bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical Characteristics of SARS-CoV-2 pneumonia diagnosed in a primary care practice in Madrid (Spain)
Authors: Guisado-Clavero Marina , Gil Ana Herrero , Álvarez Marta Pérez , Jurado Marta Castelo , Marinas Ana Herrera , Ruiz Vanesa Aguilar , Iarrondo Ileana Gefaell , Menéndez Miguel , Ares-Blanco Sara
Published: August 2020

Background: Possible cases of SARS-CoV-2 infection were diagnosed in primary care in Madrid, some of these cases had pneumonia. Most of the SARS-CoV-2 pneumonia published data came from hospitalised patients. This study set out to describe clinical characteristics of patients with SARS-CoV-2 pneumonia diagnosed in primary care across age groups and type of pneumonia.Methods: Observational retrospective study obtaining clinical data from the electronic health records of patients who were followed-up by SARS-CoV-2 possible infection in a primary care practice in Madrid. All the cases were collected by in-person or remote consultation during the 10th March to the 7th of April. Exposure: Diagnosis of SARS-CoV-2 pneumonia by chest X-ray ordered by the GP. Main outcomes and measures: Symptoms of SARS-CoV-2 pneumonia, physical examination and diagnostic tests as a blood test, nasopharyngeal swab results for RT-PCR (Reverse transcriptase-polymerase chain reaction) and chest X-ray results. Results: The overall SARS-CoV-2 pneumonias collected were 172 (female 87 [50.6%], mean age 60.5 years (standard deviation [SD] 17.0). Comorbidities were body mass index ≥25 kg/m 2 (90 [52.3%]), hypertension 83 [48.3%]), dyslipidaemia (68 [39.5%]) and diabetes (33 [19.2%]). The sample was stratified by age groups (<50 years, 50-75 years and ≥75 years). Clinical manifestations at onset were fever (144 [83.7%]), cough (140 [81.4%]), dyspnoea (103 [59.9%]) and gastrointestinal disturbances (72 [41.9%]). Day 7.8 (SD:4.1) from clinical onset was the mean day of pneumonia diagnosis. Bilateral pneumonia was more prevalent than unilateral (126 [73.3%]) and 46 [26.7%]). Patients with unilateral pneumonia were prone to higher pulse oximetry (96% vs 94%, p <0.001). We found differences between unilateral and bilateral cases in C-reactive protein (29.6 vs 81.5mg/L, p <0.001), and lymphocytes (1400.0 vs 1000.0E3/ml, p<0.001). Complications were registered: 42 (100%) of patients ≥75 years were admitted into hospital; pulmonary embolism was only present at bilateral pneumonia (7 patients [5.6%]) and death occurred in 1 patient with unilateral pneumonia (2.2%) vs 10 patients (7.9%) with bilateral pneumonia ( p 0.170).Conclusion: Clinical manifestations of SARS-CoV-2 pneumonia were fever, cough and dyspnoea; this was especially clear in the elderly. We described different characteristics between unilateral and bilateral pneumonia.
GLP-1 vasodilatation in humans with coronary artery disease is not adenosine mediated.
Authors: Aetesam-ur-Rahman Muhammad , Giblett Joel P. , Khialani Bharat , Kyranis Stephen , Clarke Sophie J. , Zhao Tian X. , Braganza Denise M. , Clarke Sarah C. , West Nick E. J. , Bennett Martin R. , Hoole Stephen P.
Published: August 2020

