ABSTRACT
Psoriatic arthritis (PsA) is a complex inflammatory disease that challenges diagnosis and complicates the rational selection of effective therapies. Although T cells are considered active effectors in psoriasis and PsA, the role of CD8+ T cells in pathogenesis is not well understood. We selected the humanized mouse model NSG-SGM3 transgenic strain to examine psoriasis and PsA endotypes. Injection of PBMCs and sera from patients with psoriasis and PsA generated parallel skin and joint phenotypes in the recipient mouse. The transfer of human circulating memory T cells was followed by migration and accumulation in the skin and synovia of these immunodeficient mice. Unexpectedly, immunoglobulins were required for recapitulation of the clinical phenotype of psoriasiform lesions and PsA domains (dactylitis, enthesitis, bone erosion). Human CD8+ T cells expressing T-bet, IL-32 and CXCL14 were detected by spatial transcriptomics in murine synovia and by immunofluorescence in the human PsA synovia. Importantly, depletion of human CD8+ T cells prevented skin and synovial inflammation in mice humanized with PsA peripheral blood cells. The humanized model of psoriasis and PsA represents a valid platform for accelerating the understanding of disease pathogenesis, improving the design of personalized therapies, and revealing psoriatic disease targets.
Subject(s)
Arthritis, Psoriatic , CD8-Positive T-Lymphocytes , Disease Models, Animal , Animals , Arthritis, Psoriatic/immunology , Arthritis, Psoriatic/pathology , Humans , Mice , CD8-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/metabolism , Mice, Transgenic , Skin/pathology , Skin/immunology , Female , Male , Phenotype , Psoriasis/immunology , Psoriasis/pathologyABSTRACT
OBJECTIVE: Our objective was to identify systemic sclerosis (SSc) patients with a high burden of autonomic symptoms and to determine whether they have a distinct clinical phenotype, gastrointestinal (GI) transit or extraintestinal features. METHODS: In a prospective cohort of SSc patients with GI disease, clinical data were systematically obtained at routine visits. Dysautonomia was identified by the Composite Autonomic Symptom Score (COMPASS)-31questionnaire. GI transit was measured by whole-gut scintigraphy. Associations between total COMPASS-31 scores and clinical features, GI symptoms, and transit were evaluated. Comparisons between patients with global autonomic dysfunction [(GAD); ≥5 positive COMPASS-31 subdomains] and those with limited autonomic dysfunction [(LAD); <5 positive subdomains] were also studied. RESULTS: 91 patients with SSc and GI involvement were included [mean age 57, 90% female, 74% limited cutaneous disease, 83% significant GI disease (Medsger score ≥2)]. The mean COMPASS-31 score in SSc was higher than controls (38.8 vs. 7.2). 33% had GAD, 67% had LAD. Patients with GAD were more likely to have limited SSc (93% vs. 65%; p<0.01) and have sicca symptoms (100% vs. 77%; p=0.01). Gastric and colonic transit were faster in patients with GAD (p<0.05). Upper GI involvement (Medsger GI score of 1 or 2) was associated with higher total COMPASS-31 scores (p=0.02). CONCLUSION: Symptoms of global dysautonomia are seen in up to one-third of patients with SSc and GI involvement. Identifying specific clinical characteristics associated with GAD in SSc will help to identify a population that may benefit from therapies that modulate the autonomic nervous system.
ABSTRACT
Age-related macular degeneration (AMD) and diabetic retinopathy (DR) are common retinal diseases responsible for most blindness in working-age and elderly populations. Oxidative stress and mitochondrial dysfunction play roles in these pathogenesis, and new therapies counteracting these contributors could be of great interest. Some molecules, like coenzyme Q10 (CoQ10), are considered beneficial to maintain mitochondrial homeostasis and contribute to the prevention of cellular apoptosis. We investigated the impact of adding CoQ10 (Q) to a nutritional antioxidant complex (Nutrof Total®; N) on the mitochondrial status and apoptosis in an in vitro hydrogen peroxide (H2O2)-induced oxidative stress model in human retinal pigment epithelium (RPE) cells. H2O2 significantly increased 8-OHdG levels (p < 0.05), caspase-3 (p < 0.0001) and TUNEL intensity (p < 0.01), and RANTES (p < 0.05), caspase-1 (p < 0.05), superoxide (p < 0.05), and DRP-1 (p < 0.05) levels, and also decreased IL1ß, SOD2, and CAT gene expression (p < 0.05) vs. control. Remarkably, Q showed a significant recovery in IL1ß gene expression, TUNEL, TNFα, caspase-1, and JC-1 (p < 0.05) vs. H2O2, and NQ showed a synergist effect in caspase-3 (p < 0.01), TUNEL (p < 0.0001), mtDNA, and DRP-1 (p < 0.05). Our results showed that CoQ10 supplementation is effective in restoring/preventing apoptosis and mitochondrial stress-related damage, suggesting that it could be a valid strategy in degenerative processes such as AMD or DR.
