bluuebunny/crossref_metadata_2025 huggingface dataset:
The Community as a Liminal Correctional Space
Authors: Anderson Jordan
Published: June 2022

Throughout the Anglophone advanced liberal democracies, punishment is increasingly creeping past the limits of traditional finite sentences and moving beyond the walls of the prison. “Regulatory” mechanisms enforcing limitations on releasees’ use of space beyond the prison walls have increased, and net widening due to technological advancement has resulted in sentenced individuals being punished within the community. At the same time, increasing numbers of released individuals are unable to be reintegrated into the community due to long-term regulatory limitations on their movement in both public and private space. Elements of the architecture of punishment continue to be reshaped and expanded by postsentence regulation, and this article explores the particular experience of released sex offenders being regulated within the community in two examples of “sex offender enclaves.” Drawing upon the experience of the community of Miracle Village (Florida, United States), as well as qualitative interviews conducted in the community of Ōtāhuhu (Auckland, New Zealand), this article begins to map the spread of the correctional apparatus beyond the prison walls and examines the way that risks are concentrated and delegated to certain communities, while the state simultaneously attempts to purge those thought to constitute the gravest risks from other communities.
Classroom acoustics and cognition: A review of the effects of noise and reverberation on primary school children’s attention and memory
Authors: Mealings Kiri
Published: June 2022

Classroom acoustic conditions are often suboptimal, so how do they affect children’s cognition? This review synthesized research assessing the effect of different classroom acoustic conditions on children’s attention and memory. A comprehensive search of four online databases was conducted in January 2022 using the search term classroom AND (noise* OR reverberat* OR acoustic*) AND (cognit* OR attention OR memory OR processing). The results revealed 21 relevant papers plus an additional 10 from their references. The papers assessed the effect of a range of chronic and acute acoustic exposures on different attention and memory processes. Overall, the majority of studies showed a negative effect or no effect of higher noise levels, longer reverberation times, or lower speech clarity on children’s cognition. It would therefore be beneficial to improve classroom acoustic conditions if possible. Suggestions for future research to more fully understand the effect of different classroom acoustic conditions on children’s cognition are posed.
Retired Orthopedic Surgeons’ Reflections on Their Lives and Careers: A Cross-Sectional Study
Authors: Lee Donald H. , Reasoner Kaitlyn , Lee Diane , Lee Daniel , Neviaser Robert J. , Hymel Alicia M. , Pennings Jacquelyn S.
Published: June 2022

Background: Retired surgeons often have limited opportunities to disseminate their wisdom and expertise in a structured manner to their younger colleagues. In addition, when asked to reflect on their personal and professional lives, many physicians say they wish they had done something differently. The extent to which this is true of retired orthopedic surgeons is not known. Purpose: We sought to determine the percentage of retired orthopedic surgeons who say that they would like to have changed something in their life/career and delineate the most commonly desired changes. Methods: We conducted a cross-sectional study of retired orthopedic surgeons, by emailing a Qualtrics survey to 5864 emeritus members of the American Academy of Orthopaedic Surgeons (AAOS), with 1 initial email invitation in April 2021 followed by 2 reminders in May 2021. The survey employed a branching logic, with up to 16 questions designed to determine whether they would have done anything differently in their life/career. Results: The survey was completed by 1165 of 5864 emeritus AAOS members, for a response rate of nearly 20%. The 3 most represented surgical subspecialties were general orthopedics, adult reconstruction, and hand and upper extremity surgery. Respondents’ average age was 74.9 years and age at retirement was 67.8 years; nearly half worked part-time before retiring. More than 80% of the participants said that they had retired at the appropriate time, and 28.5% said they wished they had done something differently. The wished-for changes most often noted were spending more time with family, spending more time on personal wellness, and selecting better practice partners. Conclusion: The results of our survey of retired orthopedic surgeons show that while most were satisfied with their lives and careers, some had regrets. These findings suggest that there may be factors in the work lives of current surgeons that could be altered to reduce regret. Further study is warranted.
Building a Covid-19 secure intensive care unit: A human-centred design approach
Authors: Ede Jody , Garry David , Barker Graham , Gustafson Owen , King Elizabeth , Routley Hannah , Biggs Christopher , Lumley Cherry , Bennett Lyn , Payne Stephanie , Ellis Andrew , Green Clinton , Smith Nathan , Vincent Laura , Holdaway Matthew , Watkinson Peter
Published: June 2022

Background

The Covid-19 pandemic has highlighted weaknesses in the National Health Service critical care provision including both capacity and infrastructure. Traditionally, healthcare workspaces have failed to fully incorporate Human-Centred Design principles resulting in environments that negatively affect the efficacy of task completion, patient safety and staff wellbeing. In the summer of 2020, we received funds for the urgent construction of a Covid-19 secure critical care facility. The aim of this project was to design a pandemic resilient facility centred around both staff and patient requirements and safety, within the available footprint.

Methods

We developed a simulation exercise, underpinned by Human-Centred Design principles, to evaluate intensive care designs through Build Mapping, Tasks Analysis and Qualitative data. Build Mapping involved taping out sections of the design and mocking up with equipment. Task Analysis and qualitative data were collected following task completion.

