Prevalence and Predictors of Burnout in Midwives: A Systematic Review and Meta-Analysis

The prevalence of burnout in midwives has been briefly studied. Given the negative effects of burnout syndrome in the physical and mental health, and also related to the quality of care provided, rates of absenteeism and sick leave; identifying related factors for the syndrome are needed. The aim was to determine the prevalence, levels, and factors related to the burnout syndrome, measured with the Copenhagen Burnout Inventory in midwives. A systematic review and meta-analysis were selected from CINAHL, LILACS, ProQuest, PsycINFO, PubMed, SciELO, and Scopus databases, with the search equation “burnout AND (midwife OR midwives OR nurses midwives)”. Fourteen articles were found with a total of 8959 midwives. Most of the studies showed moderate levels of personal burnout. The prevalence obtained was 50% (95% CI = 38–63) for personal burnout; 40% (95% CI = 32–49) for work-related burnout; and 10% (95% CI = 7–13) for client-related burnout. Midwives’ age, less experience, and living alone constitute the main related factors, as well as, the scarcity of resources, work environment, and the care model used. Most midwives present personal and work-related burnout, which indicates a high risk of developing burnout. Personal factors and working conditions should be taken into account when assessing burnout risk profiles of midwives

An Explanatory Model of Potential Changes in Burnout Diagnosis According to Personality Factors in Oncology Nurses

Burnout in a hospital oncology service takes place when there is a high level of interaction between nurses and patients. The aim of the present study is to identify models that will enable us to accurately classify a person at a given level within each of the three dimensions of burnout, according to the values presented for personality related explanatory variables, for a sample of 96 oncology nurses working in the regional health service of Andalusia (Spain). A quantitative, crosscutting, multicentre, descriptive study was designed, and for this purpose data on sociodemographic and personality variables and on the three dimensions of burnout were compiled. Three categorical-response logit ordinal models were used and the prognostic ratios for each level were obtained, with respect to every other level, according to possible changes in the explanatory variables considered. Certain personality factors are associated with one or more dimensions of burnout syndrome. Thus, nurses are more likely to develop high levels of burnout if they present high levels of neuroticism and low levels of friendliness and responsibility. Further research in this field is needed to confirm and extend these findings.This research was funded by Excellence Research Project P11HUM-7771 (Junta de Andalucía, Spain) and by Research Project mP_BS_6 (CEI BioTic Granada and Ministerio de Ciencia e Innovación, Spain)

Genome-Wide Association Study for Serum Omega-3 and Omega-6 Polyunsaturated Fatty Acids: Exploratory Analysis of the Sex-Specific Effects and Dietary Modulation in Mediterranean Subjects with Metabolic Syndrome.

Many early studies presented beneficial effects of polyunsaturated fatty acids (PUFA) on cardiovascular risk factors and disease. However, results from recent meta-analyses indicate that this effect would be very low or nil. One of the factors that may contribute to the inconsistency of the results is that, in most studies, genetic factors have not been taken into consideration. It is known that fatty acid desaturase (FADS) gene cluster in chromosome 11 is a very important determinant of plasma PUFA, and that the prevalence of the single nucleotide polymorphisms (SNPs) varies greatly between populations and may constitute a bias in meta-analyses. Previous genome-wide association studies (GWAS) have been carried out in other populations and none of them have investigated sex and Mediterranean dietary pattern interactions at the genome-wide level. Our aims were to undertake a GWAS to discover the genes most associated with serum PUFA concentrations (omega-3, omega-6, and some fatty acids) in a scarcely studied Mediterranean population with metabolic syndrome, and to explore sex and adherence to Mediterranean diet (MedDiet) interactions at the genome-wide level. Serum PUFA were determined by NMR spectroscopy. We found strong robust associations between various SNPs in the FADS cluster and omega-3 concentrations (top-ranked in the adjusted model: FADS1-rs174547, p = 3.34 × 10-14; FADS1-rs174550, p = 5.35 × 10-14; FADS2-rs1535, p = 5.85 × 10-14; FADS1-rs174546, p = 6.72 × 10-14; FADS2-rs174546, p = 9.75 × 10-14; FADS2- rs174576, p = 1.17 × 10-13; FADS2-rs174577, p = 1.12 × 10-12, among others). We also detected a genome-wide significant association with other genes in chromosome 11: MYRF (myelin regulatory factor)-rs174535, p = 1.49 × 10-12; TMEM258 (transmembrane protein 258)-rs102275, p = 2.43 × 10-12; FEN1 (flap structure-specific endonuclease 1)-rs174538, p = 1.96 × 10-11). Similar genome-wide statistically significant results were found for docosahexaenoic fatty acid (DHA). However, no such associations were detected for omega-6 PUFAs or linoleic acid (LA). For total PUFA, we observed a consistent gene*sex interaction with the DNTTIP2 (deoxynucleotidyl transferase terminal interacting protein 2)-rs3747965 p = 1.36 × 10-8. For adherence to MedDiet, we obtained a relevant interaction with the ME1 (malic enzyme 1) gene (a gene strongly regulated by fat) in determining serum omega-3. The top-ranked SNP for this interaction was ME1-rs3798890 (p = 2.15 × 10-7). In the regional-wide association study, specifically focused on the FADS1/FASD2/FADS3 and ELOVL (fatty acid elongase) 2/ELOVL 5 regions, we detected several statistically significant associations at p < 0.05. In conclusion, our results confirm a robust role of the FADS cluster on serum PUFA in this population, but the associations vary depending on the PUFA. Moreover, the detection of some sex and diet interactions underlines the need for these associations/interactions to be studied in all specific populations so as to better understand the complex metabolism of PUFA.This study was partially funded, by the Spanish Ministry of Health (Instituto de Salud Carlos III) and the Ministerio de Economía y Competitividad-Fondo Europeo de Desarrollo Regional (FEDER) (grants CIBER 06/03, PI06/1326, PI13/00728, PI16/00366, SAF2016–80532-R and FPU 18/01703); the University Jaume I (grants P1–1B2013–54 and COGRUP/2016/06); the Rei Jaume I Award for Medical Research 2018; the Fundació La Marató de TV3 (grant 538/U/2016); and the Generalitat Valenciana (grants PROMETEO2017/017, AEST/2018/044 and APOSTD/2019/136) and the US Department of Agriculture, Agriculture Research Service (grant 8050–51000--098--00D).N