Subject(s)
Apoptosis , Hydrogen Peroxide , Oxidative Stress , Retinal Pigment Epithelium , Ubiquinone , Humans , Ubiquinone/analogs & derivatives , Ubiquinone/pharmacology , Retinal Pigment Epithelium/metabolism , Retinal Pigment Epithelium/drug effects , Oxidative Stress/drug effects , Apoptosis/drug effects , Hydrogen Peroxide/metabolism , Hydrogen Peroxide/pharmacology , Mitochondria/metabolism , Mitochondria/drug effects , Antioxidants/pharmacology , Epithelial Cells/metabolism , Epithelial Cells/drug effects , Cell Line , Dietary SupplementsABSTRACT
Casein kinase 1 δ (CK1δ) controls essential biological processes including circadian rhythms and Wnt signaling, but how its activity is regulated is not well understood. CK1δ is inhibited by autophosphorylation of its intrinsically disordered C-terminal tail. Two CK1 splice variants, δ1 and δ2, are known to have very different effects on circadian rhythms. These variants differ only in the last 16 residues of the tail, referred to as the extreme C-termini (XCT), but with marked changes in potential phosphorylation sites. Here we test if the XCT of these variants have different effects in autoinhibition of the kinase. Using NMR and HDX-MS, we show that the δ1 XCT is preferentially phosphorylated by the kinase and the δ1 tail makes more extensive interactions across the kinase domain. Mutation of δ1-specific XCT phosphorylation sites increases kinase activity both in vitro and in cells and leads to changes in circadian period, similar to what is reported in vivo . Mechanistically, loss of the phosphorylation sites in XCT disrupts tail interaction with the kinase domain. δ1 autoinhibition relies on conserved anion binding sites around the CK1 active site, demonstrating a common mode of product inhibition of CK1δ. These findings demonstrate how a phosphorylation cycle controls the activity of this essential kinase. Significance: Subtle control of kinase activity is critical to physiologic modulation of multiple physiological processes including circadian rhythms. CK1δ and the closely related CK1ε regulate circadian rhythms by phosphorylation of PER2, but how kinase activity itself is controlled is not clear. Building on the prior observation that two splice isoforms of CK1δ regulate the clock differently, we show that the difference maps to three phosphorylation sites in the variably spliced region (XCT) that cause feedback inhibition of the kinase domain. More broadly, the data suggest a general model where CK1 activity on diverse substrates can be controlled by signaling pathways that alter tail phosphorylation. These inhibitory phosphorylation sites could also be targets for new therapeutic interventions.
ABSTRACT
The present work describes a quick, simple, and efficient method based on the use of layered double hydroxides (LDH) coupled to dispersive solid phase micro-extraction (DSPME) to remove α-naphthol (α-NAP) and ß-naphthol (ß-NAP) isomers from water samples. Three different LDHs (MgAl-LDH, NiAl-LDH, and CoAl-LDH) were used to study how the interlayer anion and molar ratio affected the removal performance. The critical factors in the DSPME procedure (pH, LDH amount, contact time) were optimized by the univariate method under the optimal conditions: pH, 4-8; LDH amount, 5 mg; and contact time, 2.5 min. The method can be successfully applied in real sample waters, removing NAP isomers even in ultra-trace concentrations. The large volume sample stacking (LVSS-CE) technique provides limits of detections (LODs) of 5.52 µg/L and 6.36 µg/L for α-naphthol and ß-naphthol, respectively. The methodology's precision was evaluated on intra- and inter-day repeatability, with %RSD less than 10% in all cases. The MgAl/Cl--LDH selectivity was tested in the presence of phenol and bisphenol A, with a removal rate of >92.80%. The elution tests suggest that the LDH MgAl/Cl--LDH could be suitable for pre-concentration of α-naphthol and ß-naphthol in future works.
