bluuebunny/crossref_metadata_2025 huggingface dataset:
HLA‐DR3 mediated CD4 T cell response against GAD65 in type 1 diabetes patients
Authors: Chuzho Neihenuo , Mishra Neetu , Tandon Nikhil , Kanga Uma , Mishra Gunja , Sharma Akanksha , Mehra Narinder K. , Kumar Neeraj
Published: June 2023

Aim

We planned this study to identify diabetogenic glutamic acid decarboxylase (GAD65) peptides possibly responsible for human leucocyte antigen (HLA)‐DR3/DQ2‐mediated activation of GAD65‐specific CD4 T cells in type 1 diabetes (T1D).

Methods

Top 30 GAD65 peptides, found to strongly bind in silico with HLA‐DR3/DQ2 molecules, were selected and grouped into four pools. The peptides were used to stimulate CD4 T cells of study subjects in 16‐h peripheral blood mononuclear cell culture. CD4 T cells' stimulation in terms of interferon‐gamma (IFN‐γ), interleukin (IL)‐17, tumor necrosis factor‐alpha (TNF‐α), and IL‐10 expression was analyzed using flow cytometry.

Results

Although all four GAD65 peptide pools (PP1‐4) resulted in significantly higher expression of IFN‐γ by CD4 T cells (p = .003, p < .0001, p = .026, and p = .002, respectively), only pool 2 showed significant increase in IL‐17 expression (p < .0001) in T1D patients vs healthy controls. Interpeptide group comparison for immunogenicity revealed significantly higher IFN‐γ and IL‐17 expressions and significantly lower IL‐10 expression for PP2 compared to other groups (p < .0001, p = .02, and p = .04, respectively) in patients but not in controls. Further, group 2 peptides resulted in significant increase in CD4 T cells' expression of IFN‐γ and IL‐17 (p = .002 for both) and significant decrease in IL‐10 (p = .04) in HLA‐DRB1*03‐DQA1*05‐DQB1*02+ patients vs HLA‐DRB1*03‐DQA1*05‐DQB1*02+ controls. The CD4 T cells' expression of IL‐17 was significantly higher (p = .03) in recently diagnosed vs long‐standing HLA‐DRB1*03‐DQA1*05‐DQB1*02+ T1D patients.

Conclusion

GAD65 peptides, particularly those belonging to PP2, induced CD4 T cells to express IFN‐γ and IL‐17 cytokines in T1D patients, suggesting that group 2 peptides possibly presented by HLA‐DR3 molecule to CD4 T cells shift immune balance toward inflammatory phenotype in patients.
Doing feminist longitudinal research across the COVID‐19 crisis: Unheard impacts on researchers and garment workers in Cambodia
Authors: Brickell Katherine , Chhom Theavy , Lawreniuk Sabina , McCarthy Lauren , Mony Reach , So Hengvotey
Published: June 2023

This paper is based on the ReFashion study which used mixed‐method longitudinal research to track and amplify the experiences and coping mechanisms of 200 women garment workers in Cambodia as they navigated the financial repercussions of the COVID‐19 pandemic. It develops the idea and practice of ‘feminist longitudinal research’ (FLR) through re‐centring the too often marginalised knowledges and ways of knowing of Cambodian researchers and research participants. Hearing and learning from their experiences reveal the labours and care‐work involved in the ‘doing’ of longitudinal research during a time of extraordinary crisis, and the potential for feminist consciousness raising and solidarity that can arise both within and beyond the confines of an academic study. The paper advocates for geographers and other social scientists to go beyond technically‐framed issues of participant ‘attrition’ and ‘retention’ in longitudinal studies to think more creatively and critically about the process of longitudinal research and what it means for those taking part in it. FLR not only evidences the temporally contingent gendered impacts of a phenomenon, but can be distinguished by its intentionality and/or potential to challenge the patriarchal status quo, both in the lives of researchers and participants.
Astrocyte‐derived lactoferrin reduces β‐amyloid burden by promoting the interaction between p38 kinase and PP2A phosphatase in male APP/PS1 transgenic mice
Authors: Fan Yong‐Gang , Guo Chuang , Zhao Ling‐Xiao , Ge Ri‐Le , Pang Zhong‐Qiu , He Da‐Long , Ren Hang , Wu Ting‐Yao , Zhang Yan‐Hui , Wang Zhan‐You
Published: June 2023

Background and Purpose

Overexpression of astrocytic lactoferrin (Lf) was observed in the brain of Alzheimer's disease (AD) patients, whereas the role of astrocytic Lf in AD progression remains unexplored. In this study, we aimed to evaluate the effects of astrocytic Lf on AD progression.

Experimental Approach

Male APP/PS1 mice with astrocytes overexpressing human Lf were developed to evaluate the effects of astrocytic Lf on AD progression. N2a‐sw cells also were employed to further uncover the mechanism of astrocytic Lf on β‐amyloid (Aβ) production.

Key Results

Astrocytic Lf overexpression increased protein phosphatase 2A (PP2A) activity and reduced amyloid precursor protein (APP) phosphorylation, Aβ burden and tau hyperphosphorylation in APP/PS1 mice. Mechanistically, astrocytic Lf overexpression promoted the uptake of astrocytic Lf into neurons in APP/PS1 mice, and conditional medium from astrocytes overexpressing Lf inhibited p‐APP (Thr668) expression in N2a‐sw cells. Furthermore, recombinant human Lf (hLf) significantly enhanced PP2A activity and inhibited p‐APP expression, whereas inhibition of p38 or PP2A activities abrogated the hLf‐induced p‐APP down‐regulation in N2a‐sw cells. Additionally, hLf promoted the interaction of p38 and PP2A via p38 activation, thereby enhancing PP2A activity, and low‐density lipoprotein receptor‐related protein 1 (LRP1) knockdown significantly reversed the hLf‐induced p38 activation and p‐APP down‐regulation.

