Background: Outcome measurement is essential to progress clinical practice and improve patient care.
Aim: To develop a Core Outcome Set for best care for the dying person.
Design: We followed the Core Outcome Measures in Effectiveness Trials (COMET) Initiative guidelines, which involved identifying potential outcomes via a systematic literature review (n = 619 papers) and from participants in the "iLIVE" project (10 countries: 101 patients, 37 family members, 63 clinicians), followed by a two-round Delphi study, and a consensus meeting.
Introduction: Anti-retroviral therapy (ART) simplification strategies are needed for treatment-experienced people with HIV (PWH) and multidrug-resistant viruses. These individuals are commonly treated with boosted ART regimens and are thereby at risk for harmful drug-drug interactions (DDI). In this trial, we aim to assess the efficacy of the combination doravirine, dolutegravir and lamivudine (DOR/DTG/3TC) among people with a history of virological failure who receive boosted ART.
View Article and Find Full Text PDFMultiple myeloma (MM) is linked to chronic NF-κB activity in myeloma cells, but this activity is generally considered a cell-autonomous property of the cancer cells. The precise extent of NF-κB activation and the contributions of the physical microenvironment and of cell-to-cell communications remain largely unknown. By quantitative immunofluorescence, we found that NF-κB is mildly and heterogeneously activated in a fraction of MM cells in human BMs, while only a minority of MM cells shows a strong activation.
View Article and Find Full Text PDFValproic acid (VPA) is an effective and widely used anti-seizure medication but is teratogenic when used during pregnancy, affecting brain and spinal cord development for reasons that remain largely unclear. Here we designed a genetic recombinase-based SOX10 reporter system in human pluripotent stem cells that enables tracking and lineage tracing of Neural Crest cells (NCCs) in a human organoid model of the developing neural tube. We found that VPA induces extensive cellular senescence and promotes mesenchymal differentiation of human NCCs.
View Article and Find Full Text PDFThe prospect of death influences people's thoughts about and how they deal with their remaining time. We aimed to understand whether patients with progressive, life-limiting diseases are oriented in the past, present, or future and how they deal with temporality. We conducted 57 in-depth interviews with end-of-life patients in 10 countries using thematic analysis at three levels (i.
View Article and Find Full Text PDFAdult T-cell leukemia-lymphoma (ATLL) is an aggressive malignancy driven by human T-cell leukemia virus type 1 (HTLV-1). Although patients from the Western hemisphere (Afro-Caribbean and South American) face worse prognoses, our understanding of ATLL molecular drivers derives mostly from Japanese studies. We performed multi-omic analyses to elucidate the genomic landscape of ATLL in Western cohorts.
View Article and Find Full Text PDFBackground: Family is a crucial social institution in end-of-life care. Family caregivers are encouraged to take on more responsibility at different times during the illness, providing personal and medical care. Unpaid work can be overburdening, with women often spending more time in care work than men.
View Article and Find Full Text PDFObjective: To help healthcare professionals (HCP) act with more confidence when communicating about approaching death, we sought to develop a communication model for HCP to facilitate conversations with dying patients and family caregivers (FC) in nonemergency situations.
Methods: We used a four-phase integrative approach: (1) creation of a preliminary model based on a systematic literature review and expert knowledge, (2) review of the model draft by international palliative care experts, (3) review by key stakeholders, and (4) final appraisal by communication experts.
Results: After the clinical recognition of dying, the communication model provides a structure and practical communication aids for navigating the conversation based on three phases.
Introduction: Parkinson's disease is characterised by the presence of motor symptoms including hypomimia, and by non-motor symptoms including alterations in facial recognition of basic emotions. Few studies have investigated this alteration and its relationship to the severity of hypomimia.
Objective: The objective is to study the relationship between hypomimia and the facial recognition of basic emotions in subjects with Parkinson's disease.
Premature children are at increased risk of executive functions (EF) deficits and these difficulties persist into adolescence and adulthood, potentially undermining their development and academic achievements. The aim of the present randomized controlled trial (RCT) is to evaluate the efficacy of the Intendu trainer, an adaptive virtual reality platform, at ameliorating EF in preterm children. A single-center, RCT was conducted.
View Article and Find Full Text PDFBackground: To date, there is a lack of standardization and consensus on which outcomes are central to assess the care provided to patients in the last month of life. Therefore, we aimed to conduct a systematic review to identify relevant outcomes to inform the development of a core outcome set for the best care for the dying person.
Methods: We conducted a systematic review of outcomes reported in the scientific literature about the care for the dying person in the last month of life.
Transcription factor dynamics is fundamental to determine the activation of accurate transcriptional programs and yet is heterogeneous at a single-cell level, even within homogeneous populations. We asked how such heterogeneity emerges for the nuclear factor κB (NF-κB). We found that clonal populations of immortalized fibroblasts derived from a single mouse embryo display robustly distinct NF-κB dynamics upon tumor necrosis factor ɑ (TNF-ɑ) stimulation including persistent, oscillatory, and weak activation, giving rise to differences in the transcription of its targets.
