Satisfacción laboral y calidad de vida de los médicos residentes españoles en los meses posteriores a la terminación del estado de alarma por la COVID-19 y al año de la misma / Job satisfaction and quality of life of Spanish medical residents in the months after the end of the state of alarm due to COVID-19 and one year later

Introducción: Describir y analizar la percepción existente acerca de la satisfacción laboral (SL) y la calidad de vida (CV) de los/las médicos/as residentes españoles/as en los meses posteriores a la terminación del estado de alarma por la COVID-19 y al año de la misma. Método: Estudio descriptivo-correlacional, siendo la población diana los/las residentes españoles/as a quienes se preguntó, mediante formulario online, en dos cortes (1º de 01/11 al 31/12 de 2020 y 2º entre 01/11 y 31/12 de 2021). Para la SL se utilizó el cuestionario Font-Roja y para la CV el WHOQOL-BREF (ambos mediante escala Likert de 5 valores). Resultados: Respondieron 404 residentes (1er corte) y 411 (2º corte). Los resultados para a SL global mostraron Rho = 0,09; p = 0,081, sin diferencias entre sus medias (-0,07; p = 0,090). La CV global, medida a través del cuestionario, indicó baja correlación entre ambos cortes (Rho = 0,10; p = 0,041), con diferencias entre sus medias (-0,14; p < 0,001). Conclusiones: En relación a la SL no se constató asociación entre los dos periodos estudiados. Respecto a la CV se evidenciaron mejores datos, en el 2º corte, tanto en la CV autopercibida como en el resultado global del cuestionario (AU)

Introduction: To describe and analyze the existing perception about job satisfaction (SL) and quality of life (QoL) of Spanish resident doctors in the months which follow the end of the state of alarm due to COVID-19 and one year after that.Method: A Descriptive-correlational study, being the Spanish residents the target population who was asked, using an online form, in two periods (1st from 11/01 to 12/31, 2020 and 2nd between 11/01 and 12/31, 2021). For SL, the Font-Roja questionnaire was used and for QoL, the WHOQOL-BREF (both using a 5-point Likert scale).Results: 404 residents responded (1st cut) and 411 (2nd cut). The results for the global SL showed Rho = 0.09; p = 0.081, without differences between their means (-0.07; p = 0.090). The global QoL, measured through the question-naire, evinced a low correlation between both cut-offs (Rho = 0.10; p = 0.041), with variations between their means (-0.14; p < 0.001).Conclusions: In relation to SL, no association was revealed between the two periods studied. Regarding QoL, more positive data were found in the 2nd period, both in self-perceived QoL and in the global result of the questionnaire (AU)

Satisfacción laboral y calidad de vida de los médicos residentes españoles durante la pandemia por la COVID-19 / Job satisfaction and quality of life of Spanish resident doctors during the COVID-19 pandemic

Introducción: Describir y analizar la percepción existente acerca de los factores vinculados a la satisfacción laboral (SL) y la calidad de vida (CV) de los médicos residentes españoles durante la pandemia por la COVID-19. Método: Estudio descriptivo-correlacional, siendo la población diana los residentes españoles a los que se preguntó, mediante formulario online, entre el 01/11/2020 y el 31/12/2020. Para la SL se utilizó el cuestionario Font-Roja y para la CV el WHOQOL-BREF (ambos mediante escala Likert de 5 valores). Resultados Respondieron 404 residentes, sin diferencias por sexo (p 0 0,269). La SL presentó media de 2,97 ± 0,04 y la CV de 3,27 ± 0,03. Se observó asociación en la SL de los residentes de primer año y el resto (p < 0,001). La SL no se afectó por los turnos de urgencia, pero sí la CV para las relaciones sociales (p = 0,042). La relación entre SL y CV fue buena (Rho = 0,53, p < 0,001). Conclusiones: El tutor fue referente para el residente, no así la dirección del hospital. No se encontraron diferencias en relación al sexo ni a los turnos de guardia con la SL. Los residentes de primer año presentaron mayor SL y CV, pudiendo deberse a su menor responsabilidad y cansancio acumulado durante la pandemia. Los turnos de guardia sí afectaron la CV, específicamente en las relaciones sociales. La escasa formación en investigación se vio asimismo agravada por la pandemia. (AU)