Subject(s)
Electrophoresis, Capillary , Limit of Detection , Naphthols , Solid Phase Microextraction , Water Pollutants, Chemical , Naphthols/chemistry , Naphthols/analysis , Naphthols/isolation & purification , Water Pollutants, Chemical/analysis , Water Pollutants, Chemical/isolation & purification , Water Pollutants, Chemical/chemistry , Electrophoresis, Capillary/methods , Solid Phase Microextraction/methods , Hydroxides/chemistry , Isomerism , Reproducibility of Results , Hydrogen-Ion ConcentrationABSTRACT
The placenta is crucial for fetal development, yet the impact of environmental stressors such as arsenic exposure remains poorly understood. We apply single-cell RNA sequencing to analyze the response of the mouse placenta to arsenic, revealing cell-type-specific gene expression, function, and pathological changes. Notably, the Prap1 gene, which encodes proline-rich acidic protein 1 (PRAP1), is significantly upregulated in 26 placental cell types including various trophoblast cells. Our study shows a female-biased increase in PRAP1 in response to arsenic and localizes it in the placenta. In vitro and ex vivo experiments confirm PRAP1 upregulation following arsenic treatment and demonstrate that recombinant PRAP1 protein reduces arsenic-induced cytotoxicity and downregulates cell cycle pathways in human trophoblast cells. Moreover, PRAP1 knockdown differentially affects cell cycle processes, proliferation, and cell death depending on the presence of arsenic. Our findings provide insights into the placental response to environmental stress, offering potential preventative and therapeutic approaches for environment-related adverse outcomes in mothers and children.
Subject(s)
Arsenic , Placenta , Single-Cell Analysis , Trophoblasts , Female , Pregnancy , Placenta/metabolism , Placenta/drug effects , Animals , Humans , Mice , Trophoblasts/metabolism , Trophoblasts/drug effects , Trophoblasts/cytology , Arsenic/toxicity , Sequence Analysis, RNA , Stress, Physiological/genetics , Cell Cycle/drug effects , Cell Cycle/genetics , Cell Proliferation/drug effects , Up-Regulation/drug effects , Mice, Inbred C57BLABSTRACT
The dataset provides data obtained with eye-tracking while 55 volunteers solved 3 distinct neuropsychological tests on a screen inside a closed room. Among the 55 volunteers, 22 were women and 33 were men, all with ages ranging between 9 and 50, and 5 of whom were diagnosed with Attention Deficit Hyperactivity Disorder (ADHD) [1]. The eye-tracker used for the collection of the data was an EyeTribe, which has a sampling rate of 60 Hz and an average visual angle between 0.5 and 1, which correspond to an on-screen error between 0.5 and 1cm (0.1969 to 0.393 inches aprox) respectively, when the distance to the user is around 60cm (23.62 in) [2], which was the case during the collection of these data. The neuropsychological tests were implemented in a software named NEURO-INNOVA KIDS® [3], which are the following: a domino test adapted from the D-48 intelligence test [4], an adaptation of the MASMI test consisting of unfolded cubes [5], the figures series completion test adapted from [6], and the Poppelreuter figures test [7]. Before each of the tests, a calibration process was performed, ensuring that the visual angle error was less than or equal to 0.5 cm (0.1969 in), which is considered an acceptable calibration. The collective mean duration of the four administered tests amounted to 20 minutes. This dataset exhibits significant promise for potential utilization due to the extensive prevalence of these neuropsychological assessments among healthcare practitioners for evaluating diverse cognitive faculties in individuals. Moreover, it has been empirically established that poor performance on these tests is associated with attention deficits [8].
