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1.
BMJ Open ; 14(4): e080995, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38643013

RESUMO

OBJECTIVE: The aim was to explore whether occupational balance is associated with health, health-promoting resources, healthy lifestyle and social study factors among students during higher education within healthcare and social work. DESIGN: The study has a multicentre repeated cross-sectional design. Data were collected via a self-reported, web-based questionnaire based on the validated instruments: the 11-item Occupational Balance Questionnaire (OBQ11), the Sense of Coherence (SOC) Scale, the Salutogenic Health Indicator Scale (SHIS) and five questions from the General Nordic Questionnaire (QPS Nordic) together with questions about general health and lifestyle factors. SETTING: Students at six universities in western Sweden at one of the following healthcare or social work programmes: biomedical scientists, dental hygienists, nurses, occupational therapists, physiotherapists, radiology nurses and social workers. PARTICIPANTS: Of 2283 students, 851 (37.3%) participated. RESULTS: The students experienced that occupational balance increased during education. The total OBQ11 score was higher among students in semesters 4 and 6/7, compared with semester 1 students. Students with higher OBQ11 also reported higher SOC throughout their education, while health seemed to decrease. Students who reported higher levels of OBQ11 reported lower levels of health and well-being in semesters 4 and 6/7, compared with semester 1. There was an opposite pattern for students reporting lower levels of OBQ11. CONCLUSIONS: The association between higher levels of OBQ11 and lower levels of health and well-being is remarkable. There is a need for more research on this contradiction and what it means for students' health and well-being in the long run.


Assuntos
Serviço Social , Estudantes , Humanos , Estudos Transversais , Suécia , Atenção à Saúde , Inquéritos e Questionários
2.
Allergy ; 2024 Apr 17.
Artigo em Inglês | MEDLINE | ID: mdl-38634175

RESUMO

BACKGROUND: Chronic spontaneous urticaria (CSU) is a common, debilitating skin disorder characterized by recurring episodes of raised, itchy and sometimes painful wheals lasting longer than 6 weeks. CSU is mediated by mast cells which are absent from peripheral blood. However, lineage-CD34hiCD117int/hiFcεRI+ cells in blood have previously been shown to represent a mast cell precursor. METHODS: We enumerated FcεRI-, FcεRI+ and FcεRIhi lineage-CD34+CD117+ cells using flow cytometry in blood of patients with CSU (n = 55), including 12 patients receiving omalizumab and 43 not receiving omalizumab (n = 43). Twenty-two control samples were studied. Disease control and patient response to omalizumab was evaluated using the urticaria control test. We performed single-cell RNA sequencing (scRNA-Seq) on lineage-CD34hiCD117hi blood cells from a subset of patients with CSU (n = 8) and healthy controls (n = 4). RESULTS: CSU patients had more lineage-CD34+CD117+FcεRI+ blood cells than controls. Lineage-CD34+CD117+FcεRI+ cells were significantly higher in patients with CSU who had an objective clinical response to omalizumab when compared to patients who had poor disease control 90 days after initiation of omalizumab. scRNA-Seq revealed that lineage-CD34+CD117+FcεRI+ cells contained both lymphoid and myeloid progenitor lineages, with omalizumab responsive patients having proportionally more myeloid progenitors. The myeloid progenitor lineage contained small numbers of true mast cell precursors along with more immature FcεRI- and FcεRI+ myeloid progenitors. CONCLUSION: Increased blood CD34+CD117+FcεRI+ cells may reflect enhanced bone marrow egress in the setting of CSU. High expression of these cells strongly predicts better clinical responses to the anti-IgE therapy, omalizumab.

