bluuebunny/crossref_metadata_2025 huggingface dataset:
Differences in Mechanisms of Steroid Therapy and Olfactory Training for Olfactory Loss in Mice
Authors: Kim Boo-Young , Park Ju Yeon , Kim EuiJin
Published: June 2020

Objective

Steroid therapy and olfactory training are common treatments for olfactory loss. Systemic steroid treatment is the most effective approach for treating sinonasal olfactory loss. Olfactory training is typically effective for treating sensorineural olfactory loss. However, the differences in mechanisms of steroid therapy and olfactory training for olfactory dysfunction are unclear. The aim of this study was thus to evaluate the differences in mechanisms of olfactory training and steroid therapy.

Subjects and Methods

Mice in each group were administered 3-methylindole at a dose of 300 mg/kg. Olfactory function was evaluated with a food-finding test once a week. The olfactory neuroepithelium was harvested for histologic examination and protein analysis. Subsequently, data analysis, gene ontology and pathway analysis, quantitative real-time polymerase chain reaction of mRNA, and western blot analysis were conducted.

Results

Mice were divided into four groups according to treatment. Control, anosmia, training, and steroid groups resumed food-finding. MMP27, CCL22 and IL18rap mRNA expression were significantly increased in the training group compared to that in the steroid group. IL1R2 mRNA expression was significantly higher in the olfactory neuroepithelium of steroid-treated mice than in that of the training group mice.

Conclusions

Steroid therapy improved olfactory function via anti-inflammatory effects, unlike olfactory training which involved cell regeneration and tissue remodeling. Protein and gene analyses revealed that steroid therapy and olfactory training are underpinned by distinct mechanisms. Selection of the most appropriate treatment will be dependent on the cause of olfactory loss.
Effect of Exposure to Cats and Dogs on the Risk of Asthma and Allergic Rhinitis: A Systematic Review and Meta-analysis
Authors: Gao Xiaoping , Yin Mei , Yang Pei , Li Xia , Di Lingling , Wang Wei , Cui Hua , Yan Xiaohui , Liu Jing
Published: June 2020

Background

Controversies persist regarding whether exposure to cat or dog increases the risk of asthma and allergic rhinitis.

Objective

This meta-analysis aimed to assess the associations between exposure to cats or dogs and the development of asthma and allergic rhinitis.

Methods

A systematic review was performed to identify case-control and cohort studies before May 2019, evaluating the association between exposure to cats and dogs and the risk of asthma and rhinitis. The risk of bias was assessed using the Newcastle–Ottawa Scale. The odds ratios (ORs) and risk ratios (RRs) were pooled for case-control and cohort studies, respectively. Subgroup analyses were performed on prespecified study-level characteristics.

Results

The meta-analysis of 34 cohort studies showed a protective role of exposure to cats [RR: 0.88, 95% confidence interval (CI): 0.77–0.99] or dogs (RR: 0.85, 95% CI: 0.73–0.97) in the development of asthma. The subgroup analysis of birth cohort (RR: 0.74, 95% CI: 0.56–0.93) and children population (RR: 0.83, 95% CI: 0.70–0.96) also suggested a favorable role of exposure to dogs in the development of asthma. Pooled evidence from 13 case-control studies indicated no significant impact of cats (OR: 1.66, 95% CI: 0.39–2.94) and dogs (OR: 1.22, 95% CI: 0.92–1.52) on the development of asthma. A pooled analysis of five cohort studies showed a favorable effect of exposure to cats (RR: 0.60, 95% CI: 0.33–0.86) or dogs (RR: 0.68, 95% CI 0.44–0.90) on the development of allergic rhinitis.

Conclusion

The findings indicated a protective effect of exposure to cats and dogs, especially ownership, on the development of asthma and allergic rhinitis.
Predictors of Disease Control After Endoscopic Sinus Surgery Plus Long-Term Local Corticosteroids in CRSwNP
Authors: De Corso Eugenio , Settimi Stefano , Tricarico Laura , Mele Dario Antonio , Mastrapasqua Rodolfo Francesco , Di Cesare Tiziana , Salvati Antonio , Trozzi Lucrezia , De Vita Carla , Romanello Matteo , Paludetti Gaetano , Galli Jacopo
Published: June 2020

Background

in the era of new biological agents it is important to identify patients who may benefit from conventional therapies such as endoscopic sinus surgery (ESS) plus long-term local corticosteroids from those with patterns of inflammation that are more difficult to control post-operatively and who may benefit from other therapies.

Objective

determine if preoperative assessment of type and grade of inflammation and clinical factors can predict disease control with ESS plus long-term local corticosteroids in chronic rhinosinusitis with nasal polyps (CRSwNP).

Methods

Eighty patients treated with ESS plus mometasone-furoate 200 μg BID for CRSwNP and followed for at least 1 year were enrolled (November 2017–December 2018) in this prospective observational study. Type and grade of inflammation were evaluated preoperatively by nasal cytology. Based on cellular pattern, patients were grouped as neutrophilic (n = 20), eosinophilic (n = 38), or mixed eosinophil-neutrophilic (n = 22). SNOT-22 and Lund-Kennedy Endoscopic Score were evaluated at baseline and at 3, 6, 9, and 12 months after surgery and used to define disease control.