Conclusions and Implications

Our data suggested that astrocytic Lf promoted neuronal p38 activation, via targeting to LRP1, subsequently promoting p38 binding to PP2A to enhance PP2A enzyme activity, which finally inhibited Aβ production via APP dephosphorylation. In conclusion, promoting astrocytic Lf expression may be a potential strategy against AD.

LINKED ARTICLES

This article is part of a themed issue From Alzheimer's Disease to Vascular Dementia: Different Roads Leading to Cognitive Decline. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v181.6/issuetoc
The rise of hyperabundant native generalists threatens both humans and nature
Authors: Moore Jonathan H. , Gibson Luke , Amir Zachary , Chanthorn Wirong , Ahmad Abdul Hamid , Jansen Patrick A. , Mendes Calebe P. , Onuma Manabu , Peres Carlos A. , Luskin Matthew Scott
Published: June 2023

In many disturbed terrestrial landscapes, a subset of native generalist vertebrates thrives. The population trends of these disturbance‐tolerant species may be driven by multiple factors, including habitat preferences, foraging opportunities (including crop raiding or human refuse), lower mortality when their predators are persecuted (the ‘human shield’ effect) and reduced competition due to declines of disturbance‐sensitive species. A pronounced elevation in the abundance of disturbance‐tolerant wildlife can drive numerous cascading impacts on food webs, biodiversity, vegetation structure and people in coupled human–natural systems. There is also concern for increased risk of zoonotic disease transfer to humans and domestic animals from wildlife species with high pathogen loads as their abundance and proximity to humans increases. Here we use field data from 58 landscapes to document a supra‐regional phenomenon of the hyperabundance and community dominance of Southeast Asian wild pigs and macaques. These two groups were chosen as prime candidates capable of reaching hyperabundance as they are edge adapted, with gregarious social structure, omnivorous diets, rapid reproduction and high tolerance to human proximity. Compared to intact interior forests, population densities in degraded forests were 148% and 87% higher for wild boar and macaques, respectively. In landscapes with >60% oil palm coverage, wild boar and pig‐tailed macaque estimated abundances were 337% and 447% higher than landscapes with <1% oil palm coverage, respectively, suggesting marked demographic benefits accrued by crop raiding on calorie‐rich food subsidies. There was extreme community dominance in forest landscapes with >20% oil palm cover where two pig and two macaque species accounted for >80% of independent camera trap detections, leaving <20% for the other 85 mammal species >1 kg considered. Establishing the population trends of pigs and macaques is imperative since they are linked to cascading impacts on the fauna and flora of local forest ecosystems, disease and human health, and economics (i.e., crop losses). The severity of potential negative cascading effects may motivate control efforts to achieve ecosystem integrity, human health and conservation objectives. Our review concludes that the rise of native generalists can be mediated by specific types of degradation, which influences the ecology and conservation of natural areas, creating both positive and detrimental impacts on intact ecosystems and human society.
The relationship of spiritual orientation and caregiver burden of caregiver mothers with a child with cerebral palsy in Turkey
Authors: Tuncay Suat , Sarman Abdullah
Published: June 2023

Introduction

This study aims to examine the association between spiritual orientation and the caregiving burden experienced by mothers of children with cerebral palsy.

Methods

Parents of 181 children with cerebral palsy, aged 0–18, participated in this cross‐sectional‐descriptive study. “Sociodemographic Form,” “Spiritual Orientation Scale,” “Zarit Caregiver Burden Scale,” and “Gross Motor Function Classification System” were used to collect data.

Results

The mothers who participated in the study had a mean age of 35.74 ± 5.94 years. The study showed that 17.1% of children with cerebral palsy did not receive special education, and 92.8% of them were born with a disability. Additionally, 62.4% of the children were found to be undernourished, 48.6% had irregular oral care, 43.1% had semi‐active activity, 65.7% had irregular sleeping patterns, and 50.8% only partially understood what was stated.

The study discovered that as mothers' ages increased, their spiritual orientation decreased, and their burden of caring increased. Furthermore, the mothers of children with severe disabilities had an increasing burden of care, as indicated by the gross motor classification.

Conclusions

The study found that mothers with higher spiritual orientation scores perceived less care burden. These findings suggest the need for implementing activities to provide moral support to mothers.
Children's perspectives on their play experiences during the COVID‐19 pandemic: A video‐based interview study
Authors: Graber Kelsey , O'Farrelly Christine , Ramchandani Paul
Published: June 2023

The COVID‐19 pandemic and lockdown regulations introduced many changes to children's everyday lives, including play, creating a unique pandemic experience for children. For this qualitative study, 15 children (ages 3–10) participated in virtual interviews on play during the pandemic between August and October 2020. While children recognised changes to play, it had persisted despite restrictions—play itself was not on lockdown. Children showed that play remained valuable and was an expression of adaptability, confidence and positivity. These considerations can help us support children's childhoods during crises, as children are members of society with rights to voice their opinions on matters affecting their lives.
Changes of gut microbiota in patients at different phases of stroke
Authors: Cui Wei , Xu Li , Huang Lin , Tian Yang , Yang Yan , Li Yamei , Yu Qian
Published: June 2023

Aims

Gut dysbiosis appears rapidly after acute stroke and may affect the prognosis, whereas changes in gut microbiota with gradual recovery from stroke are unknown and rarely studied. The purpose of this study is to explore the characteristics of gut microbiota changes over time after stroke.