Introduction: To describe and analyze the existing perception about the factors related to job satisfaction (LS) and quality of life (QOL) of Spanish resident doctors during the COVID-19 pandemic. Method: Descriptive-correlational study, the target population being the Spanish residents who were asked, using the online form, between 11/01/2020 and 12/31/2020. The Font-Roja questionnaire was used for LS and the WHOQOL-BREF for QOL (both using a 5-value Likert scale). Results: 404 residents responded, without differences by sex (p = 0.269). The LS presented a mean of 2.97 ± 0.04 and the CV of 3.27 ± 0.03. An association was observed in the LS of the first-year residents and the rest (p < 0.001). The LS was not affected by the emergency shifts, but the (QOL) for social relationships (p = 0.042). The relationship between SL and (QOL) was good (Rho = 0.53, p < 0.001). Conclusions: The tutor was a reference for the resident, not the hospital management. No differences were found in relation to sex or duty shifts with the LS. First-year residents presented higher LS and (QOL), which could be due to less responsibility and less accumulated fatigue during the pandemic. The shifts on duty did affect QOL, specifically in social relationships. Poor research training was also compounded by the pandemic (AU)

[Malignant Skin Neoplasms in Workers in the Fishing Industry: Systematic Review]. / Lesiones malignas de la piel en trabajadores del sector pesquero: Revisión sistemática.

OBJECTIVE: To review the scientific literature related to the effects of occupational exposure to risk factors for skin neoplasms in fishery workers. METHOD: Critical analysis of the papers recovered through systematic review from en MEDLINE (PubMed), EMBASE, The Cochrane Library, Scopus, Web of Science y Literatura Latinoamericana y del Caribe en Ciencias de la Salud (LILACS). STOROBE guidelines were followed to evaluate their quality. RESULTS: After attributing inclusion and exclusion criteria to the search, 11 articles were accepted for review and critical analysis. In 7 of them, a statistically significant association was obtained between skin neoplasia and occupational exposure in fishermen. CONCLUSIONS: Despite having found studies that were significant in terms of the relationship of malignant lesions and exposure to ultraviolet radiation in the workplace, some of them did not control possible biases, therefore the results should be taken with caution.

OBJETIVO: Revisar la literatura científica relacionada con los efectos de la exposición ocupacional a factores de riesgo para neoplasias cutáneas en trabajadores del sector pesquero. MÉTODO: Análisis crítico de los trabajos recuperados mediante revisión sistemática en MEDLINE (PubMed), EMBASE, The Cochrane Library, Scopus, Web of Science y Literatura Latinoamericana y del Caribe en Ciencias de la Salud (LILACS). Se evaluó la calidad de los artículos seleccionados mediante el cuestionario STROBE. RESULTADOS: Al atribuir los criterios de inclusión y exclusión a la búsqueda, se aceptaron 11 estudios para su revisión. En 7 de ellos, se obtuvo una asociación estadísticamente significativa entre neoplasia cutánea y exposición ocupacional.  CONCLUSIONES: Se observa una relación entre lesiones malignas y exposición a radiación ultravioleta en el ámbito laboral, no obstante, la existencia de posibles sesgos hace que los resultados deban de tomarse con precaución.

Lesiones malignas de la piel en trabajadores del sector pesquero: Revisión sistemática / Malignant Skin Neoplasms in Workers in the Fishing Industry: Systematic Review

OBJETIVO: Revisar la literatura científica relacionada con los efectos de la exposición ocupacional a factores de riesgo para neoplasias cutáneas en trabajadores del sector pesquero. MÉTODO: Análisis crítico de los trabajos recuperados mediante revisión sistemática en MEDLINE (PubMed), EMBASE, The Cochrane Library, Scopus, Web of Science y Literatura Latinoamericana y del Caribe en Ciencias de la Salud (LILACS). Se evaluó la calidad de los artículos seleccionados mediante el cuestionario STROBE. RESULTADOS: Al atribuir los criterios de inclusión y exclusión a la búsqueda, se aceptaron 11 estudios para su revisión. En 7 de ellos, se obtuvo una asociación estadísticamente significativa entre neoplasia cutánea y exposición ocupacional. CONCLUSIONES: Se observa una relación entre lesiones malignas y exposición a radiación ultravioleta en el ámbito laboral, no obstante, la existencia de posibles sesgos hace que los resultados deban de tomarse con precaución