Glaucoma: from pathogenic mechanisms to retinal glial cell response to damage

Glaucoma is a neurodegenerative disease of the retina characterized by the irreversible loss of retinal ganglion cells (RGCs) leading to visual loss. Degeneration of RGCs and loss of their axons, as well as damage and remodeling of the lamina cribrosa are the main events in the pathogenesis of glaucoma. Different molecular pathways are involved in RGC death, which are triggered and exacerbated as a consequence of a number of risk factors such as elevated intraocular pressure (IOP), age, ocular biomechanics, or low ocular perfusion pressure. Increased IOP is one of the most important risk factors associated with this pathology and the only one for which treatment is currently available, nevertheless, on many cases the progression of the disease continues, despite IOP control. Thus, the IOP elevation is not the only trigger of glaucomatous damage, showing the evidence that other factors can induce RGCs death in this pathology, would be involved in the advance of glaucomatous neurodegeneration. The underlying mechanisms driving the neurodegenerative process in glaucoma include ischemia/hypoxia, mitochondrial dysfunction, oxidative stress and neuroinflammation. In glaucoma, like as other neurodegenerative disorders, the immune system is involved and immunoregulation is conducted mainly by glial cells, microglia, astrocytes, and Müller cells. The increase in IOP produces the activation of glial cells in the retinal tissue. Chronic activation of glial cells in glaucoma may provoke a proinflammatory state at the retinal level inducing blood retinal barrier disruption and RGCs death. The modulation of the immune response in glaucoma as well as the activation of glial cells constitute an interesting new approach in the treatment of glaucoma

Gender, Marital Status, and Children as Risk Factors for Burnout in Nurses: A Meta-Analytic Study

The correlation between the burnout syndrome and sociodemographic variables in nursing professionals has been widely studied though research results are contradictory. The aim of this study was to assess the impact of gender, marital status, and children on the dimensions of the burnout syndrome (emotional exhaustion, depersonalization, and personal accomplishment) in nursing professionals, as measured with the Maslach Burnout Inventory. The search was performed in May 2018 in the next databases: CINAHL, CUIDEN, Dialnet, Psicodoc, ProQuest Platform, OVID Platform, and Scopus with the search equation (“Maslach Burnout Inventory” OR “MBI”) AND “nurs*”, without using any search restriction. The sample was n = 78 studies: 57 studies for gender; 32 for marital status; 13 for having children. A statistically significant relation between depersonalization and gender (r = 0.078), marital status (r = 0.047), and children (r = 0.053) was found. A significant relation was also found between emotional exhaustion and children (r = 0.048). The results showed that being male, being single or divorced, and not having children were related to the highest levels of burnout in nurses. Moreover, these relations could be accentuated by the influence of moderator variables (age, seniority, job satisfaction, etc.), which, in combination with the previously mentioned significant relations, should be evaluated in the design burnout risk profiles for nursing professionals.This work was funded by the Excellence Research Project P11HUM-7771 and the Research Project mP_BS_6