Methods

Stroke patients and healthy subjects were selected to compare the clinical data and gut microbiota of the patient group in two phases with that of healthy subjects and 16S rRNA gene sequencing was used to search the differences of gut microbiota in subjects.

Results

Compared with the healthy subjects, the subacute patients mainly decreased the abundance of some gut microbial communities, while the decreased communities reduced and more communities increased the abundance in the convalescent patients. The abundance of Lactobacillaceae increased in both phases in patient group, while Butyricimona, Peptostreptococaceae and Romboutsia decreased in both phases. Correlation analysis found that the MMSE scores of patients in the two phases had the greatest correlation with the gut microbiota.

Conclusion

Gut dysbiosis still existed in patients in the subacute phase and convalescent phase, and gradually improved with the recovery of stroke. Gut microbiota may affect the prognosis of stroke by affecting BMI and/or related indicators, and there is a strong correlation between gut microbiota and cognitive function after stroke.
The interaction between intestinal microenvironment and stroke
Authors: Zhao Linna , Xiao Jie , Li Songlin , Guo Yuying , Fu Rong , Hua Shengyu , Du Yuzheng , Xu Shixin
Published: June 2023

Background

Stroke is not only a major cause of disability but also the third leading cause of death, following heart disease and cancer. It has been established that stroke causes permanent disability in 80% of survivors. However, current treatment options for this patient population are limited. Inflammation and immune response are major features that are well‐recognized to occur after a stroke. The gastrointestinal tract hosts complex microbial communities, the largest pool of immune cells, and forms a bidirectional regulation brain‐gut axis with the brain. Recent experimental and clinical studies have highlighted the importance of the relationship between the intestinal microenvironment and stroke. Over the years, the influence of the intestine on stroke has emerged as an important and dynamic research direction in biology and medicine.

Aims

In this review, we describe the structure and function of the intestinal microenvironment and highlight its cross‐talk relationship with stroke. In addition, we discuss potential strategies aiming to target the intestinal microenvironment during stroke treatment.

Conclusion

The structure and function of the intestinal environment can influence neurological function and cerebral ischemic outcome. Improving the intestinal microenvironment by targeting the gut microbiota may be a new direction in treating stroke.
Medial prefrontal cortical PPM1F alters depression‐related behaviors by modifying p300 activity via the AMPK signaling pathway
Authors: Liu Jing , Meng Fantao , Wang Wentao , Wu Min , Zhang Yu , Cui Minghu , Qiu Changyun , Hu Fengai , Zhao Di , Wang Dan , Liu Cuilan , Liu Dunjiang , Xu Zhicheng , Wang Yameng , Li Wei , Li Chen
Published: June 2023

Aims

Protein phosphatase Mg2+/Mn2+‐dependent 1F (PPM1F) is a serine/threonine phosphatase, and its dysfunction in depression in the hippocampal dentate gyrus has been previously identified. Nevertheless, its role in depression of another critical emotion‐controlling brain region, the medial prefrontal cortex (mPFC), remains unclear. We explored the functional relevance of PPM1F in the pathogenesis of depression.

Methods

The gene expression levels and colocalization of PPM1F in the mPFC of depressed mice were measured by real‐time PCR, western blot and immunohistochemistry. An adeno‐associated virus strategy was applied to determine the impact of knockdown or overexpression of PPM1F in the excitatory neurons on depression‐related behaviors under basal and stress conditions in both male and female mice. The neuronal excitability, expression of p300 and AMPK phosphorylation levels in the mPFC after knockdown of PPM1F were measured by electrophysiological recordings, real‐time PCR and western blot. The depression‐related behavior induced by PPM1F knockdown after AMPKα2 knockout or the antidepressant activity of PPM1F overexpression after inhibiting acetylation activity of p300 was evaluated.

Results

Our results indicate that the expression levels of PPM1F were largely decreased in the mPFC of mice exposed to chronic unpredictable stress (CUS). Behavioral alterations relevant to depression emerged with short hairpin RNA (shRNA)‐mediated genetic knockdown of PPM1F in the mPFC, while overexpression of PPM1F produced antidepressant activity and ameliorated behavioral responses to stress in CUS‐exposed mice. Molecularly, PPM1F knockdown decreased the excitability of pyramidal neurons in the mPFC, and restoring this low excitability decreased the depression‐related behaviors induced by PPM1F knockdown. PPM1F knockdown reduced the expression of CREB‐binding protein (CBP)/E1A‐associated protein (p300), a histone acetyltransferase (HAT), and induced hyperphosphorylation of AMPK, resulting in microglial activation and upregulation of proinflammatory cytokines. Conditional knockout of AMPK revealed an antidepressant phenotype, which can also block depression‐related behaviors induced by PPM1F knockdown. Furthermore, inhibiting the acetylase activity of p300 abolished the beneficial effects of PPM1F elevation on CUS‐induced depressive behaviors.

