bluuebunny/crossref_metadata_2025 huggingface dataset:
Person-centered dementia care in home care services – highly recommended but still challenging to obtain: a qualitative interview study
Authors: Hoel Kari-Anne , Rokstad Anne Marie Mork , Feiring Ingvild Hjorth , Lichtwarck Bjørn , Selbæk Geir , Bergh Sverre
Published: July 2021

Background

Dementia is one of the main causes of disability and dependence in older people, and people with dementia need comprehensive healthcare services, preferably in their own homes. A well-organized home care service designed for people with dementia is necessary to meet their needs for health- and social care. Therefore, it is important to gain knowledge about how people with dementia experience the home care service and if the service responds to their wishes and needs. The aim of this study was to explore the experience of home care services among people with dementia, to understand the continuity in services, how the service was adapted to people with dementia, and how the patient experienced person-centered care and shared decision-making.

Methods

We used a qualitative, exploratory design based on a phenomenological-hermeneutic approach and performed individual in-depth interviews with persons with dementia. A convenience sample of 12 persons with moderate to severe degrees of dementia from four Norwegian municipalities participated in the study. The interviews were conducted in February 2019.

Results

The findings identified that the participants appreciated the possibility to stay safely in their own homes and mostly experienced good support from staff. They expressed various views and understanding of the service and experienced limited opportunities for user involvement and individualized, tailored service. The overall theme summarizing the findings was: “It is difficult for people with dementia to understand and influence home care services, but the services facilitate the possibility to stay at home and feel safe with support from staff.”

Conclusion

The participants did not fully understand the organization of the care and support they received from the home care services, but they adapted to the service without asking for changes based on their needs or desires. Although person-centered care is recommended both nationally and internationally, the participants experienced little inclusion in defining the service they received, and it was perceived as unclear how they could participate in shared decision-making.
Genomics and transcriptomics yields a system-level view of the biology of the pathogen Naegleria fowleri
Authors: Herman Emily K. , Greninger Alex , van der Giezen Mark , Ginger Michael L. , Ramirez-Macias Inmaculada , Miller Haylea C. , Morgan Matthew J. , Tsaousis Anastasios D. , Velle Katrina , Vargová Romana , Záhonová Kristína , Najle Sebastian Rodrigo , MacIntyre Georgina , Muller Norbert , Wittwer Mattias , Zysset-Burri Denise C. , Eliáš Marek , Slamovits Claudio H. , Weirauch Matthew T. , Fritz-Laylin Lillian , Marciano-Cabral Francine , Puzon Geoffrey J. , Walsh Tom , Chiu Charles , Dacks Joel B.
Published: July 2021

Background

The opportunistic pathogen Naegleria fowleri establishes infection in the human brain, killing almost invariably within 2 weeks. The amoeba performs piece-meal ingestion, or trogocytosis, of brain material causing direct tissue damage and massive inflammation. The cellular basis distinguishing N. fowleri from other Naegleria species, which are all non-pathogenic, is not known. Yet, with the geographic range of N. fowleri advancing, potentially due to climate change, understanding how this pathogen invades and kills is both important and timely.

Results

Here, we report an -omics approach to understanding N. fowleri biology and infection at the system level. We sequenced two new strains of N. fowleri and performed a transcriptomic analysis of low- versus high-pathogenicity N. fowleri cultured in a mouse infection model. Comparative analysis provides an in-depth assessment of encoded protein complement between strains, finding high conservation. Molecular evolutionary analyses of multiple diverse cellular systems demonstrate that the N. fowleri genome encodes a similarly complete cellular repertoire to that found in free-living N. gruberi. From transcriptomics, neither stress responses nor traits conferred from lateral gene transfer are suggested as critical for pathogenicity. By contrast, cellular systems such as proteases, lysosomal machinery, and motility, together with metabolic reprogramming and novel N. fowleri proteins, are all implicated in facilitating pathogenicity within the host. Upregulation in mouse-passaged N. fowleri of genes associated with glutamate metabolism and ammonia transport suggests adaptation to available carbon sources in the central nervous system.

Conclusions

In-depth analysis of Naegleria genomes and transcriptomes provides a model of cellular systems involved in opportunistic pathogenicity, uncovering new angles to understanding the biology of a rare but highly fatal pathogen.
Genomic analysis of field pennycress (Thlaspi arvense) provides insights into mechanisms of adaptation to high elevation
Authors: Geng Yupeng , Guan Yabin , Qiong La , Lu Shugang , An Miao , Crabbe M. James C. , Qi Ji , Zhao Fangqing , Qiao Qin , Zhang Ticao
Published: July 2021

Background

Understanding how organisms evolve and adapt to extreme habitats is of crucial importance in evolutionary ecology. Altitude gradients are an important determinant of the distribution pattern and range of organisms due to distinct climate conditions at different altitudes. High-altitude regions often provide extreme environments including low temperature and oxygen concentration, poor soil, and strong levels of ultraviolet radiation, leading to very few plant species being able to populate elevation ranges greater than 4000 m. Field pennycress (Thlaspi arvense) is a valuable oilseed crop and emerging model plant distributed across an elevation range of nearly 4500 m. Here, we generate an improved genome assembly to understand how this species adapts to such different environments.

