bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of social interaction on decision making in emergency ambulance teams: a statistical discourse analysis
Authors: Tekïn Murat , Uysal İbrahim , Toraman Çetin , Akman Canan , Aytuğ Koşan Ayşen Melek , Postaci Emine Sevïnç
Published: February 2023

Introduction

This study examined the effects of social interaction, cognitive flexibility, and seniority on the correct response among emergency ambulance teams during case intervention.

Methods

The research, structured with the sequential exploratory mixed method, was conducted with 18 emergency ambulance personnel. The approach process of the teams working on the scenario was video recorded. The records were transcribed by the researchers, including gestures and facial expressions. Discourses were coded and modeled with regression.

Results

The number of discourses was higher in groups with high correct intervention scores. As the level of cognitive flexibility or seniority increased, the correct intervention score tended to decrease too. Informing has been identified as the only variable that positively affects the correct response to the emergency case, especially in the first period, which is directed toward case intervention preparation.

Conclusion

Within the findings of the research, it is recommended that activities and scenario-based training practices that will increase the intra-team communication of the emergency ambulance personnel should be included in the medical education and in-service training.
“Smartphone as an educational tool” the perception of dental faculty members of all the dental colleges of Khyber Pakhtunkhwa - Pakistan
Authors: Junaid Syed Muhammad , Jamil Brekhna , Khan Muhammad Adnan , Akbar Zainab , Shah Sana , Nadeem Natasha , Nadeem Anum
Published: February 2023

Background

With the increasing advancement in the field of information technology, it’s about time we realize that our future will be shaped by this field. With more and more people using smartphones, we need to adapt them to the medical field. Already many advancements in medical field are done thanks to the advancement of computer science. But we need to implement this into our teaching and learning as well. Almost all students and faculty members use smartphones in one way or another if we can utilize the smartphone to enhance the learning opportunities for our medical students, it would greatly benefit them. But before the implementation, we need to find out if our faculty is willing to adopt this technology. The objective of this study is to find out what are the perceptions of dental faculty members about using a smartphone as a teaching tool.

Methodology

A validated questionnaire was distributed among the faculty members of all the dental colleges of KPK. The questionnaire had 2 sections. First one contains information regarding the demographics. The second one had questions related to the faculty members’ perception regarding using a smartphone as a teaching tool.

Results

The results of our study showed that the faculty (Mean 2.08) had positive perceptions regarding using a smartphone as a teaching tool.

Conclusion

Most of the Dental Faculty members of KPK agree that smartphone can be used as a teaching tool, and it can have better outcomes if proper applications and teaching strategies are used.
Mediating effect of resilience between social support and compassion fatigue among intern nursing and midwifery students during COVID-19: a cross-sectional study
Authors: Li Jia-Ning , Jiang Xiu-Min , Zheng Qing-Xiang , Lin Fen , Chen Xiao-Qian , Pan Yu-Qing , Zhu Yu , Liu Ru-Lin , Huang Ling
Published: February 2023

Aims

To examine the mediating effect of resilience between social support and compassion fatigue among intern nursing and midwifery students during COVID-19.

Background

Compassion fatigue has become exceedingly common among intern nursing and midwifery students, especially during the COVID-19 pandemic. Social support and resilience can help intern nursing and midwifery students control their negative emotions, reduce compassion fatigue, and increase their well-being. However, the mediating effect of resilience between social support and compassion fatigue remains unclear.

Design

A multicentre cross-sectional survey.

Methods

A total of 307 intern nursing and midwifery students were recruited from November 2020 to February 2021 in tertiary grade A hospitals in China. Structural equation modelling was applied to analyse the mediating effects of resilience between social support and compassion fatigue. The Social Support Rating Scale, the 10-item Connor-Davidson Resilience Scale, and the Chinese version of the Compassion Fatigue Short Scale were used to collect data. The hypothetical path model was tested by using IBM SPSS version 26.0 and AMOS version 26.0 software.

Results

Intern nursing and midwifery students had moderate compassion fatigue. Social support positively affected resilience (β = 0.514, p < 0.01). Social support negatively affected compassion fatigue (β = − 0.310, p < 0.01), while resilience negatively affected compassion fatigue (β = − 0.283, p < 0.01). Resilience played a mediating role between social support and compassion fatigue.

Conclusion

Social support can directly affect the compassion fatigue of intern nursing and midwifery students during COVID-19 and indirectly through resilience. Stronger resilience can reduce compassion fatigue. Accordingly, resilience-based interventions should be developed to reduce compassion fatigue.
Evaluation of parental stress in neonatal intensive care unit in Iran: a national study
Authors: Heidarzadeh Mohammad , Heidari Haydeh , Ahmadi Ali , Solati Kamal , sadeghi Narges
Published: February 2023

Background

More attention is paid to the survival and treatment of the sick infant in the neonatal intensive care unit (NICU) and parental stress is not considered. The purpose of this study was to determine samples of the level of parental stress in the NICU.

Method

This study is a descriptive-analytical study in which Parental Stress and General Health were used in an analytical national survey in Iran. The research sample consists of 2456 parents of infants admitted to NICU. The sampling method was multi-stage random. We used 11- item parental stress questionnaire and 28-item general health questionnaire for the data collection.