Results

56 participants completed the build simulation exercise generating 141 design suggestions (69 task related, 56 patient and relative related, 16 staff related). Suggestions translated to 18 multilevel design improvements; five significant structural changes (Macro level) including wall moves and lift size change. Minor improvements were made at a Meso and Micro design level. Critical care design drivers identified included functional drivers (visibility, Covid-19 secure environment, workflow, and task efficiency) and behavioural drivers (learning and development, light, humanising intensive care and design consistency).

Conclusion

Success of clinical tasks, infection control, patient safety and staff/patient wellbeing are highly dependent on clinical environments. Primarily, we have improved clinical design by focusing on user requirements. Secondly, we developed a replicable approach to exploring healthcare build plans revealing significant design changes, that may have only been identified once built.
Altered prerequisites: A cross-sectional survey regarding cancer care in Sweden during COVID-19 from the viewpoint of contact nurses in cancer care
Authors: Brynskog Ellen , Larsson Maria , Bjuresäter Kaisa , Rosell Linn , Smith Frida
Published: June 2022

Contact nurses in cancer care were vital in sustaining cancer care in Sweden during the COVID-19 pandemic. The aim of this study was to investigate their experiences of providing care to people with cancer in these exceptional circumstances to identify emerging challenges and opportunities that must be addressed moving forward. A survey distributed to contact nurses was supplemented with questions regarding the pandemic. The study design was a cross-sectional survey, analyzed with descriptive statistics and content analysis, reported in accordance with STROBE. Almost half of respondents ( n = 337) reported not being able to provide the same support as before the pandemic. Analysis of open-ended question responses ( n = 232) revealed a main theme: Altered prerequisites for providing care. Three categories related to altered interaction, accessibility, and nursing reality were revealed. Thorough reflection is needed to make use of lessons learned and avoid sustaining the short-term solutions needed to cope with the acute phase of the pandemic.
Staff training to improve participant recruitment into surgical randomised controlled trials: A feasibility study within a trial (SWAT) across four host trials simultaneously
Authors: Parker Adwoa , Arundel Catherine , Mills Nicola , Rooshenas Leila , Jepson Marcus , Donovan Jenny L , Blazeby Jane M , Coleman Elizabeth , Clark Laura , Doherty Laura , Hewitt Catherine E , Partha Sarathy Prasanna , Beard David , Bower Peter , Brealey Stephen , Brocklehurst Paul , Cooper Cindy , Croft Julie , Culliford Lucy , Dias Joseph , Devane Declan , Eldridge Sandra , Emsley Richard , Galvin Sandra , Gemperle-Mannion Elke , Jayne David G , Metcalfe Andrew J , Montgomery Alan , Rangan Amar , Sutton Christopher J , Tharmanathan Puvanendran , Treweek Shaun , Torgerson David
Published: June 2022

Objective

To test the feasibility of undertaking a simultaneous Study Within A Trial (SWAT) to train staff who recruit participants into surgical randomised controlled trials (RCTs), by assessing key uncertainties around recruitment, randomisation, intervention delivery and data collection.

Study design and setting

Twelve surgical RCTs were eligible. Interested sites (clusters) were randomised 1:1, with recruiting staff (surgeons and nurses) offered training or no training. The primary outcome was the feasibility of recruiting sites across multiple surgical trials simultaneously. Secondary outcomes included numbers/types of staff enrolled, attendance at training, training acceptability, confidence in recruiting and participant recruitment rates six months later.

Results

Four RCTs (33%) comprising 91 sites participated. Of these, 29 sites agreed to participate (32%) and were randomised to intervention (15 sites, 29 staff) or control (14 sites, 29 staff). Research nurses attended and found the training to be acceptable; no surgeons attended. In the intervention group, there was evidence of increased confidence when pre- and post- training scores were compared (mean difference in change 1.42; 95% CI 0.56, 2.27; p = 0.002). There was no effect on recruitment rate.

Conclusion

It was feasible to randomise sites across four surgical RCTs in a simultaneous SWAT design. However, as small numbers of trials and sites participated, and no surgeons attended training, strategies to improve these aspects are needed for future evaluations.
‘She’s mine!’ – The lived experience of becoming parents through international adoption
Authors: Gatt Mary Rose , Sammut-Scerri Clarissa
Published: June 2022

Literature on the personal and intimate process of feeling the parent of an adopted child appears to be scant. The experience of adoptive parents’ emotional and psychological process to ‘feel a parent’ is often overshadowed by literature focused on the experience of loss especially when parents adopt following infertility, and by literature focusing on the experiences of children pre-and-post-adoption. This article presents the findings of an Interpretative Phenomenological Analysis (IPA) with adoptive parents, exploring the intimate emotional and psychological process of becoming a parent and ‘feeling a parent’ through international adoption. Nine semi-structured interviews with three couples were conducted where each couple was interviewed twice, both together and separately. Six main superordinate themes emerged: Holding the child in mind and in heart before the adoption; exceeding one’s expectations of connection with the child; special intimate moments consolidating the attachment process; being acknowledged as legitimate parents by the child, by their family and community; the story of how they became parents and how their child became theirs; and creating and embracing the child’s larger context. The findings indicate that a systemic perspective is important when working with adoptive parents as a pivotal part of the parents’ experience centred around being acknowledged by their family system as legitimate parents to their child. Practitioners also need to be sensitive to the idiosyncratic, often sensory-based attachment processes between the parents and the child in the process of becoming parents through international adoption.
Touch and translanguaging in a multilingual early childhood education setting
Authors: Samuelsson Robin
Published: June 2022

