The involvement of osteocytes in multiple myeloma (MM)-induced osteoclast (OCL) formation and bone lesions is still unknown. Osteocytes regulate bone remodelling at least partially, as a result of ...their cell death triggering OCL recruitment. In this study, we found that the number of viable osteocytes was significantly smaller in MM patients than in healthy controls, and negatively correlated with the number of OCLs. Moreover, the MM patients with bone lesions had a significantly smaller number of viable osteocytes than those without, partly because of increased apoptosis. These findings were further confirmed by ultrastructural in vitro analyses of human preosteocyte cells cocultured with MM cells, which showed that MM cells increased preosteocyte death and apoptosis. A micro-array analysis showed that MM cells affect the transcriptional profiles of preosteocytes by upregulating the production of osteoclastogenic cytokines such as interleukin (IL)-11, and increasing their pro-osteoclastogenic properties. Finally, the osteocyte expression of IL-11 was higher in the MM patients with than in those without bone lesions. Our data suggest that MM patients are characterized by a reduced number of viable osteocytes related to the presence of bone lesions, and that this is involved in MM-induced OCL formation.
Health and Wellness Coaching (HWC) may be beneficial in chronic condition care. We sought to appraise its effectiveness on quality of life (QoL), self-efficacy (SE), depression, and anxiety.
We ...searched MEDLINE, EMBASE, CINAHL, PsycINFO, and Cochrane CENTRAL for randomized trials published January 2005 - March 2023 that compared HWC to standard clinical care or another intervention without coaching. We examined QoL, SE, depression, or anxiety outcomes. Meta-analysis utilizing the random-effects model was used to estimate the pooled standardized mean difference (SMD).
Thirty included studies demonstrated that HWC improved QoL within 3 months (SMD 0.62 95 % CI 0.22–1.02, p = 0.002), SE within 1.5 months (SMD 0.38, 95 % CI 0.03–0.73, p = 0.03), and depression at 3, 6, and 12 months (SMD 0.67, 95 % CI 0.13–1.20, p = 0.01), (SMD 0.72, 95 % CI 0.19–1.24, p = 0.006), and (SMD 0.41, 95 % CI 0.09–0.73, p = 0.01) Certainty in the evidence for most outcomes was either very low or low primarily due to the high risk of bias, heterogeneity, and imprecision.
HWC improves QoL, SE, and depression across chronic illness populations. Future research needs to standardize intervention reporting and outcome collection.
Future HWC studies should standardize intervention components, reporting, and outcome measures, apply relevant chronic illness theories, and aim to follow participants for greater than one year.
•Health and Wellness Coaching (HWC) improved short-term self-efficacy, quality of life, and depression for patients with chronic conditions.•HWC was not effective at reducing patient-reported anxiety at any time point.•Effective interventions typically addressed at least three capacity constructs from the Theory of Patient Capacity (TPC).•Future research should use and clearly report on high-quality HWC interventions with fidelity to published standards.
Clinicians' satisfaction with encounter decision aids is an important component in facilitating implementation of these tools. We aimed to determine the impact of decision aids supporting shared ...decision making (SDM) during the clinical encounter on clinician outcomes.
We searched nine databases from inception to June 2017. Randomised clinical trials (RCTs) of decision aids used during clinical encounters with an unaided control group were eligible for inclusion. Due to heterogeneity among included studies, we used a narrative evidence synthesis approach.
Twenty-five papers met inclusion criteria including 22 RCTs and 3 qualitative or mixed-methods studies nested in an RCT, together representing 23 unique trials. These trials evaluated healthcare decisions for cardiovascular prevention and treatment (n=8), treatment of diabetes mellitus (n=3), treatment of osteoporosis (n=2), treatment of depression (n=2), antibiotics to treat acute respiratory infections (n=3), cancer prevention and treatment (n=4) and prenatal diagnosis (n=1). Clinician outcomes were measured in only a minority of studies. Clinicians' satisfaction with decision making was assessed in only 8 (and only 2 of them showed statistically significantly greater satisfaction with the decision aid); only three trials asked if clinicians would recommend the decision aid to colleagues and only five asked if clinicians would use decision aids in the future. Outpatient consultations were not prolonged when a decision aid was used in 9 out of 13 trials. The overall strength of the evidence was low, with the major risk of bias related to lack of blinding of participants and/or outcome assessors.
Decision aids can improve clinicians' satisfaction with medical decision making and provide helpful information without affecting length of consultation time. Most SDM trials, however, omit outcomes related to clinicians' perspective on the decision making process or the likelihood of using a decision aid in the future.
Ecotoxicological and pathological research on Grampus griseus (Cuvier, 1812) (Risso's dolphins) is scarce both globally and in the Mediterranean Sea. This species has been classified as “Vulnerable” ...by the International Union for Conservation of Nature (IUCN) in the Mediterranean Sea.
To evaluate the presence of “persistent organic pollutants” (POPs), especially organochlorine compounds (OCs), in the animals, chemical analyses were performed on tissues and organs of Risso's dolphin stranded along the Italian coasts between 1998 and 2021. Toxic contaminants such as hexachlorobenzene (HCB), polychlorinated biphenyls (PCBs), dichlorodiphenyltrichloroethane and its metabolites (DDTs) were examined in the blubber, liver, muscle, and brain of 20 animals, and data was correlated with sex, age, and stranding locations.