Result

Baloch ethnicity with an average of 11.52 had the highest level of stress. The mean stress score of mothers was higher than fathers. The mean score of all dimensions of physical symptoms, anxiety, social functioning, depression, and total mental health score in mothers was higher than fathers. There was a statistically significant difference in the length of hospitalization in terms of different levels of parental stress scores (p < 0.002). Lack of decisive response to parents was one of the most stressful issues (8.1%).

Conclusion

Our result shows mothers' stress was higher than fathers. So that health policymakers should pay attention to stress risk factors to provide appropriate interventions according stress risk factors Future studies should design appropriate interventions to reduce parental stress, especially in high-risk mothers.
How did healthcare professionals define patient engagement in quality management? A survey study
Authors: Saut Ana Maria , Ho Linda Lee , Berger Simone , Berssaneti Fernando Tobal
Published: February 2023

Background

Patient and family engagement (PFE) can positively impact the patient experience and care process outcomes. There is no unique type of PFE, and the process is usually defined by the quality management department or professionals responsible for this process in the hospital. The objective of this study is to define PFE in quality management based on the professional’s perspective.

Method

A survey was carried out with 90 professionals from Brazilian hospitals. There were two questions aimed at understanding the concept. The first was a multiple-choice question to identify synonyms. The second was an open-ended question to develop the definition. A content analysis methodology was employed by applying techniques for thematic and inferential analysis.

Results

Three words were classified as synonyms by more than 60% of respondents: involvement, participation, and centered care. The participants described patient participation at both the individual (related to the treatment) and organizational levels (related to quality improvement). The PFE in the treatment is related to the development, discussion and decision-making about the therapeutic plan, participation in each step of care, and knowledge of the institution's quality and safety processes. At the organizational level, engagement in quality improvement includes the involvement of the P/F in all processes of the institution, from strategic planning to the design or improvement processes, as well as active participation in institutional committees or commissions.

Conclusion

The professionals defined engagement in two levels (individual and organizational) and the results suggest that their point of view can influence the practice in the hospitals. Professionals of hospitals that implemented mechanisms of consult defined PFE more in the individual level. On the other hand, professionals of hospitals that implemented mechanisms of involvement considered PFE more focus in the organizational level.
Identification and profiling of microRNAs during yak’s testicular development
Authors: La Yongfu , Ma Xiaoming , Bao Pengjia , Chu Min , Guo Xian , Liang Chunnian , Yan Ping
Published: February 2023

Background

Normal testicular development is highly crucial for male reproduction and is a precondition for spermatogenesis that is the production of spermatozoa in the testes. MiRNAs have been implicated in several testicular biological processes, including cell proliferation, spermatogenesis, hormone secretion, metabolism and reproductive regulation. In the present study, we used deep sequencing data to study the functions of miRNAs during testicular development and spermatogenesis, by analyzing the expression patterns of small RNAs in 6-, 18- and 30-month-old yak testis tissues.

Results

A total of 737 known and 359 novel miRNAs were obtained from 6-, 18- and 30-month-old yak testes. In all, we obtained 12, 142 and 139 differentially expressed (DE) miRNAs in 30- vs. 18-, 18- vs. 6-, and 30- vs. 6-month-old testes, respectively. Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of all DE miRNA target genes revealed BMP2, TGFB2, GDF6, SMAD6, TGFBR2 and other target genes as participants in different biological processes, including TGF-β, GnRH, Wnt, PI3K–Akt, MAPK signaling pathways and several other reproductive pathways. In addition, quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was used to detect the expression of seven randomly selected miRNAs in 6-, 18- and 30-month-old testes, and the results were consistent with the sequencing data.

Conclusions

The differential expression of miRNAs in yak testes at different development stages was characterized and investigated using deep sequencing technology. We believe that the results will contribute to further understanding the functions of miRNAs in regulating the development of yak testes and improving the reproductive performance of male yaks.
AZU1 (HBP/CAP37) and PRKCG (PKC-gamma) may be candidate genes affecting the severity of acute mountain sickness
Authors: Xu Zhichao , Li Qiong , Shen Xiaobing
Published: February 2023

Background

Acute Mountain Sickness (AMS) is one of the diseases that predispose to sudden ascent to high altitudes above 2500 m. Among the many studies on the occurrence and development of AMS, there are few studies on the severity of AMS. Some unidentified phenotypes or genes that determine the severity of AMS may be vital to elucidating the mechanisms of AMS. This study aims to explore the underlying genes or phenotypes associated with AMS severity and to provide evidence for a better understanding of the mechanisms of AMS.

Methods

GSE103927 dataset was downloaded from the Gene Expression Omnibus database, and a total of 19 subjects were enrolled in the study. Subjects were divided into a moderate to severe AMS (MS-AMS, 9 subjects) group and a no or mild AMS (NM-AMS, 10 subjects) group based on the Lake Louise score (LLS). Various bioinformatics analyses were used to compare the differences between the two groups. Another dataset, Real-time quantitative PCR (RT-qPCR), and another grouping method were used to validate the analysis results.

