Exposure-response modeling for nausea incidence for cotadutide using a Markov modeling approach.

Cotadutide is a dual glucagon-like peptide-1 (GLP-1)/glucagon receptor agonist. Gastrointestinal adverse effects are known to be associated with GLP-1 receptor agonism and can be mitigated through tolerance development via a gradual up-titration. This analysis aimed to characterize the relationship between exposure and nausea incidence and to optimize titration schemes.

Pain sensitization and atrophy of deep cervical muscles in patients with chronic tension-type headache.

Objective: The aim of this study was to compare the pressure pain threshold and the thickness of the cervical muscles in patients with tension-type headache versus healthy participants.

Methods: An observational, retrospective, cross-sectional study was conducted at the Universidad Europea de Madrid between May and June 2022. Adults aged 18-65 years with tension-type headache diagnosed for more than 6 months were compared to healthy controls.

Pharmacokinetics and Safety of Cotadutide, a GLP-1 and Glucagon Receptor Dual Agonist, in Individuals with Renal Impairment: A Single-Dose, Phase I, Bridging Study.

Background And Objective: Cotadutide is a balanced glucagon-like peptide-1 and glucagon receptor dual agonist under development for the treatment of non-alcoholic steatohepatitis and type 2 diabetes with chronic kidney disease. We evaluated the pharmacokinetics (PK), safety and immunogenicity of a single dose of cotadutide in individuals with varying degrees of renal impairment.

Methods: In this phase I bridging study, individuals 18-85 years of age, with a body mass index of 17-40 kg/m and varying degrees of renal function {end-stage renal disease (ESRD; creatinine clearance [CrCl] < 20 mL/min); severe renal impairment (CrCl ≥ 20 to < 30 mL/min); lower moderate renal impairment (CrCl ≥ 30 to < 44 mL/min); upper moderate renal impairment (CrCl ≥ 45 to < 60 mL/min); normal renal function (CrCl ≥ 90 mL/min)} were treated with a single dose of subcutaneous cotadutide 100 µg under fasted conditions in the lower abdomen.

Improvement of Teamwork Nontechnical Skills Through Polytrauma Simulation Cases Using the Communication and Teamwork Skills (CATS) Assessment Tool.

Objective: To assess acquisition of nontechnical skills (NTS) through clinical simulation cases by healthcare personnel who participated in a Crisis Resource Management (CRM) training program for the initial care of polytraumatisms.

Design: Pre-and postintervention study.

Setting: Acute-care teaching hospital in Sabadell, Barcelona (Spain).

Far-red Fluorescent Senescence-associated β-Galactosidase Probe for Identification and Enrichment of Senescent Tumor Cells by Flow Cytometry.

Cellular senescence is a state of proliferative arrest induced by biological damage that normally accrues over years in aging cells but may also emerge rapidly in tumor cells as a response to damage induced by various cancer treatments. Tumor cell senescence is generally considered undesirable, as senescent cells become resistant to death and block tumor remission while exacerbating tumor malignancy and treatment resistance. Therefore, the identification of senescent tumor cells is of ongoing interest to the cancer research community.

Friendship in Befriending? Older Service Users' Notions of Friendship in a Befriending Scheme.

Social isolation and feelings of loneliness are main reasons that befriending services are approached by older adults. The promise of an individually matched volunteer, a befriender, paying them regular visits, offers hope of increased social interaction, meaningfulness, and connectedness in everyday life. The current consensus in qualitative research literature is that loneliness and isolation may be alleviated by such home visits.

Effect of an app on students' knowledge about diabetes during the COVID-19 pandemic.

Objective: to analyze the effect of an app on Nursing students' knowledge about diabetes during the COVID-19 pandemic, as well as their self-assessment and satisfaction level.

Method: a quasi-experimental study carried out with 40 Nursing students from the Brazilian Northeast region. The E-MunDiabetes® app was used to assess the participants' knowledge at the pre-test, immediate post-test and after 15 days, as well as their self-assessment and satisfaction level in relation to using the app.