Background Incretin therapies appear to provide cardioprotection and improve cardiovascular outcomes in patients with diabetes, but the mechanism of this effect remains elusive. We have previously shown that glucagon-like peptide (GLP)-1 is a coronary vasodilator and we sought to investigate if this is an adenosine-mediated effect.Methods We recruited 41 patients having percutaneous coronary intervention (PCI) for stable angina and allocated them into four groups administering a specific study-related infusion following successful PCI: GLP-1 infusion (Group G) (n = 10); Placebo, normal saline infusion (Group P) (n = 11); GLP-1 + Theophylline infusion (Group GT)(n = 10); and Theophylline infusion (Group T) (n = 10). A pressure wire assessment of coronary distal pressure and flow velocity (thermodilution transit time – Tmn) at rest and hyperaemia was performed after PCI and repeated following the study infusion to derive basal and index of microvascular resistance (BMR and IMR).Results There were no significant differences in the demographics of patients recruited to our study. Most of the patients were not diabetic. GLP-1 caused significant reduction of resting Tmn that was not attenuated by theophylline: mean delta Tmn (SD) group G -0.23 s (0.27) vs. group GT -0.18 s (0.37), p = 0.65. Theophylline alone (group T) did not significantly alter resting flow velocity compared to group GT: delta Tmn in group T 0.04 s (0.15), p = 0.30. The resulting decrease in BMR observed in group G persisted in group GT: -20.83 mmHg.s (24.54 vs. -21.20 mmHg.s (30.41), p = 0.97. GLP-1 did not increase circulating adenosine levels in group GT more than group T: delta median adenosine − 2.0 ng/ml (-117.1, 14.8) vs. -0.5 ng/ml (-19.6, 9.4); p = 0.60.Conclusion The vasodilatory effect of GLP-1 is not abolished by theophylline and GLP-1 does not increase adenosine levels, indicating an adenosine-independent mechanism of GLP-1 coronary vasodilatation..
Integrating expert opinions with clinical trial data to analyse low-powered subgroup analyses: a Bayesian analysis of the VeRDiCT trial
Authors: Thirard Russell , Ascione Raimondo , Blazeby Jane , Rogers Chris A
Published: August 2020

Background

Typically, subgroup analyses in clinical trials are conducted by comparing the intervention effect in each subgroup by means of an interaction test. However, trials are rarely, if ever, adequately powered for interaction tests, so clinically important interactions may go undetected. We discuss the application of Bayesian methods by using expert opinions alongside the trial data. We applied this methodology to the VeRDiCT trial investigating the effect of preoperative volume replacement therapy (VRT) versus no VRT (usual care) in diabetic patients undergoing cardiac surgery. Two subgroup effects were of clinical interest, a) preoperative renal failure and b) preoperative type of antidiabetic medication.

Methods

Clinical experts were identified within the VeRDiCT trial centre in the UK. A questionnaire was designed to elicit opinions on the impact of VRT on the primary outcome of time from surgery until medically fit for hospital discharge, in the different subgroups. Prior beliefs of the subgroup effect of VRT were elicited face-to-face using two unconditional and one conditional questions per subgroup analysis. The robustness of results to the ‘community of priors’ was assessed. The community of priors was built using the expert priors for the mean average treatment effect, the interaction effect or both in a Bayesian Cox proportional hazards model implemented in the STAN software in R.

Results

Expert opinions were obtained from 7 clinicians (6 cardiac surgeons and 1 cardiac anaesthetist). Participating experts believed VRT could reduce the length of recovery compared to usual care and the greatest benefit was expected in the subgroups with the more severe comorbidity. The Bayesian posterior estimates were more precise compared to the frequentist maximum likelihood estimate and were shifted toward the overall mean treatment effect.

Conclusions

In the VeRDiCT trial, the Bayesian analysis did not provide evidence of a difference in treatment effect across subgroups. However, this approach increased the precision of the estimated subgroup effects and produced more stable treatment effect point estimates than the frequentist approach. Trial methodologists are encouraged to prospectively consider Bayesian subgroup analyses when low-powered interaction tests are planned.

Trial registration

ISRCTN, ISRCTN02159606. Registered 29th October 2008.
Wind and Gravity in Shaping Picea Trunks
Authors: Larjavaara Markku , Auvinen Mikko , Kantola Anu , Mäkelä Annikki
Published: August 2020

Background:Understanding why trunks (tree stems) are the size that they are is important. However, this understanding is fragmented into isolated schools of thought and has been far from complete. Realistic calculations on minimum trunk diameters needed to resist bending moments caused by wind and gravity would be a significant step forward. However, advancements using this biomechanical approach have been delayed by difficulties in modelling wind gusts. We felled and measured five Norway spruces (Picea abies) in an unthinned monoculture in southeastern Finland planted 67 years earlier. We focused on forces working on storm-bent (maximally bent) trees caused by gravity and the strongest gust in a one-hour simulation with a large-eddy simulation model. Results:The three largest trees resisted mean above-canopy wind speeds ranging from 10.2 m s-1 to 12.7 m s-1 (3.3-fold in the gust), but the two smallest were well protected by a dense layer of leaves from the bending tops of larger trees, and could have resisted stronger winds. Gravity caused approximately one quarter of the critical bending moments. Conclusions:Our biomechanical modelling of trunk taper based on wind and gravity leads to diameters close to those measured, and we discuss the potential causes of the deviations. This approach could also be used to model tree biomasses and how those may change with changing climate.
Comparison of Clinicopathological Features and Long-Term Prognosis Between Mixed Predominantly Differentiated-Type and Pure Differentiated-Type Early Gastric Cancer
Authors: Okagawa Yutaka , Sumiyoshi Tetsuya , Kondo Hitoshi , Tomita Yusuke , Uozumi Takeshi , Iida Reiichi , Sakano Hiroya , Tokuchi Kaho , Jin Takashi , Yoshida Masahiro , Fujii Ryoji , Minagawa Takeyoshi , Morita Kohtaro , Yane Kei , Ihara Hideyuki , Hirayama Michiaki , Oyamada Yumiko , Okushiba Shunichi
Published: August 2020