3.
Int J Mol Sci ; 25(3)2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38338947

RESUMO

The extended cleavage specificities of two hematopoietic serine proteases originating from the ray-finned fish, the spotted gar (Lepisosteus oculatus), have been characterized using substrate phage display. The preference for particular amino acids at and surrounding the cleavage site was further validated using a panel of recombinant substrates. For one of the enzymes, the gar granzyme G, a strict preference for the aromatic amino acid Tyr was observed at the cleavable P1 position. Using a set of recombinant substrates showed that the gar granzyme G had a high selectivity for Tyr but a lower activity for cleaving after Phe but not after Trp. Instead, the second enzyme, gar DDN1, showed a high preference for Leu in the P1 position of substrates. This latter enzyme also showed a high preference for Pro in the P2 position and Arg in both P4 and P5 positions. The selectivity for the two Arg residues in positions P4 and P5 suggests a highly specific substrate selectivity of this enzyme. The screening of the gar proteome with the consensus sequences obtained by substrate phage display for these two proteases resulted in a very diverse set of potential targets. Due to this diversity, a clear candidate for a specific immune function of these two enzymes cannot yet be identified. Antisera developed against the recombinant gar enzymes were used to study their tissue distribution. Tissue sections from juvenile fish showed the expression of both proteases in cells in Peyer's patch-like structures in the intestinal region, indicating they may be expressed in T or NK cells. However, due to the lack of antibodies to specific surface markers in the gar, it has not been possible to specify the exact cellular origin. A marked difference in abundance was observed for the two proteases where gar DDN1 was expressed at higher levels than gar granzyme G. However, both appear to be expressed in the same or similar cells, having a lymphocyte-like appearance.


Assuntos
Peixes , Serina Proteases , Animais , Serina Proteases/genética , Granzimas , Endopeptidases , Sequência Consenso , Especificidade por Substrato
4.
BMC Nurs ; 23(1): 124, 2024 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-38365670

RESUMO

BACKGROUND: Older persons with age-related and complex health problems will increasingly depend on care provision from nurses in their own homes. However, a barrier to quality care is ageism and nursing students´ disinterest in geriatrics. In addition, nurse education often falls short in preparing students for the complexity of geriatric care. Welfare technology (WT) is progressively implemented in home care to help older persons live at home despite their health problems. However, this process is intricate and requires acceptance and digital literacy among caregivers and older persons. Despite these challenges, nurse education can address and change negative attitudes through innovative teaching methods such as age suit simulation. Therefore, the study aims to describe nursing students´ experiences of age suit simulation in a home-like environment with WT and technical aids, and will reveal their perspective on ageing and providing care to older adults. METHODS: A qualitative explorative design using semi-structured group interviews (n=39) among nursing students. Data was analysed through reflexive thematic analysis. RESULTS: The analysis generated three main themes; "It's like walking in a bubble", "An eye opener" and "Concerns about ageing and the current structure of geriatric care". The main themes included eight subthemes. Adapting to the sensory and physical limitations of the age suit was an immersive experience and caused feelings of frustration, loneliness and disconnection. A prominent result was a raised awareness of cognitive loss, especially impaired vision, and students felt the simulations had made them aware of the everyday challenges older persons faced. Students highlighted the importance of patience and giving enough time in care situations by being present and having a critical perspective of WT. The students were mostly negative towards their own ageing and could better relate to older persons´ vulnerability. CONCLUSIONS: Age suit simulation was described as an embodied and eye-opening experience, raising nursing students´ awareness of older persons´ functional limitations and the consequences for dignity and independence. Coping with cognitive loss was especially difficult. Students were motivated to apply their new knowledge to clinical practice. Age suit simulation can complement geriatric education, preparing students for the complex care needs of older persons.