Results

The cumulative probability of remaining free of significant modification of endoscopic score (Lund-Kennedy Endoscopic Score >2) at 3, 6, 9, and 12 months was 0.84, 0.76, 0.71, and 0.68, respectively. At 12-month postoperative evaluation good disease control was observed in 54 of 80 patients (67.5%). Compared to those with good post-operative disease control, those with poor control had a significantly higher pre-operative mean count of eosinophils and neutrophils (p < 0.05). The preoperative inflammatory pattern was associated with relative risk of poor control: neutrophilia (RR: 3.10; CI:1.24–7.71), eosinophilia (RR:8.42; CI:2.72–15.12), and mixed eosinophilic and neutrophilic (RR:25.11; CI:19.41–30.01). We also confirmed that asthma, allergy, blood eosinophilia, and ASA triad could predict poor control.

Conclusions

The type and load of inflammation evaluated preoperatively and selected clinical factors can predict poor control of CRSwNP treated with ESS and local corticosteroids.
The power divide: Mobile communication in Los Angeles’ Skid Row
Authors: Galperin Hernan , Bar François , Nguyen Hoan
Published: June 2020

This study explores mobile phone use among people experiencing homelessness in downtown Los Angeles. It explores usage patterns and connectivity challenges, and how these affect access to social services as well as opportunities for information seeking, skills building, and social capital formation. To characterize the unreliable conditions under which this population uses mobile phones, we introduce the concept of access instability to capture not simply the obstacles to technology access imposed by poverty but more broadly those stemming from a combination of poverty, housing insecurity, and discrimination. The study is primarily based on a survey among adults experiencing homelessness (or at risk of) conducted over a span of 5 months, complemented by findings from a participatory research intervention carried out in collaboration with a local advocacy organization. Among the key findings is that reliable access to electrical power represents a fundamental yet understudied barrier to mobile use among marginalized populations, including (but not limited to) those experiencing homelessness. Lacking a safe and reliable place to charge their devices, the unstably housed must activate coping strategies that limit digital engagement and constrain use. Overall, access instability disrupts the expectation of constant reachability that underpins modern economic and social relations. Ultimately, this narrows pathways out of homelessness by limiting the ability to gain or sustain employment, to connect with healthcare providers and other vital resources, and to maintain networks of personal support.
Pediatric pharmaceutical care with anti-infective medication in a patient with acute hematogenous osteomyelitis caused by methicillin-resistant Staphylococcus aureus
Authors: Lv Chanmei , Lv Jiantao , Liu Yue , Liu Qifeng , Zou Dongna
Published: June 2020

The infection of the bone marrow system caused by methicillin-resistant Staphylococcus aureus (MRSA) leads to a variety of common diseases which usually occur in children under the age of 12. Vancomycin (VCM) is the first-line therapy for MRSA-caused serious infections such as bacteremia, infective endocarditis, osteomyelitis, meningitis, pneumonia, and severe skin and soft-tissue infection (e.g. necrotizing fasciitis) with a recommended dosage of 15–20 μg/mL. In this study, we first report a case of a child with MRSA-caused osteomyelitis who was successfully cured by VCM at a concentration of 4.86 μg/mL. VCM’s clinical daily dose of more than 4 g was of concern in light of recent evidence suggesting the increased risks of nephrotoxicity and red man syndrome when Cmin ⩾15 μg/mL and doses ⩾10 mg/kg in children. As far as we know, this is the first report on the lower dose of VCM in children with MRSA osteomyelitis.
Blue bioeconomy localities at the margins: Reconnecting Norwegian seaweed farming and Finnish small-scale lake fisheries with blue policies
Authors: Albrecht Moritz , Lukkarinen Jani
Published: June 2020

The blue bioeconomy is gaining momentum in EU policy debate and various national government strategies as a pathway towards a more sustainable society. Linked to the circularity of economic processes, it combines the promise of (regional) economic development with a sustainable, bio-based transition focused on increased and novel utilisation of aquatic resources. Nonetheless, portrayed as a holistic approach, the political visions of blue bioeconomy reside predominantly in marine environments with little integration of freshwater perspectives or alternative development paths. Rooted in concepts of policy mobility, assembling processes and the positionalities of involved entities, this paper displays two regionally embedded blue bioeconomy developments – Norwegian coastal seaweed farming and Finnish lake fisheries – and their spatially diverse reconnections with national and international policy narratives. By framing a freshwater and a coastal marine case, and their spatial reconnections with an overarching yet diversely translated policy realm, the paper taps into the multiple ontologies of water in blue bioeconomy governance and presents initial empirical and methodological steps towards a relational understanding of its governance processes. Based on four key topical reconnections, the article points to a variety of challenging mismatches between policy narratives, local development processes and potentials. It also suggests conceptual and methodological implications of this approach for further research into “blue” resource governance.
Polymeric nanocomposite via electrospinning: Assessment of morphology, physical properties and applications
Authors: Kausar Ayesha
Published: June 2020