Results

We sequenced and assembled de novo the chromosome-level pennycress genome of 527.3 Mb encoding 31,596 genes. Phylogenomic analyses based on 2495 single-copy genes revealed that pennycress is closely related to Eutrema salsugineum (estimated divergence 14.32–18.58 Mya), and both species form a sister clade to Schrenkiella parvula and genus Brassica. Field pennycress contains the highest percentage (70.19%) of transposable elements in all reported genomes of Brassicaceae, with the retrotransposon proliferation in the Middle Pleistocene being likely responsible for the expansion of genome size. Moreover, our analysis of 40 field pennycress samples in two high- and two low-elevation populations detected 1,256,971 high-quality single nucleotide polymorphisms. Using three complementary selection tests, we detected 130 candidate naturally selected genes in the Qinghai-Tibet Plateau (QTP) populations, some of which are involved in DNA repair and the ubiquitin system and potential candidates involved in high-altitude adaptation. Notably, we detected a single base mutation causing loss-of-function of the FLOWERING LOCUS C protein, responsible for the transition to early flowering in high-elevation populations.

Conclusions

Our results provide a genome-wide perspective of how plants adapt to distinct environmental conditions across extreme elevation differences and the potential for further follow-up research with extensive data from additional populations and species.
Prevalence of toxoplasmosis in semi-domesticated and pet cats within and around Bangkok, Thailand
Authors: Inpankaew Tawin , Sattasathuchana Panpicha , Kengradomkij Chanya , Thengchaisri Naris
Published: July 2021

Background

Toxoplasmosis is one of the most common parasitic zoonoses worldwide. Cats become infected after ingesting infected tissue cysts. The objective of the present study was to compare the prevalence of toxoplasmosis in pet cats and semi-domesticated cats in the Bangkok metropolitan region. A survey of Toxoplasma infection was conducted in 260 cats (median age [range]: 3 years [10 months–10 years]; 155 females and 105 males) by collecting blood samples from 130 client-owned pet cats and 130 semi-domesticated cats within and around Bangkok during 2016–2017 using indirect fluorescence antibody tests. An IgG antibody to Toxoplasma antigen ratio of ≥1:100 was considered positive for Toxoplasma infection.

Results

The overall prevalence of T. gondii in cats was 6.5% (17/260). The prevalence of T. gondii in semi-domesticated cats and pet cats was 11.5 and 1.5%, respectively. Semi-domesticated cats aged 1–5 years (14.9%) had a higher prevalence of infection than domesticated cats (1.3%, p = 0.002) of the same age. The odds (95% confidence interval [CI]) of having T. gondii infection in semi-domesticated cats were 8.34 (1.86–76.29, p = 0.0017) times higher than in pet cats. Interestingly, there was an association between T. gondii infection according to city ​region (p = 0.002). The odds (95% CI) of having T. gondii infection in cats living in the inner city were 4.96 (1.03–47.16, p = 0.023) times higher than cats living in the suburb and the vicinity.

Conclusions

The present study identified a higher prevalence of Toxoplasma infection in semi-domesticated cats compared with pet cats. The semi-domesticated cats could serve as a zoonotic reservoir. Public health regulations should be implemented to prevent toxoplasmosis spread.
Retinoblastoma genetics screening and clinical management
Authors: Gupta Himika , Malaichamy Sivasankar , Mallipatna Ashwin , Murugan Sakthivel , Jeyabalan Nallathambi , Suresh Babu Vishnu , Ghosh Anuprita , Ghosh Arkasubhra , Santhosh Sam , Seshagiri Somasekar , Ramprasad Vedam L. , Kumaramanickavel Govindasamy
Published: July 2021

Background

India accounts for 20% of the global retinoblastoma (RB) burden. However, the existing data on RB1 gene germline mutations and its influence on clinical decisions is minimally explored.

Methods

Fifty children with RB underwent complete clinical examination and appropriate multidisciplinary management. Screening of germline RB1 gene mutations was performed through next-generation sequencing and Multiplex Ligation-dependent Probe Amplification (MLPA) analysis. The mutation and non-mutation groups were compared for clinical parameters especially severity, progression and recurrence.

Results

Twenty-nine patients had bilateral RB (BLRB) and 21 had unilateral RB (ULRB). The genetic analysis revealed 20 RB1 variations in 29 probands, inclusive of 3 novel mutations, known 16 mutations and heterozygous whole gene deletions. The mutation detection rate (MDR) was 86.2% in BLRB and 19% in ULRB. Associations of disease recurrence (p = 0.021), progression (p = 0.000) and higher percentage of optic nerve invasion, subretinal seeds and high-risk pathological factors were observed in the mutation group. Clinical management was influenced by the presence of germline mutations, particularly while deciding on enucleation, frequency of periodic follow up and radiotherapy.

Conclusions

We identified novel RB1 mutations, and our mutation detection rate was on par with the previous global studies. In our study, genetic results influenced clinical management and we suggest that it should be an essential and integral component of RB-care in India and elsewhere.
Effects of acuC on the growth development and spinosad biosynthesis of Saccharopolyspora spinosa
Authors: Liu Zhudong , Xiao Jie , Tang Jianli , Liu Yang , Shuai Ling , Cao Li , Xia Ziyuan , Ding Xuezhi , Rang Jie , Xia Liqiu
Published: July 2021

Background

Acetoin utilization protein (acuC) is a type I histone deacetylase which is highly conserved in bacteria. The acuC gene is related to the acetylation/deacetylation posttranslational modification (PTM) system in S. spinosa. Spinosyns, the secondary metabolites produced by Saccharopolyspora spinosa, are the active ingredients in a family of insect control agents. However, the specific functions and influences of acuC protein in S. spinosa are yet to be characterized.