Background: Recent studies have shown that mixed predominantly differentiated-type (MD) early gastric cancer (EGC) might have more malignant potential than pure differentiated-type (PD) EGC. However, no study has analyzed all differentiated-type EGC cases treated endoscopically and surgically. This study aimed to compare the differences in clinicopathological features and long-term prognosis between MD- and PD-EGC. Methods: We evaluated all patients with differentiated-type EGCs who were treated endoscopically and surgically in our hospital between January 2010 and October 2014. The clinicopathological features and long-term prognosis of MD-EGC were compared with those of PD-EGC.Results: A total of 459 patients with 459 lesions were evaluated in this study; of them, 409 (89.1%) and 50 (10.9%) were classified into the PD and MD group, respectively. Submucosal invasion was found in 96 (23.5%) of the PD group and in 33 (66.0%) of the MD group (p<0.01). The rates of positive lymphatic and vascular invasion and ulceration were significantly higher in the MD group than in the PD group (p<0.01). The proportion of patients with lymph node metastasis was also significantly higher in the MD group than in the PD group (5 (10%) vs 6 (1.5%), p<0.01). The 5-year overall and EGC-specific survival rates in the PD were 88.3% and 99.5%, respectively, while they were 94.0% and 98.0% in the MD group, respectively. Conclusions: MD-EGC has more malignant potential than PD-EGC. However, the long-term prognosis of MD-EGC is good and is not significantly different from that of PD-EGC when treated appropriately.
Health-related quality of life in children with congenital heart disease aged 5 to 7 years: a multicentre controlled cross-sectional study
Authors: Abassi Hamouda , Huguet Helena , Picot Marie-Christine , Vincenti Marie , Gauillaumont Sophie , Auer Annie , Werner Oscar , Villeon Grégoire De La , Lavastre Kathleen , Gavotto Arthur , Auquier Pascal , Amedro Pascal
Published: August 2020

Background
In the context of tremendous progress in congenital cardiology, more attention has been given to patient-related outcomes, especially in assessing health-related quality of life (HRQoL) of patients with congenital heart diseases (CHD). However, most studies have mainly focused on teenagers or adults and currently, few HRQoL controlled data is available in young children. This study aimed to evaluate HRQoL of children with CHD aged 5 to 7 y.o., in comparison with contemporary peers recruited in school, as well as the factors associated with HRQoL in this population.
Methods
This multicentre controlled prospective cross-sectional study included 124 children with a CHD (mean age = 6.0 ± 0.8 y, 45% female) during their outpatient visit and 125 controls (mean age = 6.2 ± 0.8 y, 54% female) recruited at school. A generic paediatric HRQoL instrument was used (PedsQL 4.0).
Results
Self-reported HRQoL in children with CHD was similar to controls, overall (73.5 ± 1.2 vs. 72.8 ± 1.2, P = 0.7, respectively), and for each dimension. Parents-reported HRQoL was significantly lower in the CHD group than in controls. HRQoL was predicted by the disease severity and by repeated invasive cardiac procedures (surgery or catheterization).
Conclusion
HRQoL in young children with CHD aged 5 to 7 years old was good and similar to controls. This study contributed to the growing body of knowledge on HRQoL in congenital cardiology and emphasized the need for child and family support in the most complex CHD.
Trial registration:
This study was approved by the institutional review board of Montpellier University Hospital (2019_IRB-MTP_02–19) on 22 February 2019 and was registered on ClinicalTrials.gov (NCT03931096) on 30 April 2019, https://clinicaltrials.gov/ct2/show/NCT03931096.
Assessment of Sodium Thiosulfate Neutralizing Effect on Micro-hardness of Dentin Treated With Sodium Hypochlorite
Authors: Sahebi Safoora , Sobhnamayan fereshteh , Naseri Mohammadhasan , Moazami Fariborz
Published: August 2020