Conclusion

Our findings demonstrate that PPM1F in the mPFC modulates depression‐related behavioral responses by regulating the function of p300 via the AMPK signaling pathway.
Involvement of the scalloped gene in morphogenesis of the wing margin via regulating cell growth in a hemimetabolous insect Gryllus bimaculatus
Authors: Yamashita Takahisa , Ohde Takahiro , Nakamura Taro , Ishimaru Yoshiyasu , Watanabe Takahito , Tomonari Sayuri , Nakamura Yuki , Noji Sumihare , Mito Taro
Published: June 2023

The acquisition of wings was a key event in insect evolution. As hemimetabolous insects were the first group to acquire functional wings, establishing the mechanisms of wing formation in this group could provide useful insights into their evolution. In this study, we aimed to elucidate the expression and function of the gene scalloped (sd), which is involved in wing formation in Drosophila melanogaster, and in Gryllus bimaculatus mainly during postembryonic development. Expression analysis showed that sd is expressed in the tergal edge, legs, antennae, labrum, and cerci during embryogenesis and in the distal margin of the wing pads from at least the sixth instar in the mid to late stages. Because sd knockout caused early lethality, nymphal RNA interference experiments were performed. Malformations were observed in the wings, ovipositor, and antennae. By analyzing the effects on wing morphology, it was revealed that sd is mainly involved in the formation of the margin, possibly through the regulation of cell proliferation. In conclusion, sd might regulate the local growth of wing pads and influence wing margin morphology in Gryllus.
Risk factors of menopause after allogeneic hematopoietic cell transplantation in premenopausal adult women
Authors: Lee Yoo Jin , Kim Jeong Sook , Jo Jae‐Cheol , Kim Youjin , Im Hyeon‐Soo , Kim Hyeyeong , Koh SuJin , Min Young Joo , Park Sang‐Hyuk , Ahn Jun Woo , Choi Yunsuk
Published: June 2023

Objectives

Allogeneic hematopoietic stem‐cell transplantation (HCT) is the only curative option for most hematologic malignancies. However, HSCT can cause early menopause and various complications in premenopausal women. Therefore, we aimed to investigate risk factors predicting early menopause and its clinical implications among survivors post HCT.

Methods

We retrospectively analyzed 30 adult women who had received HCT at premenopausal status between 2015 and 2018. We excluded patients who had received autologous stem cell transplantation, had relapsed, or died of any cause within 2 years of HCT.

Results

The median age at HCT was 41.6 years (range, 22–53). Post‐HCT menopause was identified in 90% of myeloablative conditioning (MAC) HCT and 55% of reduced‐intensity conditioning (RIC) HCT (p = .101). In the multivariate analysis, the post‐HCT menopausal risk was 21 times higher in a MAC regimen containing 4 days of busulfan (p = .016) and 9.3 times higher in RIC regimens containing 2–3 days of busulfan (p = .033) than that of non‐busulfan‐based conditioning regimens.

Conclusions

Higher busulfan dose in conditioning regimens is the most significant risk factor affecting post‐HCT early menopause. Considering our data, we need to decide on conditioning regimens and individualized fertility counseling before HCT for premenopausal women.
A narrative review of the socioeconomic burden associated with generalised pustular psoriasis
Authors: Zimmermann Thomas M. , Hofmann Patrick , Chiu Gretchen R.
Published: June 2023

Generalised pustular psoriasis (GPP) is a rare, chronic and life‐threatening inflammatory skin disease characterised by widespread eruption of sterile pustules. With the approval of a GPP flare treatment in several countries occurring only recently, the socioeconomic burden associated with GPP is not well established. To highlight current evidence for patient burden, healthcare resource utilization (HCRU) and costs associated with GPP. Patient burden results from serious complications including sepsis and cardiorespiratory failure causing hospitalization and death. HCRU is driven by high hospitalization rates and treatment costs. The mean duration of a GPP hospital stay ranges from 10 to 16 days. A quarter of patients require intensive care, and the mean intensive care stay is 18 days. In comparison to patients with plaque psoriasis (PsO), patients with GPP have: a 64% higher score on the Charlson Comorbidity Index; higher hospitalization rates (≤36.3% vs. ≤23.3%); lower overall quality of life, and higher symptom scores for pain, itch, fatigue, anxiety and depression; direct costs associated with treatment 1.3‐ to 4.5‐fold higher; higher rates of disabled work status (20.0% vs. 7.6%); and increased presenteeism (i.e. worse impairment at work), impaired daily activities, and medically related absenteeism. Current medical management and drug treatment utilising non‐GPP‐specific therapies impose a significant patient and direct economic burden. GPP also imposes an indirect economic burden by increasing work productivity impairment and medically related absenteeism. This high level of socioeconomic burden reinforces the need for new therapies with proven efficacy in the treatment of GPP.
Does corporate diversification retrench the effects of firm‐level political risk?
Authors: Hassan M. Kabir , Karim M. Sydul , Mukherjee Tarun
Published: June 2023

This study investigates the effects of firm‐level political risk on corporate investments. We find that diversified firms are better able than focused firms in mitigating the impact of idiosyncratic political risk on investments. Diversified firms accomplish this feat via efficient use of the internal capital market that allows segments to alleviate political risk adversity. The effect is working through the channel of exacerbation of financial constraints. When exposed to political risk, diversified firms do not spend more on lobbying and political donations than the focused firms in the subsequent period, implying that diversified firms do not manage political risk politically. Our main findings are robust to a battery of endogeneity tests.
Niche breadth explains the range size of European‐centred butterflies, but dispersal ability does not
Authors: Hausharter Johannes , Rashid Sonia , Wessely Johannes , Strutzenberger Patrick , Moser Dietmar , Gattringer Andreas , Fiedler Konrad , Hülber Karl , Dullinger Stefan
Published: June 2023

Aim

The breadth of ecological niches and dispersal abilities have long been discussed as important determinants of species' range sizes. However, studies directly comparing the relative effects of both factors are rare, taxonomically biased and revealed inconsistent results.