Many children grow up in multilingual communities characterised by linguistic heterogeneity and semiotic and cultural complexity. Translanguaging theory has provided a perspective attuned to communication and education in multilingual settings. However, translanguaging pedagogies have not yet had a broad uptake in early educational settings. The recent interest in embodiment within translanguaging studies and the study of touch combinedly provide a potential perspective for early childhood education. This study examines the role of touch in a multilingual preschool featuring 2-year-olds. The results point to two key functions for touch. One is that touch creates a shared experiential ground where languages can be learned. The other function is that touch allows children to sensorially explore and learn multicultural experiences from the diverse cultural and linguistic systems available. Based on the results, the role of touch in early childhood translanguaging is discussed as a way forward for translanguaging pedagogies for creating both equitable and diverse educational opportunities for children in multicultural and multilingual communities.
Metformin inhibits melanoma cell metastasis by suppressing the miR-5100/SPINK5/STAT3 axis
Authors: Suwei Dong , Yanbin Xiao , Jianqiang Wang , Xiang Ma , Zhuohui Peng , Jianping Kang , Yunqing Wang , Zhen Li
Published: June 2022

Melanoma is the most lethal skin cancer characterized by its high metastatic potential. It is urgent to find novel therapy strategies to overcome this feature. Metformin has been confirmed to suppress invasion and migration of various types of cancer. However, additional mechanisms underlying the antimetastatic effect of metformin on melanoma require further investigation. Here, we performed microarray analysis and uncovered an altered mRNA and miRNA expression profile between melanoma and nevus. Luciferase reporter assay confirmed that miR-5100 targets SPINK5 to activate STAT3 phosphorylation. Migration and wound healing assays showed that the miR-5100/SPINK5/STAT3 axis promotes melanoma cell metastasis; the mechanism was proven by initiation of epithelial–mesenchymal transition. Co-immunoprecipitation (Co-IP) further confirmed an indirect interaction between SPINK5 and STAT3. Furthermore, metformin dramatically inhibited miR-5100/SPINK5/STAT3 pathway, and decreased B16-F10 cell metastasis to lung in C57 mouse module. Intriguingly, pretreatment of metformin before melanoma cell injection improved this effect further. These findings exposed the underlying mechanisms of action of metformin and update the use of this drug to prevent metastasis in melanoma.
Benign prostatic hyperplasia morphological parameters for assessing risk of acute urinary retention
Authors: Gabr Ahmed H. , Abdelatif Ahmed , sharkawy Mostafa S. El , Ismail Ahmed H. , Batnanonuy Ahmed El , Eissawy Mohamed Gaber , Ali Ahmed Issam
Published: June 2022

Aim of the study

To evaluate objective measurements of morphological changes of the prostate in Benign Prostatic Hyperplasia (BPH) as predictors of acute urinary retention (AUR).

Methods

Overall 169 consecutive patients older than 50 years of age were prospectively divided into group A (n = 61); men with acute urinary retention (AUR), or group B (n = 108); men with different degrees of lower urinary tract symptoms (LUTS). Transrectal ultrasound (TRUS) measurements of total prostate volume (TPV), transitional zone volume (TZV), ratio of TZV to TPV (TZV/TPV), and vesico-urethral angle (VUA) were recorded. Group B patients also had post-void residual (PVR) and maximum flow rate (Q-max) recorded. TZV/TPV and VUA were correlated with Q-max and PVR, and a comparison was made between the two groups.

Results

Group A had significantly larger TPV (p = 0.03) and TZV/TPV (p = 0.04) compared to Group B. VUA in Group A had a significant correlation with AUR (p = 0.02). In Group B, both TZV/TPV and VUA had significant correlation with PVR and Q-max. A TZV/TPV cutoff ratio of 0.67 as a predictor of AUR had a 68% overall accuracy with sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 88%, 53%, 44%, and 97%, respectively. VUA of < 90º as a predictor factor of AUR had a 67% overall accuracy with sensitivity, specificity, PPV and NPV of 88%, 50%, 44%, and 97%, respectively.

Conclusion

Morphological changes in BPH can be objectively quantified using ultrasound by TZV/TPV and VUA. These parameters may potentially serve as predictors of AUR in patients with BPH.
The power of local research to inform adverse childhood experiences in substance use prevention in adolescents and adults
Authors: Wu Shiyou , Lindstrom Johnson Sarah , Wolfersteig Wendy , Diaz Marisol Juarez , Aguilar-Amaya Maria
Published: June 2022

Background

The impact of adverse childhood experiences on substance use has been well reported, however, less well documented is looking at the comparison of youth and adult substance use and their respective adverse childhood experiences. This study leveraged local data sources to support prevention efforts inside a state-level working group and examined research questions that explored the relationship between reported adverse childhood experiences and substance use for youth and adult samples at the state level.

Methods

This study conducted a series of logistic regression models (95% CI) between substance use outcomes with different age group populations to investigate the relationship between adverse childhood experiences and substance use for each group. Adverse childhood experiences scores and substance use were examined using two Arizona datasets: 1) Arizona Youth Survey (n = 42,009) and 2) the Behavioral Risk Factor Surveillance System (n = 5328).