Background
The aim of this study is to evaluate the ability of sodium thiosulfate (STS) to reverse the adverse effect of sodium hypochlorite (NaOCl) on dentin microhardness.
Methods
Fifty single-rooted teeth were decoronated and longitudinally sectioned. The samples were divided into a control and four sample groups (n = 20): Normal saline for 15 min as the control group, G1: 2.5% NaOCl for 15 min without an incubation period, G2: 2.5% NaOCl for 15 min, G3: 2.5% NaOCl for 15 min irrigated with normal saline followed by 5% Na2S2O3 for 10 min, G4: Normal saline for 15 min followed by 5% Na2S2O3 for 10 min. All groups except G1 were incubated for 1 week. The microhardness measurements were determined using the Vickers micro-hardness test. Data were analyzed using the Kruskal-Wallis test for pairwise comparisons. A p-value < 0.05 was considered significant.
Results
All groups showed a significant decrease in the micro-hardness value compared with the control group. NaOCl for 1 week (G2) reduced the micro-hardness of dentine compared with samples, tested immediately after immersion in NaOCl (G1) (p < 0.05). NaOCl alone (G2) or treated with Na2S2O3 (G3) resulted in a significant decrease in microhardness compared with the Na2S2O3 group (G4) (p < 0.05).
Conclusions
Sodium thiosulfate as a neutralizing agent could not prevent the microhardness downturn caused by sodium hypochlorite
Complaints of Paediatric Patients After Dental Treatment Under General Anaesthesia I: Pain. A Prospective Observational Study.
Authors: Radácsi Andrea , Katona Krisztián , Farkas Nelli , Kövesi Tamás , Szántó Ildikó , Sandor Balazs
Published: August 2020

Background: Dental treatment under general anaesthesia for children is a useful option in behaviour management. However, this treatment modality may also be accompanied by considerable postoperative pain. We aimed to specify factors related to postoperative pain and those that alleviate complaints. Methods: Children treated in general anaesthesia and their parents voluntarily participated in the study. Pain was reported daily by children using Wong Baker FACES Pain Rating Scale and by caregivers, using a yes/no questionnaire during hospitalization and throughout the postoperative week. The relation of patient and operation linked factors were evaluated in accordance with the duration and severity of pain. Results: Based on children’s responses and parental feedback, no significant difference was found in pain level between extraction and non-extraction cases. Intraoperative local anaesthesia did not influence pain during hospitalization. Compared to other analgesics postoperative intravenous opioid administration was more effective in pain management. Older patients reported more durable and severe pain during the postoperative week. Treatment time, airway management and the class of extracted primary tooth (molar, anterior) significantly influenced pain during postoperative week. Additionally, parental questionnaires revealed correlation between gender and postoperative pain.Conclusion: Few of the influencing factors are alterable, but with precise and meticulous treatment planning postoperative pain, thereby the distress on families may be reduced.
Antibacterial and Antibiofilm Studies of Synthetic Copper(I)-containing Small Molecule Complexes Against Streptococcus Mutans in Vitro
Authors: Pan Ting , Wang Yinuo , Liu Fengshou , Lin Huancai , Zhou Yan
Published: August 2020

Background

With the goal to develop high efficiency oral antimicrobial agents to prevent dental caries, a collection of copper(I)-containing small molecule complexes with different substitution were synthesized and characterized. In current research, we screened these complexes and explored their antimicrobial activities, especially against cariogenic bacteria Streptococcus mutans.
Methods

The characterization and minimum inhibitory concentrations of these complexes have been determined by NMR spectroscopy and standard broth microdilution, respectively. Biofilm formation and morphology were evaluated using crystal violet staining, MTT, confocal laser scanning microscope and scanning electron microscope. Finally, we tested the biocompatibility.
Results

Cu1 was screened and presented excellent performance, which suggested that the less lipophilic and less steric copper complexes would be effective toward the bacterial. Cu1 also effectively inhibited the formation of S.mutans biofilm at its minimum inhibitory concentration.
Conclusions