Polymeric nanofibers have appeared as unique one-dimensional nanomaterials. Nanofibers possess exceptionally high specific surface area and essential properties. Various polymeric nanofibers and nanocomposite nanofibers have been developed using thermoplastic and thermosetting matrices and organic and inorganic nanoparticles. This review documents the worth of nanofiber technology regarding the synthesis, morphology, physical properties, and applications of the nanostructures. The nanofiber surface morphology and diameter directly influence the physical characteristics such as electrical conductivity, mechanical properties, and thermal stability. Fiber processing techniques and related parameters also affect their texture and properties. In this regard, electrospinning is frequently used to form polymeric nanofibers and nanocomposite nanofibers. Electrospun nanofibers having large surface area and excellent fiber orientation, alignment, and morphology. The polymer nanocomposites with different nanofillers (carbon nanotube, graphene, carbon nanofibers, and other nanoparticles) have been processed into high performance electrospun nanofibers. Electrospun nanomaterials have been applied in engineered structures, nanofibrous membranes, electronic devices, tissue engineering, drug delivery, antibacterial materials and other biomedical applications. Henceforth, this is a comprehensive review on physical characteristics, morphology, processing aspects, and application areas for polymeric and nanocomposite nanofibers.
Molecular landscape and clonal architecture of adult myelodysplastic/myeloproliferative neoplasms
Authors: Palomo Laura , Meggendorfer Manja , Hutter Stephan , Twardziok Sven , Ademà Vera , Fuhrmann Irene , Fuster-Tormo Francisco , Xicoy Blanca , Zamora Lurdes , Acha Pamela , Kerr Cassandra M. , Kern Wolfgang , Maciejewski Jaroslaw P. , Solé Francesc , Haferlach Claudia , Haferlach Torsten
Published: June 2020

More than 90% of patients with myelodysplastic/myeloproliferative neoplasms (MDSs/MPNs) harbor somatic mutations in myeloid-related genes, but still, current diagnostic criteria do not include molecular data. We performed genome-wide sequencing techniques to characterize the mutational landscape of a large and clinically well-characterized cohort including 367 adults with MDS/MPN subtypes, including chronic myelomonocytic leukemia (CMML; n = 119), atypical chronic myeloid leukemia (aCML; n = 71), MDS/MPN with ring sideroblasts and thrombocytosis (MDS/MPN-RS-T; n = 71), and MDS/MPN unclassifiable (MDS/MPN-U; n = 106). A total of 30 genes were recurrently mutated in ≥3% of the cohort. Distribution of recurrently mutated genes and clonal architecture differed among MDS/MPN subtypes. Statistical analysis revealed significant correlations between recurrently mutated genes, as well as genotype-phenotype associations. We identified specific gene combinations that were associated with distinct MDS/MPN subtypes and that were mutually exclusive with most of the other MDSs/MPNs (eg, TET2-SRSF2 in CMML, ASXL1-SETBP1 in aCML, and SF3B1-JAK2 in MDS/MPN-RS-T). Patients with MDS/MPN-U were the most heterogeneous and displayed different molecular profiles that mimicked the ones observed in other MDS/MPN subtypes and that had an impact on the outcome of the patients. Specific gene mutations also had an impact on the outcome of the different MDS/MPN subtypes, which may be relevant for clinical decision-making. Overall, the results of this study help to elucidate the heterogeneity found in these neoplasms, which can be of use in the clinical setting of MDS/MPN.
Impacts of drug resistance mutations on the structural asymmetry of the HIV-2 protease
Authors: Laville Pierre , Fartek Sandrine , Cerisier Natacha , Flatters Delphine , Petitjean Michel , Regad Leslie
Published: June 2020

Background

Drug resistance is a severe problem in HIV treatment. HIV protease is a common target for the design of new drugs for treating HIV infection. Previous studies have shown that the crystallographic structures of the HIV-2 protease (PR2) in bound and unbound forms exhibit structural asymmetry that is important for ligand recognition and binding. Here, we investigated the effects of resistance mutations on the structural asymmetry of PR2. Due to the lack of structural data on PR2 mutants, the 3D structures of 30 PR2 mutants of interest have been modeled using an in silico protocol. Structural asymmetry analysis was carried out with an in-house structural-alphabet-based approach.

Results

The systematic comparison of the asymmetry of the wild-type structure and a large number of mutants highlighted crucial residues for PR2 structure and function. In addition, our results revealed structural changes induced by PR2 flexibility or resistance mutations. The analysis of the highlighted structural changes showed that some mutations alter protein stability or inhibitor binding.

Conclusions

This work consists of a structural analysis of the impact of a large number of PR2 resistant mutants based on modeled structures. It suggests three possible resistance mechanisms of PR2, in which structural changes induced by resistance mutations lead to modifications in the dimerization interface, ligand recognition or inhibitor binding.
The origins and developments of sulfation-prone tyrosine-rich and acidic N- and C-terminal extensions of class ll and lll small leucine-rich repeat proteins shed light on connective tissue evolution in vertebrates
Authors: Jensen Morten M. , Karring Henrik
Published: June 2020

Background

Small leucine-rich repeat protein (SLRP) family members contain conserved leucine-rich repeat motifs flanked by highly variable N- and C-terminal regions. Most class II and III SLRPs have tyrosine-rich N-terminal regions and some of these are sulfated. However, the evolutionary origin and conservation of the tyrosine-rich and acidic terminal regions remain undetermined. In this study, we present the most comprehensive multiple sequence alignment (MSA) analyses of all eight class II and III SLRPs to date. Based on the level of conservation of tyrosine residues and adjacent sequences, we predict which tyrosine residues are most likely to be sulfated in the terminal regions of human class II and III SLRPs.