OBJECTIVE: To review the scientific literature related to the effects of occupational exposure to risk factors for skin neoplasms in fishery workers. METHOD: Critical analysis of the papers recovered through systematic review from en MEDLINE (PubMed), EMBASE, The Cochrane Library, Scopus, Web of Science y Literatura Latinoamericana y del Caribe en Ciencias de la Salud (LILACS). STOROBE guidelines were followed to evaluate their quality. RESULTS: After attributing inclusion and exclusion criteria to the search, 11 articles were accepted for review and critical analysis. In 7 of them, a statistically significant association was obtained between skin neoplasia and occupational exposure in fishermen. CONCLUSIONS: Despite having found studies that were significant in terms of the relationship of malignant lesions and exposure to ultraviolet radiation in the workplace, some of them did not control possible biases, therefore the results should be taken with caution

Detection of SUMOylated Phytochromes in Plants.

Posttranslational modifications (PTMs) happen after or during protein translation. Small Ubiquitin-like Modifier (SUMO) proteins are covalently attached to certain lysine residues of the target proteins to modify their activity, stability, or localization. This process is called SUMOylation, which is a reversible PTM: SUMO protease enzymes can cleave SUMOs off the target protein backbone. Although many ubiquitinated proteins are targeted for degradation, SUMOylation does not necessary lead to the degradation of the modified protein but lead to the regulation of various physiological responses. SUMOylation of the examined protein cannot simply be monitored by immunoblotting techniques performed on total protein extracts, due to the SUMO-specific signals derived from other modified molecules. Furthermore, the fact that only a limited fraction of the target protein pool is SUMOylated makes the detection of SUMOylated proteins challenging. This protocol shows how SUMOylated phytochrome B (phyB) molecules can be detected using homologous and heterologous experimental systems in planta.

SUMO conjugation to the pattern recognition receptor FLS2 triggers intracellular signalling in plant innate immunity.

Detection of conserved microbial patterns by host cell surface pattern recognition receptors (PRRs) activates innate immunity. The FLAGELLIN-SENSITIVE 2 (FLS2) receptor perceives bacterial flagellin and recruits another PRR, BAK1 and the cytoplasmic-kinase BIK1 to form an active co-receptor complex that initiates antibacterial immunity in Arabidopsis. Molecular mechanisms that transmit flagellin perception from the plasma-membrane FLS2-associated receptor complex to intracellular events are less well understood. Here, we show that flagellin induces the conjugation of the SMALL UBIQUITIN-LIKE MODIFIER (SUMO) protein to FLS2 to trigger release of BIK1. Disruption of FLS2 SUMOylation can abolish immune responses, resulting in susceptibility to bacterial pathogens in Arabidopsis. We also identify the molecular machinery that regulates FLS2 SUMOylation and demonstrate a role for the deSUMOylating enzyme, Desi3a in innate immunity. Flagellin induces the degradation of Desi3a and enhances FLS2 SUMOylation to promote BIK1 dissociation and trigger intracellular immune signalling.

SUMO Suppresses the Activity of the Jasmonic Acid Receptor CORONATINE INSENSITIVE1.