Results

The knockout strain and overexpression strain were constructed separately with the shuttle vector pOJ260. The production of spinosyns A and D from S. spinosa-acuC were 105.02 mg/L and 20.63 mg/L, which were 1.82-fold and 1.63-fold higher than those of the wild-type strain (57.76 mg/L and 12.64 mg/L), respectively. The production of spinosyns A and D from S. spinosa-ΔacuC were 32.78 mg/L and 10.89 mg/L, respectively. The qRT-PCR results of three selected genes (bldD, ssgA and whiA) confirmed that the overexpression of acuC affected the capacities of mycelial differentiation and sporulation. Comparative proteomics analysis was performed on these strains to investigate the underlying mechanism leading to the enhancement of spinosad yield.

Conclusions

This study first systematically analysed the effects of overexpression acuC on the growth of S. spinosa and the production of spinosad. The results identify the differentially expressed proteins and provide evidences to understand the acetylation metabolic mechanisms which can lead to the increase of secondary metabolites.
Assessing the impact of the 2008 health reform in Ecuador on the performance of primary health care services: an interrupted time series analysis
Authors: Flores Jimenez Sergio E , San Sebastián Miguel
Published: July 2021

Background

In 2008, Ecuador started a national health reform based on the principles of Alma Ata to achieve Universal Health Coverage. While coverage indicators have increased, a systematic assessment of the impact of the reform on the delivery of health services at primary level is lacking. The aim of this study was to assess the impact of the 2008 health reform on the performance of primary health care services in Ecuador.

Methods

Ambulatory Care Sensitive Conditions (ACSC) are a subset of diseases where hospital admission is potentially avoidable by high quality well-functioning primary care. Thus, observing the behaviour of ACSC hospitalizations can serve as an indicator of how the primary health care level is performing. Crude and adjusted rates, stratified by sex, were calculated from ten selected ACSC hospitalization discharges during 22 years of data representing 11 years before and after the health reform. An interrupted time series analysis was then conducted by applying a negative binomial regression and adjusting for overdispersion and autocorrelation.

Results

Overall higher crude and adjusted rates for ACSC hospitalizations were observed in women compared to men; both increased gradually since the start of the observation, reaching a peak around 2010, and then started a downwards trend. In men, the incidence rate ratio increased significantly by 3 % per year during the period before the intervention. During the first year after intervention, an increase (13 %) was detected, and then a statistically significant 1 % decrease (IRR = 0.99; 95 % CI: 0.98, 0.99) was observed in the ACSC rate ratio per year in the period after the intervention. Similar trends and effect sizes were found for women.

Conclusions

The study revealed significant decreasing trends of the ACSC hospitalization rates in both sexes, indicating an improvement of the performance of the primary health care services following the 2008 national health reform. A continuous strengthening of the primary care model as well as a regular monitoring of ACSC hospitalization rates in the country is recommended. A health economic evaluation considering hospitalizations avoided and associated costs is also advisable.
Situational analysis and reflections on the introduction of advanced practice nurses in Brazilian primary healthcare
Authors: Magnago Carinne , Pierantoni Celia Regina
Published: July 2021

Background

The shortage of doctors and their unequal distribution serve as challenges to advancing primary healthcare (PHC) and achieving effective universal healthcare coverage in Brazil. In an effort to use nurses’ potential more efficiently, the country is investigating the introduction of the advanced practice nurse (APN) into PHC. This paper presents a situational analysis of the practices of Brazilian nurses based on the following components: regulation, practice, and education.

Methods

This is a national multi-method study with triangulated data from a documentary study, a scoping review, and an exploratory study. The regulation component involved the analysis of official normative documents on the regulation of nursing education and nurses’ scope of practice. The practice component aimed to identify the practices performed by nurses in Brazilian PHC based on primary studies. The education component intended to identify the practices taught in nursing training based on a survey and interviews with directors of undergraduate nursing programs.

Results

Federal legislation in Brazil authorizes nursing graduates to perform a set of advanced practices as part of the PHC nurse's daily routine. They can request and interpret complementary tests and prescribe medication. However, in the local context, municipalities define the scope of this assistance based on technical norms or nursing protocols. Furthermore, this study indicates that undergraduate nursing programs do not fully prepare students to adequately execute these tasks.

Conclusions

In the context of Brazilian PHC, advanced practices have already been implemented and respond to main healthcare demands. Therefore, it is unnecessary to introduce the APN as a new professional category. Upon detecting deficiencies in the training process, the current education model should undergo reforms that seek to incorporate the skills compatible with the regulated advanced practices and in-service training for practicing nurses. Regarding the introduction of APN along international lines, this article presents recommendations that may support the operationalization of a Brazilian APN model.
N6-Methyladenosine RNA modification in cerebrospinal fluid as a novel potential diagnostic biomarker for progressive multiple sclerosis
Authors: Ye Fei , Wang Tianzhu , Wu Xiaoxin , Liang Jie , Li Jiaoxing , Sheng Wenli
Published: July 2021

Background

Progressive multiple sclerosis (PMS) is an uncommon and severe subtype of MS that worsens gradually and leads to irreversible disabilities in young adults. Currently, there are no applicable or reliable biomarkers to distinguish PMS from relapsing–remitting multiple sclerosis (RRMS). Previous studies have demonstrated that dysfunction of N6-methyladenosine (m6A) RNA modification is relevant to many neurological disorders. Thus, the aim of this study was to explore the diagnostic biomarkers for PMS based on m6A regulatory genes in the cerebrospinal fluid (CSF).