Results

Using this novel approach, we predict a total of 22 tyrosine sulfation sites in human SLRPs, of which only 8 sites had been experimentally identified in mammals. Our analyses suggest that sulfation-prone, tyrosine-rich and acidic terminal regions of the class II and III SLRPs emerged via convergent evolution at different stages of vertebrate evolution, coinciding with significant evolutionary events including the development of endochondral bones and articular cartilage, the aquatic to terrestrial transition, and the formation of an amnion.

Conclusions

Our study suggests that selective pressures due to changes in life conditions led to the formation of sulfotyrosine-rich and acidic terminal regions. We believe the independent emergence and evolution of sulfotyrosine-rich and acidic N- and C-terminal regions have provided each class II and III SLRP member with novel vital functions required to develop new specialized extracellular matrices and tissues in vertebrate species.
Intravenous lidocaine to prevent endothelial dysfunction after major abdominal surgery: a randomized controlled pilot trial
Authors: Pustetto Marco , Goldsztejn Nicolas , Touihri Karim , Engelman Edgard , Ickx Brigitte , Van Obbergh Luc
Published: June 2020

Background

Major abdominal surgery is associated with endothelial glycocalyx disruption. The anti-inflammatory effects of lidocaine were recently associated with endothelial barrier protection.

Methods

This was a single-centre, parallel group, randomized, controlled, double blind, pilot trial. Forty adult patients scheduled for major abdominal surgery were included between December 2016 and March 2017 in the setting of a University Hospital in Brussels (Belgium); reasons for non-inclusion were planned liver resection and conditions associated to increased risk of local anesthetics systemic toxicity. Patients were randomized to receive either lidocaine by continuous intravenous administration or an equivalent volume of 0.9% saline.

The primary endpoint was the postoperative syndecan-1 concentration (difference between groups). Near-infrared spectroscopy of the thenar eminence in association with the vascular occlusion test, and contemporary analysis of flow-mediated dilation of the brachial artery were the secondary outcomes, along with haemodynamic data. Blood samples and data were collected before surgery (T0), and at 1–3 h (T1) and 24 h (T2) post-surgery.

Results

Syndecan-1 concentration increased significantly post-surgery (P < 0.001), but without any difference between groups. The near-infrared spectroscopy-derived and flow-mediated dilation-derived variables showed minor changes unrelated to group assignment. Compared with the placebo group, the intervention group had a significantly lower peri-operative mean arterial pressure and cardiac index, despite equally conducted goal-directed haemodynamic management. Postoperative lactate concentrations were similar between groups.

Conclusions

Lidocaine failed to have any effect on endothelial function. Since in comparisons to other types of clinical situations, syndecan-1 was only slightly upregulated, endothelial dysfunction after major abdominal surgery might be overestimated.

Trial registration

« ISRCTN Registry » identifier: ISRCTN63417725. Date: 15/06/2020. Retrospectively registered.
Barriers and facilitators of medicines reconciliation at transitions of care in Ireland – a qualitative study
Authors: Redmond Patrick , Munir Khalid , Alabi Oludare , Grimes Tamasine , Clyne Barbara , Hughes Carmel , Fahey Tom
Published: June 2020

Background

Medication error at transitions of care is common. The implementation of medicines reconciliation processes to improve this issue has been recommended by many regulatory and safety organisations. The aim of this study was to gain insight from healthcare professionals on the barriers and facilitators to the medicines reconciliation implementation process.

Methods

Semi-structured interviews were conducted in Ireland with a wide range of healthcare professionals (HCPs) involved with medicines reconciliation at transitions of care. Thematic analysis was undertaken using an adaptation of a combined theoretical framework of Grol, Cabana and Sluisveld to classify the barriers and facilitators to implementation of medicines reconciliation.

Results

Thirty-five participants were interviewed, including eleven community pharmacists (CPs), eight hospital pharmacists (HPs), nine hospital consultants (HCs), five general practitioners (GPs), and two non-consultant hospital doctors (NCHDs). Themes were categorized into barriers and facilitators. Barriers included resistance from existing professional cultures, staff interest and training, poor communication and minimal information and communications technology (ICT) support. Solutions (facilitators) suggested included supporting effective multidisciplinary teams, greater involvement of pharmacists in medicines reconciliation, ICT solutions (linked prescribing databases, decision support systems) and increased funding to provide additional (e.g. admission and discharge reconciliation) and more advanced services (e.g. community pharmacist delivered medicines use review).

Conclusions

Medicines reconciliation is advocated as a solution to the known problem of medication error at transitions of care. This study identifies the key challenges and potential solutions that policy makers, managers and HCPs should consider when reviewing the practices and processes of medicines reconciliation in their own organisations.
Pre-stroke adherence to a Mediterranean diet pattern is associated with lower acute ischemic stroke severity: a cross-sectional analysis of a prospective hospital-register study
Authors: Lavados Pablo M. , Mazzon Enrico , Rojo Alexis , Brunser Alejandro M. , Olavarría Verónica V.
Published: June 2020

Background

High adherence to a Mediterranean Diet is associated with reduced incidence and mortality of acute ischemic stroke (AIS) but may also be associated with severity. Our purpose was to investigate the association of adherence to a Mediterranean diet and severity in a prospective hospital register of AIS patients.