View Article and Find Full Text PDFObjectives: Although caring for dying patients and their family caregivers (FC) is integral to patient care, training in communication about approaching death is almost inexistent in medical and nursing curricula. Consequently, many health professionals have insufficient knowledge about conducting these conversations. In order to gain a broader insight into essential aspects of this communication from different perspectives, we conducted focus groups with key stakeholders.
View Article and Find Full Text PDFVeterinary pharmaceuticals have become of interest due to their indiscriminate use. Thus, this paper compiles studies on detection in surface and wastewater, and the treatment applied for their removal. Additionally, a case study was performed to evaluate its commercialization, as the ecological risk assessment for the most relevant compounds.
View Article and Find Full Text PDFBackground: In recent decades some studies described the frequent co-occurrence of celiac disease autoimmunity and overt celiac disease in patients with autism. Therefore, it was suggested that celiac disease could play a possible role in the etiopathogenesis of autism spectrum disorder. However, several other studies have not confirmed this association.
View Article and Find Full Text PDFBackground: Communities and local governments invest in compassionate communities (CCs) a great deal of time, money, effort, and work. However, it is not known whether the CCs are having the effect they are expected to have, so the value of continuing with these initiatives is unknown, and there is a need for a model for evaluating CCs to solve the question.
Objectives: To identify a set of core outcomes or benefits that should be measured to assess the impact of the CCs.
Echinoderm mass mortality events shape marine ecosystems by altering the dynamics among major benthic groups. The sea urchin , virtually extirpated in the Caribbean in the early 1980s by an unknown cause, recently experienced another mass mortality beginning in January 2022. We investigated the cause of this mass mortality event through combined molecular biological and veterinary pathologic approaches comparing grossly normal and abnormal animals collected from 23 sites, representing locations that were either affected or unaffected at the time of sampling.
View Article and Find Full Text PDFAutism Spectrum Disorder (ASD) is a complex neurodevelopmental disorder that can be associated with intellectual disability (ID) and epilepsy (E). The etiology and the pathogenesis of this disorder is in most cases still to be clarified. Several studies have underlined that the EEG recordings in children with these clinical pictures are abnormal, however the precise frequency of these abnormalities and their relationship with the pathogenic mechanisms and in particular with epileptic seizures are still unknown.
View Article and Find Full Text PDFEcancermedicalscience
November 2022
The seventh session of the Oncological Pathology Conference (JoPaO) entitled 'Pathological Anatomy in the context of the National Cancer Law: An overview of the Latin American experience', was held virtually on July 15, 22 and 23. Peru was the headquarters for this event, where 17 national and international professors of high academic standing participated. They interacted in a multidisciplinary context through talks with national panellists and the general public.
View Article and Find Full Text PDFαKlotho (Klotho) has well established renoprotective effects; however, the molecular pathways mediating its glomerular protection remain incompletely understood. Recent studies have reported that Klotho is expressed in podocytes and protects glomeruli through auto- and paracrine effects. Here, we examined renal expression of Klotho in detail and explored its protective effects in podocyte-specific Klotho knockout mice, and by overexpressing human Klotho in podocytes and hepatocytes.
View Article and Find Full Text PDFObjective: Trained immunity (TI) is a de facto memory program of innate immune cells, characterized by immunometabolic and epigenetic changes sustaining enhanced production of cytokines. TI evolved as a protective mechanism against infections; however, inappropriate activation can cause detrimental inflammation and might be implicated in the pathogenesis of chronic inflammatory diseases. In this study, we investigated the role of TI in the pathogenesis of giant cell arteritis (GCA), a large-vessel vasculitis characterized by aberrant macrophage activation and excess cytokine production.
View Article and Find Full Text PDFEarly identification of patients at risk for severe coronavirus disease 2019 (COVID-19) is crucial for appropriate triage and determination of need for closer monitoring. Few studies have examined laboratory trends in COVID-19 infection and sought to quantify the degree to which laboratory values affect mortality. We conducted a retrospective cohort (n = 407) study of hospitalized patients with COVID-19 early in the course of the pandemic, from March 16th to April 8th, 2020 and compared baseline to repeat laboratory testing 72 hours into admission.
View Article and Find Full Text PDFThe transcription factor family of nuclear factor kappa B (NF-κB) proteins is widely recognized as a key player in inflammation and the immune responses, where it plays a fundamental role in translating external inflammatory cues into precise transcriptional programs, including the timely expression of a wide variety of cytokines/chemokines. Live cell imaging in single cells showed approximately 15 years ago that the canonical activation of NF-κB upon stimulus is very dynamic, including oscillations of its nuclear localization with a period close to 1.5 hours.
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