5.
Nat Commun ; 15(1): 904, 2024 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-38291037

RESUMO

Mast cells localize to mucosal tissues and contribute to innate immune defense against infection. How mast cells sense, differentiate between, and respond to bacterial pathogens remains a topic of ongoing debate. Using the prototype enteropathogen Salmonella Typhimurium (S.Tm) and other related enterobacteria, here we show that mast cells can regulate their cytokine secretion response to distinguish between extracellular and invasive bacterial infection. Tissue-invasive S.Tm and mast cells colocalize in the mouse gut during acute Salmonella infection. Toll-like Receptor 4 (TLR4) sensing of extracellular S.Tm, or pure lipopolysaccharide, causes a modest induction of cytokine transcripts and proteins, including IL-6, IL-13, and TNF. By contrast, type-III-secretion-system-1 (TTSS-1)-dependent S.Tm invasion of both mouse and human mast cells triggers rapid and potent inflammatory gene expression and >100-fold elevated cytokine secretion. The S.Tm TTSS-1 effectors SopB, SopE, and SopE2 here elicit a second activation signal, including Akt phosphorylation downstream of effector translocation, which combines with TLR activation to drive the full-blown mast cell response. Supernatants from S.Tm-infected mast cells boost macrophage survival and maturation from bone-marrow progenitors. Taken together, this study shows that mast cells can differentiate between extracellular and host-cell invasive enterobacteria via a two-step activation mechanism and tune their inflammatory output accordingly.


Assuntos
Infecções por Enterobacteriaceae , Infecções por Salmonella , Camundongos , Animais , Humanos , Mastócitos , Infecções por Salmonella/microbiologia , Salmonella typhimurium/genética , Citocinas/metabolismo
7.
BMC Nurs ; 23(1): 7, 2024 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-38163862

RESUMO

Efficient teamwork is crucial to provide optimal health care. This paper focuses on teamwork between Anaesthesiologists (ANES), Certified Registered Nurse Anaesthetists' (CRNA) and Critical Care Registered Nurses (CCRN) working in challenging environments such as the intensive care unit (ICU) and the operating room (OR). Conflicts are common between physicians and nurses, negatively impacting teamwork. Social hierarchies based on professional status and power inequalities between nurses and physicians plays a vital role in influencing teamwork. Foucault was a famous thinker especially known for his reasoning regarding power/knowledge. A Foucauldian perspective was therefore incorporated into this paper and the overall aim was to explore CCRN/CRNA perception of knowledge/power in teamwork with ANES.Methods A mixed-method approach was applied in this study. Data was collected using a web-based questionnaire containing both closed-end and open-ended questions. A total of 289 CCRNs and CRNAs completed the questionnaire. Data analysis was then conducted through five stages as outlined by Onwuebugzie and Teddlie; analysing quantitative data in SPSS 27.0 and qualitative data with a directed content analysis, finally merging data together in ATLAS.ti v.23.Results The result reveals a dissonance between quantitative and qualitative data; quantitative data indicates a well-functioning interdisciplinary teamwork between CCRN/CRNA and ANES - qualitative data highlights that there are several barriers and inequalities between the two groups. Medicine was perceived as superior to nursing, which was reinforced by both social and organisational structures at the ICU and OR.Conclusion Unconscious rules underlying current power structures in the ICU and OR works in favour of the ANES and biomedical paradigm, supporting medical knowledge. To achieve a more equal power distribution between CCRN/CRNAs and ANES, the structural hierarchies between nursing and medicine needs to be addressed. A more equal power balance between the two disciplines can improve teamwork and thereby reduce patient mortality and improve patient outcomes.