Methods

We included AIS patients admitted from February 2017 to July 2019. All were assessed by a neurologist with a standard stroke protocol, including NIHSS. Adherence to Mediterranean diet was prospectively measured by the 14-point Mediterranean Diet Adherence Screener (MEDAS) and defined as low (0–6 points) or high (7–14 points). Demographic and clinical characteristics were compared by group with univariate analysis. A Generalized Linear Model (GLM) was used to investigate the association of admission NIHSS as a continuous ordinal variable and an ordinal logistic regression (OLR) analysis to determine the independent association of the NIHSS quartiles with adherence to Mediterranean diet.

Results

Three hundred sixty-eight patients were included, mean age 68.3 (17.7), 158 (42.9%) females. The median NIHSS score was 3 (IQR 1–9) and the median MEDAS score was 6 (IQR 4.5–8). Patients with high MEDAS scores had significantly lower; admission NIHSS scores, sedentary lifestyle, body mass index, total and LDL cholesterol levels, but higher alcohol consumption. After adjustments, high adherence to Mediterranean diet remained independently associated with lower stroke severity both in the GLM (β coefficient = − 0.19,p = 0.01) and in the OLR model (OR for lower NIHSS quartiles 0.6 (95% CI 0.37–0.98,p = 0.04).

Conclusions

Higher pre-stroke adherence to a Mediterranean diet is independently associated with lower AIS severity.
Trends in psychiatric diagnoses, medications and psychological therapies in a large Swedish region: a population-based study
Authors: Forslund T. , Kosidou K. , Wicks S. , Dalman C.
Published: June 2020

Background

Health services utilization for mental health disorders is reported to increase sharply in many countries. The aim of this study was to report trends in all aspects of mental health care utilization in a total population sample.

Methods

Repeated cross-sectional register study of the Stockholm Region (VAL) including both primary and secondary care. Trends in the proportion of adults in the total population of Stockholm Region with a recorded ICD-10 psychiatric diagnosis or psychological therapy during 2007–2017 as well as claims of psychiatric medication from 2011 were calculated.

Results

The proportion of adults utilizing any mental health care increased from 13.2% in 2011 to 16.1% in 2017. In 2017, 49.3% were treated in primary care, 32.2% in secondary care and 18.5% were jointly managed. The increase was most pronounced in younger adults. Women were more likely to receive mental health care than men in all ages. Medication decreased from 71.0 to 67.7%, while psychological therapy increased from 33.1 to 37.6%. The use of psychiatric medication increased with age while psychological therapy decreased. All time trends were statistically significant (p < .0001).

Conclusion

Care for mental health disorders has been increasing mainly in primary care and was delivered to one in seven adult individuals in 2017. Interventions are needed to address the growing burden of mental health disorders while avoiding overtreatment.
An observational study of self-monitoring in ad hoc health care teams
Authors: Hautz Stefanie C. , Oberholzer Daniel L. , Freytag Julia , Exadaktylos Aristomenis , Kämmer Juliane E. , Sauter Thomas C. , Hautz Wolf E.
Published: June 2020

Background

Working in ad hoc teams in a health care environment is frequent but a challenging and complex undertaking. One way for teams to refine their teamwork could be through post-resuscitation reflection and debriefing. However, this would require that teams have insight into the quality of their teamwork. This study investigates (1) the accuracy of the self-monitoring of ad hoc resuscitation teams and their leaders relative to external observations of their teamwork and (2) the relationship of team self-monitoring and external observations to objective performance measures.

Methods

We conducted a quantitative observational study of real-world ad hoc interprofessional teams responding to a simulated cardiac arrest in an emergency room. Teams consisting of residents, consultants, and nurses were confronted with an unexpected, simulated, standardized cardiac arrest situation. Their teamwork was videotaped to allow for subsequent external evaluation on the team emergency assessment measure (TEAM) checklist. In addition, objective performance measures such as time to defibrillation were collected. All participants completed a demographic questionnaire prior to the simulation and a questionnaire tapping their perceptions of teamwork directly after it.

Results

22 teams consisting of 115 health care professionals showed highly variable performance. All performance measures intercorrelated significantly, with the exception of team leaders’ evaluations of teamwork, which were not related to any other measures. Neither team size nor cumulative experience were correlated with any measures, but teams led by younger leaders performed better than those led by older ones.

Conclusion

Team members seem to have better insight into their team’s teamwork than team leaders. As a practical consequence, the decision to debrief and the debriefing itself after a resuscitation should be informed by team members, not just leaders.
Enterocytozoon bieneusi in donkeys from Xinjiang, China: prevalence, molecular characterization and the assessment of zoonotic risk
Authors: Zhao Aiyun , Zhang Ying , Wang Wen , Jing Bo , Xing Jinming , Tao Dayong , Zhao Wei , Qi Meng
Published: June 2020

Background

Enterocytozoon bieneusi, a zoonotic pathogen, has the potential to infect both immunocompromised and immunocompetent humans. It is found in large number of animals; however, not much is known regarding its prevalence in equine animals, particularly donkeys. This is the first molecular epidemiological evaluation of E. bieneusi in 178 free-ranging donkeys from five countrysides; and 502 farmed donkeys from 18 farms in 12 cities of Xinjiang, China by Nested PCR.

