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Journal of Clinical Immunology Dec 2023Genetic variants in IL6ST encoding the shared cytokine receptor for the IL-6 cytokine family GP130 have been associated with a diverse number of clinical phenotypes and... (Review)
Review
Genetic variants in IL6ST encoding the shared cytokine receptor for the IL-6 cytokine family GP130 have been associated with a diverse number of clinical phenotypes and disorders. We provide a molecular classification for 59 reported rare IL6ST pathogenic or likely pathogenic variants and additional polymorphisms. Based on loss- or gain-of-function, cytokine selectivity, mono- and biallelic associations, and variable cellular mosaicism, we grade six classes of IL6ST variants and explore the potential for additional variants. We classify variants according to the American College of Medical Genetics and Genomics criteria. Loss-of-function variants with (i) biallelic complete loss of GP130 function that presents with extended Stüve-Wiedemann Syndrome; (ii) autosomal recessive hyper-IgE syndrome (HIES) caused by biallelic; and (iii) autosomal dominant HIES caused by monoallelic IL6ST variants both causing selective IL-6 and IL-11 cytokine loss-of-function defects; (iv) a biallelic cytokine-specific variant that exclusively impairs IL-11 signaling, associated with craniosynostosis and tooth abnormalities; (v) somatic monoallelic mosaic constitutively active gain-of-function variants in hepatocytes that present with inflammatory hepatocellular adenoma; and (vi) mosaic constitutively active gain-of-function variants in hematopoietic and non-hematopoietic cells that are associated with an immune dysregulation syndrome. In addition to Mendelian IL6ST coding variants, there are common non-coding cis-acting variants that modify gene expression, which are associated with an increased risk of complex immune-mediated disorders and trans-acting variants that affect GP130 protein function. Our taxonomy highlights IL6ST as a gene with particularly strong functional and phenotypic diversity due to the combinatorial biology of the IL-6 cytokine family and predicts additional genotype-phenotype associations.
Topics: Humans; Cytokine Receptor gp130; Cytokines; Interleukin-11; Interleukin-6; Job Syndrome; Receptors, Cytokine; STAT3 Transcription Factor
PubMed: 38133879
DOI: 10.1007/s10875-023-01603-7 -
Preventive Medicine Reports Dec 2023A wide range in prevalence rates of burnout among general practitioners (GPs) has been reported in various regions, with an increasing trend. This nationwide...
OBJECTIVE
A wide range in prevalence rates of burnout among general practitioners (GPs) has been reported in various regions, with an increasing trend. This nationwide cross-sectional study aimed to estimate the prevalence and associated determinants of burnout in Czech GPs.
METHODS
1000 randomly selected physicians from the Czech Society of General Practitioners (through a pseudorandom number generator) were emailed an online survey based on the Maslach Burnout Inventory - Human Services Survey. Data collection was performed between January and February 2023.
RESULTS
331 questionnaires were obtained (227 females and 104 males, mean age - 49.9 years, the mean number of registered patients - 1951). 21.8 % of GPs scored a high level of burnout in all three of its dimensions and 23.9 % in no dimension at all. The most prevalent dimension was reduced personal accomplishment (PA, 56.2 %) followed by emotional exhaustion (EE, 50.2 %) and depersonalization (DP, 40.5 %). Reaching burnout in all three dimensions was significantly more frequent in males and in GPs registering a number of patients above the median. Increasing age and years of practice were protective factors for DP but risk factors for reduced PA. Employed GPs had lower EE scores than GP practice owners. The respondents' basic characteristics reflected their presence among Czech GPs, which testifies against selection bias.
CONCLUSIONS
The high rate of burnout (∼22 %) should be addressed by promoting personal resources along with the perception of the importance of GPs in society. A sufficiently dense network of GPs should allow them to register a lower number of patients.
PubMed: 38116278
DOI: 10.1016/j.pmedr.2023.102502 -
Archives of Biochemistry and Biophysics Feb 2024Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a positive-stranded RNA virus that sits at the centre of the recent global pandemic. As a member of the... (Review)
Review
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a positive-stranded RNA virus that sits at the centre of the recent global pandemic. As a member of the coronaviridae family of viruses, it shares features such as a very large genome (>30 kb) that is replicated in a purpose-built replication organelle. Biogenesis of the replication organelle requires significant and concerted rearrangement of the endoplasmic reticulum membrane, a job that is carried out by a group of integral membrane non-structural proteins (NSP3, 4 and 6) expressed by the virus along with a host of viral replication enzymes and other factors that support transcription and replication. The primary sites for RNA replication within the replication organelle are double membrane vesicles (DMVs). The small size of DMVs requires generation of high membrane curvature, as well as stabilization of a double-membrane arrangement, but the mechanisms that underlie DMV formation remain elusive. In this review, we discuss recent breakthroughs in our understanding of the molecular basis for membrane rearrangements by coronaviruses. We incorporate established models of NSP3-4 protein-protein interactions to drive double membrane formation, and recent data highlighting the roles of lipid composition and host factor proteins (e.g. reticulons) that influence membrane curvature, to propose a revised model for DMV formation in SARS-CoV-2.