8.
BMC Nurs ; 22(1): 428, 2023 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-37964266

RESUMO

BACKGROUND: Implementation of digital technology has been suggested as a potential solution to future healthcare challenges. Healthcare personnel's attitudes are important in the acceptance and implementation of digital technologies. AIM: The aims of this study were to (1) translate and validate two different questionnaires to Norwegian and Swedish respectively, and then (2) use these to examine nursing students' attitudes towards digital technology in healthcare, as well as their attitudes towards older adults' abilities to use digital technology. DESIGN: Cross-sectional. METHODS: A web-based questionnaire was distributed in first year nursing students in a Norwegian and a Swedish university college, respectively. The questionnaire consisted of the short form of the 'Information Technology Attitude Scales for Health (ITASH)' and the 'Attitudes Towards Older Adults Using Digital technology (ATOAUT-11)' questionnaire. The questionnaires were translated and validated in both countries. Frequencies, Student's t-test, and one-way ANOVA were used to analyze the data. RESULTS: In total 236 students responded to the questionnaire in the period September 2022 to April 2023. Students mainly reported positive attitudes towards digital technology use in general. They most agreed with the items 'Using digital technology devices makes my communication with other health professionals faster', 'The sort of information I can get from the digital technology devices helps me give better care to patient', and 'Digital technology skills are becoming more and more necessary for healthcare professionals'. However, they reported more negative attitudes towards older adults using digital technology. They most agreed with the items 'One needs a lot of patience to explain to an older adult how to use digital technologies', 'It's hard to explain to older adults how to use digital technology', 'Using digital technology is harder for most older adults', and 'Most older adults fear using digital technology because they fear of being scammed or cheated'. CONCLUSION: The ITASH and the ATOAUT-11 is appropriate for use in a Norwegian and Swedish setting. Even if nursing students are positive to digital technology in healthcare in general, they are sceptical to older adults using digital technology. This may impact on their attitudes to using digital technology in the healthcare of older adults. These aspects need emphasis when revising nursing education curricula focusing on developing technological competencies in nursing, and gaining knowledge regarding older adults' use of digital technology.

9.
BMC Health Serv Res ; 23(1): 921, 2023 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-37644455

RESUMO

BACKGROUND: The organizational principle of remaining at home has offset care from the hospital to the home of the older person where care from formal and informal caregivers is needed. Globally, formal care is often organized to handle singular and sporadic health problems, leading to the need for several health care providers. The need for an integrated care model was therefore recognized by health care authorities in one county in Sweden, who created a cross-organisational integrated care model to meet these challenges. The Mobile integrated care model with a home health care physician (MICM) is a collaboration between regional and municipal health care. Descriptions of patients' and next of kin's experiences of integrated care is however lacking, motivating exploration. METHOD: A qualitative thematic study. Data collection was done before the patients met the MICM physician, and again six months later. RESULTS: The participants expected a sense of relief when admitted to MICM, and hoped for shared responsibility, building a personal contact and continuity but experienced lack of information about what MICM was. At the follow-up interview, participants described having an easier daily life. The increased access to the health care personnel (HCP) allowed participants to let go of responsibility, and created a sense of safety through the personalised contact and continuity. However, some felt ignored and that the personnel teamed up against the patient. The MICM structure was experienced as hierarchical, which influenced the possibility to participate. However, the home visits opened up the possibility for shared decision making. CONCLUSION: Participants had an expectation of receiving safe and coherent health care, to share responsibility, personal contact and continuity. After six months, the participants expressed that MICM had provided an easier daily life. The direct access to HCP reduced their responsibility and they had created a personalised contact with the HCP and that the individual HCP mattered to them, which could be perceived as in line with the goals in the shift to local health care. The MICM was experienced as a hierarchic structure with impact on participation, indicating that all dimensions of person-centred care were not fulfilled.


Assuntos
Prestação Integrada de Cuidados de Saúde , Serviços de Assistência Domiciliar , Médicos , Humanos , Idoso , Motivação , Pessoal de Saúde
10.
Allergy ; 78(11): 2959-2968, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37615432

RESUMO

BACKGROUND: Mast cells (MCs) develop from a rare population of peripheral blood circulating MC progenitors (MCps). Here, we investigated whether the frequency of circulating MCps is altered in asthma patients sensitized to birch pollen during pollen season, compared to out of season. METHODS: Asthma patients were examined during birch pollen season in late April to early June (May), and out of season in November-January. Spirometry measurements, asthma and allergy-related symptoms, asthma control questionnaire (ACQ), and asthma control test (ACT) scores were assessed at both time points. The MCp frequency was determined by flow cytometry in ficoll-separated blood samples from patients with positive birch pollen-specific IgE, and analyzed in relation to basic and disease parameters. RESULTS: The frequency of MCps per liter of blood was higher in May than in November (p = .004), particularly in women (p = .009). Patients that reported moderate to severe asthma symptoms (<.0001), nose or eye symptoms (p = .02; p = .01), or reduced asthma control (higher ACQ, p = .01) had higher MCp frequency in May than those that did not report this. These associations remained significant after adjusting for sex and BMI. The change in asthma control to a lower ACT score in May correlated with an increase in MCp frequency in May (p = .006, rho = 0.46). CONCLUSIONS: The data suggest that the frequency of MCps increases in symptomatic patients with allergic asthma. Our results unravel a link between asthma symptoms and circulating MCps, and bring new insight into the impact of natural allergen exposure on the expansion of MCs.