Result

No statistically significant differences in phenotypic and clinical data existed between the MS-AMS and NM-AMS groups. Eight differential expression genes are associated with LLS, and their biological functions are related regulating of the apoptotic process and programmed cell death. The ROC curves showed that AZU1 and PRKCG had a better predictive performance for MS-AMS. AZU1 and PRKCG were significantly associated with the severity of AMS. The expression of AZU1 and PRKCG were significantly higher in the MS-AMS group compared to the NM-AMS group. The hypoxic environment promotes the expression of AZU1 and PRKCG. The results of these analyses were validated by an alternative grouping method and RT-qPCR results. AZU1 and PRKCG were enriched in the Neutrophil extracellular trap formation pathway, suggesting the importance of this pathway in influencing the severity of AMS.

Conclusion

AZU1 and PRKCG may be key genes influencing the severity of acute mountain sickness, and can be used as good diagnostic or predictive indicators of the severity of AMS. Our study provides a new perspective to explore the molecular mechanism of AMS.
Long-term increase in fasting blood glucose is associated with increased risk of sudden cardiac arrest
Authors: Kim Yun Gi , Roh Seung-Young , Jeong Joo Hee , Lee Hyoung Seok , Min Kyongjin , Choi Yun Young , Han Kyung-Do , Shim Jaemin , Choi Jong-Il , Kim Young-Hoon
Published: February 2023

Background

Diabetes mellitus (DM) is associated with various cardiovascular complications, including sudden cardiac arrest (SCA). Furthermore, the severity of DM, as assessed by fasting blood glucose (FBG), is associated with the risk of SCA. However, whether long-term changes in FBG influence on SCA risk remains to be determined.

Methods

This study used sequential nationwide health screening data from 2009 and 2011. FBG was measured at each health screening, and ΔFBG was calculated as FBG in 2011–FBG in 2009.

Results

Overall, 2,801,153 people were analyzed, and the mean follow-up duration was 6.33 years. Compared with the euglycemic group (− 20 ≤ ΔFBG < 20), the 20 ≤ ΔFBG < 40, 40 ≤ ΔFBG < 100, and ΔFBG ≥ 100 groups had increased SCA risks of 25% (adjusted hazard ratio [HR] = 1.25; 95% confidence interval [CI] 1.16–1.35; p < 0.001), 66% (adjusted HR = 1.66; 95% CI 1.49–1.86; p < 0.001), and 2.9-fold (adjusted HR = 2.85; 95% CI 2.37–3.44; p < 0.001), respectively. The association between ΔFBG and SCA was maintained in people with DM but not in people without DM. However, sex, age, blood pressure, and presence of heart failure did not affect the association between ΔFBG and SCA. A decrease in ΔFBG over time was not associated with reduced risk of SCA: the adjusted HR was 1.11 (95% CI 0.98–1.27; p = 0.113) for the ΔFBG < –40 group and 1.12 (95% CI 1.03–1.22; p = 0.009) for the − 40 ≤ ∆FBG < − 20 group.

Conclusions

A long-term increase in ΔFBG can be associated with increased risk of SCA in people with DM. However, a long-term decrease in ΔFBG was not associated with reduced risk of SCA. Actions to prevent increase in FBG can have significant effects on public health in terms of SCA prevention.
Exploring the potential of Rhizopus oryzae AUMC14899 as a novel endophytic fungus for the production of l-tyrosine and its biomedical applications
Authors: El-Zawawy Nessma A. , Ali Sameh Samir , Nouh Hoda S.
Published: February 2023

Background

A significant threat to the public's health is the rise in antimicrobial resistance among numerous nosocomial bacterial infections. This may be a detriment to present initiatives to enhance the health of immune-compromised patients. Consequently, attention has been devoted to exploring new bioactive compounds in the field of drug discovery from endophytes. Therefore, this study is the first on the production of l-tyrosine (LT) as a promising bio-therapeutic agent from endophytic fungi.

Results

A new endophytic fungal isolate has been identified for the first time as Rhizopus oryzae AUMC14899 from Opuntia ficus-indica (L.) and submitted to GenBank under the accession number MZ025968. Separation of amino acids in the crude extract of this fungal isolate was carried out, giving a higher content of LT, which is then characterized and purified. LT exhibited strong antibacterial and anti-biofilm activities against multidrug-resistant Gram-negative and Gram-positive bacteria. The recorded minimum inhibitory concentration (MIC) values ranged from 6 to 20 µg/ml. In addition, LT caused a strong reduction in biofilm formation and disrupted the preformed biofilm. Moreover, results indicated that LT supported cell viability, evidencing hemocompatibility and no cytotoxicity.

Conclusion

Our findings suggest that LT has potential as a therapeutic agent due to its potential antibacterial, anti-biofilm, hemocompatibility, and lack of cytotoxic activities, which may also increase the range of therapy options for skin burn infections, leading to the development of a novel fungal-based drug.
The role of LncRNAs in tumor immunotherapy
Authors: Pan Xuan , Li Chenchen , Feng Jifeng
Published: February 2023