Topics: Cell Line; Viral Nonstructural Proteins; Endoplasmic Reticulum; Membrane Proteins; Virus Replication
PubMed: 38104958
DOI: 10.1016/j.abb.2023.109856 -
Frontiers in Public Health 2023Most individuals recover from the acute phase of infection with the SARS-CoV-2 virus, however, some encounter prolonged effects, referred to as the Post-COVID syndrome....
BACKGROUND
Most individuals recover from the acute phase of infection with the SARS-CoV-2 virus, however, some encounter prolonged effects, referred to as the Post-COVID syndrome. Evidence exists that such persistent symptoms can significantly impact patients' ability to return to work. This paper gives a comprehensive overview of different care pathways and resources, both personal and external, that aim to support Post-COVID patients during their work-life reintegration process. By describing the current situation of Post-COVID patients pertaining their transition back to the workplace, this paper provides valuable insights into their needs.
METHODS
A quantitative research design was applied using an online questionnaire as an instrument. Participants were recruited via Post-COVID outpatients, rehab facilities, general practitioners, support groups, and other healthcare facilities.
RESULTS
The analyses of 184 data sets of Post-COVID affected produced three key findings: (1) The evaluation of different types of personal resources that may lead to a successful return to work found that particularly the individuals' ability to cope with their situation (measured with the FERUS questionnaire), produced significant differences between participants that had returned to work and those that had not been able to return so far (F = 4.913, = 0.001). (2) In terms of organizational provisions to facilitate successful reintegration into work-life, predominantly structural changes (i.e., modification of the workplace, working hours, and task) were rated as helpful or very helpful on average (mean 2.55/SD = 0.83, mean 2.44/SD = 0.80; mean 2.55/SD = 0.83), while the remaining offerings (i.e., job coaching or health courses) were rated as less helpful or not helpful at all. (3) No significant correlation was found between different care pathways and a successful return to work.
CONCLUSION
The results of the in-depth descriptive analysis allows to suggests that the level of ability to cope with the Post-COVID syndrome and its associated complaints, as well as the structural adaptation of the workplace to meet the needs and demands of patients better, might be important determinants of a successful return. While the latter might be addressed by employers directly, it might be helpful to integrate training on coping behavior early in care pathways and treatment plans for Post-COVID patients to strengthen their coping abilities aiming to support their successful return to work at an early stage.
Topics: Humans; COVID-19; Critical Pathways; Return to Work; SARS-CoV-2; Workplace
PubMed: 38089028
DOI: 10.3389/fpubh.2023.1282507 -
Global Public Health Jan 2023Poverty, lack of education and gender inequality make unemployed and out-of-school young women extremely vulnerable to HIV infection. Promotive social protection...
Vulnerable young women and frontline service providers identify options to improve the HIV-sensitivity of social protection programmes in Botswana: A modified Policy Delphi approach.
Poverty, lack of education and gender inequality make unemployed and out-of-school young women extremely vulnerable to HIV infection. Promotive social protection programmes aim to increase livelihood and capabilities and could empower this priority population to act on HIV prevention choices. In Botswana, they rarely benefit from such programmes.A modified Policy Delphi engaged a panel of 22 unemployed and out-of-school young women and eight frontline service providers to consider alternative policy and practice options, and tailor available programmes to their own needs and social situation. The panel assessed the desirability and feasibility of improvement proposals and, in a second round, ranked them for relative importance.Nearly all 40 improvement proposals were considered very desirable and definitely, or possibly, feasible, and panellists prioritised a wide range of proposals. Frontline service providers stressed foundational skills, like life skills and second chance education. Young women preferred options with more immediate benefits. Overall, panellists perceived positive role models for programme delivery, access to land and water, job skills training, and stipends as most important to empower HIV-vulnerable young women. Results suggest ample policy space to make existing social protection programmes in Botswana more inclusive of unemployed and out-of-school young women, hence more HIV-sensitive.