Results

The results of youth and adult datasets were consistent: users with adverse childhood experiences scores of 4 to 6 had a positive association with more substance use. When the variables were examined, showing the entire sample of youth and adult groups compared to those subgroups with a score of zero, a score of 1 to 3, and a score of 4 to 6, the overall pattern was the same; the more frequent use of substances was directly associated to the group with higher scores. Additionally, findings support increased attention on prevention and intervention efforts with higher reports of adverse childhood experiences as well as substance use.

Conclusions

These findings demonstrate how local research can help prioritize prevention resources and increase the value of data-based decision-making. Policy-makers and providers can examine youth and adult data to compare priorities and assess for planning purposes. Specifically, it is possible to replicate known research findings, identify the most impacted subpopulations, and forecast the community’s future needs.
A systematic review and meta-analysis on the preventive behaviors in response to the COVID-19 pandemic among children and adolescents
Authors: Li Feifei , Liang Wei , Rhodes Ryan E. , Duan Yanping , Wang Xiang , Shang Borui , Yang Yide , Jiao Jiao , Yang Min , Supriya Rashmi , Baker Julien S. , Yi Longyan
Published: June 2022

Purpose

The purpose of this review was to synthesize the empirical evidence of relevant studies related to preventive behaviors in response to the COVID-19 pandemic among children and adolescents. Further to this, we aimed to identify the demographic, psychological, and social and environmental correlates of such behaviors.

Methods

Following PRISMA guidelines, eligible literature was identified by searching seven databases (PsycINFO, PubMed, MEDLINE, EMBASE, Cochrane Library, PROSPERO registry platform, and ClinicalTrials.gov website) and reference list of included studies and relevant review papers from 1stJan 2020 to 28thFeb 2021. The standardized mean difference and correlation coefficientsrwere extracted to estimate the effect sizes. Analyses were conducted using R software.

Results

Of the 35,271 original papers, 23 eligible studies were included in the qualitative synthesis and all these studies were of moderate-to-high quality, of which 17 studies were further included into the quantitative analysis. Children and adolescents (6–20 yrs.) showed a poorer practice of COVID-19 preventive behaviors compared to younger adults (21–59 yrs.) with a small-to-medium effect size (SMD = -.25, 95%CI = -.41 to -.09). For the demographic correlates, children and adolescents’ COVID-19 preventive practice was found to be significantly associated with gender (r = .14, 95%CI = .10 to .18), while not with age (r = -.02, 95%CI = -.14 to .10). Narratively, knowledge was found to be consistently and significantly correlated. For the psychological correlates, small-to-medium overall effects were identified for the association with attitudes (r = .26, 95%CI = .21 to .31) and perceived severity (r = .16, 95%CI = .01 to .30). For the family and social correlates, a non-significant association was identified between family economic status and COVID-19 preventive behaviors (r = .004, 95%CI = -.12 to .12).

Conclusions

Interventions and relevant policies of promoting children and adolescent’s preventive measures should be a priority. Further, empirical studies identifying the demographic, psychological, and family and social correlates of children and adolescents’ preventive behaviors are needed.
Knowledge, attitudes, and practices of active surveillance in prostate cancer among urologists: a real-life survey from Brazil
Authors: Wroclawski Marcelo Langer , Amaral Breno Santos , Kayano Paulo Priante , Busato Wilson Francisco Schreiner , Westphal Sebastião José , Montagna Erik , Bianco Bianca , Soares Andrey , Maluf Fernando Cotait , Lemos Gustavo Caserta , Carneiro Arie
Published: June 2022

Background

Active surveillance (AS) is the preferred treatment for patients with very low-and low-risk prostate cancer (PCa), but it is underperformed worldwide. This study aimed to report knowledge, attitudes, and practices (KAP) of AS for PCa among urologists in Brazil.

Methods

This cross-sectional study used a questionnaire with 50 questions divided into participant characteristics, knowledge regarding inclusion criteria for AS, follow-up, intervention triggers, acceptance, and practice for an index patient. Data analysis comprises absolute and relative frequencies of the variables. After that, a logistic regression was performed in order to verify possible patterns of answers provided by the respondents in the index patient questionnaire.

Results

Questionnaires were sent through the SurveyMonkey® platform to 5,015 urologists using email addresses and through social media. A total of 600 (12%) questionnaires returned and 413 (8.2%) were completed and included in the analysis. Only 53% of urologists adopt AS for low- and very-low-risk PCa. Inclusion criteria were patients with age > 50 years (32.2%), prostate specific antigen (PSA) < 10 ng/mL (87.2%), T1 clinical stage (80.4%), Biopsy Gleason score ≤ 6, positive cores ≤ 2 (44.3%), positive core involvement < 50% (45.3%), and magnetic resonance imaging findings (38.7%). The PSA doubling time was still used by 60.3%. Confirmatory biopsy (55.9%), PSA level (36.6%), and digital rectal examination (34.4%) were considered by most urologists for follow-ups. Patient preference (85.7%), upgrade of Gleason score (73.4%), and increased number of positive cores (66.8%) were associated with conversion to definitive treatment. In an index patient, non-acceptance and active treatment request were the most cited reasons for not performing AS.