Cancer immunotherapy is a major breakthrough in the history of tumor therapy in the last decade. Immune checkpoint inhibitors blocking CTLA-4/B7 or PD-1/PD-L1 pathways have greatly prolonged the survival of patients with different cancers. Long non-coding RNAs (lncRNAs) are abnormally expressed in tumors and play an important role in tumor immunotherapy through immune regulation and immunotherapy resistance. In this review, we summarized the mechanisms of lncRNAs in regulating gene expression and well-studied immune checkpoint pathways. The crucial regulatory function of immune-related lncRNAs in cancer immunotherapy was also described. Further understanding of the underlying mechanisms of these lncRNAs is of great importance to the development of taking lncRNAs as novel biomarkers and therapeutic targets for immunotherapy.
Status of malaria in pregnancy services in Madagascar 2010–2021: a scoping review
Authors: Malpass Ashley , Hansen Natasha , Dentinger Catherine M. , Youll Susan , Cotte Annett , Mattern Chiarella , Ravaoarinosy Aimée
Published: February 2023

Background

Malaria in pregnancy (MIP) increases the risk of poor maternal and infant outcomes. To reduce these risks, WHO recommends insecticide-treated net (ITN) use, intermittent preventive treatment during pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP), and prompt case management. However, uptake of these interventions remains sub-optimal in Madagascar. A scoping review was conducted to determine the breadth and depth of information available during 2010–2021 about Madagascar’s MIP activities and to identify barriers and facilitators to MIP interventions uptake.

Methods

PubMed, Google Scholar, and USAID’s files (Development Experience Catalog) were searched using the terms “Madagascar AND pregnancy AND malaria,” and reports and materials from stakeholders were collected. Documents in English and French from 2010 to 2021 with data regarding MIP were included. Documents were systematically reviewed and summarized; results were captured in an Excel database.

Results

Of 91 project reports, surveys and published articles, 23 (25%) fell within the stated time period and contained relevant data on MIP activities in Madagascar and were categorized accordingly: eight (35%) quality of care, including health facility readiness, provider knowledge and commodity availability; nine (39%) care-seeking behaviour; and, six (26%) prevention of MIP. Key barriers were identified: nine articles mentioned SP stockouts; seven found limitations of provider knowledge, attitudes, and behaviours (KAB) regarding MIP treatment and prevention; and, one reported limited supervision. MIP care seeking and prevention barriers and facilitators included women’s KAB regarding MIP treatment and prevention, distance, wait times, poor service quality, cost, and/or unwelcoming providers. A 2015 survey of 52 health facilities revealed limited client access to antenatal care due to financial and geographic barriers; two 2018 surveys revealed similar findings. Self-treatment and care-seeking delays were reported even when distance was not a barrier.

Conclusion

Among the studies and reports on MIP in Madagascar, the scoping review frequently noted barriers that could be mitigated by reducing stockouts, improving provider knowledge and attitudes, refining MIP communication, and improving service access. There is a need for coordinated efforts to address the identified barriers is the key implication of the findings.
Convection-enhanced delivery of nanoencapsulated gene locoregionally yielding ErbB2/Her2-specific CAR-macrophages for brainstem glioma immunotherapy
Authors: Gao Lin , Shi Chongdeng , Yang Zhenmei , Jing Weiqiang , Han Maosen , Zhang Jing , Zhang Cai , Tang Chunwei , Dong Yuanmin , Liu Ying , Chen Chen , Jiang Xinyi
Published: February 2023

Locoregional delivery of chimeric antigen receptor (CAR)-modified T (CAR-T) cells has emerged as a promising strategy for brain tumors. However, the complicated ex vivo cell manufacturing procedures and the rapid progression of the disease have limited its broader applications. Macrophages (MΦs) exhibit unique effector functions and a high degree of infiltration within the solid tumor microenvironment (TME), especially in the brain, where MΦs function as structural support, and the main immune effector cells of the CNS represent 5–12% of brain cells. Here, we report a synthetic universal DNA nanocarrier for in situ genetic editing of intratumoral MΦs with an ErbB2-specific CAR to direct their phagocytic activity towards tumors and subsequently initiate a locoregional antitumor immune response. Specifically, we demonstrated that when delivered locoregionally, the RP-182 peptide, located in the shell of a nanoparticle, targeted MΦs and reprogrammed M2-like tumor-associated macrophages (TAMs) to an antitumor M1-like phenotype. Subsequently, the CAR gene-laden DNA nanocomplex can be used to introduce ErbB2-targeted CAR, and the generated CAR-MΦs then act as “living” cures, thereby serially clearing the invasive tumor cells. Our work demonstrates a practical antitumor immunotherapy for brainstem gliomas (BSGs) that may be broadly applicable for patients suffering from other ErbB2-positive solid malignancies.
Monitoring heparin therapy: stability of two different anti-Xa assays using blood samples collected in citrate-containing and CTAD tubes
Authors: Gremillet Marion , Talon Laurie , Lebreton Aurélien , Sinegre Thomas
Published: February 2023

Background

Anti-factor Xa assays and activated partial thromboplastin time (aPTT) are mainly employed to monitor patients treated with heparins. According to the Clinical and Laboratory Standards Institute and the French Working Group on Haemostasis and Thrombosis, anti-factor Xa activity and aPTT should be tested within 2 h of blood sampling for unfractionated heparin (UFH) monitoring. However, discrepancies exist depending on the used reagents and collecting tubes. The study aim was to determine the stability of aPTT and anti-factor Xa measurements using blood samples collected in citrate-containing or citrate-theophylline-adenosine-dipyridamole (CTAD) tubes and stored for up to 6 h.