Location

Europe.

Time Period

Cenozoic.

Major Taxa

Butterflies, Lepidoptera.

Methods

We relate climate, diet and habitat niche breadth and two indicators of dispersal ability, wingspan and a dispersal tendency index, to the global range size of 369 European‐centred butterfly species. The relative effects of these five predictors and their variation across the butterfly phylogeny were assessed by means of phylogenetic generalized least squares models and phylogenetically weighted regressions respectively.

Results

Climate niche breadth was the most important single predictor, followed by habitat and diet niche breadth, while dispersal tendency and wingspan showed no relation to species' range size. All predictors together explained 59% of the variation in butterfly range size. However, the effects of each predictor varied considerably across families and genera.

Main Conclusions

Range sizes of European‐centred butterflies are strongly correlated with ecological niche breadth but apparently independent of dispersal ability. The magnitude of range size–niche breadth relationships is not stationary across the phylogeny and is often negatively correlated across the different dimensions of the ecological niche. This variation limits the generalizability of range size–trait relationships across broad taxonomic groups.
Patient engagement in health implementation research: A logic model
Authors: Bisson Mathieu , Aubrey‐Bassler Kris , Chouinard Maud‐Christine , Doucet Shelley , Ramsden Vivian R. , Dumont‐Samson Olivier , Howse Dana , Lambert Mireille , Schwarz Charlotte , Luke Alison , Rabbitskin Norma , Gaudreau André , Porter Jude , Rubenstein Donna , Taylor Jennifer , Warren Mike , Hudon Catherine
Published: June 2023

Introduction

Growing evidence supports patient engagement (PE) in health implementation research to improve the quality, relevance and uptake of research. However, more guidance is needed to plan and operationalize PE before and throughout the research process. The aim of the study was to develop a logic model illustrating the causal links between context, resources, activities, outcomes and impact of PE in an implementation research programme.

Methods

The Patient Engagement in Health Implementation Research Logic Model (hereafter the Logic Model) was developed using a descriptive qualitative design with a participatory approach, in the context of the PriCARE programme. This programme aims to implement and evaluate case management for individuals who frequently use healthcare services in primary care clinics across five Canadian provinces. Participant observation of team meetings was performed by all team members involved in the programme and in‐depth interviews were conducted by two external research assistants with team members (n = 22). A deductive thematic analysis using components of logic models as coding categories was conducted. Data were pooled in the first version of the Logic Model, which was refined in research team meetings with patient partners. The final version was validated by all team members.

Results

The Logic Model highlights the importance of integrating PE into the project before its commencement, with appropriate support in terms of funding and time allocation. The governance structure and leadership of both principal investigators and patient partners have significant effects on PE activities and outcomes. As an empirical and standardized illustration that facilitates a shared understanding, the Logic Model provides guidance for maximizing the impact of patient partnership in various contexts for research, patients, providers and health care.

Conclusion

The Logic Model will help academic researchers, decision makers and patient partners plan, operationalize, and assess PE in implementation research for optimal outcomes.

Patient or Public Contribution

Patient partners from the PriCARE research programme contributed to developing the research objectives and designing, developing and validating data collection tools, producing data, developing and validating the Logic Model and reviewing the manuscript.
Nursing home staff perceptions of well‐being during the COVID‐19 pandemic: A qualitative study
Authors: van Diepen Cornelia , Vestjens Lotte , Nieboer Anna P. , Scheepers Renée
Published: June 2023

Aims

To explore how nursing home staff perceived their work environment during the COVID‐19 pandemic and how this impacted their well‐being.

Design

A qualitative interview study.

Methods

Interviews were held with twenty‐two registered nurses and assistant nurses from five nursing homes in the Netherlands between April 2021 and July 2021. The interviews were analysed using qualitative content analysis. The Standards for Reporting Qualitative Research (SRQR) were followed.

Results

Five themes emerged from the interviews and indicated that working during the COVID‐19 pandemic impacted perceived well‐being of nursing home staff. Three themes concerned experiences at work: eroding care, additional roles and workplace support. Specifically, the increased workload with additional tasks, the constant stream of new guidelines and constrictive personal protective equipment caused discomfort and anxiety. Two other themes concerned experiences outside of work: work‐life interference and social interactions and status. The nurses reported that when they returned home after work, they were tired and worried about spreading the virus while facing limited social interactions and support.

Conclusion

The social distancing measures due to the COVID‐19 pandemic negatively impacted nursing home staff well‐being by increasing demands in the absence of adequate resources.

Implications for the Profession and/or Patient Care

The well‐being needs of nurses should receive continued attention to ensure the sustainability of healthcare during future crises.

Patient or Public Contribution

The nursing home managers participated in recommending the topics to be covered during interviews.

Impact

What problem did the study address? The pressure of stressful working conditions on the well‐being of nurses during the pandemic.

What were the main findings? Nurses created strategies to cope with declining well‐being. However, the available resources did not alleviate the increased demands caused by the pandemic.