Methods

Gene expression matrices were downloaded from the ArrayExpress database. Then, we identified differentially expressed m6A regulatory genes between MS and non-MS patients. MS clusters were identified by consensus clustering analysis. Next, we analyzed the correlation between clusters and clinical characteristics. The random forest (RF) algorithm was applied to select key m6A-related genes. The support vector machine (SVM) was then used to construct a diagnostic gene signature. Receiver operating characteristic (ROC) curves were plotted to evaluate the accuracy of the diagnostic model. In addition, CSF samples from MS and non-MS patients were collected and used for external validation, as evaluated by an m6A RNA Methylation Quantification Kit and by real-time quantitative polymerase chain reaction.

Results

The 13 central m6A RNA methylation regulators were all upregulated in MS patients when compared with non-MS patients. Consensus clustering analysis identified two clusters, both of which were significantly associated with MS subtypes. Next, we divided 61 MS patients into a training set (n = 41) and a test set (n = 20). The RF algorithm identified eight feature genes, and the SVM method was successfully applied to construct a diagnostic model. ROC curves revealed good performance. Finally, the analysis of 11 CSF samples demonstrated that RRMS samples exhibited significantly higher levels of m6A RNA methylation and higher gene expression levels of m6A-related genes than PMS samples.

Conclusions

The dynamic modification of m6A RNA methylation is involved in the progression of MS and could potentially represent a novel CSF biomarker for diagnosing MS and distinguishing PMS from RRMS in the early stages of the disease.
Persons living with HIV in sero-discordant partnerships experience improved HIV care engagement compared with persons living with HIV in sero-concordant partnerships: a cross-sectional analysis of four African countries
Authors: Reed Domonique M. , Esber Allahna L. , Crowell Trevor A. , Ganesan Kavitha , Kibuuka Hannah , Maswai Jonah , Owuoth John , Bahemana Emmanuel , Iroezindu Michael , Ake Julie A. , Polyak Christina S. ,   The AFRICOS Study Team
Published: July 2021

Background

Persons living with HIV (PLWH) who are members of sero-discordant and sero-concordant relationships may experience psychological stressors or motivators that affect HIV care. We assessed the association between sero-discordance status, antiretroviral therapy (ART) uptake, and viral suppression in the African Cohort Study (AFRICOS).

Methods

AFRICOS enrolls PLWH and HIV-uninfected individuals at 12 sites in Uganda, Kenya, Tanzania, and Nigeria. At enrollment, we determined ART use through self-report. Viral suppression was defined as HIV RNA < 1000 copies/mL. We analyzed PLWH who were index participants within two types of sexual dyads: sero-discordant or sero-concordant. Binomial regression models were used to estimate prevalence ratios (PRs) and 95% confidence intervals (95% CIs) for factors associated with ART use and viral suppression at study enrollment.

Results

From January 2013 through March 2018, 223 index participants from sero-discordant dyads and 61 from sero-concordant dyads were enrolled. The majority of the indexes were aged 25–34 years (50.2%), female (53.4%), and married (96.5%). Sero-discordant indexes were more likely to disclose their status to partners compared with sero-concordant indexes (96.4% vs. 82.0%, p < 0.001). After adjustment, sero-discordant index participants were more likely to be on ART (aPR 2.8 [95% CI 1.1–6.8]), but no more likely to be virally suppressed. Results may be driven by unique psycho-social factors and global implementation of treatment as prevention.

Conclusions

PLWH in sero-discordant sexual partnerships demonstrated improved uptake of ART compared with those in sero-concordant partnerships. Interventions are needed to increase care engagement by individuals in sero-concordant relationships to improve HIV outcomes.
Lineage analysis of human papillomavirus type 39 in cervical samples of Iranian women
Authors: Hosseini Neda , Shoja Zabihollah , Arashkia Arash , Khodadadi Amir-Hossein , Jalilvand Somayeh
Published: July 2021

Background

The data with regards to the regional variants of distinct HPV types is of great value. Accordance with this, this study aimed to investigate the sequence variations of E6 gene and long control region of HPV 39 among normal, premalignant and malignant cervical samples in order to characterize the frequent HPV 39 variants circulating in Tehran, Iran.

Methods

In total, 70 cervical samples (45 normal, 16 premalignant, and 9 malignant samples) infected with HPV 39 were analyzed by nested-PCR and sequencing.

Results

Our results revealed that all samples belonged to A lineage. Almost all sequences (98.6%) were classified in A1 sublineage and only one sample (1.4%) was A2 sub lineage.