ABSTRACT
BACKGROUND: stevia and D-tagatose have shown a reduction in total calorie and carbohydrate intake as a substitute for sucrose, demonstrating a stabilizing effect on pH and bacterial proliferation. OBJECTIVE: to evaluate the effect of D-tagatose, stevia and sucrose on salivary pH and bacterial activity in odontology students. METHODOLOGY: a controlled study of parallel and randomized groups with a single blind, whose sample considered three groups subjected to a mouthwash of D-tagatose (n = 10), stevia (n = 10) and sucrose (n = 10). These solutions were administered over 1 minute in a single 6.4 % concentrated dose. Data collection and analysis considered the recording of salivary pH 5 min before exposure to the sweetener, immediately after expulsion of the mouthwash and 15 min later, 30 min, 45 min and 48 hours. The counting of the final number of colony-forming units per mL (CFU/mL) was counted using the salivary samples obtained immediately after exposure of the sweetener together with the sample obtained 30 minutes later, with the cultures performed on agar plates. RESULTS: D-tagatose, stevia and sucrose presented significant differences in total CFU/mL at 30 minutes (p < 0.001), while salivary pH showed significant differences at 48 hours after administration (p < 0.001). CONCLUSION: D-tagatose, stevia and sucrose present significant differences in total CFU/mL and salivary pH, these findings being a possible indication of a partial inhibitory effect on bacterial metabolism.
ABSTRACT
This study aimed to analyse the impact of a simulated human digestion process on the composition and functional properties of dietary fibres derived from pomegranate-peel, tomato-peel, broccoli-stem and grape-stem by-products. For this purpose, a computer-controlled simulated digestion system consisting of three bioreactors (simulating the stomach, small intestine and colon) was utilised. Non-extractable phenols associated with dietary fibre and their influence on antioxidant capacity and antiproliferative activity were investigated throughout the simulated digestive phases. Additionally, the modifications in oligosaccharide composition, the microbiological population and short-chain fatty acids produced within the digestion media were examined. The type and composition of each dietary fibre significantly influenced its functional properties and behaviour during intestinal transit. Notably, the dietary fibre from the pomegranate peel retained its high phenol content throughout colon digestion, potentially enhancing intestinal health due to its strong antioxidant activity. Similarly, the dietary fibre from broccoli stems and pomegranate peel demonstrated anti-proliferative effects in both the small and the large intestines, prompting significant modifications in colonic microbiology. Moreover, these fibre types promoted the growth of bifidobacteria over lactic acid bacteria. Thus, these results suggest that the dietary fibre from pomegranate peel seems to be a promising functional food ingredient for improving human health.
ABSTRACT
OBJECTIVE: Pediatric spondylodiscitis (PSD) is an uncommon condition, for which there are no specific international clinical guidelines. Factors related to complications have not been stablished. Our aim was to describe clinical and epidemiological characteristics of PSD, to analyze factors associated with complications and to evaluate adherence to the recommendations of the Spanish National Consensus Document (NCD) for the diagnostic and therapeutic approach to acute osteoarticular infections. MATERIAL AND METHODS: Ambispective, multicenter, national study of two PSD cohorts: historical (2008-2012) and prospective (2015-2020, after publication of NCD). Patients with diagnosis of PSD were included. Demographic, clinical, microbiological and radiological data were recorded. Factors related to the development of complications were analized by logistic regression. Comparisons between both cohorts were performed. RESULTS: Ninety-eight PSD were included. In 84.7%, diagnosis was confirmed by magnetic resonance imaging. Microbiological isolation was obtained in 6.1%, with methicillin-sensitive S. aureus as the main etiologic agent. Complications occurred in 18.9%, the most frequent being soft tissue abscess. Of the 8.6% of patients with sequelae, persistent pain was the most common. Comparing cohorts, there was better adherence to NCD treatment recommendations in the prospective one (57.6% vs. 12.9%, pâ¯<â¯0.01), including a reduction in the length of intravenous antibiotic therapy (10 vs. 14 days, pâ¯<â¯0.01). CONCLUSIONS: The evolution of PSD in our series was favorable, with low frequency of complications and sequelae. The adherence to the recommendations of the NCD was high. Studies with larger sample size are needed to establish new recommendations to optimize the approach to these infections.