This study demonstrates a high potential of copper(I)-containing small molecule complexes as broad-spectrum inhibitors to treat oral bacterial, especially for diminishing S.mutans biofilm formation.
Empagliflozin Leads to a Rapid and Sustained Improvement of Left Ventricular Filling Pressure in Patients With Type 2 Diabetes: a Randomized Controlled Study
Authors: Rau Matthias , Thiele Kirsten , Hartmann Niels-Ulrik Korbinian , Schuh Alexander , Altiok Ertunc , Möllmann Julia , Keszei András P. , Böhm Michael , Marx Nikolaus , Lehrke Michael
Published: August 2020

BackgroundIn the EMPA-REG OUTCOME trial (Empagliflozin Cardiovascular Outcome Event Trial) treatment with the sodium-glucose cotransporter-2 (SGLT2) inhibitor empagliflozin significantly reduced heart failure hospitalization (HHF) in patients with type 2 diabetes mellitus (T2D) and established cardiovascular disease. The early separation of the HHF event curves within the first 3 months of the trial suggest that early hemodynamic effects may play a role, potentially mediated by direct diuretic effects of the drug. In this study we examined immediate and more delayed effects of empagliflozin on urinary volume excretion, left ventricular filling pressure and function in addition to hemodynamic parameters.MethodsIn this placebo-controlled, randomized, double blind, exploratory study patients with T2D were randomized to empagliflozin 10 mg or placebo for a period of 3 months. Urinary volume excretion, echocardiographic and hemodynamic parameters were assessed after 1 day, 3 days and 3 months of treatment.ResultsBaseline characteristics were comparable in the empagliflozin (n = 20) and placebo (n = 22) group. Empagliflozin led to a significant increase of urinary glucose excretion (baseline: 7.3 ± 22.7 g/24 hrs; day 1: 48.4 ± 34.7 g/24 hrs; p < 0.001) as well as urinary volume (1740 ± 601 mL/24 hrs to 2112 ± 837 mL/24 hrs; p = 0.011) at day one of treatment which remained significant after 3 months. In addition empagliflozin significantly improved left ventricular filling pressure as assessed by a reduction of early mitral inflow velocity relative to early diastolic left ventricular relaxation (E/e’) which became significant at day 1 of treatment (baseline: 9.2 ± 2.6; day 1: 8.5 ± 2.2; p = 0.005) and remained apparent throughout the study. This was primarily attributable to reduced early mitral inflow velocity E (baseline: 0.8 ± 0.2 m/sec; day 1: 0.73 ± 0.2 m/sec; p = 0.003). No difference in left ventricular function or hemodynamic parameters was observed.ConclusionEmpagliflozin treatment of patients with T2D led to a significant rapid and sustained improvement of left ventricular filling pressure.Trial Registration: EudraCT Number: 2016-000172-19; date of registration: 2017-02-20 (clinicaltrialregister.eu)
Platelet Proteome Changes in Dogs with Chronic Heart Failure
Authors: LEVENT Pinar , KOCATÜRK Meriç , AKGÜN Emel , SARIL Ahmet , ÇEVİK Ozge , BAYKAL Ahmet Tarik , TANAKA Ryou , CERON Jose Joaquin , YILMAZ Zeki
Published: August 2020

Background: Platelets play a central role in the development of cardiovascular diseases and changes in their proteins are involved in the pathophysiology of heart diseases in humans. There is lack of knowledge about the possible role of platelets in chronic heart failure (CHF) in dogs. Thus, this study aimed to investigate the changes in global platelet proteomes in dogs with CHF, to clarify the possible role of platelets in the physiopathology of this disease. Healthy-dogs (n=10) and dogs with CHF due to myxomatous mitral valve degeneration (n=10) were used. Blood samples were collected into tubes with acid-citrate-dextrose, and platelet-pellets were obtained by centrifuge and washing steps. Platelet-proteomes were identified using LC-MS based label-free differential proteome expression analysis method and matched according to protein database for Canis lupus familiaris. Results: Totally 107 different proteins were identified in the platelets of the dogs being 4 out of them were significantly up-regulated and 6 down-regulated in the CHF dogs. Guanine-nucleotide-binding protein, apolipoproteins (A-II and C-III) and clusterin levels increased, but CXC-motif-chemokine-10, cytochrome-C-oxidase-subunit-2, cathepsin-D, serine/threonine-protein-phosphatase-PP1-gamma-catalytic-subunit, creatine-kinase-B-type and myotrophin levels decreased in the CHF dogs. These proteins are associated with several molecular functions, biological processes, signaling systems and immune-inflammatory responses.Conclusion: This study describes by first time the changes in the protein composition in platelets of dogs with CHF. Our findings provide a resource for increase the knowledge about the proteome of canine platelets and their roles in CHF and could be a tool for further investigations about the prevention and treatment of this disease.
Development and Evaluation of Recombinant GRA8 Protein for the Serodiagnosis of Toxoplasma Gondii Infection in Goats
Authors: Jirapattharasate Charoonluk , Udonsom Ruenruetai , Prachasuphap Apichai , Jongpitisub Kodcharad , Dhepakson Panadda
Published: August 2020