Conclusions

Our findings showed that lineages A, sublineage A1, is dominant in Tehran, Iran. However, the small sample size was the most important limitations of this study. Further studies with larger sample size from different geographical regions of Iran are necessary to estimate the pathogenicity risk of HPV 39 variants in this population.
Evaluating risk detection methods to uncover ontogenic-mediated adverse drug effect mechanisms in children
Authors: Giangreco Nicholas P. , Tatonetti Nicholas P.
Published: July 2021

Background

Identifying adverse drugs effects (ADEs) in children, overall and within pediatric age groups, is essential for preventing disability and death from marketed drugs. At the same time, however, detection is challenging due to dynamic biological processes during growth and maturation, called ontogeny, that alter pharmacokinetics and pharmacodynamics. As a result, methodologies in pediatric drug safety have been limited to event surveillance and have not focused on investigating adverse event mechanisms. There is an opportunity to identify drug event patterns within observational databases for evaluating ontogenic-mediated adverse event mechanisms. The first step of which is to establish statistical models that can identify temporal trends of adverse effects across childhood.

Results

Using simulation, we evaluated a population stratification method (the proportional reporting ratio or PRR) and a population modeling method (the generalized additive model or GAM) to identify and quantify ADE risk at varying reporting rates and dynamics. We found that GAMs showed improved performance over the PRR in detecting dynamic drug event reporting across child development stages. Moreover, GAMs exhibited normally distributed and robust ADE risk estimation at all development stages by sharing information across child development stages.

Conclusions

Our study underscores the opportunity for using population modeling techniques, which leverage drug event reporting across development stages, as biologically-inspired detection methods for evaluating ontogenic mechanisms.
Tonsillectomy versus tonsillotomy for recurrent acute tonsillitis in children and adults (TOTO): study protocol for a randomized non-inferiority trial
Authors: Guntinas-Lichius Orlando , Geißler Katharina , Asendorf Thomas , Tostmann Ralf , Löhler Jan
Published: July 2021

Background

Tonsillectomy is one of the most frequently performed surgeries in children and young adults worldwide. For decades, tonsillectomy was the surgical treatment of choice for recurrent acute tonsillitis. Tonsillotomy was used in some countries as an alternative to tonsillectomy only for the treatment of obstructive sleep apnea in young children. In recent years, an increase of tonsillotomy also to treat recurrent acute tonsillitis can be observed. Therefore, the German Institute for Quality and Efficiency in Health Care (IQWiG) was commissioned by the Federal Joint Committee (G-BA) to investigate whether tonsillotomy offers advantages compared to tonsillectomy. The meta-analysis of the IQWiG including studies until 2016 revealed that the long-term benefits and harms of tonsillotomy compared to tonsillectomy are unclear. Consequently, the G-BA performed a European call for a clinical trial. A consortium of the German Professional Association of ENT-surgeons (BVHNO), the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery (DGHNO-KHC), and the Jena University Hospital were finally selected to perform the TOTO study.

Methods

TOTO is a multicenter, 1:1 two-arm, randomized non-blinded non-inferiority trial. Four hundred fifty-four patients ≥ 3 years of age will be randomly allocated to undergo either tonsillotomy or tonsillectomy as surgical treatment of recurrent acute tonsillitis. All participants will be followed up for a total of 24 months. The primary outcome is the number of sore throat days experienced over the 24-month follow-up.

Discussion

TOTO is designed to evaluate the effectiveness and efficiency of tonsillectomy versus tonsillectomy for the management of patients with recurrent acute tonsillitis. Tonsil disease and surgery have a major impact on preschool and school children as well as on economically active young adults, with individual and societal costs through loss of school visits, earnings, and productivity. If tonsillotomy is at least as effective as tonsillectomy but with reduced morbidity, this would reduce costs to the healthcare system and society.

Trial registration

German Clinical Trials Register DRKS00020823. Registered on 04 September 2020.
A cultural experience to support mental health in people aged 16–24 during the COVID-19 pandemic compared to a typical museum website: study protocol of an online randomised controlled trial
Authors: Syed Sheriff Rebecca J. , Vuorre Matti , Riga Evgenia , Przybylski Andrew K. , Adams Helen , Harmer Catherine J. , Geddes John R.
Published: July 2021

Background

Despite the high prevalence of common mental disorders in adolescents and young adults, and their association with poor health and socio-economic outcomes throughout the lifespan, many young people do not seek or receive help for such disorders. There is growing interest in the community sector in supporting mental health in young people; however, there is little by way of experimental research in this area. During the COVID-19 pandemic and lockdown, we designed an online cultural experience to reduce anxiety and depression and support mental health in people aged 16–24.

Methods/design

The O-ACE POP (Online Active Community Engagement Proof of Principle) study is a UK-based online randomised controlled trial of an online cultural experience named Ways of Being, involving human centred narratives and viewpoints, compared with a typical museum website (the Ashmolean Museum). We aim to compare efficacy on  affect,  symptoms of epression and anxiety, flourishing and loneliness as well as investigating potential mechanisms of action.

Discussion

The COVID-19 pandemic has provided a unique opportunity to design an innovative approach to supporting mental health in young adults. Findings derived from this study will allow us to evaluate the efficacy of this intervention and will inform the design of studies to further refine the resource and test it further.