Treatment with the senolytics dasatinib/quercetin reduces SARS-CoV-2-related mortality in mice

The enormous societal impact of the ongoing COVID-19 pandemic has been particularly harsh for some social groups, such as the elderly. Recently, it has been suggested that senescent cells could play a central role in pathogenesis by exacerbating the pro-inflammatory immune response against SARS-CoV-2. Therefore, the selective clearance of senescent cells by senolytic drugs may be useful as a therapy to ameliorate the symptoms of COVID-19 in some cases. Using the established COVID-19 murine model K18-hACE2, we demonstrated that a combination of the senolytics dasatinib and quercetin (D/Q) significantly reduced SARS-CoV-2-related mortality, delayed its onset, and reduced the number of other clinical symptoms. The increase in senescent markers that we detected in the lungs in response to SARS-CoV-2 may be related to the post-COVID-19 sequelae described to date. These results place senescent cells as central targets for the treatment of COVID-19, and make D/Q a new and promising therapeutic too

A new regulatory mechanism of protein phosphatase 2A activity via SET in acute myeloid leukemia

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy. Although novel emerging drugs are available, the overall prognosis remains poor and new therapeutic approaches are required. PP2A phosphatase is a key regulator of cell homeostasis and is recurrently inactivated in AML. The anticancer activity of several PP2A-activating drugs (e.g., FTY720) depends on their interaction with the SET oncoprotein, an endogenous PP2A inhibitor that is overexpressed in 30% of AML cases. Elucidation of SET regulatory mechanisms may therefore provide novel targeted therapies for SET-overexpressing AMLs. Here, we show that upregulation of protein kinase p38 beta is a common event in AML. We provide evidence that p38 beta potentiates SET-mediated PP2A inactivation by two mechanisms: facilitating SET cytoplasmic translocation through CK2 phosphorylation, and directly binding to and stabilizing the SET protein. We demonstrate the importance of this new regulatory mechanism in primary AML cells from patients and in zebrafish xenograft models. Accordingly, combination of the CK2 inhibitor CX-4945, which retains SET in the nucleus, and FTY720, which disrupts the SET-PP2A binding in the cytoplasm, significantly reduces the viability and migration of AML cells. In conclusion, we show that the p38 beta/CK2/SET axis represents a new potential therapeutic pathway in AML patients with SET-dependent PP2A inactivation

Inhibition of inflammatory signaling in Pax5 mutant cells mitigates B-cell leukemogenesis

Altres ajuts: We would like to thank the "Fundación Ramón Areces," a Research Contract with the "Fundación Síndrome de Wolf-Hirschhorn o 4p-", and institutional grants from the "Fundación Ramón Areces" and "Banco de Santander" to the CBMSO. Research in the ISG group is partially supported by by Junta de Castilla y León (UIC-017, CSI001U16, and CSI234P18), and by the German Jose Carreras Foundation (DJCLS R13/26; DJCLS 07R/2019). AC-G and M.I.-H. are supported by FSE-Conserjería de Educación de la Junta de Castilla y León 2019 and 2020 (ESF- European Social Fund) fellowship, respectively. J.R.-G. is supported by a scholarship from University of Salamanca co-financed by Banco Santander and ESF.PAX5 is one of the most frequently mutated genes in B-cell acute lymphoblastic leukemia (B-ALL), and children with inherited preleukemic PAX5 mutations are at a higher risk of developing the disease. Abnormal profiles of inflammatory markers have been detected in neonatal blood spot samples of children who later developed B-ALL. However, how inflammatory signals contribute to B-ALL development is unclear. Here, we demonstrate that Pax5 heterozygosis, in the presence of infections, results in the enhanced production of the inflammatory cytokine interleukin-6 (IL-6), which appears to act in an autocrine fashion to promote leukemia growth. Furthermore, in vivo genetic downregulation of IL-6 in these Pax5 heterozygous mice retards B-cell leukemogenesis, and in vivo pharmacologic inhibition of IL-6 with a neutralizing antibody in Pax5 mutant mice with B-ALL clears leukemic cells. Additionally, this novel IL-6 signaling paradigm identified in mice was also substantiated in humans. Altogether, our studies establish aberrant IL6 expression caused by Pax5 loss as a hallmark of Pax5-dependent B-ALL and the IL6 as a therapeutic vulnerability for B-ALL characterized by PAX5 loss