Assuntos
Asma , Betula , Humanos , Feminino , Mastócitos , Pólen , Asma/diagnóstico , Asma/epidemiologia , Alérgenos
11.
Front Immunol ; 14: 1211295, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37497217

RESUMO

Granzymes A and K are two highly homologous serine proteases expressed by mammalian cytotoxic T cells (CTL) and natural killer cells (NK). Granzyme A is the most abundant of the different granzymes (gzms) expressed by these two cell types. Gzms A and K are found in all jawed vertebrates and are the most well conserved of all hematopoietic serine proteases. Their potential functions have been studied extensively for many years, however, without clear conclusions. Gzm A was for many years thought to serve as a key component in the defense against viral infection by the induction of apoptosis in virus-infected cells, similar to gzm B. However, later studies have questioned this role and instead indicated that gzm A may act as a potent inducer of inflammatory cytokines and chemokines. Gzms A and K form clearly separate branches in a phylogenetic tree indicating separate functions. Transcriptional analyses presented here demonstrate the presence of gzm A and K transcripts in both CD4+ and CD8+ T cells. To enable screening for their primary biological targets we have made a detailed analysis of their extended cleavage specificities. Phage display analysis of the cleavage specificity of the recombinant enzymes showed that both gzms A and K are strict tryptases with high selectivity for Arg over Lys in the P1 position. The major differences in the specificities of these two enzymes are located N-terminally of the cleavage site, where gzm A prefers small amino acids such as Gly in the P3 position and shows a relatively relaxed selectivity in the P2 position. In contrast, gzm K prefers large amino acids such as Phe, Tyr, and Trp in both the P2 and P3 positions and does not tolerate negatively charged residues in the P2 position. This major distinction in extended specificities is likely reflected also in preferred in vivo targets of these two enzymes. This information can now be utilized for high-precision screening of primary targets for gzms A and K in search of their highly conserved but still poorly defined functions in vertebrate immunity.


Assuntos
Linfócitos T CD8-Positivos , Células Matadoras Naturais , Animais , Humanos , Granzimas/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Filogenia , Serina Proteases , Imunidade Celular , Mamíferos/metabolismo
13.
BMC Prim Care ; 23(1): 325, 2022 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-36517792

RESUMO

BACKGROUND: Since COVID-19 emerged, over 514 million COVID-19 cases and 6 million COVID-19-related deaths have been reported worldwide. Older persons receiving home health care often have co-morbidities that require advanced medical care, and are at risk of becoming severely ill or dying from COVID-19. In Sweden, over 10,000 COVID-19-related deaths have been reported among persons receiving municipal home health and social care. Home health care professionals have been working with the patients most at risk if infected. Most research has focused on the experiences of professionals in hospitals and assistant nurses in a home care setting. It is therefore valuable to study the experiences of the registered nurses and physicians working in home health care during the COVID-19 pandemic to learn lessons to inform future work. METHOD: A thematic qualitative study design using a semi-structured interview guide. RESULTS: The health care professionals experienced being forced into changed ways of working, which disrupted building and maintaining relationships with other health care professionals, and interrupted home health care. The health care professionals described being forced into digital and phone communication instead of in-person meetings, which negatively influenced the quality of care. The COVID-19 pandemic brought worry about illness for the health care professionals, including worrying about infecting patients, co-workers, and themselves, as well as worry about upholding the provision of health care because of increasing sick leave. The health care professionals felt powerless in the face of their patients' declining health. They also faced worry and guilt from the patients' next of kin. CONCLUSION: Home health care professionals have faced the COVID-19 pandemic while working across organizational borders, caring for older patients who have been isolated during the pandemic and trying to prevent declining health and feelings of isolation. Due to the forced use of digital and phone communication instead of in-person visits, the home health care professionals experienced a reduction in the patients' quality of care and difficulty maintaining good communication between the professions.