Trial registration

ClinicalTrials.gov NCT04663594. Registered on 11 December 2020 (submitted in same form 27 November 2020). Protocol v1.0: 27 November 2020. Date recruitment began: 4 December 2020. Recruitment complete (estimate): February 2021
Effect of opposing needling on motor cortex excitability in healthy participants and in patients with post-stroke hemiplegia: study protocol for a single-blind, randomised controlled trial
Authors: Xu Mindong , Zi Yinyu , Wu Jianlu , Xu Nenggui , Lu Liming , Liu Jiahui , Yu Yanling , Mo Haofeng , Wen Weifeng , Tang Xiaorong , Fan Wenjuan , Zhang Yu , Liu Churong , Yi Wei , Wang Lin
Published: July 2021

Background

Opposing needling has an obvious curative effect in the treatment of post-stroke hemiplegia; however, the mechanism of the opposing needling in the treatment of post-stroke hemiplegia is still not clear. The purpose of this study is to investigate the effect of opposing needling on the excitability of primary motor cortex (M1) of healthy participants and patients with post-stroke hemiplegia, which may provide insight into the mechanisms of opposing needling in treating post-stroke hemiplegia.

Methods

This will be a single-blind, randomised, sham-controlled trial in which 80 healthy participants and 40 patients with post-stroke hemiplegia will be recruited. Healthy participants will be randomised 1:1:1:1 to the 2-Hz, 50-Hz, 100-Hz, and sham electroacupuncture groups. Patients with post-stroke hemiplegia will be randomised 1:1 to the opposing needling or conventional treatment groups. The M1 will be located in all groups by using neuroimaging-based navigation. The stimulator coil of transcranial magnetic stimulation (TMS) will be moved over the left and right M1 in order to identify the TMS hotspot, followed by a recording of resting motor thresholds (RMTs) and motor-evoked potentials (MEPs) of the thenar muscles induced by TMS before and after the intervention. The primary outcome measure will be the percent change in the RMTs of the thenar muscles at baseline and after the intervention. The secondary outcome measures will be the amplitude (μV) and latency (ms) of the MEPs of the thenar muscles at baseline and after the intervention.

Discussion

The aim of this trial is to explore the effect of opposing needling on the excitability of M1 of healthy participants and patients with post-stroke hemiplegia.

Trial registration

Chinese Clinical Trial Registry ChiCTR1900028138. Registered on 13 December 2019.
Abdominal angiostrongyliasis in the Americas: fifty years since the discovery of a new metastrongylid species, Angiostrongylus costaricensis
Authors: Rojas Alicia , Maldonado-Junior Arnaldo , Mora Javier , Morassutti Alessandra , Rodriguez Rubens , Solano-Barquero Alberto , Tijerino Anamariela , Vargas Marianela , Graeff-Teixeira Carlos
Published: July 2021

Angiostrongylus costaricensis is a zoonotic parasitic nematode described for the first time in 1971 by Pedro Morera and Rodolfo Céspedes in Costa Rica. This parasite causes an infection known as abdominal angiostrongyliasis, affecting mainly school-aged children and young adults. Infection with A. costaricensis has been associated with a myriad of rodent and mollusk species in the Americas and the Caribbean, as its natural hosts and reservoirs. In this commemorative review, we highlight the extensive research collected through a 50-year journey, which includes ecological, pathological, and molecular studies on A. costaricensis and its implicated disease. We also identify major knowledge gaps in its evolutionary history, the ecological role of imported and invasive mollusk species, and immune response. We propose that the advent of -omics analyses will allow us to gather novel information regarding A. costaricensis biology and infection dynamics, as well as to promote the design of much-needed sensitive and specific diagnostic tools.
Methylation status of nc886 epiallele reflects periconceptional conditions and is associated with glucose metabolism through nc886 RNAs
Authors: Marttila Saara , Viiri Leena E. , Mishra Pashupati P. , Kühnel Brigitte , Matias-Garcia Pamela R. , Lyytikäinen Leo-Pekka , Ceder Tiina , Mononen Nina , Rathmann Wolfgang , Winkelmann Juliane , Peters Annette , Kähönen Mika , Hutri-Kähönen Nina , Juonala Markus , Aalto-Setälä Katriina , Raitakari Olli , Lehtimäki Terho , Waldenberger Melanie , Raitoharju Emma
Published: July 2021

Background

Non-coding RNA 886 (nc886) is coded from a maternally inherited metastable epiallele. We set out to investigate the determinants and dynamics of the methylation pattern at the nc886 epiallele and how this methylation status associates with nc886 RNA expression. Furthermore, we investigated the associations between the nc886 methylation status or the levels of nc886 RNAs and metabolic traits in the YFS and KORA cohorts. The association between nc886 epiallele methylation and RNA expression was also validated in induced pluripotent stem cell (iPSC) lines.

Results

We confirm that the methylation status of the nc886 epiallele is mostly binomial, with individuals displaying either a non- or hemi-methylated status, but we also describe intermediately and close to fully methylated individuals. We show that an individual’s methylation status is associated with the mother’s age and socioeconomic status, but not with the individual’s own genetics. Once established, the methylation status of the nc886 epiallele remains stable for at least 25 years. This methylation status is strongly associated with the levels of nc886 non-coding RNAs in serum, blood, and iPSC lines. In addition, nc886 methylation status associates with glucose and insulin levels during adolescence but not with the indicators of glucose metabolism or the incidence of type 2 diabetes in adulthood. However, the nc886-3p RNA levels also associate with glucose metabolism in adulthood.