Where and on whom will the research have an impact? This study is important for healthcare organizations to understand how the COVID‐19 pandemic affected nurses so that they may better prepare for future crises.
Toll‐like receptor 4‐mediated microglial inflammation exacerbates early white matter injury following experimental subarachnoid hemorrhage
Authors: Peng Jianhua , Xie Yuke , Pang Jinwei , Wu Yue , Zhou Jian , Gu Long , Guo Kecheng , Zhang Lifang , Xie Bingqing , Yin Shigang , Sun Xiaochuan , Chen Ligang , Jiang Yong
Published: June 2023

Neuroinflammation has been reported to be associated with white matter injury (WMI) after subarachnoid hemorrhage (SAH). As the main resident immune cells of the brain, microglia can be activated into proinflammatory and anti‐inflammatory phenotypes. Toll‐like receptor 4 (TLR4), expressed on the surface of the microglia, plays a key role in microglial inflammation. However, the relationship between TLR4, microglial polarization, and WMI following SAH remains unclear. In this study, a total of 121 male adult C57BL/6 wild‐type (WT) mice, 20 WT mice at postnatal day 1 (P1), and 41 male adult TLR4 gene knockout (TLR4−/−) mice were used to investigate the potential role of TLR4‐induced microglial polarization in early WMI after SAH by radiological, histological, microstructural, transcriptional, and cytological evidence. The results indicated that microglial inflammation was associated with myelin loss and axon damage, shown as a decrease in myelin basic protein (MBP), as well as increase in degraded myelin basic protein (dMBP) and amyloid precursor protein (APP). Gene knockout of TLR4 revised microglial polarization toward the anti‐inflammatory phenotype and protected the white matter at an early phase after SAH (24 h), as shown through reduction of toxic metabolites, preservation of myelin, reductions in APP accumulation, reductions in white matter T2 hyperintensity, and increases in FA values. Cocultures of microglia and oligodendrocytes, the cells responsible for myelin production and maintenance, were established to further elucidate the relationship between microglial polarization and WMI. In vitro, TLR4 inhibition decreased the expression of microglial MyD88 and phosphorylated NF‐κB, thereby inhibiting M1 polarization and mitigating inflammation. Decrease in TLR4 in the microglia increased preservation of neighboring oligodendrocytes. In conclusion, microglial inflammation has dual effects on early WMI after experimental SAH. Future explorations on more clinically relevant methods for modulating neuroinflammation are warranted to combat stroke with both WMI and gray matter destruction.

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Difficulties in nurturing a sense of justice
Authors: Kuch Hannes
Published: June 2023

The paper analyzes Rawls's moral psychology and the claim that a just society must foster a sufficiently strong sense of justice. When Rawls investigates the development of the sense of justice under a just basic structure, he tacitly narrows down the focus: he only demonstrates the development of a sense of justice on the premise that all members of society are already in possession of a full‐fledged sense of justice, save the one individual under investigation. This begs the question, largely presupposing what needs to be explained, namely, how citizens at large develop a sense of justice. Rawls's narrowing of perspective leads to distortions in the analysis of stability, particularly with regard to a property‐owning democracy. However, in lesser known parts of his work, Rawls offers clues for a more plausible account. Here, the idea is that institutions must be structured such that they enable all of us to nurture the sense of justice of each of us. With this idea of collective self‐transformation in place, it becomes clear that economic institutions must be broadly democratized because of their profound educational role. Thus, the choice between a property‐owning democracy and liberal socialism falls more strongly upon the latter.
Multicentre sleep‐stage scoring agreement in the Sleep Revolution project
Authors: Nikkonen Sami , Somaskandhan Pranavan , Korkalainen Henri , Kainulainen Samu , Terrill Philip I. , Gretarsdottir Heidur , Sigurdardottir Sigridur , Olafsdottir Kristin Anna , Islind Anna Sigridur , Óskarsdóttir María , Arnardóttir Erna Sif , Leppänen Timo
Published: June 2023

Determining sleep stages accurately is an important part of the diagnostic process for numerous sleep disorders. However, as the sleep stage scoring is done manually following visual scoring rules there can be considerable variation in the sleep staging between different scorers. Thus, this study aimed to comprehensively evaluate the inter‐rater agreement in sleep staging. A total of 50 polysomnography recordings were manually scored by 10 independent scorers from seven different sleep centres. We used the 10 scorings to calculate a majority score by taking the sleep stage that was the most scored stage for each epoch. The overall agreement for sleep staging was κ = 0.71 and the mean agreement with the majority score was 0.86. The scorers were in perfect agreement in 48% of all scored epochs. The agreement was highest in rapid eye movement sleep (κ = 0.86) and lowest in N1 sleep (κ = 0.41). The agreement with the majority scoring varied between the scorers from 81% to 91%, with large variations between the scorers in sleep stage‐specific agreements. Scorers from the same sleep centres had the highest pairwise agreements at κ = 0.79, κ = 0.85, and κ = 0.78, while the lowest pairwise agreement between the scorers was κ = 0.58. We also found a moderate negative correlation between sleep staging agreement and the apnea–hypopnea index, as well as the rate of sleep stage transitions. In conclusion, although the overall agreement was high, several areas of low agreement were also found, mainly between non‐rapid eye movement stages.
Mortality and morbidity related to hepatitis C virus infection in hospitalized adults—A propensity score matched analysis
Authors: Hovaguimian Frédérique , Beeler Patrick E. , Müllhaupt Beat , Günthard Huldrych F. , Maeschli Bettina , Bruggmann Philip , Fehr Jan S. , Kouyos Roger D.
Published: June 2023