Results

E. bieneusi was detected in 2.5% (17/680) donkeys, with 2.6% (13/502) in farmed and 2.2% (4/178) in free-ranging ones. Sequence analysis identified eight ITS genotypes, all belonging to zoonotic Groups 1 or 2, including six known genotypes: horse1 (n = 5), D (n = 3), NCD-2 (n = 3), BEB6 (n = 2), BEB4 (n = 1), and NIAI (n = 1); and two new genotypes: XJD1 (n = 1) and XJD2 (n = 1).

Conclusions

This is the first report confirming the presence of E. bieneusi in donkeys in Xinjiang, China, and indicates the possibility of zoonotic transmission of this pathogenic parasite.
Assays for quantification of male and female gametocytes in human blood by qRT-PCR in the absence of pure sex-specific gametocyte standards
Authors: Wang Claire Y. T. , Ballard Emma , Llewellyn Stacey , Marquart Louise , Bousema Teun , McCarthy James S. , Collins Katharine A.
Published: June 2020

Background

Malaria transmission from humans to Anopheles mosquitoes requires the presence of gametocytes in human peripheral circulation, and the dynamics of transmission are determined largely by the density and sex ratio of the gametocytes. Molecular methods are thus employed to measure gametocyte densities, particularly when assessing transmission epidemiology and the efficacy of transmission-blocking interventions. However, accurate quantification of male and female gametocytes with molecular methods requires pure male and female gametocytes as reference standards, which are not widely available.

Methods

qRT-PCR assays were used to quantify levels of sex-specific mRNA transcripts in Plasmodium falciparum female and male gametocytes (pfs25 and pfMGET, respectively) using synthetic complimentary RNA standards and in vitro cultured gametocytes. Assays were validated and assay performance was investigated in blood samples of clinical trial participants using these standards and compared to absolute quantification by droplet digital PCR (ddPCR).

Results

The number of transcript copies per gametocyte were determined to be 279.3 (95% CI 253.5–307.6) for the female-specific transcript pfs25, and 12.5 (95% CI 10.6–14.9) for the male-specific transcript pfMGET. These numbers can be used to convert from transcript copies/mL to gametocyte/mL. The reportable range was determined to be 5.71 × 106 to 5.71 female gametocytes/mL for pfs25, and 1.73 × 107 to 1.73 × 101 male gametocytes/mL for pfMGET. The limit of detection was 3.9 (95% CI 2.5–8.2) female gametocytes/mL for pfs25, and 26.9 (95% CI 19.3–51.7) male gametocytes/mL for PfMGET. Both assays showed minimal intra-assay and inter-assay variability with coefficient of variation < 3%. No cross-reactivity was observed in both assays in uninfected human blood samples. Comparison of results from ddPCR to qRT-PCR assays on clinical blood samples indicated a high-level agreement (ICC = 0.998 for pfs25 and 0.995 for pfMGET).

Conclusions

This study reports the validation of qRT-PCR assays that are able to accurately quantify female and male P. falciparum gametocytes at sub-microscopic densities. The assays showed excellent reproducibility, sensitivity, precision, specificity, and accuracy. The methodology will enable the estimation of gametocyte density in the absence of pure female and male gametocyte standards, and will facilitate clinical trials and epidemiological studies.
A spatially explicit analysis of chronic diseases in small areas: a case study of diabetes in Santiago, Chile
Authors: Crespo Ricardo , Alvarez Claudio , Hernandez Ignacio , García Christian
Published: June 2020

Background

There is a strong spatial correlation between demographics and chronic diseases in urban areas. Thus, most of the public policies aimed at improving prevention plans and optimizing the allocation of resources in health networks should be designed specifically for the socioeconomic reality of the population. One way to tackle this challenge is by exploring within a small geographical area the spatial patterns that link the sociodemographic attributes that characterize a community, its risk of suffering chronic diseases, and the accessibility of health treatment. Due to the inherent complexity of cities, soft clustering methods are recommended to find fuzzy spatial patterns. Our main motivation is to provide health planners with valuable spatial information to support decision-making. For the case study, we chose to investigate diabetes in Santiago, Chile.

Methods

To deal with spatiality, we combine two statistical techniques: spatial microsimulation and a self-organizing map (SOM). Spatial microsimulation allows spatial disaggregation of health indicators data to a small area level. In turn, SOM, unlike classical clustering methods, incorporates a learning component through neural networks, which makes it more appropriate to model complex adaptive systems, such as cities. Thus, while spatial microsimulation generates the data for the analysis, the SOM method finds the relevant socio-economic clusters. We selected age, sex, income, prevalence of diabetes, distance to public health services, and type of health insurance as input variables. We used public surveys as input data.

Results

We found four significant spatial clusters representing 75 percent of the whole population in Santiago. Two clusters correspond to people with low educational levels, low income, high accessibility to public health services, and a high prevalence of diabetes. However, one presents a significantly higher level of diabetes than the other. The second pair of clusters is made up of people with high educational levels, high income, and low prevalence of diabetes. What differentiates both clusters is accessibility to health centers. The average distance to the health centers of one group almost doubles that of the other.