Topics: Humans; Female; HIV Infections; Botswana; Acquired Immunodeficiency Syndrome; Public Policy; Poverty
PubMed: 38081774
DOI: 10.1080/17441692.2023.2255030 -
Healthcare (Basel, Switzerland) Nov 2023The aim of this study was to use latent profile analysis to identify specific profiles of burnout syndrome in combination with work engagement and to identify whether...
The aim of this study was to use latent profile analysis to identify specific profiles of burnout syndrome in combination with work engagement and to identify whether job satisfaction, psychological well-being, and other sociodemographic and work variables affect the probability of presenting a profile of burnout syndrome and low work enthusiasm. A total of 355 healthcare professionals completed the Spanish Burnout Inventory, the Utrecht Work Engagement Scale, the Job Satisfaction Scale, and the Psychological Well-Being Scale for Adults. Latent profile analysis identified four profiles: (1) burnout with high indolence (BwHIn); (2) burnout with low indolence (BwLIn); (3) high engagement, low burnout (HeLb); and (4) in the process of burning out (IPB). Multivariate logistic regression showed that a second job in a government healthcare institution; a shift other than the morning shift; being divorced, separated or widowed; and workload are predictors of burnout profiles with respect to the HeLb profile. These data are useful for designing intervention strategies according to the needs and characteristics of each type of burnout profile.
PubMed: 38063610
DOI: 10.3390/healthcare11233042 -
International Journal of Environmental... Dec 2023Burnout syndrome can arise due to either situational factors such as working conditions, or dispositional factors such as certain temperaments, like a high sensory...
BACKGROUND
Burnout syndrome can arise due to either situational factors such as working conditions, or dispositional factors such as certain temperaments, like a high sensory processing sensitivity. We aim to address the relative absence of studies on speech-language therapists and seek to determine the role of high sensitivity for these healthcare workers in relation to burnout syndrome.
METHOD
The sample consisted of 602 female speech-language pathologists who anonymously completed a questionnaire measuring burnout (ProQOL 5th edition) and sensory processing sensitivity (HSPS-FR).
RESULTS
The results revealed that 77.41% of the participants reported moderate or high burnout scores. Furthermore, the analyses revealed that highly sensitive participants are more vulnerable to burnout than others.
CONCLUSION
This study highlights the negative impact of high sensory processing sensitivity on burnout. However, according to the kind of sensitivity, we discuss the way in which highly sensitive caregivers can master this sensitivity in order to use it as a strength in their professions and to spare themselves from suffering deleterious effects, such as compassion fatigue and/or burnout.
Topics: Humans; Female; Speech; Burnout, Psychological; Burnout, Professional; Compassion Fatigue; Surveys and Questionnaires; Perception; Quality of Life; Job Satisfaction
PubMed: 38063562
DOI: 10.3390/ijerph20237132 -
MedRxiv : the Preprint Server For... Nov 2023Posterior Cortical Atrophy (PCA) is a syndrome characterized by a progressive decline in higher-order visuospatial processing, leading to symptoms such as space...
INTRODUCTION
Posterior Cortical Atrophy (PCA) is a syndrome characterized by a progressive decline in higher-order visuospatial processing, leading to symptoms such as space perception deficit, simultanagnosia, and object perception impairment. While PCA is primarily known for its impact on visuospatial abilities, recent studies have documented language abnormalities in PCA patients. This study aims to delineate the nature and origin of language impairments in PCA, hypothesizing that language deficits reflect the visuospatial processing impairments of the disease.
METHODS
We compared the language samples of 25 patients with PCA with age-matched cognitively normal (CN) individuals across two distinct tasks: a visually-dependent picture description and a visually-independent job description task. We extracted word frequency, word utterance latency, and spatial relational words for this comparison. We then conducted an in-depth analysis of the language used in the picture description task to identify specific linguistic indicators that reflect the visuospatial processing deficits of PCA.
RESULTS
Patients with PCA showed significant language deficits in the visually-dependent task, characterized by higher word frequency, prolonged utterance latency, and fewer spatial relational words, but not in the visually-independent task. An in-depth analysis of the picture description task further showed that PCA patients struggled to identify certain visual elements as well as the overall theme of the picture. A predictive model based on these language features distinguished PCA patients from CN individuals with high classification accuracy.
DISCUSSION
The findings indicate that language is a sensitive behavioral construct to detect visuospatial processing abnormalities of PCA. These insights offer theoretical and clinical avenues for understanding and managing PCA, underscoring language as a crucial marker for the visuospatial deficits of this atypical variant of Alzheimer's disease.
PubMed: 38045263
DOI: 10.1101/2023.11.21.23298864 -
Frontiers in Public Health 2023Burnout among Health Care workers (HCWs) impacts on provider-patient relations and quality of care. Anova Health Institute (Anova) is a large South African non-profit...