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•Analysis of the concentrations of POPs in Grampus griseus stranded along the Italian coasts in the last 23 years•Highest recorded concentrations of HCB, DDTs and PCBs found in Risso's dolphins•Use of blubber of stranded individuals to assess toxicity levels in the Mediterranean Sea•Comparison with studies carried out on individuals stranded in other parts of the world•Increased knowledge about the toxicological status of this species in the Mediterranean Sea
Abstract
Nyctiphanes simplex (Euphausiidae) is the key prey for numerous pelagic predators because it is the most abundant of the 12 krill species present in the Gulf of California, forming dense and ...complex ontogenetic social interactions throughout its life cycle. We describe the diverse social behaviors of N. simplex and estimate its seasonal abundance in the Gulf of California accounting on average 74% of the krill assemblage. N. simplex exhibited complex and dynamic social repertoires of intraspecific behavioral interactions as early as Calyptopis 1 to adult phase, showing all possible ranges of social behavior known for pelagic invertebrates (aggregations, swarms, schools, shoals). We conclude that N. simplex displays different degrees of social behavior that concentrate abundance throughout their life cycle in epibenthic, pelagic and near surface habitats being highly adaptive behavior for feeding and reproduction. However, social interactions also pose a negative effect, facilitating parasite and disease transmission among conspecifics and facilitate predation for diverse visual predators adapted to find and prey on N. simplex aggregations and swarms. We report the most complete integrated evidence of social behavior and dataset of abundance data of any krill species in tropical and subtropical regions that have remained overlooked using traditional zooplankton net sampling methods.
The nature of the early post-natal immune response in rodents appears to influence cardiac regeneration even though the underlying molecules remain poorly understood. Consistent with this idea, we ...show now significant changes in the expression of immune and cell movement gene pathways in heart samples from 1- and 7-day-old rats with ventricle resection. We then tested whether conditioned media from adult M2 anti-inflammatory macrophages target neonatal cardiac cells to a pro-regenerative like phenotype compared to the M1 pro-inflammatory macrophages. We found that M2 compared to M1 macrophage-conditioned media upregulates neonatal cardiomyocyte proliferation, suppresses myofibroblast-induced differentiation and stimulates endothelial cell tube formation. Using a cytokine array, we selected four candidate cytokine molecules uniquely expressed in M2 macrophage-conditioned media and showed that two of them (IL-4 and IL-6) induce endothelial cell proliferation whilst IL-4 promotes proliferation in neonatal cardiomyocytes and prevents myofibroblast-induced collagen type I secretion. Altogether, we provided evidence that adult M2 macrophage-conditioned media displays a paracrine beneficial pro-regenerative response in target cardiac cells and that IL-4 and IL-6 recapitulate, at least in part, these pleiotropic effects. Further characterization of macrophage immune phenotypes and their secreted molecules may give rise to novel therapeutic approaches for post-natal cardiac repair.
The alarming spread and impact of multidrug-resistant Candida auris infections alongside the limited therapeutic options have prompted the development of new antifungals. These promising agents are ...currently in different stages of development, offering novel dosing regimens and mechanisms of action. A systematic search in MEDLINE, EMBASE, Web of Science, and Scopus up to 27 June 2022 was conducted to find relevant articles reporting data of in vitro activity and in vivo efficacy of investigational antifungals against C. auris. These included new additions to existing antifungal classes (rezafungin and opelconazole), first-in-class drugs such as ibrexafungerp, manogepix/fosmanogepix, olorofim and tetrazoles (quilseconazole, oteseconazole and VT-1598), as well as other innovative agents like ATI-2307, MGCD290 and VL-2397. From 592 articles retrieved in the primary search, 27 met the eligibility criteria. The most studied agent was manogepix/fosmanogepix (overall MIC90: 0.03 mg/L), followed by ibrexafungerp (overall MIC90: 1 mg/L) and rezafungin (overall MIC mode: 0.25 mg/L), while VT-1598 and ATI-2307 were the least explored drugs against C. auris. All these compounds demonstrated significant improvements in survival and reduction in tissue fungal burden on neutropenic animal models of candidemia due to C. auris. Continual efforts towards the discovery of new treatments against this multidrug-resistant fungus are essential.
•A higher prevalence of seniors with disability and multimorbity/disability.•30.7% of octogenarians had no multimorbity, frailty and disability.•Number of chronic diseases mediated the relation ...between sex and number of frailty.•Number of frailty mediated the relation between number of diseases and disability.
Path analysis allows for an understanding of the complex interrelationships between multiple variables and interactions in the octogenarians. The aim of this study was to estimate the isolated and combined prevalence of multimorbidity, frailty and functional disability and the direct and indirect association of these conditions in octogenarians. A cross-sectional study was conducted with 166 community-dwelling individuals aged 80 years or older participating in the FIBRA80+ epidemiological study. Multimorbidity was defined by three or more chronic diseases, frailty according to 3 or more components of physical frailty phenotype and functional disability as aid needed to perform one or more activities of daily living (ADLs). Associations were tested by Pearson's chi-square test; the relationship between the variables of interest and the mediating variables was tested with structural equation (path) analysis. We observed a higher prevalence of seniors with disability and multimordibity/disability. In path analysis, number of chronic diseases mediated the relation between sex and number of frailty components (p = 0.031), and these mediated the relation between number of diseases and disability (p = 0.008). The study points out the relationship between the simultaneous presence and interaction between multimorbidity, functional disability and frailty. Through path analysis, our findings provide characteristics in relation to the health-disease process, mainly mediation and interaction among octogenarians.
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