Background The development of sensitive and specific methods for detecting Toxoplasma gondii infection is critical for preventing and controlling toxoplasmosis in humans and other animals. Recently, various recombinant proteins have been used in serological tests for diagnosing toxoplasmosis. The production of these antigens is associated with live tachyzoites obtained from cell cultures or laboratory animals for genomic extraction to amplify target genes. Synthetic genes have gained a key role in recombinant protein production. For the first time, we demonstrated the production of the recombinant protein of the T. gondii dense granular antigen 8 (TgGRA8) gene based on commercial gene synthesis. Recombinant TgGRA8 plasmids were successfully expressed in an Escherichia coli system. The recombinant protein was affinity-purified and characterized via sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blotting. Furthermore, the diagnostic potential of the recombinant protein was assessed using 306 field serum samples from goats via indirect enzyme-linked immunosorbent assay (iELISA) and the latex agglutination test (LAT).Results Western blotting using known positive serum samples from goats identified a single antigen at the expected molecular weight of TgGRA8 (27 kDa). iELISA illustrated that 15.40% of goat samples were positive for T. gondii-specific IgG antibodies. In addition, TgGRA8 provided high sensitivity and specificity, with significant concordance (91.83) and kappa values (0.69) compared with the results obtained using LAT.Conclusion Our findings highlight the production of a recombinant protein from a synthetic TgGRA8 gene and the ability to detect T. gondii infection in field samples. The sensitivity and specificity of TgGRA8 demonstrated that this protein could be a good serological marker for detecting specific IgG in goat sera.
Genomic and clinical characterisation of multidrug-resistant carbapenemase-producing ST231 and ST16 Klebsiella pneumoniae isolates colonising and causing disease in hospitalised patients at Siriraj Hospital, Bangkok, Thailand from 2015 to 2017
Authors: Boonyasiri Adhiratha , Jauneikaite Elita , Brinkac Lauren M. , Greco Chris , Lerdlamyong Kanokorn , Tangkoskul Teerawit , Nguyen Kevin , Thamlikitkul Visanu , Fouts Derrick E.
Published: August 2020

Background: Infections caused by carbapenemase-producing Enterobacteriaceae (CPE) have continually grown as a global public health threat, with significant mortality rates observed across the world. We examined the clinical data from patients with CPE infections and their outcomes, concentrating on Klebsiella pneumoniae isolates. We analysed the clinical information, performed antimicrobial susceptibility testing, and conducted molecular epidemiological and genomic analyses on the isolates to identify patterns in the data.Methods: The clinical characteristics of 33 hospitalised patients with confirmed CPE, including patient-related factors associated with the development of CPE infections, were examined. Patients were divided according to whether they were “colonised” or “infected” with CPE and by the timing and frequency of their rectal swab collections, from which 45 swabs were randomly selected for analysis. CPE isolates were purified, and antimicrobial susceptibility tests performed. Whole genome sequences of these isolates were determined and analysed to compute bacterial multilocus sequence types and plasmid replicon types, infer phylogenetic relationships, and identify antimicrobial resistance and virulence genes.Results: Altogether, 88.9% (40/45) of the CPE isolates were K. pneumoniae. The most abundant carbapenemase gene family in the K. pneumoniae isolates (33/39) was blaOXA-232, with blaNDM-1 additionally identified in 19 of them. All CPE isolates carrying either blaOXA-232 or blaNDM-1 were resistant to meropenem, but only 40 from 45 were susceptible to colistin. Among the CPE-infected patients (n=18) and CPE-colonised patients who developed CPE infections during the study (n=3), all but one received standard colistin-based combination therapy. Phylogenetic analysis revealed the polyclonal spread of carbapenemase-producing K. pneumoniae (CPKP) within the patient population, with the following two major subclades identified: ST16 (n=15) and ST231 (n=14). CPKP-ST231 had the highest virulence score of 4 and was associated with primary bacteraemia. The siderophores yersiniabactin and aerobactin, considered to be important virulence factors, were only identified in the CPKP-ST231 genomes.Conclusions: This study has revealed the genomic features of disease-causing or colonising CPE isolates, focusing on antimicrobial resistance and virulence determinants. This type of multi-layered analysis can be further exploited in Thailand and elsewhere to modify the regimes used for empirical antibiotic treatment and improve the management strategies for CPE infections in hospitalised patients.
Long-Term HbA1c Variability and Cardiovascular Death: Insights from the EMPA-REG OUTCOME Trial
Authors: Ceriello Antonio , Ofstad Anne Pernille , Zwiener Isabella , Kaspers Stefan , George Jyothis , Nicolucci Antonio
Published: August 2020