Methods

Patients receiving UFH or low molecular weight heparin (LMWH) were enrolled; aPTT and anti-factor Xa activity were tested using two different analyser/reagent pairs (Stago and reagent without dextran sulfate; Siemens and reagent with dextran sulfate) after 1, 4 and 6 h of sample storage as whole blood or as plasma.

Results

For UFH monitoring, comparable anti-factor Xa activity and aPTT results were obtained with both analyser/reagent pairs when samples were stored as whole blood before plasma isolation. With samples stored as plasma, anti-factor Xa activity and aPTT were not affected up to 6 h after sampling when using the Stago/no-dextran sulfate reagent pair. With the Siemens/dextran sulfate-containing reagent, aPTT was significantly altered after 4 h of storage. For LMWH monitoring, anti-factor Xa activity remained stable (whole blood and plasma) for at least 6 h. Results were comparable with citrate-containing and CTAD tubes.

Conclusions

Anti-factor Xa activity in samples stored as whole blood or plasma was stable for up to 6 h, regardless of the reagent (with/without dextran sulfate)/collection tube. Conversely, aPTT was more variable because other plasma parameters can influence its measure and complicate the interpretation of its variations after 4 h.
From pressure in the pipeline to accelerating ascension: a survey to understand professional experiences of and opportunities for Canadian women in the healthcare sector
Authors: Desveaux L. , Pirmohamed J. , Hussain-Shamsy N. , Gray C. Steele
Published: February 2023

Background

Much has been written about the state and persistent lack of progress regarding gender equity and the commonly referenced phenomenon of a ‘leaking pipeline’. This framing focuses attention on the symptom of women leaving the workforce, rather than the well-documented contributing factors of hindered recognition, advancement, and financial opportunities. While attention shifts to identifying strategies and practices to address gender inequities, there is limited insight into the professional experiences of Canadian women, specifically in the female-dominated healthcare sector.

Methods

We conducted a survey of 420 women working across a range of roles within healthcare. Frequencies and descriptive statistics were calculated for each measure as appropriate. For each respondent, two composite Unconscious Bias (UCB) scores were created using a meaningful grouping approach.

Results

Our survey results highlight three key areas of focus to move from knowledge to action, including (1) identifying the resources, structural factors, and professional network elements that will enable a collective shift towards gender equity; (2) providing women with access to formal and informal opportunities to develop the strategic relational skills required for advancement; and (3) restructuring social environments to be more inclusive. Specifically, women identified that self-advocacy, confidence building, and negotiation skills were most important to support development and leadership advancement.

Conclusions

These insights provide systems and organizations with practical actions they can take to support women in the health workforce amid a time of considerable workforce pressure.
BMAL1/p53 mediating bronchial epithelial cell autophagy contributes to PM2.5-aggravated asthma
Authors: Chen Shuai-Jun , Huang Yi , Yu Fan , Feng Xiao , Zheng Yuan-Yi , Li Qian , Niu Qian , Jiang Ye-Han , Zhao Li-Qin , Wang Meng , Cheng Pei-Pei , Song Lin-Jie , Liang Li-Mei , He Xin-Liang , Xiong Liang , Xiang Fei , Wang Xiaorong , Ma Wan-Li , Ye Hong
Published: February 2023

Background

Fine particulate matter (PM2.5) is associated with increased incidence and severity of asthma. PM2.5 exposure disrupts airway epithelial cells, which elicits and sustains PM2.5-induced airway inflammation and remodeling. However, the mechanisms underlying development and exacerbation of PM2.5-induced asthma were still poorly understood. The aryl hydrocarbon receptor nuclear translocator-like protein 1 (BMAL1) is a major circadian clock transcriptional activator that is also extensively expressed in peripheral tissues and plays a crucial role in organ and tissue metabolism.

Results

In this study, we found PM2.5 aggravated airway remodeling in mouse chronic asthma, and exacerbated asthma manifestation in mouse acute asthma. Next, low BMAL1 expression was found to be crucial for airway remodeling in PM2.5-challenged asthmatic mice. Subsequently, we confirmed that BMAL1 could bind and promote ubiquitination of p53, which can regulate p53 degradation and block its increase under normal conditions. However, PM2.5-induced BMAL1 inhibition resulted in up-regulation of p53 protein in bronchial epithelial cells, then increased-p53 promoted autophagy. Autophagy in bronchial epithelial cells mediated collagen-I synthesis as well as airway remodeling in asthma.

Conclusions

Taken together, our results suggest that BMAL1/p53-mediated bronchial epithelial cell autophagy contributes to PM2.5-aggravated asthma. This study highlights the functional importance of BMAL1-dependent p53 regulation during asthma, and provides a novel mechanistic insight into the therapeutic mechanisms of BMAL1.

Graphic abstract
Not1 and Not4 inversely determine mRNA solubility that sets the dynamics of co-translational events
Authors: Allen George , Weiss Benjamin , Panasenko Olesya O. , Huch Susanne , Villanyi Zoltan , Albert Benjamin , Dilg Daniel , Zagatti Marina , Schaughency Paul , Liao Susan E. , Corden Jeff , Polte Christine , Shore David , Ignatova Zoya , Pelechano Vicent , Collart Martine A.
Published: February 2023

Background

The Ccr4-Not complex is mostly known as the major eukaryotic deadenylase. However, several studies have uncovered roles of the complex, in particular of the Not subunits, unrelated to deadenylation and relevant for translation. In particular, the existence of Not condensates that regulate translation elongation dynamics has been reported. Typical studies that evaluate translation efficiency rely on soluble extracts obtained after the disruption of cells and ribosome profiling. Yet cellular mRNAs in condensates can be actively translated and may not be present in such extracts.