The World Health Organization (WHO) aims to reduce HCV mortality, but estimates are difficult to obtain. We aimed to identify electronic health records of individuals with HCV infection, and assess mortality and morbidity. We applied electronic phenotyping strategies on routinely collected data from patients hospitalized at a tertiary referral hospital in Switzerland between 2009 and 2017. Individuals with HCV infection were identified using International Classification of Disease (ICD)‐10 codes, prescribed medications and laboratory results (antibody, PCR, antigen or genotype test). Controls were selected using propensity score methods (matching by age, sex, intravenous drug use, alcohol abuse and HIV co‐infection). Main outcomes were in‐hospital mortality and attributable mortality (in HCV cases and study population). The non‐matched dataset included records from 165,972 individuals (287,255 hospital stays). Electronic phenotyping identified 2285 stays with evidence of HCV infection (1677 individuals). Propensity score matching yielded 6855 stays (2285 with HCV, 4570 controls). In‐hospital mortality was higher in HCV cases (RR 2.10, 95%CI 1.64 to 2.70). Among those infected, 52.5% of the deaths were attributable to HCV (95%CI 38.9 to 63.1). When cases were matched, the fraction of deaths attributable to HCV was 26.9% (HCV prevalence: 33%), whilst in the non‐matched dataset, it was 0.92% (HCV prevalence: 0.8%). In this study, HCV infection was strongly associated with increased mortality. Our methodology may be used to monitor the efforts towards meeting the WHO elimination targets and underline the importance of electronic cohorts as a basis for national longitudinal surveillance.
Impact of prior HBV, HAV, and HEV infection on non‐alcoholic fatty liver disease
Authors: Vassilopoulos Stephanos , Kalligeros Markos , Vassilopoulos Athanasios , Shehadeh Fadi , Benitez Gregorio , Kaczynski Matthew , Lazaridou Ingrid , Promrat Kittichai , Wands Jack R. , Mylonakis Eleftherios
Published: June 2023

Non‐alcoholic fatty liver disease (NAFLD) is a leading cause of chronic liver disease. The association between prior hepatitis B virus (HBV), hepatitis A virus (HAV), hepatitis E virus (HEV) infection and NAFLD remains unclear. We utilized the 2017–2020 National Health and Nutrition Examination Survey (NHANES) and performed multivariable logistic regression analyses to examine the association of prior HBV, HAV and HEV infection with NAFLD, as well as high risk non‐alcoholic steatohepatitis (NASH) and liver fibrosis. Our analysis included 2565 participants with available anti‐HBc serology results, 1480 unvaccinated participants with anti‐HAV results, and 2561 participants with anti‐HEV results. Among participants with NAFLD, the age‐adjusted prevalence of prior HBV, HAV and HEV infection was 3.48%, 32.08% and 7.45%, respectively. Prior infection with HBV, HAV and HEV was not associated with NAFLD (cut‐off 285 dB/m) [aOR: 0.99 (95% CI, 0.77–1.29), 1.29 (95% CI, 0.95–1.75), and 0.94 (95% CI, 0.70–1.27), respectively] or high‐risk NASH [aOR 0.72 (95% CI, 0.45–1.17), 0.92 (95% CI, 0.55–1.52), and 0.89 (95% CI, 0.41–1.94), respectively]. Participants with anti‐HBc and anti‐HAV seropositivity were more likely to have significant fibrosis [aOR: 1.53 (95% CI, 1.05–2.23) and 1.69 (95% CI, 1.16–2.47), respectively]. The odds of significant fibrosis are 53%, and 69% greater for participants with prior history of HBV and HAV infection. Healthcare providers should prioritize vaccination efforts and employ a tailored approach to NAFLD in patients with prior viral hepatitis and especially HBV or HAV infection to limit disease‐related outcomes.
Use of midazolam and butorphanol to sedate harbor seal pups (Phoca vitulina) undergoing rehabilitation
Authors: Anderson Chelsea E. , Tang Karisa , Pace Courtney , Rosen David A. S. , Haulena Martin
Published: June 2023

Between 2012 and 2022, the Vancouver Aquarium Marine Mammal Rescue Centre sedated 110 harbor seal pups for physical examinations, diagnostic procedures, or treatment. A sedation protocol of butorphanol and midazolam (0.1–0.2 mg/kg each) was administered via a single i.v. injection in 171 procedures. Of these, 21 pups were anesthetized only with the injectables, while supplemental isoflurane inhalation anesthesia by mask was provided during 58 procedures; 92 other animals required intubation for respiratory support due to apnea or to achieve a deeper plane of anesthesia to facilitate more invasive procedures. Of the 171 sedations, five were euthanized due to poor prognosis and six failed to recover. Maximum sedation, sufficient for intended procedure or anesthesia induction, was achieved within a mean of 8.5 ± 5.8 min for i.v. injection (n = 133). Sedation duration (drug administration to full recovery) without supplemental inhalation anesthesia had a mean of 30.2 min and ranged from 14 to 52 min (n = 13). When used in stabilized young harbor seals, administration of injectable butorphanol and midazolam proved to be an effective protocol to obtain safe and reliable sedation for physical examination, minimally invasive diagnostic procedures, or as a premedication for general anesthesia.
Revisiting the pathogenesis of dermatophytosis: A cross‐sectional analytic study of serum levels of interleukins‐2, 8, 10 and 17
Authors: Dev Prabin P. , Bansal Shikha , Bhargava Aradhana
Published: June 2023

Background

Given the current epidemic‐like scenario of dermatophyte infections, it is prudent to revisit the immunopathogenesis of dermatophytosis. Comprehending the intricate interactions among interleukins can aid in understanding the recent trends in infection. There is a paucity of literature on the various cytokine levels observed in the serum of patients suffering from various dermatophytoses.

Aim

To study serum cytokine levels of interleukins 2, 8, 10 and 17 in patients with dermatophytosis.