Conclusions

These results indicate that nc886 metastable epiallele methylation is tuned by the periconceptional conditions and it associates with glucose metabolism through the expression of the ncRNAs coded in the epiallele region.
Hypoxic preconditioning rejuvenates mesenchymal stem cells and enhances neuroprotection following intracerebral hemorrhage via the miR-326-mediated autophagy
Authors: Liu Jianyang , He Jialin , Ge Lite , Xiao Han , Huang Yan , Zeng Liuwang , Jiang Zheng , Lu Ming , Hu Zhiping
Published: July 2021

Background

Intracerebral hemorrhage (ICH) is a major public health concern, and mesenchymal stem cells (MSCs) hold great potential for treating ICH. However, the quantity and quality of MSCs decline in the cerebral niche, limiting the potential efficacy of MSCs. Hypoxic preconditioning is suggested to enhance the survival of MSCs and augment the therapeutic efficacy of MSCs in ICH. MicroRNAs (miRNAs) are known to mediate cellular senescence. However, the precise mechanism by which miRNAs regulate the senescence of hypoxic MSCs remains to be further studied. In the present study, we evaluated whether hypoxic preconditioning enhances the survival and therapeutic effects of olfactory mucosa MSC (OM-MSC) survival and therapeutic effects in ICH and investigated the mechanisms by which miRNA ameliorates hypoxic OM-MSC senescence.

Methods

In the in vivo model, ICH was induced in mice by administration of collagenase IV. At 24 h post-ICH, 5 × 105 normoxia or hypoxia OM-MSCs or saline was administered intracerebrally. The behavioral outcome, neuronal apoptosis, and OM-MSC survival were evaluated. In the in vitro model, OM-MSCs were exposed to hemin. Cellular senescence was examined by evaluating the expressions of P16INK4A, P21, P53, and by β-galactosidase staining. Microarray and bioinformatic analyses were performed to investigate the differences in the miRNA expression profiles between the normoxia and hypoxia OM-MSCs. Autophagy was confirmed using the protein expression levels of LC3, P62, and Beclin-1.

Results

In the in vivo model, transplanted OM-MSCs with hypoxic preconditioning exhibited increased survival and tissue-protective capability. In the in vitro model, hypoxia preconditioning decreased the senescence of OM-MSCs exposed to hemin. Bioinformatic analysis identified that microRNA-326 (miR-326) expression was significantly increased in the hypoxia OM-MSCs compared with that of normoxia OM-MSCs. Upregulation of miR-326 alleviated normoxia OM-MSC senescence, whereas miR-326 downregulation increased hypoxia OM-MSC senescence. Furthermore, we showed that miR-326 alleviated cellular senescence by upregulating autophagy. Mechanistically, miR-326 promoted the autophagy of OM-MSCs via the PI3K signaling pathway by targeting polypyrimidine tract-binding protein 1 (PTBP1).

Conclusions

Our study shows that hypoxic preconditioning delays OM-MSC senescence and augments the therapeutic efficacy of OM-MSCs in ICH by upregulating the miR-326/PTBP1/PI3K-mediated autophagy.
hucMSC-derived exosomes attenuate colitis by regulating macrophage pyroptosis via the miR-378a-5p/NLRP3 axis
Authors: Cai Xiu , Zhang Zhi-yu , Yuan Jin-tao , Ocansey Dickson Kofi Wiredu , Tu Qiang , Zhang Xu , Qian Hui , Xu Wen-rong , Qiu Wei , Mao Fei
Published: July 2021

Background

Human umbilical cord mesenchymal stem cell (hucMSC)-derived exosomes are recognized as novel cell-free therapeutic agents for inflammatory bowel disease (IBD), a condition caused by dysregulated intestinal mucosal immunity. In this event, macrophage pyroptosis, a process of cell death following the activation of NLRP3 (NOD-like receptor family, pyrin domain-containing 3) inflammasomes, is believed to partially account for inflammatory reactions. However, the role of macrophage pyroptosis in the process of hucMSC-derived exosomes alleviating colitis remains unknown. This study aimed at exploring the therapeutic effect and mechanism of hucMSC-derived exosomes on colitis repair.

Methods

In vivo, we used BALB/c mice to establish a dextran sulfate sodium (DSS)-induced colitis model and administrated hucMSC-derived exosomes intravenously to estimate its curative effect. Human myeloid leukemia mononuclear (THP-1) cells and mouse peritoneal macrophages (MPMs) were stimulated with lipopolysaccharides (LPS) and Nigericin to activate NLRP3 inflammasomes, which simulated an inflammation environment in vitro. A microRNA mimic was used to verify the role of miR-378a-5p/NLRP3 axis in the colitis repair.

Results

hucMSC-derived exosomes inhibited the activation of NLRP3 inflammasomes in the mouse colon. The secretion of interleukin (IL)-18, IL-1β, and Caspase-1 cleavage was suppressed, resulting in reduced cell pyroptosis. The same outcome was observed in the in vitro cell experiments, where the co-culture of THP-1 cells and MPMs with hucMSC-derived exosomes caused decreased expression of NLRP3 inflammasomes and increased cell survival. Furthermore, miR-378a-5p was highly expressed in hucMSC-derived exosomes and played a vital function in colitis repair.

Conclusion

hucMSC-derived exosomes carrying miR-378a-5p inhibited NLRP3 inflammasomes and abrogated cell pyroptosis to protect against DSS-induced colitis.
Dental health of preschool children after two-years of a supervised tooth brushing program in Southern Israel
Authors: Natapov Lena , Dekel Dan , Pikovsky Vadim , Zusman Shlomo Paul
Published: July 2021

Background

Supervised tooth brushing is an important part of leading national oral health improvement programs in different countries.