Conclusions

In this study, we combined two statistical techniques: spatial microsimulation and selforganising maps to explore the relationship between diabetes and socio-demographics in Santiago, Chile. The results have allowed us to corroborate the importance of the spatial factor in the analysis of chronic diseases as a way of suggesting differentiated solutions to spatially explicit problems. SOM turned out to be a good choice to deal with fuzzy health and socioeconomic data. The method explored and uncovered valuable spatial patterns for health decision-making. In turn, spatial microsimulation.
Unmet supportive care needs and its relation to quality of life among adult acute leukaemia patients in China: a cross-sectional study
Authors: Jie Yan , Wang Ying , Chen Jingyi , Wang Chunfeng , Lin Yingchun , Hu Rong , Wu Yong
Published: June 2020

Background

Patients with acute leukaemia (AL) usually require prolonged periods of hospitalisation. The treatment and clinical symptoms may lead to patients’ supportive care needs (SCNs) not being met and impairs their quality of life (QoL). Studies on QoL and SCNs among AL patients are limited. This study aimed to identify the unmet SCNs and its relation to QoL of adult AL patients in China.

Methods

This multicentre cross-sectional study recruited 346 participants to complete a self-developed questionnaire, detailing demographic information and disease-related variables. A 34-item Supportive Care Needs Survey (SCNS-SF34) was used to identify unmet SCNs, and the Functional Assessment of Cancer Therapy-Leukaemia (FACT-Leu) questionnaire measured patients’ QoL.

Results

Unmet SCN rates for the 34 items ranged from17.6 to 81.7%. Patients’ needs were high for health systems and information, but low in the sexual domain. The results reveal nine factors associated with the unmet SCNs of adult AL patients, including marital status, original residence, age, education, occupation, other diseases, chemotherapy course, disease course, and treatment stage (p < 0.05). The total score of the FACT-Leu negatively correlated with the SCNS-SF34 in the physical/daily living (r = − 0.527, p < 0.01), psychological (r = − 0.688, p < 0.01), sexual (r = − 0.170, p < 0.01), patient care and support (r = − 0.352, p < 0.01), and health systems and information (r = − 0.220, p < 0.01) domains.

Conclusions

Adult AL patients exhibit a high demand for unmet SCNs, especially in the domain of health systems and information. There was a significant association between patients’ unmet SCNs and QoL. Future research should develop tailored interventions to address the unmet SCNs of adult AL patients, to further improve their QoL.
Measurement properties of the musculoskeletal health questionnaire (MSK-HQ): a between country comparison
Authors: Christiansen David Høyrup , McCray Gareth , Winding Trine Nøhr , Andersen Johan Hviid , Nielsen Kent Jacob , Karstens Sven , Hill Jonathan C.
Published: June 2020

Background

The Musculoskeletal Health Questionnaire (MSK-HQ) has been developed to measure musculoskeletal health status across musculoskeletal conditions and settings. However, the MSK-HQ needs to be further evaluated across settings and different languages.

Objective

The objective of the study was to evaluate and compare measurement properties of the MSK-HQ across Danish (DK) and English (UK) cohorts of patients from primary care physiotherapy services with musculoskeletal pain.

Methods

MSK-HQ was translated into Danish according to international guidelines. Measurement invariance was assessed by differential item functioning (DIF) analyses. Test-retest reliability, measurement error, responsiveness and minimal clinically important change (MCIC) were evaluated and compared between DK (n = 153) and UK (n = 166) cohorts.

Results

The Danish version demonstrated acceptable face and construct validity. Out of the 14 MSK-HQ items, three items showed DIF for language (pain/stiffness at night, understanding condition and confidence in managing symptoms) and three items showed DIF for pain location (walking, washing/dressing and physical activity levels). Intraclass Correlation Coefficients for test-retest were 0.86 (95% CI 0.81 to 0.91) for DK cohort and 0.77 (95% CI 0.49 to 0.90) for the UK cohort. The systematic measurement error was 1.6 and 3.9 points for the DK and UK cohorts respectively, with random measurement error being 8.6 and 9.9 points. Receiver operating characteristic (ROC) curves of the change scores against patients’ own judgment at 12 weeks exceeded 0.70 in both cohorts. Absolute and relative MCIC estimates were 8–10 points and 26% for the DK cohort and 6–8 points and 29% for the UK cohort.

Conclusions

The measurement properties of MSK-HQ were acceptable across countries, but seem more suited for group than individual level evaluation. Researchers and clinicians should be aware that some discrepancy exits and should take the observed measurement error into account when evaluating change in scores over time.
Loss-of-function mutations in KEAP1 drive lung cancer progression via KEAP1/NRF2 pathway activation
Authors: Gong Meiling , Li Yan , Ye Xiaoping , Zhang Linlin , Wang Zhifang , Xu Xiaowen , Shen Yejing , Zheng Cuixia
Published: June 2020

Background and purpose

Targeted therapy and immunotherapy have led to dramatic change in the treatment of lung cancer, however, the overall 5-year survival rate of lung cancer patients is still suboptimal. It is important to exploit new potential of molecularly targeted therapies. High-frequency somatic mutations in KEAP1/NRF2 (27.9%) have been identified in lung squamous cell carcinoma. In this research, we explored the role of KEAP1 somatic mutations in the development of LSCC and whether a nuclear factor erythroid 2-related factor 2(NRF2) inhibitor be potential to target lung cancer carrying KEAP1/NRF2 mutations.

Methods

Lung cancer cell lines A549 and H460 with loss-of-function mutations in KEAP1 stably transfected with wild-type (WT) KEAP1 or somatic mutations in KEAP1 were used to investigate the functions of somatic mutations in KEAP1. Flow cytometry, plate clone formation experiments, and scratch tests were used to examine reactive oxygen species, proliferation, and migration of these cell lines.