Plants respond rapidly to sudden environmental cues, often responding prior to changes in the hormone levels that coordinate these responses. How this is achieved is not fully understood. The integrative role of the phytohormone jasmonic acid (JA) relies upon the plant's ability to control the levels of JASMONATE ZIM (JAZ) domain-containing repressor proteins. Here, we demonstrate that regardless of intrinsic JA levels, Small Ubiquitin-like Modifier (SUMO)-conjugated JAZ proteins inhibit the JA receptor CORONATINE INSENSITIVE1 (COI1) from mediating non-SUMOylated JAZ degradation. The SUMO-deconjugating proteases OVERLY TOLERANT TO SALT1 (OTS1) and OTS2 regulate JAZ protein SUMOylation and stability. The ots1 ots2 double mutants accumulate SUMOylated and non-SUMOylated JAZ repressor proteins but show no change in endogenous JA levels compared with wild-type plants. SUMO1-conjugated JAZ proteins bind to COI1 independently of the JA mimic coronatine. SUMO inhibits JAZ binding to COI1. We identify the SUMO interacting motif in COI1 and demonstrate that this is vital to SUMO-dependent inhibition of COI1. Necrotroph infection of Arabidopsis thaliana promotes SUMO protease degradation, and this increases JAZ SUMOylation and abundance, which in turn inhibits JA signaling. This study reveals a mechanism for rapidly regulating JA responses, allowing plants to adapt to environmental changes.

BTB-BACK Domain Protein POB1 Suppresses Immune Cell Death by Targeting Ubiquitin E3 ligase PUB17 for Degradation.

Hypersensitive response programmed cell death (HR-PCD) is a critical feature in plant immunity required for pathogen restriction and prevention of disease development. The precise control of this process is paramount to cell survival and an effective immune response. The discovery of new components that function to suppress HR-PCD will be instrumental in understanding the regulation of this fundamental mechanism. Here we report the identification and characterisation of a BTB domain E3 ligase protein, POB1, that functions to suppress HR-PCD triggered by evolutionarily diverse pathogens. Nicotiana benthamiana and tobacco plants with reduced POB1 activity show accelerated HR-PCD whilst those with increased POB1 levels show attenuated HR-PCD. We demonstrate that POB1 dimerization and nuclear localization are vital for its function in HR-PCD suppression. Using protein-protein interaction assays, we identify the Plant U-Box E3 ligase PUB17, a well established positive regulator of plant innate immunity, as a target for POB1-mediated proteasomal degradation. Using confocal imaging and in planta immunoprecipitation assays we show that POB1 interacts with PUB17 in the nucleus and stimulates its degradation. Mutated versions of POB1 that show reduced interaction with PUB17 fail to suppress HR-PCD, indicating that POB1-mediated degradation of PUB17 U-box E3 ligase is an important step for negative regulation of specific immune pathways in plants. Our data reveals a new mechanism for BTB domain proteins in suppressing HR-PCD in plant innate immune responses.

Expression, Purification, and Enzymatic Analysis of Plant SUMO Proteases.

The conjugation of SUMO can profoundly change the behavior of substrate proteins, impacting a wide variety of cellular responses. SUMO proteases are emerging as key regulators of plant adaptation to its environment because of their instrumental role in the SUMO deconjugation process. Here, we describe how to express, purify, and determine SUMO deconjugation activity of a plant SUMO protease.

SUMOylation represses SnRK1 signaling in Arabidopsis.

The SnRK1 protein kinase balances cellular energy levels in accordance with extracellular conditions and is thereby key for plant stress tolerance. In addition, SnRK1 has been implicated in numerous growth and developmental processes from seed filling and maturation to flowering and senescence. Despite its importance, the mechanisms that regulate SnRK1 activity are poorly understood. Here, we demonstrate that the SnRK1 complex is SUMOylated on multiple subunits and identify SIZ1 as the E3 Small Ubiquitin-like Modifier (SUMO) ligase responsible for this modification. We further show that SnRK1 is ubiquitinated in a SIZ1-dependent manner, causing its degradation through the proteasome. In consequence, SnRK1 degradation is deficient in siz1-2 mutants, leading to its accumulation and hyperactivation of SnRK1 signaling. Finally, SnRK1 degradation is strictly dependent on its activity, as inactive SnRK1 variants are aberrantly stable but recover normal degradation when expressed as SUMO mimetics. Altogether, our data suggest that active SnRK1 triggers its own SUMOylation and degradation, establishing a negative feedback loop that attenuates SnRK1 signaling and prevents detrimental hyperactivation of stress responses.

SUMOylation of phytochrome-B negatively regulates light-induced signaling in Arabidopsis thaliana.