Results

In this work, by analyzing soluble and insoluble mRNA decay intermediates in yeast, we determine that insoluble mRNAs are enriched for ribosomes dwelling at non-optimal codons compared to soluble mRNAs. mRNA decay is higher for soluble RNAs, but the proportion of co-translational degradation relative to the overall mRNA decay is higher for insoluble mRNAs. We show that depletion of Not1 and Not4 inversely impacts mRNA solubilities and, for soluble mRNAs, ribosome dwelling according to codon optimality. Depletion of Not4 solubilizes mRNAs with lower non-optimal codon content and higher expression that are rendered insoluble by Not1 depletion. By contrast, depletion of Not1 solubilizes mitochondrial mRNAs, which are rendered insoluble upon Not4 depletion.

Conclusions

Our results reveal that mRNA solubility defines the dynamics of co-translation events and is oppositely regulated by Not1 and Not4, a mechanism that we additionally determine may already be set by Not1 promoter association in the nucleus.
Digital peer-to-peer support programme for informal caregivers of people living with motor neuron disease: study protocol for a multi-centre parallel group, single-blinded (outcome assessor) randomised controlled superiority trial
Authors: Rose Louise , Thaventhiran Thilipan , Hobson Esther , Rogers Rebecca , James Kirsty , Chu Petrina , Carter Ben , Faull Christina , Saha Sian , Lee Jeong Su , Kaltsakas Georgios , McDermott Christopher , Ramsay Michelle
Published: February 2023

Background

Peer support is effective in improving psychological well-being of family caregivers of people with conditions such as dementia, cancer, and brain injury. However, there are limited data on effective psychological interventions for family caregivers of people living with motor neurone disease. Our objective is to evaluate the efficacy of a virtual peer support programme for improving caregiver psychological wellbeing and caregiving related outcomes.

Methods

We will conduct a multi-centre parallel group randomised controlled superiority trial. Using a multi-modal recruitment strategy, we will recruit informal caregivers from UK MND clinics, in-patient units, and hospices. We will randomise (1:1, stratified by gender) participants to either a 12-week virtual peer support programme or usual care comprising provision of online information resources publicly available via the MND Association website. Peer support programme elements will be delivered via a secure digital e-platform aTouchAway™ (Aetonix, Canada). Our target sample size is 160 (80 each arm). Our primary outcome is the Hospital Anxiety and Depression Scale (HADS) assessed at 12 weeks (primary endpoint). Secondary outcomes that will also be assessed at 12 weeks include the Zarit Burden Interview, Pearlin Mastery Scale, Personal Gain Scale, Positive Affect Scale, and the Brief COPE. Outcome assessors will be blinded to allocation. Tertiary outcomes include perceived usability (1 item 9-point Likert scale) and acceptability (semi-structured qualitative interviews) of the peer support programme. Intervention fidelity measures will comprise frequency, type (text, audio, video), and duration (audio and video) of peer support contact downloaded from the aTouchAway AWS server. We will use a mixed-effects linear model to test the effect of the intervention on the primary outcome. Secondary outcomes will be analysed using linear regression. We have ethical approval (21/NW/0269) from the North-West Research Ethics Committee, UK.

Discussion

This single-blinded randomised controlled trial will determine the effect of a virtual peer support programme on caregiver psychological wellbeing and caregiver burden. This study will examine the impact of a virtual peer support intervention on quality-of-life measures in informal caregivers of individuals with MND living in the community.

Trial registration

ClinicalTrials.gov: NCT04695210
Development of a TaqMan qPCR assay for trypanosomatid multi-species detection and quantification in insects
Authors: Barranco-Gómez Olga , De Paula Jessica Carreira , Parada Jennifer Solano , Gómez-Moracho Tamara , Marfil Ana Vic , Zafra María , Orantes Bermejo Francisco José , Osuna Antonio , De Pablos Luis Miguel
Published: February 2023

Background

Trypanosomatid parasites are widely distributed in nature and can have a monoxenous or dixenous life-cycle. These parasites thrive in a wide number of insect orders, some of which have an important economic and environmental value, such as bees. The objective of this study was to develop a robust and sensitive real-time quantitative PCR (qPCR) assay for detecting trypanosomatid parasites in any type of parasitized insect sample.

Methods

A TaqMan qPCR assay based on a trypanosomatid-conserved region of the α-tubulin gene was standardized and evaluated. The limits of detection, sensitivity and versatility of the α-tubulin TaqMan assay were tested and validated using field samples of honeybee workers, wild bees, bumblebees and grasshoppers, as well as in the human infective trypanosomatid Leishmania major.