Conclusion

There is significant variability in the KAP of AS in Brazil, which indicates the need to reinforce AS, its inclusion and follow-up criteria, and the benefits for physicians and the general population.

Trial registration: Not applicable.
Investigation of two different human d-dimer assays in the horse
Authors: Honoré Marie Louise , Pihl Tina H. , Busk-Anderson Tanne M. , Flintrup Laura L. , Nielsen Lise N.
Published: June 2022

Background

D-dimer has value as a marker of thrombosis in critically ill horses and can provide additional information about prognosis. However, there are currently no equine species-specific d-dimer assays available, nor has there been any formal investigation of the applicability of human d-dimer assays in horses, so it is unknown, which assay performs best in this species. The aim of this study was therefore to evaluate and compare two human d-dimer assays for their applicability in horses.

The study included four groups of horses: clinically healthy horses, horses with gastrointestinal (GI) disease and mild systemic inflammation based on low serum amyloid A (SAA) (low SAA group), horses with GI disease and strong systemic inflammation based on high SAA (high SAA group) and, horses with thrombotic GI disease caused byStrongylus vulgaris(also called non-strangulating intestinal infarction (NSII)) (NSII group). The assays evaluated were the STAGO STA-Liatest D-di + (Stago) and NycoCard™ D-dimer (NycoCard). Intra- and inter-coefficients of variation (CV) were assessed on two d-dimer concentrations, and linearity under dilution was evaluated. A group comparison was performed for both assays across the four groups of horses. A Spaghetti plot, Spearman Correlation, Passing Bablok regression and Bland–Altman plot were used to compare methods in terms of agreement.

Results

Ten horses were included in the clinically healthy group, eight in the low SAA group, eight in the high SAA group, and seven in the NSII group. For the Stago assay, intra- and inter-CVs were below the accepted level except for one inter-CV. The NycoCard assay did not meet the accepted level for any of the CVs. The linearity under dilution was acceptable for both the Stago and NycoCard. In the group comparison, both methods detected a significantly higher d-dimer concentration in the high SAA and NSII groups compared to the clinically healthy group. Method agreement showed slightly higher d-dimer concentrations with NycoCard compared to Stago. The overall agreement was stronger for the lower d-dimer concentrations.

Conclusion

Both the Stago and the NycoCard were found to be applicable for use in horses but were not directly comparable.
Proteome analysis of urinary biomarkers in a cigarette smoke-induced COPD rat model
Authors: Qin Weiwei , Huang He , Dai Yuting , Han Wei , Gao Youhe
Published: June 2022

Background

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory airway disease caused by inhalation of cigarette smoke (CS) and other harmful gases and particles.

Methods

This study aimed to explore potential urinary biomarkers for CS-induced COPD based on LC–MS/MS analysis.

Results

A total of 340 urinary proteins were identified, of which 79 were significantly changed (30, 31, and 37 at week 2, 4 and 8, respectively). GO annotation of the differential urinary proteins revealed that acute-phase response, response to organic cyclic compounds, complement activation classical pathway, and response to lead ion were significantly enriched at week 2 and 4. Another four processes were only enriched at week 8, namely response to oxidative stress, positive regulation of cell proliferation, thyroid hormone generation, and positive regulation of apoptotic process. The PPI network indicated that these differential proteins were biologically connected in CS-exposed rats. Of the 79 differential proteins in CS-exposed rats, 56 had human orthologs. Seven proteins that had changed at week 2 and 4 when there were no changes of pulmonary function and pathological morphology were verified as potential biomarkers for early screening of CS-induced COPD by proteomic analysis. Another six proteins that changed at week 8 when obvious airflow obstruction was detected were verified as potential biomarkers for prognostic assessment of CS-induced COPD.

Conclusions

These results reveal that the urinary proteome could sensitively reflect pathological changes in CS-exposed rats, and provide valuable clues for exploring COPD biomarkers.
Empagliflozin attenuates cardiac microvascular ischemia/reperfusion injury through improving mitochondrial homeostasis
Authors: Zou Rongjun , Shi Wanting , Qiu Junxiong , Zhou Na , Du Na , Zhou Hao , Chen Xinxin , Ma Li
Published: June 2022

Background

Empagliflozin has been reported to protect endothelial cell function, regardless of diabetes status. However, the role of empagliflozin in microvascular protection during myocardial ischemia reperfusion injury (I/R) has not been fully understood.

Methods

Electron microscopy, western blots, immunofluorescence, qPCR, mutant plasmid transfection, co-immunoprecipitation were employed to explore whether empagliflozin could alleviate microvascular damage and endothelial injury during cardiac I/R injury.

Results

In mice, empagliflozin attenuated I/R injury-induced microvascular occlusion and microthrombus formation. In human coronary artery endothelial cells, I/R injury led to adhesive factor upregulation, endothelial nitric oxide synthase inactivation, focal adhesion kinase downregulation, barrier dysfunction, cytoskeletal degradation and cellular apoptosis; however, empagliflozin treatment diminished these effects. Empagliflozin improved mitochondrial oxidative stress, mitochondrial respiration and adenosine triphosphate metabolism in I/R-treated human coronary artery endothelial cells by preventing the phosphorylation of dynamin-related protein 1 (Drp1) and mitochondrial fission 1 protein (Fis1), thus repressing mitochondrial fission. The protective effects of empagliflozin on mitochondrial homeostasis and endothelial function were abrogated by the re-introduction of phosphorylated Fis1, but not phosphorylated Drp1, suggesting that Fis1 dephosphorylation is the predominant mechanism whereby empagliflozin inhibits mitochondrial fission during I/R injury. Besides, I/R injury induced Fis1 phosphorylation primarily by activating the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) pathway, while empagliflozin inactivated this pathway by exerting anti-oxidative effects.

