HSCT with graft-versus-host disease (GVHD) prophylaxis using post-transplant cyclophosphamide (PTCY), sirolimus or calcineurin inhibitors, and mycophenolate mofetil. This retrospective, single-center study included all adult patients who underwent allogeneic HSCT at a single institution between January 2017 and December 2023.