ABSTRACT
Examining underlying neurostructural correlates of specific cognitive abilities is practically and theoretically complicated by the existence of the positive manifold (all cognitive tests positively correlate): if a brain structure is associated with a cognitive task, how much of this is uniquely related to the cognitive domain, and how much is due to covariance with all other tests across domains (captured by general cognitive functioning, also known as general intelligence, or 'g')? We quantitatively address this question by examining associations between brain structural and diffusion MRI measures (global tissue volumes, white matter hyperintensities, global white matter diffusion fractional anisotropy and mean diffusivity, and FreeSurfer processed vertex-wise cortical volumes, smoothed at 20mm fwhm) with g and cognitive domains (processing speed, crystallised ability, memory, visuospatial ability). The cognitive domains were modelled using confirmatory factor analysis to derive both hierarchical and bifactor solutions using 13 cognitive tests in 697 participants from the Lothian Birth Cohort 1936 study (mean age 72.5 years; SD = .7). Associations between the extracted cognitive factor scores for each domain and g were computed for each brain measure covarying for age, sex and intracranial volume, and corrected for false discovery rate. There were a range of significant associations between cognitive domains and global MRI brain structural measures (r range .008 to .269, p < .05). Regions implicated by vertex-wise regional cortical volume included a widespread number of medial and lateral areas of the frontal, temporal and parietal lobes. However, at both global and regional level, much of the domain-MRI associations were shared (statistically accounted for by g). Removing g-related variance from cognitive domains attenuated association magnitudes with global brain MRI measures by 27.9-59.7% (M = 46.2%), with only processing speed retaining all significant associations. At the regional cortical level, g appeared to account for the majority (range 22.1-88.4%; M = 52.8% across cognitive domains) of regional domain-specific associations. Crystallised and memory domains had almost no unique cortical correlates, whereas processing speed and visuospatial ability retained limited cortical volumetric associations. The greatest spatial overlaps across cognitive domains (as denoted by g) were present in the medial and lateral temporal, lateral parietal and lateral frontal areas.
ABSTRACT
Cardiovascular diseases continue to be the main cause of death in Venezuela, and hypertension is the principal risk factor. The May Measurement Month (MMM) campaign is a global initiative aimed to raising awareness of hypertension, which has been conducted in Venezuela since 2017. May Measurement Month 2021 included 46 732 participants with a mean age of 56.4 years (SD 14.4), 57.9% of whom were female. The percentage with hypertension was 60.3% (57.9% of females and 63.7% of males), 82.3% (84.8% of females and 79.2% of males) were aware, and 80.2% were taking antihypertensive medication. Of those on antihypertensive medication, 44.2% (41.2% of females and 48.2% of males) were not controlled [blood pressure (BP) ≥ 140/≥90â mmHg], with 61.3% receiving one drug, 30.0% two drugs, and 8.7% three or more drugs. 87.5% of those on treatment reported taking it regularly. Conditions associated with higher BP levels include fewer years of education, having a previous diagnosis of hypertension, and women who were hypertensive during a previous pregnancy. Physical activity and pregnancy were conditions associated with lower BP levels. A previous positive COVID-19 test was reported in 11.1%, and one or more COVID-19 vaccinations reported in 22.7% of participants. Of those on antihypertensive medication, 78.8% reported their treatment was not affected by COVID-19. Results are consistent with previous MMM campaigns and indicate that the screening campaign is feasible and useful to identify hypertension even in exceptional conditions such as the COVID-19 pandemic.
ABSTRACT
Background: Clostridioides difficile infection (CDI) occurs in various contexts and care settings and is managed by multiple specialists who are not experts in its management. While there are many initiatives to improve the diagnosis and avoid overdiagnosis, there is less focus on the overall management of the infection. Methods: We studied a cohort of patients with a positive test result for toxigenic C difficile in 2 hospitals. Hospital A has a program that provides advice from an infectious disease specialist (IDS) and promotes continuity of care by providing a phone number to contact the IDS. Hospital B does not have any specific CDI program. The evaluation assessed the proportion of patients not treated (carriers or self-limited disease), adherence to Infectious Diseases Society of America guidelines, access to novel therapies, recurrence and mortality rates, and readmission and emergency department visits due to CDI. We assessed the program's effectiveness through a logistic regression model adjusted for covariates chosen by clinical criteria. Results: Hospital A avoided more unnecessary treatments (19.3% vs 11.5%), provided access to novel therapies more frequently (35.3% vs 13%), and adhered more closely to current guidelines (95.8% vs 71.3%). Although the mortality and recurrence rates did not differ, the absence of an intervention program was associated with greater odds of admission due to recurrence (odds ratio, 4.19; P = .037) and more visits to the emergency department due to CDI (odds ratio, 8.74; P = .001). Conclusions: Implementation of a CDI intervention program based on recommendations from IDSs and improved access to specialized care during the follow-up is associated with enhanced quality of CDI management and potential reductions in hospital resource utilization.