Assuntos
COVID-19 , Visitadores Domiciliares , Humanos , Idoso , Idoso de 80 Anos ou mais , COVID-19/epidemiologia , Pandemias , Pesquisa Qualitativa , Pessoal de Saúde
14.
BMC Geriatr ; 22(1): 554, 2022 07 04.
Artigo em Inglês | MEDLINE | ID: mdl-35787260

RESUMO

BACKGROUND: An increasing older population, along with the organizational principle of remaining at home, has moved health care from institutions into the older person's home, where several health care providers facilitate care. The Mobile Integrated Care Model strives to provide cost-efficient, coherent, person-centered health care in the home. In the integrated care team, where the home health care physician is the medical authority, several health care professions work across organizational borders. Therefore, the aim of this study was to describe Home Health Care Physicians perceptions of working and providing health care in the Mobile Integrated Care Model, as well as perceptions of participating in and forming health care. METHODS: A phenomenographic qualitative study design, with semi-structured interviews using an interview guide. RESULTS: Working within Mobile Integrated Care Model was a different way of working as a physician. The physicians' role was to support the patient by making safe medical decisions. Physicians described themselves as a piece in the team puzzle, where the professional knowledge of others was crucial to give quality health care. Being in the patients' homes was expressed as adding a unique dimension in the provision of health care, and the physicians learned more about the patients by meeting them in their homes than at an institution. This aided the physicians in respecting patient autonomy in medical decision making, even though the physicians sometimes disregarded patient autonomy in favor of their own medical experience. There was a divided view on next of kin participation among the home health care physicians, ranging from always including to total absence of involving next of kin in decision making. CONCLUSIONS: The home health care physicians described the Mobile Integrated Care Model as the best way to work, but there was still a need for additional resources and structure when working in different organizations. The need for full-time employment, additional time or hours, more equipment, access to each other's medical records, and additional collaboration with other health care providers were expressed, which could contribute to increased work satisfaction and facilitate further development of person-centered care in the Mobile Integrated Care Model.


Assuntos
Prestação Integrada de Cuidados de Saúde , Serviços de Assistência Domiciliar , Médicos , Idoso , Pessoal de Saúde , Humanos , Pesquisa Qualitativa
15.
BMC Public Health ; 22(1): 1314, 2022 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-35804344

RESUMO

BACKGROUND: Educational environments are considered important in strengthening students' health status and knowledge, which are associated with good educational outcomes. It has been suggested to establish healthy universities based on a salutogenic approach - namely, health promotion. The aim of this study was to describe health-promoting resources and factors among first-semester students in higher education in healthcare and social work. METHODS: This cross-sectional study is based on a survey distributed among all students in seven healthcare and social work programmes at six universities in southern Sweden. The survey was carried out in 2018 using a self-reported, web-based questionnaire focussing on general health and well-being, lifestyle factors together with three validated instruments measuring health-promoting factors and processes: the Sense of Coherence (SOC) scale, Salutogenic Health Indicator Scale (SHIS) and Occupational Balance Questionnaire (OBQ). RESULTS: Of 2283 students, 851 (37.3%) completed the survey, of whom 742 (87.1%) were women; 722 (84.8%) were enrolled on healthcare programmes, and 129 (15.2%) were enrolled on social work programmes. Most reported good general health and well-being (88.1% and 83.7%, respectively). The total mean scores for the SOC scale, SHIS and OBQ were, respectively, 59.09 (SD = 11.78), 44.04 (SD = 9.38) and 26.40 (SD = 7.07). Well-being and several healthy lifestyles were related to better general health and higher SOC, SHIS and OBQ scores. Multiple linear and logistic regressions showed that perceived well-being and no sleeping problems significantly predicted higher general health and higher SOC, SHIS and OBQ scores. Being less sedentary and non-smoking habits were significant predictors of higher SOC. CONCLUSIONS: Swedish students in higher education within the healthcare and social work sector report good general health and well-being in the first semester, as well as health-promoting resources (i.e. SOC, SHIS and OBQ), and in some aspects, a healthy lifestyle. High-intensity exercise, no sleeping problems and non-smoking seem to be of importance to both general health and health-promotive resources. This study contributes to knowledge about the health promotive characteristics of students in the healthcare and social work fields, which is of importance for planning universities with a salutogenic approach.