BACKGROUND
Burnout among Health Care workers (HCWs) impacts on provider-patient relations and quality of care. Anova Health Institute (Anova) is a large South African non-profit organization and PEPFAR/USAID implementing partner. We conducted a study among HCWs providing HIV-related services in primary care settings in Johannesburg, South Africa, to examine levels of burnout, understand factors affecting workplace wellbeing, and explore strategies to prevent burnout.
METHODS
We used a sequential mixed-method approach. Data were collected between February and April 2022. The first phase consisted of a survey using the Maslach Burnout Inventory Human Services Survey (MBI-HSS) to measure levels of burnout. We then interviewed a subset of survey participants to understand the experiences that may affect wellbeing. We used descriptive statistics to quantify burnout rates for each MBI dimension (emotional exhaustion, personal accomplishment, and depersonalization). Qualitative data analysis was guided by the Job Demands-Resources Framework that explores the interactions between demands and resources in the workplace.
RESULTS
Survey findings ( = 194) revealed that although depersonalization rates were low at 6%, 21% of participants had high emotional exhaustion and 24% reported low professional accomplishment. Less than half (41%, = 80) had scores in the high category for any one of the three MBI-HSS dimensions. The MBI-HSS dimensions differed significantly by type of work and job title. Roving positions (HCW working in more than one health facility) were more likely to experience higher emotional exhaustion and lower professional accomplishment. Qualitative findings ( = 25) indicate that a number of job demands, including high workload, inadequate mental health support, and challenging relationships with stakeholders, had a negative effect on HCWs' wellbeing. However, finding meaningfulness in their work, working as a team, and practicing autonomy were experienced as resources that reduced the negative effect of these demands.
CONCLUSION
While measured burnout syndrome rates were low, various experiences negatively impacted at least one in five HCW. We identified key resources that provided buffering against workplace stressors. We recommend that as well as addressing key drivers of burnout, access to these resources should be fostered, for example by strengthening interventions that offer recognition, and promoting team interactions through social activities and support groups.
Topics: Humans; South Africa; Workplace; Burnout, Professional; Health Personnel; HIV Infections; Primary Health Care
PubMed: 38026318
DOI: 10.3389/fpubh.2023.1220301 -
Journal of Immunology (Baltimore, Md. :... Jan 2024Staphylococcus aureus is a significant cause of morbidity and mortality in pulmonary infections. Patients with autosomal-dominant hyper-IgE syndrome due to STAT3...
Staphylococcus aureus is a significant cause of morbidity and mortality in pulmonary infections. Patients with autosomal-dominant hyper-IgE syndrome due to STAT3 deficiency are particularly susceptible to acquiring staphylococcal pneumonia associated with lung tissue destruction. Because macrophages are involved in both pathogen defense and inflammation, we investigated the impact of murine myeloid STAT3 deficiency on the macrophage phenotype in vitro and on pathogen clearance and inflammation during murine staphylococcal pneumonia. Murine bone marrow-derived macrophages (BMDM) from STAT3 LysMCre+ knockout or Cre- wild-type littermate controls were challenged with S. aureus, LPS, IL-4, or vehicle control in vitro. Pro- and anti-inflammatory responses as well as polarization and activation markers were analyzed. Mice were infected intratracheally with S. aureus, bronchoalveolar lavage and lungs were harvested, and immunohistofluorescence was performed on lung sections. S. aureus infection of STAT3-deficient BMDM led to an increased proinflammatory cytokine release and to enhanced upregulation of costimulatory MHC class II and CD86. Murine myeloid STAT3 deficiency did not affect pathogen clearance in vitro or in vivo. Matrix metalloproteinase 9 was upregulated in Staphylococcus-treated STAT3-deficient BMDM and in lung tissues of STAT3 knockout mice infected with S. aureus. Moreover, the expression of miR-155 was increased. The enhanced inflammatory responses and upregulation of matrix metalloproteinase 9 and miR-155 expression in murine STAT3-deficient as compared with wild-type macrophages during S. aureus infections may contribute to tissue damage as observed in STAT3-deficient patients during staphylococcal pneumonia.
Topics: Humans; Mice; Animals; Pneumonia, Staphylococcal; Job Syndrome; Staphylococcus aureus; Macrophage Activation; Matrix Metalloproteinase 9; Inflammation; Staphylococcal Infections; Mice, Knockout; MicroRNAs; Mice, Inbred C57BL; STAT3 Transcription Factor
PubMed: 37982695
DOI: 10.4049/jimmunol.2300151