Methods

A cross‐sectional analytic study was conducted on 64 cases of clinical dermatophyte infections (KOH confirmed) and 64 controls. The clinico‐epidemiological profile of the cases was studied. By using a solid phase sandwich ELISA (enzyme‐linked immunosorbent assay), the serum levels of interleukins 2, 8, 10 and 17 were measured and compared between cases and controls. Serum interleukin‐2, 8, 10 and 17 levels were studied among cases based on mode of onset, duration of illness, treatment history, site of infection and multiple other morphological characteristics of the infection.

Results

The cases had statistically higher levels of interleukins‐8, 10 and 17 in comparison with controls. The levels of interleukin‐8 were significantly lower (p < .05) among those who had received oral antifungals. In cases where the lesion had scaling, the serum levels of interleukin‐10 were significantly higher (p < .05). The lesional hyperpigmentation was significantly (p < .05) associated with low levels of interleukin‐17. Also, interleukin‐17 was significantly (p < .05) elevated in patients with lesions in the abdomen.

Conclusion

It is the first time that serum interleukin levels are studied in dermatophytosis. There is an immunological dysfunction specific to dermatophytoses initiated by their infection. Key factor in this dysfunction is the elevation of IL‐10, contributing to persistent infection. In turn, causing an increase in IL‐17, promoting inflammation and tissue damage. This cycle of elevated IL‐10 and IL‐17 can further exacerbate the infection and lead to chronicity. The activity of IL‐2 and the Th1 immune pathway is reduced by two opposing immune pathways: the Th17 and Th2 axes.
A systematic review of economic evidence for community‐based obesity prevention interventions in children
Authors: Sultana Marufa , Nichols Melanie , Moodie Marj , Allender Steven , Brown Vicki
Published: June 2023

Multicomponent community‐based obesity prevention interventions that engage multiple sectors have shown promise in preventing obesity in childhood; however, economic evaluations of such interventions are limited. This systematic review explores the methods used and summarizes current evidence of costs and cost‐effectiveness of complex obesity prevention interventions. A systematic search was conducted using 12 academic databases and grey literature from 2006 to April 2022. Studies were included if they reported methods of costing and/or economic evaluation of multicomponent, multisectoral, and community‐wide obesity prevention interventions. Results were reported narratively based on the Consolidated Health Economic Evaluation Reporting Standards. Seventeen studies were included, reporting costing or economic evaluation of 13 different interventions. Five interventions reported full economic evaluations, five interventions reported economic evaluation protocols, two interventions reported cost analysis, and one intervention reported a costing protocol. Five studies conducted cost‐utility analysis, three of which were cost‐effective. One study reported a cost‐saving return‐on‐investment ratio. The economic evidence for complex obesity prevention interventions is limited and therefore inconclusive. Challenges include accurate tracking of costs for interventions with multiple actors, and the limited incorporation of broader benefits into economic evaluation. Further methodological development is needed to find appropriate pragmatic methods to evaluate complex obesity prevention interventions.
Efficacy and safety of Proglide use and early discharge after atrial fibrillation ablation compared to standard approach. PROFA trial
Authors: Castro‐Urda Víctor , Segura‐Dominguez Melodi , Jiménez‐Sánchez Diego , Aguilera‐Agudo Cristina , García‐Izquierdo Eusebio , De la Rosa Rojas Yuleisi , Pham‐Trung Chinh , Hernández‐Terciado Fernando , Lorente‐Ros Alvaro , Matutano‐Muñoz Andrea , García‐Rodriguez Daniel , Toquero‐Ramos Jorge , Fernández‐Lozano Ignacio
Published: June 2023

Background and Objectives

The common practice after atrial fibrillation ablation is to admit patients for an overnight stay. The aim of this study was to compare a strategy of vascular suture mediated closure system utilization and early discharge (strategy A) compared to traditional closure and overnight hospitalization (strategy B) regarding feasibility, safety, quality of life and health care cost effectiveness.

Methods and Results

Hundred patients were randomized to compare both strategies. No clinical differences were reported except diabetes mellitus. Six patients (6%) had and emergency visit or were admitted in the first 30 days after procedure. Three occurred in strategy A versus three in strategy B (p = 1) (p < .005 for non‐inferiority). Forty out of 50 patients (80%) were safely discharged in a time frame of 3 h and 42 patients (84%) were discharged in the same day of the procedure in strategy A. Time to discharge was shorter in strategy A compared to strategy B. (5.89 ± 7.47 h vs. 27.09 ± 2.29 p < .005). No differences were obtained in quality‐of‐life outcomes. Mean (95% CI) euros cost saving per patient in strategy A was 379.16 ± 93.55 p < .001. Ten acute complications (10% patients CI 95% 4.02%–15.98%) were reported during the trial. Seven (14% CI 95% 4.04%–23.96%) occurred in strategy A patients versus 3 (6% CI 95% 0.8%–12.8%) in strategy B. (p = .182)

Conclusion

A strategy of vascular suture mediated closure system utilization and early discharge was feasible, reduced time to discharge, saved costs and was not associated with more complications or admissions/emergency visits in a 30‐day time frame after procedure compared to a strategy of regular admission and discharge after overnight stay. There were no differences regarding quality‐of‐life parameters between both strategies.
THE MORALITY OF BELIEF I: HOW BELIEFS WRONG
Authors: Basu Rima
Published: June 2023

It is no surprise that we should be careful when it comes to what we believe. Believing false things can be costly. The morality of belief, also known as doxastic wronging, takes things a step further by suggesting that certain beliefs can not only be costly, they can also wrong. This article surveys some accounts of how this could be so. That is, how beliefs wrong.