The red/far red light absorbing photoreceptor phytochrome-B (phyB) cycles between the biologically inactive (Pr, λmax, 660 nm) and active (Pfr; λmax, 730 nm) forms and functions as a light quality and quantity controlled switch to regulate photomorphogenesis in Arabidopsis. At the molecular level, phyB interacts in a conformation-dependent fashion with a battery of downstream regulatory proteins, including PHYTOCHROME INTERACTING FACTOR transcription factors, and by modulating their activity/abundance, it alters expression patterns of genes underlying photomorphogenesis. Here we report that the small ubiquitin-like modifier (SUMO) is conjugated (SUMOylation) to the C terminus of phyB; the accumulation of SUMOylated phyB is enhanced by red light and displays a diurnal pattern in plants grown under light/dark cycles. Our data demonstrate that (i) transgenic plants expressing the mutant phyB(Lys996Arg)-YFP photoreceptor are hypersensitive to red light, (ii) light-induced SUMOylation of the mutant phyB is drastically decreased compared with phyB-YFP, and (iii) SUMOylation of phyB inhibits binding of PHYTOCHROME INTERACTING FACTOR 5 to phyB Pfr. In addition, we show that OVERLY TOLERANT TO SALT 1 (OTS1) de-SUMOylates phyB in vitro, it interacts with phyB in vivo, and the ots1/ots2 mutant is hyposensitive to red light. Taken together, we conclude that SUMOylation of phyB negatively regulates light signaling and it is mediated, at least partly, by the action of OTS SUMO proteases.

The autotaxin-lysophosphatidic acid pathway in pathogenesis of rheumatoid arthritis.

Lysophosphatidic acid (LPA) is a phospholipid that is mainly produced by the hydrolysis of lysophosphatidylcholine (LPC) by lysophospholipase D, which is also called autotaxin (ATX). LPA interacts with specific G-protein coupled receptors and is involved in the regulation of cellular survival, proliferation, differentiation and motility. LPA also has roles in several pathological disorders, such as cancer and pulmonary, dermal and renal fibrosis. The involvement of the ATX-LPA pathway has recently been demonstrated in inflammatory responses and apoptosis of fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis and during the development of experimental arthritis. This review summarises the current literature of the ATX-LPA pathway in rheumatoid arthritis.

Functional analysis of a Wheat Homeodomain protein, TaR1, reveals that host chromatin remodelling influences the dynamics of the switch to necrotrophic growth in the phytopathogenic fungus Zymoseptoria tritici.

A distinguishing feature of Septoria leaf blotch disease in wheat is the long symptomless growth of the fungus amongst host cells followed by a rapid transition to necrotrophic growth resulting in disease lesions. Global reprogramming of host transcription marks this switch to necrotrophic growth. However no information exists on the components that bring about host transcriptional reprogramming. Gene-silencing, confocal-imaging and protein-protein interaction assays where employed to identify a plant homeodomain (PHD) protein, TaR1 in wheat that plays a critical role during the transition from symptomless to necrotrophic growth of Septoria. TaR1-silenced wheat show earlier symptom development upon Septoria infection but reduced fungal sporulation indicating that TaR1 is key for prolonging the symptomless phase and facilitating Septoria asexual reproduction. TaR1 is localized to the nucleus and binds to wheat Histone 3. Trimethylation of Histone 3 at lysine 4 (H3K4) and lysine 36 (H3K36) are found on open chromatin with actively transcribed genes, whereas methylation of H3K27 and H3K9 are associated with repressed loci. TaR1 specifically recognizes dimethylated and trimethylated H3K4 peptides suggesting that it regulates transcriptional activation at open chromatin. We conclude that TaR1 is an important component for the pathogen life cycle in wheat that promotes successful colonization by Septoria.

Effect of lysophosphatidic acid receptor inhibition on bone changes in ovariectomized mice.