Assuntos
Senso de Coerência , Estudos Transversais , Atenção à Saúde , Feminino , Humanos , Estudos Longitudinais , Masculino , Serviço Social , Estudantes , Inquéritos e Questionários
17.
Front Immunol ; 13: 830859, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35493481

RESUMO

IL-33 and its receptor ST2, as well as mast cells and their mediators, have been implicated in the development of chronic obstructive pulmonary disease (COPD). However, whether mast cells and the ST2 receptor play a critical role in COPD pathophysiology remains unclear. Here, we performed repeated intranasal administrations of porcine pancreatic elastase and LPS for four weeks to study COPD-like disease in wildtype, ST2-deficient, and Cpa3Cre/+ mice, which lack mast cells and have a partial reduction in basophils. Alveolar enlargement and changes in spirometry-like parameters, e.g. increased dynamic compliance and decreased expiratory capacity, were evident one day after the final LPS challenge and worsened over time. The elastase/LPS model also induced mild COPD-like airway inflammation, which encompassed a transient increase in lung mast cell progenitors, but not in mature mast cells. While ST2-deficient and Cpa3Cre/+ mice developed reduced pulmonary function uninterruptedly, they had a defective inflammatory response. Importantly, both ST2-deficient and Cpa3Cre/+ mice had fewer alveolar macrophages, known effector cells in COPD. Elastase/LPS instillation in vivo also caused increased bronchiole contraction in precision cut lung slices challenged with methacholine ex vivo, which occurred in a mast cell-independent fashion. Taken together, our data suggest that the ST2 receptor and mast cells play a minor role in COPD pathophysiology by sustaining alveolar macrophages.


Assuntos
Elastase Pancreática , Doença Pulmonar Obstrutiva Crônica , Animais , Integrases , Proteína 1 Semelhante a Receptor de Interleucina-1/genética , Lipopolissacarídeos/toxicidade , Camundongos , Doença Pulmonar Obstrutiva Crônica/induzido quimicamente , Suínos
18.
J Allergy Clin Immunol ; 149(6): 1833-1844, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35276243

RESUMO

Mast cells are highly granular tissue-resident cells and key drivers of inflammation, particularly in allergies as well as in other inflammatory diseases. Most mast cell research was initially conducted in rodents but has increasingly shifted to the human system, with the advancement of research technologies and methodologies. Today we can analyze primary human cells including rare subpopulations, we can produce and maintain mast cells isolated from human tissues, and there are several human mast cell lines. These tools have substantially facilitated our understanding of their role and function in different organs in both health and disease. We can now define more clearly where human mast cells originate from, how they develop, which mediators they store, produce de novo, and release, how they are activated and by which receptors, and which neighboring cells they interact with and by which mechanisms. Considerable progress has also been made regarding the potential contribution of mast cells to disease, which, in turn, has led to the development of novel approaches for preventing key pathogenic effects of mast cells, heralding the era of mast cell-targeted therapeutics. In this review, we present and discuss a selection of some of the most significant advancements and remaining gaps in our understanding of human mast cells during the last 25 years, with a focus on clinical relevance.