Results

The assay showed a detection limit of 1 parasite equivalent/µl and successfully detected trypanosomatids in 10 different hosts belonging to the insect orders Hymenoptera and Orthoptera. The methodology was also tested using honeybee samples from four apiaries (n = 224 worker honeybees) located in the Alpujarra region (Granada, Spain). Trypanosomatids were detected in 2.7% of the honeybees, with an intra-colony prevalence of 0% to 13%. Parasite loads in the four different classes of insects ranged from 40.6 up to 1.1 × 108 cell equivalents per host.

Conclusions

These results show that the α-tubulin TaqMan qPCR assay described here is a versatile diagnostic tool for the accurate detection and quantification of trypanosomatids in a wide range of environmental settings.

Graphical Abstract
Emerging role of mesenchymal stem/stromal cells (MSCs) and MSCs-derived exosomes in bone- and joint-associated musculoskeletal disorders: a new frontier
Authors: Gerami Mohammad Hadi , Khorram Roya , Rasoolzadegan Soheil , Mardpour Saeid , Nakhaei Pooria , Hashemi Soheyla , Al-Naqeeb Bashar Zuhair Talib , Aminian Amir , Samimi Sahar
Published: February 2023

Exosomes are membranous vesicles with a 30 to 150 nm diameter secreted by mesenchymal stem/stromal cells (MSCs) and other cells, such as immune cells and cancer cells. Exosomes convey proteins, bioactive lipids, and genetic components to recipient cells, such as microRNAs (miRNAs). Consequently, they have been implicated in regulating intercellular communication mediators under physiological and pathological circumstances. Exosomes therapy as a cell-free approach bypasses many concerns regarding the therapeutic application of stem/stromal cells, including undesirable proliferation, heterogeneity, and immunogenic effects. Indeed, exosomes have become a promising strategy to treat human diseases, particularly bone- and joint-associated musculoskeletal disorders, because of their characteristics, such as potentiated stability in circulation, biocompatibility, low immunogenicity, and toxicity. In this light, a diversity of studies have indicated that inhibiting inflammation, inducing angiogenesis, provoking osteoblast and chondrocyte proliferation and migration, and negative regulation of matrix-degrading enzymes result in bone and cartilage recovery upon administration of MSCs-derived exosomes. Notwithstanding, insufficient quantity of isolated exosomes, lack of reliable potency test, and exosomes heterogeneity hurdle their application in clinics. Herein, we will deliver an outline respecting the advantages of MSCs-derived exosomes-based therapy in common bone- and joint-associated musculoskeletal disorders. Moreover, we will have a glimpse the underlying mechanism behind the MSCs-elicited therapeutic merits in these conditions.
Acute appendicitis and situs viscerum inversus: radiological and surgical approach—a systematic review
Authors: Di Buono Giuseppe , Buscemi Salvatore , Galia Massimo , Maienza Elisa , Amato Giuseppe , Bonventre Giulia , Vella Roberta , Saverino Marta , Grassedonio Emanuele , Romano Giorgio , Agrusa Antonino
Published: February 2023

Introduction

Acute appendicitis is one of the most frequent intra-abdominal diseases requiring emergency surgical consult and treatment. The diagnosis of this condition is based on clinical features and radiologic findings. One-third of patients with acute appendicitis present unusual symptoms. There are several circumstances that may cause misdiagnosis and unclear prognostic prediction. Among these, situs viscerum inversus totalis and midgut malrotation can be challenging scenarios, leading to a delay in treatment, especially when these conditions are unknown. We decided to carry on a systematic review of published cases of acute appendicitis in the context of anatomical anomalies.

Methods

We used the MESH terms “appendicitis” AND “situs inversus” AND/OR “gut malrotation” to search for titles and abstracts. Inclusion criteria were patients with clinical and/or radiological diagnosis of acute appendicitis, with conservative or surgical management and with preoperative/intraoperative findings of situs viscerum inversus or gut malrotation. Additionally, previous reviews were examined. Exclusion criteria of the studies were insufficient patient clinical and demographic data.

Results

We included in this review 70 articles concerning 73 cases of acute appendicitis with anatomical anomaly. Patients were aged from 8 to 86 years (median: 27.0 years). 50 were male and 23 were female. 46 patients (63%) had situs viscerum inversus, 24 (33%) had midgut malrotation, 2 (2.7%) had Kartagener’s syndrome, one of them (1.4%) had an undetermined anomaly In 61 patients the anatomical anomaly was unknown previously (83.6%), while 16,4% already were aware of their condition.

Conclusion

Acute appendicitis can occur in association of rare anatomical anomalies and in these cases diagnosis can be challenging. Situs viscerum inversus and midgut malrotation should always be considered in the differential diagnosis of a patient with left lower quadrant pain, especially in younger population. Besides clinical features, it is fundamental to implement the diagnostic progress with radiological examination. Laparoscopic approach is useful to identify and treat acute surgical emergency and it is also a diagnostic tool and can be tailored in order to offer the best exposition of the operatory field for each single case.
Neurofibromatosis-Noonan syndrome and growth deficiency in an Iranian girl due to a pathogenic variant in NF1 gene
Authors: Dalili Setila , Hoseini Nouri Seyyedeh Azade , Bayat Reza , Koohmanaee Shahin , Tabrizi Manijeh , Zarkesh Marjaneh , Tarang Alireza , Mahdieh Nejat
Published: February 2023

Background

Mutations in NF1 gene could cause allelic disorders with clinical spectrum of Neurofibromatosis type 1 to Noonan syndrome. Here, a 7-year-old Iranian girl is described with Neurofibromatosis-Noonan syndrome due to a pathogenic variant in NF1 gene.