With the cessation of water fluoridation in 2014, a new program was immediately required to provide community-based caries prevention, especially amongst young children.

The aim of this study was to determine whether a supervised tooth brushing program (STBP) in kindergartens could reduce dental caries amongst preschool children, when compared with children from the same community who did not participate in the program. The study was performed 2 years after the start of the program.

Methods

Two Jewish and two Arab local authorities (one participating and one control) were randomly chosen. In each local authority, 4 kindergartens (children aged 5) were randomly chosen, giving a total of 16 kindergartens. Children in the intervention group brushed once daily at kindergartens, with fluoridated toothpaste, for two school- years. All the children were examined using the WHO Oral Health Survey Methods Ed.4.

Results

Two hundred eighty-three five-year-old children were examined, 157 of them Jewish (86 participants in STBP, 71 non-participants) and 126 Arab (59 vs 67 respectively). Among Jewish children, the fraction of untreated decayed teeth was 61% in the participant group and 65% for non-participants, and amongst the Arab children 69% vs. 90% respectively. The fraction of treated decayed teeth for the participant group was 37% compared to 29% for the non-participants among Jewish children, whilst for the Bedouin group it was 23% vs. 8% respectively.

Conclusions

After 2 years, supervised tooth brushing with fluoride toothpaste shows a favorable effect. This study suggests that dental health of children participating in STBP was better than the control group. Fewer carious teeth and more treated carious lesions were recorded in this group. This program can be applied to low SES communities nationwide.

Guidelines for fluoride concentration in toothpaste for children should be re-considered based on high caries levels.
Dynamical analysis of a stochastic three-species predator–prey system with distributed delays
Authors: Zhao Jinxing , Shao Yuanfu
Published: July 2021

A stochastic two-prey one-predator system with distributed delays is proposed in this paper. Firstly, applying the linear chain technique, we transform the predator–prey system with distributed delays to an equivalent system with no delays. Then, by use of the comparison method and the inequality technique, we investigate the stability in mean and extinction of species. Further, by constructing some suitable functionals, using M-matrix theory and three important lemmas, we establish sufficient conditions assuring the existence of distribution and the attractivity of solutions. Finally, some numerical simulations are given to illustrate the main results.
Implications of food-for-work programs for consumption and production diversity: Evidence from the Tigray Region of Ethiopia
Authors: Debela Bethelhem Legesse , Shively Gerald E. , Holden Stein T.
Published: July 2021

Food-based transfer programs have the potential to change diets or alter basic crop mixes. This study empirically investigates the associations between participating in food-for-work (FFW) programs and the diversity of food consumption and production. Four waves of panel data from the Tigray Region of Northern Ethiopia, covering the period 2001–2010, are used to estimate a series of panel data regressions. A dose-response model is used to measure how the intensity of FFW participation aligns with dietary outcomes. Results show that FFW participants had greater household dietary diversity compared with non-participants, with an average magnitude equivalent to one-fifth of a standard deviation in the food variety score. When items directly provided by the FFW program are excluded from the variety score, the overall effect is statistically weaker, but similar in sign and magnitude, suggesting modest “crowding in” of dietary diversity from FFW participation. FFW participation was not correlated with changes in production diversity, suggesting that the labor demands of the program did not alter crop choice. Findings have relevance for interventions that aim to improve food security and promote dietary quality in low-income populations.
A systematic review of enteral feeding by nasogastric tube in young people with eating disorders
Authors: Hindley Kristen , Fenton Clare , McIntosh Jennifer
Published: July 2021

Background

Adolescents with severe restrictive eating disorders often require enteral feeding to provide lifesaving treatment.

Nasogastric feeding (NG) is a method of enteral nutrition often used in inpatient settings to treat medical instability, to supplement poor oral intake or to increase nutritional intake. This systematic review sets out to describe current practice of NG in young people with eating disorders.

Methods

A systematic review following PRISMA guidelines was conducted by searching AMED, EMBASE and MEDLINE databases from 2000 to 2020. Inclusion terms were: enteral feeding by nasogastric tube, under 18 years, eating disorders, and primary research. Exclusion terms: psychiatric disorders other than eating disorders; non-primary research; no outcomes specific to NG feeding and participants over 18 years. Titles and abstracts were screened by all authors before reviewing full length articles. Quality assessment, including risk of bias, was conducted by all authors.

Results

Twenty-nine studies met the full criteria. 86% of studies were deemed high or medium risk of bias due to the type of study: 34.4% retrospective cohort and 10.3% RCT; 17.2% were qualitative. Studies identified 1) a wide range of refeeding regimes depending on country, settings, and the reason for initiation; 2) standard practice is to introduce Nasogastric feeds (NG) if medically unstable or oral intake alone is inadequate; 3) NG may enable greater initial weight gain due to increased caloric intake; 4) there are 3 main types of feeding regime: continuous, nocturnal and bolus; 5) complications included nasal irritation, epistaxis, electrolyte disturbance, distress and tube removal; 6) where NG is routinely implemented to increase total calorie intake, length of stay in hospital may be reduced; however where NG is implemented in correlation to severity of symptoms, it may be increased; 7) both medical and psychiatric wards most commonly report using NG in addition to oral intake.

Conclusions

NG feeding is a safe and efficacious method of increasing total calorie intake by either supplementing oral intake or continuously. There are currently no direct comparisons between continuous, nocturnal or bolus regimes, which may be used to direct future treatment for YP with ED.