Assuntos
Hipersensibilidade , Mastócitos , Humanos , Hipersensibilidade/metabolismo , Inflamação/metabolismo , Mastócitos/patologia
19.
Aust Crit Care ; 35(1): 52-58, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34955333

RESUMO

BACKGROUND: During the COVID-19 pandemic, the workload on the intensive care unit (ICU) increased nationally in Sweden as well as globally. Certified registered nurse anaesthetists (CRNAs) in Sweden were transferred at short notice to work with seriously ill patients with COVID-19 in the ICU, which is not part of the CRNAs' specialist area. However, limited research has shed light on healthcare professionals' experiences of the pandemic. OBJECTIVES: This study illuminates CRNAs' experiences of working in the ICU during the COVID-19 pandemic. METHODS: This study used a qualitative method with an inductive approach to interview nurse anaesthetists who worked in the ICU during the COVID-19 pandemic. FINDINGS: The participants experienced ambivalent feelings towards their work in the ICU. They also lacked information, which created feelings of uncertainty and resulted in expectations that did not correspond to the reality. They described that owing to an inadequate introduction, they could only provide "sufficient" care, which in many cases caused ethical stress. Not being able to get to know their new colleagues well enough to create effective cooperation created frustration. Even though the participants experienced the work in the ICU as demanding and challenging, overall, they enjoyed their time in the ICU and were treated well by their colleagues. CONCLUSIONS: Although CRNAs cannot replace intensive care nurses, they are a useful resource in the ICU in the care of patients with COVID-19. Healthcare workers who are allocated from their ordinary units to the ICU need adequate information and support from their work managers to be able to provide the best possible care and to stay healthy themselves.


Assuntos
COVID-19 , Humanos , Unidades de Terapia Intensiva , Enfermeiras Anestesistas , Pandemias , SARS-CoV-2
20.
J Allergy Clin Immunol ; 149(4): 1458-1463, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34492259

RESUMO

BACKGROUND: The concept of innate and adaptive effector cells that are repleted by maturing inert progenitor cell populations is changing. Mast cells develop from rare mast cell progenitors populating peripheral tissues at homeostatic conditions, or as a result of induced recruitment during inflammatory conditions. OBJECTIVE: Because FcεRI-expressing mast cell progenitors are the dominating mast cell type during acute allergic lung inflammation in vivo, we hypothesized that they are activated by IgE cross-linking. METHODS: Mouse peritoneal and human peripheral blood cells were sensitized and stimulated with antigen, or stimulated with anti-IgE, and the mast cell progenitor population analyzed for signs of activation by flow cytometry. Isolated peritoneal mast cell progenitors were studied before and after anti-IgE stimulation at single-cell level by time-lapse fluorescence microscopy. Lung mast cell progenitors were analyzed for their ability to produce IL-13 by intracellular flow cytometry in a mouse model of ovalbumin-induced allergic airway inflammation. RESULTS: Sensitized mouse peritoneal mast cell progenitors demonstrate increased levels of phosphorylation of tyrosines on intracellular proteins (total tyrosine phosphorylation), and spleen tyrosine kinase (Syk) phosphorylation after antigen exposure. Anti-IgE induced cell surface-associated lysomal-associated membrane protein-1 (LAMP-1) in naive mast cell progenitors, and prompted loss of fluorescence signal and altered morphology of isolated cells loaded with lysotracker. In human mast cell progenitors, anti-IgE increased total tyrosine phosphorylation, cell surface-associated LAMP-1, and CD63. Lung mast cell progenitors from mice with ovalbumin-induced allergic airway inflammation produce IL-13. CONCLUSIONS: Mast cell progenitors become activated by IgE cross-linking and may contribute to the pathology associated with acute allergic airway inflammation.


Assuntos
Hipersensibilidade , Mastócitos , Animais , Humanos , Hipersensibilidade/metabolismo , Imunoglobulina E/metabolismo , Inflamação/metabolismo , Interleucina-13/metabolismo , Camundongos , Ovalbumina , Receptores de IgE , Tirosina/metabolismo
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