Conclusions

These results demonstrated that empagliflozin can protect the microvasculature by inhibiting the DNA-PKcs/Fis1/mitochondrial fission pathway during myocardial I/R injury.
Cigarette smoke extract-mediated FABP4 upregulation suppresses viability and induces apoptosis, inflammation and oxidative stress of bronchial epithelial cells by activating p38 MAPK/MK2 signaling pathway
Authors: Zhang Wei , Zhang Yibin , Zhu Qi
Published: June 2022

Background

Long-term inhalation of cigarette smoke is considered to be one of the main causes of bronchial epithelioid cell damage, but its underlying mechanism has to be further clarified.

Methods

Gene expression at mRNA level and protein levels were detected by qRT-PCR and western blot analysis respectively. CCK-8, TUNEL assays, ELISA, western blot analysis and commercial kits were utilized to test cell viability, apoptosis inflammatory response and oxidative stress. The correlation between fatty acid binding protein 4 (FABP4) and the p38 mitogen-activated protein kinase (MAPK)/MAPK activated kinase 2 (MK2) signaling pathway was verified by western blot analysis and rescue assays.

Results

Cigarette smoke extract (CSE) exposure decreased viability, induced apoptosis and inflammatory response in 16HBE cells. Moreover, the expression of FABP4 in CSE-treated 16HBE cells was up-regulated in a time and dose-dependent manner. Ablation of FABP4 in 16HBE cells significantly protected against CSE-mediated cell viability decline and apoptosis. Further, FABP4 knockdown suppressed inflammatory response by down-regulating the elevated levels of cellular inflammatory factors including TNF-α, IL-1β, IL-6, Cyclooxygenase-2 (Cox-2) and inducible nitric oxide synthase (iNOS) in CSE-treated 16HBE cells. The oxidative stress induced by CSE in 16HBE cells was also inhibited by FABP4 silence as evidence by reduced ROS and MDA level but increased SOD activity caused by FABP4 silence. Finally, all the above effects of FABP4 silence on CSE-treated 16HBE cells were reversed by asiatic acid, an agonist of p38 mitogen-activated protein kinase (MAPK).

Conclusions

The up-regulation of FABP4 expression mediated by CSE exerted pro-inflammatory, pro-oxidative stress and pro-apoptotic effects on bronchial epithelial cells by activating the p38 MAPK/MK2 signaling pathway. Our findings help to further understand the underlying mechanism of cigarette smoke-induced bronchial inflammation.
Strategies to adapt and implement health system guidelines and recommendations: a scoping review
Authors: Breneol Sydney , Curran Janet A. , Marten Robert , Minocha Kirti , Johnson Catie , Wong Helen , Langlois Etienne V. , Wozney Lori , Vélez C. Marcela , Cassidy Christine , Juvekar Sanjay , Rothfus Melissa , Aziato Lydia , Keeping-Burke Lisa , Adjorlolo Samuel , Patiño-Lugo Daniel F.
Published: June 2022

Background

Evidence-based health system guidelines are pivotal tools to help outline the important financial, policy and service components recommended to achieve a sustainable and resilient health system. However, not all guidelines are readily translatable into practice and/or policy without effective and tailored implementation and adaptation techniques. This scoping review mapped the evidence related to the adaptation and implementation of health system guidelines in low- and middle-income countries.

Methods

We conducted a scoping review following the Joanna Briggs Institute methodology for scoping reviews. A search strategy was implemented in MEDLINE (Ovid), Embase, CINAHL, LILACS (VHL Regional Portal), and Web of Science databases in late August 2020. We also searched sources of grey literature and reference lists of potentially relevant reviews. All findings were reported following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews.

Results

A total of 41 studies were included in the final set of papers. Common strategies were identified for adapting and implementing health system guidelines, related barriers and enablers, and indicators of success. The most common types of implementation strategies included education, clinical supervision, training and the formation of advisory groups. A paucity of reported information was also identified related to adaptation initiatives. Barriers to and enablers of implementation and adaptation were reported across studies, including the need for financial sustainability. Common approaches to evaluation were identified and included outcomes of interest at both the patient and health system level.

Conclusions

The findings from this review suggest several themes in the literature and identify a need for future research to strengthen the evidence base for improving the implementation and adaptation of health system guidelines in low- and middle-income countries. The findings can serve as a future resource for researchers seeking to evaluate implementation and adaptation of health system guidelines. Our findings also suggest that more effort may be required across research, policy and practice sectors to support the adaptation and implementation of health system guidelines to local contexts and health system arrangements in low- and middle-income countries.
Transforming growth factor-β1 negatively regulates SOCS7 via EGR1 during wound healing
Authors: Feng Xiao , Feng Wei , Ji Yu , Jin Tingting , Li Jingyu , Guo Jincai
Published: June 2022

Background

TGF-β1 promotes keratinocyte migration and re-epithelialization of cutaneous wounds during the wound healing process. Decreased SOCS7 expression has been associated with increased healing potential. However, the relationship between TGF-β1 and SOCS7 in wound re-epithelialization remains unclear.