Methods

Clinical evaluations were performed along with genetic testing using whole exome sequencing (WES). The variant analysis including pathogenicity prediction was also done using bioinformatics tools.

Results

The chief compliant of the patient was short stature and lack of proper weight gain. Other symptoms were developmental delay, learning disability, inadequate speech skill, broad forehead, hypertelorism, and epicanthal folds, low set ears and webbed neck. A small deletion, c.4375-4377delGAA, was found in NF1 gene using WES. This variant was classified as pathogenic according to ACMG.

Conclusions

NF1 variants may show variable phenotypes among the patients; identifying such variants is helpful in therapeutic management of the disease. WES is considered as an appropriate test to diagnose Neurofibromatosis-Noonan syndrome.
The mother–daughter Shared Agency in Weight Management Scale (SAWMS): development, validation, and implications for body dissatisfaction
Authors: Shao Jianmin , Chang Esther S. , Tsong Yuying , Chen Chuansheng , Borelli Jessica L.
Published: February 2023

Background

Much research suggests that mothers play an important role in shaping daughters’ body image, yet less is known about how mother–daughter relationship dynamics in weight management affect daughters’ body dissatisfaction. The current paper described the development and validation of the mother–daughter Shared Agency in Weight Management Scale (SAWMS) and examined its associations with daughter’s body dissatisfaction.

Methods

In Study 1 (N = 676 college students), we explored the factor structure of the mother–daughter SAWMS and identified three processes (control, autonomy support, and collaboration) whereby mothers work with daughters in weight management. In Study 2 (N = 439 college students), we finalized the factor structure of the scale by conducting two CFAs and assessing the test–retest reliability of each subscale. In Study 3 (same sample as Study 2), we examined the psychometric properties of the subscales and their associations with daughters’ body dissatisfaction.

Results

Combining results from EFA and IRT, we identified three mother–daughter dynamics in weight management—maternal control, maternal autonomy support, and maternal collaboration. However, based on various empirical results indicating poor psychometric properties of the maternal collaboration subscale, we removed it from the mother–daughter SAWMS and only evaluated the psychometric properties of the remaining two subscales (i.e., control and autonomy support). They explained a significant amount of variance in daughters’ body dissatisfaction over and above the effect of maternal pressure to be thin. Maternal control was a significant and positive predictor of daughters’ body dissatisfaction; maternal autonomy support was a significant and negative predictor.

Conclusions

Results suggested that maternal control in weight management was associated with daughters’ increased body dissatisfaction, whereas maternal autonomy support in weight management was associated with daughters’ lower body dissatisfaction. These specific ways in which mother work with daughters in weight management provide nuances in understanding young women’s body dissatisfaction. Our SAWMS offers new ways to examine body image among young women through the mother–daughter relationship dynamics in weight management.
Oseltamivir phosphate for suspension is bioequivalent to TAMIFLU in healthy volunteers: a randomized, open-label clinical study
Authors: Wang Ying , Tang Bangzhong , Xie Jing , Wang Xiaoqin , Ren Peng , Wu Guangmei , He Cuixia , Zhu Minhui , Su Yue , Ding Jiaxiang , Xu Yuanyuan , Fan Ling , Ge Qin , Ding Yuzhou , Zhu Juan , Liu Bingyan , Shan Rongfang , Zhou Huan
Published: February 2023

Purpose

The study was aimed at evaluating the bioequivalence and safety of oseltamivir phosphate for suspension, provided by Shenzhen Beimei Pharmaceutical Co. Ltd. and manufactured by Hetero Labs Limited, and the reference product TAMIFLU® in healthy Chinese subjects.

Methods

A single-dose, randomized, two-phase, self-crossed model was adopted. Among 80 healthy subjects, 40 subjects in the fasting group and 40 subjects in the fed group. Subjects in the fasting group were randomized into two sequences according to the proportion of 1:1, each given 75 mg/12.5 mL of Oseltamivir Phosphate for Suspension or TAMIFLU®, and cross-administered after 7 days. Postprandial group is the same as fasting group.

Results

The Tmax of TAMIFLU® and Oseltamivir Phosphate for Suspension in the fasting group were 1.50 h and 1.25 h, which in the fed group were both 1.25 h. Geometrically adjusted mean ratios of the PK parameters of Oseltamivir Phosphate for Suspension along with TAMIFLU® under fasting and postprandial conditions were in the range of 80.00–125.00% at the 90% confidence interval (CI). The 90% CI of Cmax, AUC0-t, AUC0-∞ for fasting group and postprandial group were (92.39,106.50), (94.26,100.67), (94.32,100.89) and (93.61,105.83),(95.64,100.19),(96.06,102.66). Among the subjects on medication, a total of 18 subjects reported 27 adverse events, all of which were treatment-emergent adverse events (TEAEs), six of these TEAEs were rated as grade 2 in severity and the rest were as grade 1. The number of TEAEs in the test product and the reference product were 14,13 respectively.

Conclusion

Two Oseltamivir phosphate for suspensions are safe and bioequivalent.