Telematics program of breathing exercises and mindfulness for post-coronavirus disease 2019 patients.

Objective: The coronavirus disease 2019 pandemic is an economic, social, and health challenge. During the coronavirus disease 2019 lockdown, a telematics platform for respiratory physiotherapy and mindfulness was created, aiming to reduce dyspnea and anxiety and to increase quality of life in post-coronavirus disease 2019 patient.

Methods: A quasi-experimental study was performed on post-coronavirus disease 2019 patients, with breathing exercises and mindfulness with remote supervision by a respiratory physiotherapist.

E-MunDiabetes: A Mobile Application for Nursing Students on Diabetes Education During the COVID-19 Pandemic.

The COVID-19 pandemic caused tremendous disruption of health systems worldwide. Patients with diabetes are at a high risk of COVID-19 exposure because face-to-face consultations have been standard for diabetes management. This study describes the development and validation of a mobile application for nursing students on diabetes education during the COVID-19 pandemic.

Effects of chronic dietary nitrate supplementation on longevity, vascular function and cancer incidence in rats.

Rationale: Dietary nitrate and nitrite have a notoriously bad reputation because of their proposed association with disease, in particular cancer. However, more recent lines of research have challenged this dogma suggesting that intake of these anions also possess beneficial effects after in vivo conversion to the vital signaling molecule nitric oxide. Such effects include improvement in cardiovascular, renal and metabolic function, which is partly mediated via reduction of oxidative stress.

UltraPlex Hapten-Based Multiplexed Fluorescent Immunohistochemistry.

The UltraPlex method for multiplexed two-dimensional fluorescent immunohistochemistry is described, in which hapten tags conjugated to primary antibodies facilitate multiplexed imaging of four or more antigens per tissue section at once. Anti-hapten secondary antibodies labeled with fluorophores provide amplified signal for detection, which is accomplished using a standard fluorescent microscope or digital slide scanner. The protocol is rapid and straightforward and utilizes conventionally prepared tissue samples.

Multiplexed Tissue Tomography.

Multiplexed tissue tomography enables comprehensive spatial analysis of markers within a whole tissue or thick tissue section. Clearing agents are often used to make tissue transparent and facilitate deep tissue imaging. Many methods of clearing and tissue tomography are currently used in a variety of tissue types.

Previous SARS-CoV-2 Infection Increases B.1.1.7 Cross-Neutralization by Vaccinated Individuals.

With the spread of new variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), there is a need to assess the protection conferred by both previous infections and current vaccination. Here we tested the neutralizing activity of infected and/or vaccinated individuals against pseudoviruses expressing the spike of the original SARS-CoV-2 isolate Wuhan-Hu-1 (WH1), the D614G mutant and the B.1.

Lipid-derived electrophiles mediate the effects of chemotherapeutic topoisomerase I poisons.

Topoisomerase 1 (Top1) reversibly nicks chromosomal DNA to relax strain accumulated during transcription, replication, chromatin assembly, and chromosome condensation. The Top1 poison camptothecin targets cancer cells by trapping the enzyme in the covalent complex Top1, tethered to cleaved DNA by a tyrosine-3'-phosphate bond. In vitro mechanistic studies point to interfacial inhibition, where camptothecin binding to the Top1-DNA interface stabilizes Top1.

PhysioArt: a teaching tool to motivate students to learn physiology.

Learning physiology is challenging for students. The nature of the discipline, which includes many complex mechanisms, makes the subject complicated. Furthermore, the length of the textbooks and the usual multiple-choice tests, which prioritize memorizing instead of understanding, tend to discourage the students.

Environmental and genetic determinants of amphicarpy in Pisum fulvum, a wild relative of domesticated pea.

Pisum fulvum is an annual legume native to Syria, Lebanon, Israel and Jordan. In certain locations, P. fulvum individuals were documented to display a reproductive dimorphism - amphicarpy, with both above and below ground flowers and pods.