ABSTRACT
Metabolic syndrome (MetS) is a group of clinical traits directly linked to type 2 diabetes mellitus and cardiovascular diseases, whose prevalence has been rising nationally and internationally. We aimed to evaluate ten known and novel surrogate markers of insulin resistance and obesity to identify MetS in Mexican adults. The present cross-sectional study analyzed 10575 participants from ENSANUT-2018. The diagnosis of MetS was based on the Adult Treatment Panel III (ATP III) criteria and International Diabetes Federation (IDF) criteria, stratified by sex and age group. According to ATP III, the best biomarker was the metabolic score for insulin resistance (METS-IR) in men aged 20-39 and 40-59 years and lipid accumulation product (LAP) in those aged ≥60 years. The best biomarker was LAP in women aged 20-39 and triglyceride-glucose index (TyG) in those aged 40-59 and ≥60 years. Using the IDF criteria, the best biomarker was LAP in men of all ages. TyG gave the best results in women of all ages. The best biomarker for diagnosis of MetS in Mexican adults depends on the criteria, including sex and age group. LAP and TyG are easy to obtain, inexpensive, and especially useful at the primary care level.
ABSTRACT
The selection of suitable combinations of chiral stationary phases (CSPs) and mobile phases (MPs) for the enantioresolution of chiral compounds is a complex issue that often requires considerable experimental effort and can lead to significant waste. Linking the structure of a chiral compound to a CSP/MP system suitable for its enantioseparation can be an effective solution to this problem. In this study, we evaluate algorithmic tools for this purpose. Our proposed consensus model, which uses multiple optimized artificial neural networks (ANNs), shows potential as an intelligent recommendation system (IRS) for ranking chromatographic systems suitable for the enantioresolution of chiral compounds with different molecular structures. To evaluate the IRS potential in a proof-of-concept stage, 56 structural descriptors for 56 structurally unrelated chiral compounds across 14 different families are considered. Chromatographic systems under study comprise 7 cellulose and amylose derivative CSPs and acetonitrile or methanol aqueous MPs (14 chromatographic systems in all). The ANNs are optimized using a fit-for-purpose version of the chaotic neural network algorithm with competitive learning (CCLNNA), a novel approach not previously applied in the chemical domain. CCLNNA is adapted to define the inner ANN complexity and perform feature selection of the structural descriptors. A customized target function evaluates the correctness of recommending the appropriate CSP/MP system. The ANN-consensus model exhibits no advisory failures and requires only an experimental attempt to verify the IRS recommendation for complete enantioresolution. This outstanding performance highlights its potential to effectively resolve this problem.
ABSTRACT
Obesity is a major public health issue that is associated with metabolic diseases including diabetes mellitus type 2 and metabolic syndrome. This pathology leads to detrimental cardiovascular health and secondary effects, such as lipotoxicity, inflammation, and oxidative stress. Recently, extracellular vesicles (EVs) have been highlighted as novel players participating in human physiology and pathophysiology. In obesity, adipose tissue is related to the active shedding of adipocyte-derived extracellular vesicles (AdEVs). The current review explores and highlights the role of AdEVs and their cargo in obesity and metabolic syndrome. AdEVs are proposed to play an important role in obesity and its comorbidities. AdEVs are biological nanoparticles mainly shed by visceral and subcutaneous adipose tissue, acting in physiological and pathophysiological conditions, and also carrying different cargo biomolecules, such as RNA, microRNA (miRNA), proteins, and lipids, among others. RNA and miRNA have local and systemic effects affecting gene expression in target cell types via paracrine and endocrine actions. State of the art analyses identified some miRNAs, such as miR-222, miR-23b, miR-4429, miR-148b, and miR-4269, that could potentially affect cell pathways involved in obesity-related comorbidities, such as chronic inflammation and fibrosis. Similarly, AdEVs-proteins (RBP4, perilipin-A, FABP, mimecan, TGFBI) and AdEVs-lipids (sphingolipids) have been linked to the obesity pathophysiology. The current knowledge about AdEVs along with further research would support and reveal novel pathways, potential biomarkers, and therapeutic options in obesity.