Results

The expression of NRF2 and its target genes increased, and tumor cell proliferation, migration, and tumor growth were accelerated in A549 and H460 cells stably transfected with KEAP1 mutants compared to control cells with a loss-of-function KEAP1 mutation and stably transfected with WT KEAP1 in both in vitro and in vivo studies. The proliferation of A549 cell line trasfected with the R320Q KEAP1 mutant was inhibited more apparent than that of the A549 cell line trasfected with WT KEAP1 after treatment with NRF2 inhibitor ML385.

Conclusion

Somatic mutations of KEAP1 identified from patients with LSCC likely promote tumorigenesis mediated by activation of the KEAP1/NRF2 antioxidant stress response pathway. NRF2 inhibition with ML385 could inhibit the proliferation of tumor cells with KEAP1 mutation.
Direct anterior versus posterolateral approaches for clinical outcomes after total hip arthroplasty: a systematic review and meta-analysis
Authors: Chen Wang , Sun Jian-Ning , Zhang Ye , Zhang Yu , Chen Xiang-Yang , Feng Shuo
Published: June 2020

Objective

The main objective of our study was to compare the intraoperative and postoperative outcomes of direct anterior approach (DAA) with posterolateral approaches (PLA).

Methods

We searched Cochrane library, Web of Science, and PubMed for literatures comparing DAA with PLA. On the basis of inclusion and exclusion criteria, relevant literatures were selected. Two members independently screened qualified literatures, evaluated the literature quality, and extracted data information.

Results

Eighteen randomized controlled trials (RCTs) and non-RCTs totaling 34,873 patients (DAA = 9636, PLA = 25237) were contained in this systematic review and meta-analysis. The results showed that DAA were reduced in terms of length of hospital stay (weighted mean difference (WMD) = −0.43, 95% confidence interval (CI) −0.78 to −0.09, P = 0.01), LLD (WMD = −2.00, 95% CI −2.75 to −1.25, P < 0.00001), PE/DVT (WMD = 0.36, 95% CI 0.15 to 0.85, P = 0.02), dislocation (WMD = 0.42, 95% CI 0.30 to 0.59, P < 0.00001) and visual analog scale (VAS) (WMD = −0.57, 95% CI −0.91 to −0.23, P = 0.0009) compared with PLA; however, DAA compared with the PLA was increasing in terms of operative time (WMD = 14.81, 95% CI 7.18 to 22.44, P = 0.0001), intraoperative blood loss (WMD = 105.13, 95% CI 25.35 to 184.90, P = 0.01), fracture (WMD = 1.46, 95% CI 1.00 to 2.11, P = 0.05), and Harris hip score (HHS) (WMD = 1.19, 95% CI 0.77 to 1.61, P < 0.00001).

Conclusions

DAA was preferable effectiveness to PLA in early pain relief and functional recovery; however, PLA has a shorter operation time, intraoperative less blood loss and fracture.

Trial registration

Registration ID, CRD42020151208
Raising rare disease awareness using red flags, role play simulation and patient educators: results of a novel educational workshop on Raynaud phenomenon and systemic sclerosis
Authors: Sanges S. , Farhat M.-M. , Assaraf M. , Galland J. , Rivière E. , Roubille C. , Lambert M. , Yelnik C. , Maillard H. , Sobanski V. , Lefèvre G. , Launay D. , Morell-Dubois S. , Hachulla E.
Published: June 2020

Background

As lack of awareness of rare diseases (RDs) among healthcare professionals results in delayed diagnoses, there is a need for a more efficient approach to RD training during academic education. We designed an experimental workshop that used role-play simulation with patient educators and focused on teaching “red flags” that should raise the suspicion of an RD when faced with a patient with frequently encountered symptoms. Our objective was to report our experience, and to assess the improvement in learners’ knowledge and the satisfaction levels of the participants.

Results

The workshop consisted of 2 simulated consultations that both started with the same frequent symptom (Raynaud phenomenon, RP) but led to different diagnoses: a frequent condition (idiopathic RP) and an RD (systemic sclerosis, SSc). In the second simulated consultation, the role of the patient was played by a patient educator with SSc. By juxtaposing 2 seemingly similar situations, the training particularly highlighted the elements that help differentiate SSc from idiopathic RP.

When answering a clinical case exam about RP and SSc, students that had participated in the workshop had a higher mean mark than those who had not (14 ± 3.7 vs 9.6 ± 5.5 points out of 20, p = 0.001).

Participants mostly felt “very satisfied” with this training (94%), and “more comfortable” about managing idiopathic RP and SSc (100%). They considered the workshop “not very stressful” and “very formative” (both 71%). When asked about the strengths of this training, they mentioned the benefits of being put in an immersive situation, allowing a better acquisition of practical skills and a more interactive exchange with teachers, as well as the confrontation with a real patient, leading to a better retention of semiological findings and associating a relational component with this experience.

Conclusions

Through the use of innovative educational methods, such as role-play simulation and patient educators, and by focusing on teaching “red flags”, our workshop successfully improved RP and SSc learning in a way that satisfied students. By modifying the workshop’s scenarios, its template can readily be applied to other clinical situations, making it an interesting tool to teach other RDs.