Adherence to standards of care and mortality in the management of Staphylococcus aureus bacteraemia in Peru: A prospective cohort study.

Background: Despite high mortality rates, physicians can alter the course of the Staphylococcus aureus bacteraemia (SAB) by following recommended standards of care. We aim to assess the adherence of these guidelines and their impact on mortality.

Methods: Substudy from a prospective cohort of hospitalized patients with SAB from three hospitals from Peru.

Sex Bias and Genotype Influence on Opioid Safety Profile in Chronic Low Back Pain.

Objectives: The use of opioids to relieve pain is a challenge because of the high variability in dose requirements and tolerance profiles. Among potential modulators are the individual's genetic background and being female. Our aim was to evaluate sex bias and genotype-related influence on opioid titration safety, in chronic low back pain (CLBP), the most frequent chronic noncancer pain.

Association between tuberculosis and depression on negative outcomes of tuberculosis treatment: A systematic review and meta-analysis.

Background: Depression is a common comorbidity of tuberculosis (TB) and is associated with poor adherence to treatment of multiple disorders. We conducted a systematic review to synthesize the existing evidence on the relationship between depression and negative outcomes of TB treatment.

Methods: We systematically reviewed studies that evaluated depressive symptoms (DS) directly or indirectly through psychological distress (PD) and measured negative treatment outcomes of drug-sensitive pulmonary TB, defined as death, loss to follow-up, or non-adherence.

Mevalonate pathway activity as a determinant of radiation sensitivity in head and neck cancer.

Radioresistance is a major hurdle in the treatment of head and neck squamous cell carcinoma (HNSCC). Here, we report that concomitant treatment of HNSCCs with radiotherapy and mevalonate pathway inhibitors (statins) may overcome resistance. Proteomic profiling and comparison of radioresistant to radiosensitive HNSCCs revealed differential regulation of the mevalonate biosynthetic pathway.

Vibrational Properties of Pd Nanocubes.

The atomic disorder and the vibrational properties of Pd nanocubes have been studied through a combined use of X-ray diffraction and molecular dynamics simulations. The latter show that the trend of the mean square relative displacement as a function of the radius of the coordination shells is characteristic of the nanoparticle shape and can be described by a combined model: A correlated Debye model for the thermal displacement and a parametric expression for the static disorder. This combined model, supplemented by results of line profile analysis of the diffraction patterns collected at different temperatures (100, 200, and 300 K) can explain the observed increase in the Debye-Waller coefficient, and shed light on the effect of the finite domain size and of the atomic disorder on the vibrational properties of metal nanocrystals.

O-GlcNAcylation Enhances Double-Strand Break Repair, Promotes Cancer Cell Proliferation, and Prevents Therapy-Induced Senescence in Irradiated Tumors.

The metabolic reprogramming associated with characteristic increases in glucose and glutamine metabolism in advanced cancer is often ascribed to answering a higher demand for metabolic intermediates required for rapid tumor cell growth. Instead, recent discoveries have pointed to an alternative role for glucose and glutamine metabolites as cofactors for chromatin modifiers and other protein posttranslational modification enzymes in cancer cells. Beyond epigenetic mechanisms regulating gene expression, many chromatin modifiers also modulate DNA repair, raising the question whether cancer metabolic reprogramming may mediate resistance to genotoxic therapy and genomic instability.

Pharmacogenetics and prediction of adverse events in prescription opioid use disorder patients.

The threats involved in the long-term opioid treatment of chronic non-cancer pain (CNCP) have increased notably. Strategies to identify at-risk patients are important because there is no clear evidence showing which screening or deprescription programmes are appropriate. Our aim was to evaluate the evidence provided by pharmacogenetics applied to predict an analgesic toxicity profile in prescription opioid use disorder (POUD) patients participating in an opioid deprescription programme.