Subject(s)
CD47 Antigen , Neoplasms , Receptors, Immunologic , Humans , CD47 Antigen/metabolism , CD47 Antigen/antagonists & inhibitors , Neoplasms/drug therapy , Neoplasms/metabolism , Receptors, Immunologic/metabolism , Receptors, Immunologic/antagonists & inhibitors , Animals , Signal Transduction/drug effects , Antineoplastic Agents/therapeutic use , Molecular Targeted Therapy/methods , Antigens, DifferentiationABSTRACT
OBJECTIVE: To analyse the impact of the COVID-19 pandemic on the mental health of nurses in Spanish out-of-hospital Emergency Services, identifying predictor factors of greater severity. METHOD: A multicentre cross-sectional descriptive study was designed, including all nurses working in any Spanish out-of-hospital Emergency Services between 01/02/2021 and 30/04/2021. The main outcomes were the level of depression, anxiety and stress assessed through the DASS-21 scale. Sociodemographic, clinical, and occupational information was also collected. Univariate and multivariate analyses were conducted to determine possible associations between variables. RESULTS: The sample included 474 nurses. 32.91%, 32.70% and 26.33% of the participants had severe or extremely severe levels of depression, anxiety and stress, respectively. Professionals with fewer competencies to handle stressful situations, those who had used psychotropic drugs and/or psychotherapy on some occasion before the pandemic onset, or those who had changed their working conditions presented more likelihood of developing more severe levels of depression, anxiety and/or stress. CONCLUSION: Nurses in Spanish out-of-hospital Emergency Services have presented medium levels of depression, anxiety and stress during the pandemic. Clinical and occupational factors have been associated with a higher degree of psychological distress. It is necessary to adopt strategies that promote professionals' self-efficacy and mitigate the triggers of negative emotional states.
ABSTRACT
Ovarian cancer (OC) is the leading cause of death in women with gynecological cancers. Its diagnosis is more likely in advanced ages, with the older population being the most seen in consultations. Poly(ADP-ribose) inhibitors (PARPi) have changed OC clinical practice and evolution, showing great benefit. However, there is a lack of evidence of PARPi in elderly population that can impact the therapeutic decision and the safety/efficacy. It is necessary to avoid age as limiting factor in PARPis prescription. We conducted a review of the most relevant randomized phase III trials of maintenance PARPi after first-line treatment of advanced OC. We observed the lack of a single criterion for considering older patients, varying among trials. There is a benefit of PARPis in different populations. However, PARPi effect on quality of life is not reported, something of great relevance considering their vulnerability. Measures are needed to benefit older patients to better adapt PARPi treatment.
ABSTRACT
Introduction: This study investigated a remotely delivered, therapist-facilitated, personalized music listening intervention for community-dwelling older adults experiencing loneliness during the Covid-19 pandemic. We assessed its feasibility and individuals' experiences of social connection and emotional well-being during the intervention. Methods: Ten cognitively unimpaired older adults who endorsed loneliness completed eight weekly sessions with a board-certified music therapist via Zoom. Participants were guided in developing two online personalized music playlists and were asked to listen to playlists for at least one hour daily. Feasibility metrics were attendance, accessibility, and compliance rates. Post-study interview responses were analyzed using a rapid qualitative methodology. Exploratory pre- and post-study measures of loneliness and other aspects of psychological well-being were obtained using validated questionnaires. Results: Ten participants (mean age 75.38 [65 to 85] years, 80% women) were enrolled from March to August 2021. Attendance and compliance rates were 100% and the accessibility rate was 90%. Most participants associated music with positive memories before the program and many reported that the intervention prompted them to reconnect with music or listen to music with greater intention. They cited increased connection from interacting with the music therapist and the music itself, as well as specific positive emotional impacts from integrating music into their daily lives. Median pre- to post-questionnaire measures of psychological function all changed in an improved direction. Discussion: Remotely delivered music therapy may be a promising intervention to promote regular music listening and socioemotional well-being in lonely older adults.