Pharmacological inhibition of signaling through lysophosphatidic acid (LPA) receptors reduces bone erosions in an experimental model of arthritis by mechanisms involving reduced osteoclast differentiation and bone resorption and increased differentiation of osteoblasts and bone mineralization. These results led us to hypothesize that LPA receptor inhibition would be beneficial in osteoporosis. Our aim was to test this hypothesis with the LPA receptor antagonist, Ki16425, in ovariectomized mice, a model of postmenopausal osteoporosis. Ovariectomized mice treated with Ki16425 showed bone loss similar to that observed in the controls. Osteoblast markers, Alpl, Bglap and Col1a1, were increased at the mRNA level but no changes were detected in serum. No additional difference was observed in the Ki16425-treated mice relative to the ovariectomized controls with regard to osteoclast function markers or assays of matrix mineralization or osteoclast differentiation. Thus, pharmacological inhibition of LPA receptor was not beneficial for preventing bone loss in ovariectomized mice, indicating that its favorable effect on bone remodeling is less general than hypothesized.

Lysophosphatidic acid receptor inhibition as a new multipronged treatment for rheumatoid arthritis.

OBJECTIVE: To investigate the effect of lysophosphatidic acid (LPA) receptor inhibition in a mouse model of autoantibody-mediated arthritis. METHODS: Arthritis was induced in C57BL/6 mice by K/BxN serum transfer. Arthritic mice were treated with the LPA receptor antagonist, Ki16425 and arthritis severity was assessed clinically and histologically. Expression of inflammatory mediators in joints was identified by a mouse cytokine array and validated by western blot and real-time PCR assays. Effects of treatment with LPA receptor antagonist or with small interfering RNA on bone metabolism were assessed by in vitro assays of osteoclastogenesis, bone resorption, osteoblasts differentiation and bone mineralisation. RESULTS: Mice treated with the LPA receptor antagonist Ki16425 showed attenuated arthritis characterised by reduction of synovial inflammation, cartilage damage and, more markedly, bone erosion. We detected increased apoptosis, reduction of inflammatory mediators and of bone remodelling proteins in arthritic joints from mice treated with Ki16425. In addition, we demonstrated that inhibition or suppression of LPA1 receptor reduces osteoclast differentiation and bone resorption and, on the contrary, it promotes differentiation of osteoblasts and bone mineralisation. CONCLUSIONS: Pharmacological inhibition of LPA1 receptor in the K/BxN serum-transfer arthritis model led to reduction of severity of arthritis involving multiple mechanisms, increased apoptosis, reduced inflammatory mediators and proteins involved in bone remodelling, that show LPA1 as a very promising target in rheumatoid arthritis treatment.

Lysophosphatidic acid receptor 1 suppression sensitizes rheumatoid fibroblast-like synoviocytes to tumor necrosis factor-induced apoptosis.

OBJECTIVE: To investigate the role of lysophosphatidic acid (LPA) receptors in the proliferation and apoptosis of fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA). METHODS: Expression of LPA receptors 1-3 was analyzed by real-time polymerase chain reaction (PCR). LPAR1 and LPAR2 were suppressed in RA FLS by small interfering RNA (siRNA) transfection. Proliferation of RA FLS after tumor necrosis factor (TNF) and LPA stimulation was determined with a luminescent cell viability assay. Apoptosis was analyzed by quantification of nucleosome release and measurement of activated caspase 3/7. Genes involved in the apoptotic response were identified with a human apoptosis PCR array and validated with Western blot assays. The requirement of these genes for apoptosis sensitization was assessed by siRNA transfection. Secretion of mediators of inflammation was analyzed by enzyme-linked immunosorbent assay. RESULTS: Only LPAR1 and LPAR2 were expressed by RA FLS, and their levels were higher than those in osteoarthritis (OA) FLS. Suppression of LPAR1 abrogated TNF-induced proliferation and sensitized the RA FLS, but not the OA FLS, to TNF-induced apoptosis. These changes occurred despite an increased early inflammatory response to TNF. Sensitization to apoptosis was associated with changes in expression of multiple apoptosis-related genes. Three of the up-regulated proapoptotic genes were further studied to confirm their involvement. In contrast, suppression of LPAR2 showed no effect in any of these analyses. CONCLUSION: LPA(1) is an important receptor in RA FLS. Its suppression is accompanied by a global increase in the response to TNF that is ultimately dominated by sensitization to apoptosis.