Objectives

To investigate the relationship between TGF-β1 and SOCS7 in the re-epithelialization of keratinocytes during skin wound healing.

Methods

The expression of SOCS7 under different concentrations of TGF-β1 was detected by WB and qPCR. The migration ability of keratinocytes was detected by scratch and Transwell assay. Protein interactions were detected by ChIP and luciferase assay. The effect of SOCS7 on skin healing in mice was detected in animal model.

Results

In this study, we found that SOCS7 was downregulated by TGF-β1 and that overexpression of SOCS7 led to suppression of TGF-β1-induced keratinocyte migration through inhibition of the PI3K/AKT and MEK/ERK pathways. Also, TGF-β1 negatively regulated SOCS7 expression at the transcriptional level through the binding of EGR1 to the EGR1/SP1 overlapping binding sites in the SOCS7 promoter.

Conclusion

Taken together, our findings show that TGF-β1-induced EGR1 expression is required for repression of SOCS7, which promotes keratinocyte migration and re-epithelialization during wound healing. Finally, our study identifies the TGF-β1/EGR1/SOCS7 pathway as a potential therapeutic target to promote wound healing.
GDF-11 promotes human trophoblast cell invasion by increasing ID2-mediated MMP2 expression
Authors: Wu Ze , Fang Lanlan , Yang Sizhu , Gao Yibo , Wang Zhen , Meng Qingxue , Dang Xuan , Sun Ying-Pu , Cheng Jung-Chien
Published: June 2022

Background

Growth differentiation factor-11 (GDF-11), also known as bone morphogenetic protein-11, belongs to the transforming growth factor-beta superfamily. GDF-11 was first identified as an important regulator during embryonic development. Increasing evidence has demonstrated that GDF-11 regulates the development of various organs and its aberrant expressions are associated with the risk of cardiovascular diseases and cancers. Extravillous trophoblast (EVT) cells invasion is a critical event for placenta development and needs to be finely regulated. However, to date, the biological function of GDF-11 in the human EVT cells remains unknown.

Methods

HTR-8/SVneo, a human EVT cell line, and primary cultures of human EVT cells were used to examine the effect of GDF-11 on matrix metalloproteinase 2 (MMP2) expression. Matrigel-coated transwell invasion assay was used to examine cell invasiveness. A series of in vitro experiments were applied to explore the underlying mechanisms that mediate the effect of GDF-11 on MMP2 expression and cell invasion.

Results

Treatment with GDF-11 stimulates MMP2 expression, in the HTR-8/SVneo and primary human EVT cells. Using a pharmacological inhibitor and siRNA-mediated knockdown approaches, our results demonstrated that the stimulatory effect of GDF-11 on MMP2 expression was mediated by the ALK4/5-SMAD2/3 signaling pathways. In addition, the expression of inhibitor of DNA-binding protein 2 (ID2) was upregulated by GDF-11 and that was required for the GDF-11-stimulated MMP2 expression and EVT cell invasion.

Conclusions

These findings discover a new biological function and underlying molecular mechanisms of GDF-11 in the regulation of human EVT cell invasion.
Sciatic nerve stimulation alleviates acute neuropathic pain via modulation of neuroinflammation and descending pain inhibition in a rodent model
Authors: Wong Chia-En , Hu Chia-Ying , Lee Po-Hsuan , Huang Chi-Chen , Huang Han-Wei , Huang Chih-Yuan , Lo Hsin-Tien , Liu Wentai , Lee Jung-Shun
Published: June 2022

Background

Neuropathic pain (NP) is characterized by abnormal activation of pain conducting pathways and manifests as mechanical allodynia and thermal hypersensitivity. Peripheral nerve stimulation is used for treatment of medically refractory chronic NP and has been shown to reduce neuroinflammation. However, whether sciatic nerve stimulation (SNS) is of therapeutic benefit to NP remains unclear. Moreover, the optimal frequency for SNS is unknown. To address this research gap, we investigated the effect of SNS in an acute NP rodent model.

Methods

Rats with right L5 nerve root ligation (NRL) or Sham surgery were used. Ipsilateral SNS was performed at 2 Hz, 20 Hz, and 60 Hz frequencies. Behavioral tests were performed to assess pain and thermal hypersensitivity before and after NRL and SNS. Expression of inflammatory proteins in the L5 spinal cord and the immunohistochemical alterations of spinal cord astrocytes and microglia were examined on post-injury day 7 (PID7) following NRL and SNS. The involvement of the descending pain modulatory pathway was also investigated.

Results

Following NRL, the rats showed a decreased pain threshold and latency on the von Frey and Hargreaves tests. The immunofluorescence results indicated hyperactivation of superficial spinal cord dorsal horn (SCDH) neurons. Both 2-Hz and 20-Hz SNS alleviated pain behavior and hyperactivation of SCDH neurons. On PID7, NRL resulted in elevated expression of spinal cord inflammatory proteins including NF-κB, TNF-α, IL-1β, and IL-6, which was mitigated by 2-Hz and 20-Hz SNS. Furthermore, 2-Hz and 20-Hz SNS suppressed the activation of spinal cord astrocytes and microglia following NRL on PID7. Activity of the descending serotoninergic pain modulation pathway showed an increase early on PID1 following 2-Hz and 20-Hz SNS.

Conclusions

Our results support that both 2-Hz and 20-Hz SNS can alleviate NP behaviors and hyperactivation of pain conducting pathways. We showed that SNS regulates neuroinflammation and reduces inflammatory protein expression, astrocytic gliosis, and microglia activation. During the early post-injury period, SNS also facilitates the descending pain modulatory pathway. Taken together, these findings support the therapeutic potential of SNS for acute NP.
Early-life stress elicits peripheral and brain immune activation differently in wild type and 5xFAD mice in a sex-specific manner
Authors: Bachiller S. , Hidalgo I. , Garcia M. G. , Boza-Serrano A. , Paulus A. , Denis Q. , Haikal C. , Manouchehrian O. , Klementieva O. , Li J. Y. , Pronk C. J. , Gouras G. K. , Deierborg T.
Published: June 2022

Background

The risk of developing Alzheimer’s disease (AD) is modulated by genetic and environmental factors. Early-life stress (ELS) exposure during critical periods of brain development can impact later brain function and health, including increasing the risk of developing AD. Microglial dysfunction and neuroinflammation have been implicated as playing a role in AD pathology and may be modulated by ELS. To complicate matters further, sex-specific effects have been noted in response to ELS and in the incidence and progression of AD.

Methods

Here, we subjected male and female mice with either a wild type or 5xFAD familial AD-model background to maternal separation (MS) from postnatal day 2 to 14 to induce ELS.

Results

We detected hippocampal neuroinflammatory alterations already at postnatal day 15. By 4 months of age, MS mice presented increased immobility time in the forced swim test and a lower discrimination index in the novel object recognition memory test compared to controls. We found alteredBdnfandArcexpression in the hippocampus and increased microglial activation in the prefrontal cortex due to MS in a sex-dependent manner. In 5xFAD mice specifically, MS exacerbated amyloid-beta deposition, particularly in females. In the periphery, the immune cell population was altered by MS exposure.

Conclusion

Overall, our results demonstrate that MS has both short- and long-term effects on brain regions related to memory and on the inflammatory system, both in the brain and periphery. These ELS-related effects that are detectable even in adulthood may exacerbate pathology and increase the risk of developing AD via sex-specific mechanisms.
FKBP51 mediates resilience to inflammation-induced anxiety through regulation of glutamic acid decarboxylase 65 expression in mouse hippocampus
Authors: Gan Yu-Ling , Wang Chen-Yu , He Rong-Heng , Hsu Pei-Chien , Yeh Hsin-Hsien , Hsieh Tsung-Han , Lin Hui-Ching , Cheng Ming-Yen , Jeng Chung-Jiuan , Huang Ming-Chyi , Lee Yi-Hsuan
Published: June 2022

Background

Inflammation is a potential risk factor of mental disturbance.FKBP5that encodes FK506-binding protein 51 (FKBP51), a negative cochaperone of glucocorticoid receptor (GR), is a stress-inducible gene and has been linked to psychiatric disorders. Yet, the role of FKBP51 in the inflammatory stress-associated mental disturbance remained unclear.

Methods

Fkbp5-deficient (Fkbp5-KO) mice were used to study inflammatory stress by a single intraperitoneal injection of lipopolysaccharide (LPS). The anxiety-like behaviors, neuroimaging, immunofluorescence staining, immunohistochemistry, protein and mRNA expression analysis of inflammation- and neurotransmission-related mediators were evaluated. A dexamethasone drinking model was also applied to examine the effect ofFkbp5-KO in glucocorticoid-induced stress.

Results

LPS administration induced FKBP51 elevation in the liver and hippocampus accompanied with transient sickness. Notably,Fkbp5-KO but not wild-type (WT) mice showed anxiety-like behaviors 7 days after LPS injection (LPS-D7). LPS challenge rapidly increased peripheral and central immune responses and hippocampal microglial activation followed by a delayed GR upregulation on LPS-D7, and these effects were attenuated inFkbp5-KO mice. Whole-brain [18F]-FEPPA neuroimaging, which target translocator protein (TSPO) to indicate neuroinflammation, showed thatFkbp5-KO reduced LPS-induced neuroinflammation in various brain regions including hippocampus. Interestingly, LPS elevated glutamic acid decarboxylase 65 (GAD65), the membrane-associated GABA-synthesizing enzyme, in the hippocampus of WT but notFkbp5-KO mice on LPS-D7. This FKBP51-dependent GAD65 upregulation was observed in the ventral hippocampal CA1 accompanied by the reduction of c-Fos-indicated neuronal activity, whereas both GAD65 and neuronal activity were reduced in dorsal CA1 in a FKBP51-independent manner. GC-induced anxiety was also examined, which was attenuated inFkbp5-KO and hippocampal GAD65 expression was unaffected.

Conclusions

These results suggest that FKBP51/FKBP5is involved in the systemic inflammation-induced neuroinflammation and hippocampal GR activation, which may contribute to the enhancement of GAD65 expression for GABA synthesis in the ventral hippocampus, thereby facilitating resilience to inflammation-induced anxiety.