Background: Glucose variability has been associated with cardiovascular (CV) outcomes in type 2 diabetes, however, the interplay between glucose variability, empagliflozin and CV death has not been explored. In the EMPA-REG OUTCOME trial, empagliflozin reduced the risk of CV death by 38%. We explore post-hoc the association between HbA1c variability and CV death, and the potential mediating effects of HbA1c variability on empagliflozin’s CV death reductions.Methods: In total, 7,020 patients with type 2 diabetes and established CV disease received placebo, empagliflozin 10 mg or 25 mg. We defined within-patient HbA1c variability as standard deviation, coefficient of variation and range of HbA1c measurements (%) post-baseline. First, we compared HbA1c variability until week 28 and 52 by Wilcoxon tests. We explored the association between CV death and HbA1c variability in placebo and pooled empagliflozin arms separately with landmark analyses at week 28 and 52, and additionally with HbA1c variability as a time-dependent co-variate. We used Cox regression models adjusted for baseline risk factors including changes in HbA1c from baseline to week 12, and the interaction term HbA1c variability* treatment.Results: HbA1c variability was lower with empagliflozin compared to placebo. In all Cox analyses, high HbA1c variability increased the risk for CV death in both treatment arms with no interaction with treatment.Conclusions: HbA1c variability was reduced by empagliflozin and high values of HbA1c variability were associated with an increased risk of CV death. Empagliflozin’s reduction in CV death did not appear to be mediated by reductions in HbA1c variability.ClinicalTrials.gov number, NCT01131676. Registered May 27 2010. https://clinicaltrials.gov/ct2/show/NCT01131676
Survival of Silver Diamine Fluoride Among Patients Treated in Community Dental Clinics: A Naturalistic Study
Authors: Raskin Sarah Elaine , Tranby Eric , Ludwig Sharity , Okunev Ilya , Frantsve-Hawley Julie , Boynes Sean
Published: August 2020

Objectives: To describe survival outcomes of silver diamine fluoride (SDF) among a population-based sample receiving care in community settings.Methods: We analyzed data on SDF applications from de-identified dental claims on Oregon Health Plan patients served by Advantage Dental in 2016, who had been seen in 2015. Survival rates of SDF alone, SDF applied with a sedative filling, and SDF with a same-day restoration were compared. Failure was defined as a restoration or extraction of the tooth 7 to 365 days after initial application, while survival was defined a patient that returned 180 or more days after application and the tooth did not have restoration or extraction. Differences were assessed through Wilcoxon equality of survivor function tests and log-rank equality of survivor tests to compare failure rates, Cox Proportional Hazards models to assess factors associated with survival of SDF, and Kaplan-Meier survival estimate to calculate the probability of survival over time. Results: SDF alone had an overall survival rate of 76%. SDF placed with sedative filling and with a same-day restoration had survival rates of 50% and 84% respectively, likely reflecting the intent of treatment. SDF alone survived exceptionally well on primary cuspids, permanent molars, and permanent bicuspids and among patients aged 10 to 20 years, with modest variation across caries risk assessment categories. A single annual application of SDF was successful in 68% of cases. Among SDF failures on permanent dentition, more than two-thirds of teeth received a minor restoration.Conclusions: SDF is a minimally invasive non-aerosolizing option that demonstrably prevented and arrested early stage dental caries among patients in one “real world” community dentistry setting. Professional organizations, policy makers, providers, and payors should consider broadening the option to use SDF by informing clinical guidelines, reimbursement policies, and treatment decisions, especially amidst COVID-19 pandemic driven guidelines to minimize risk of exposure to airborne pathogens. Future research should address clinical, social, health service delivery, workforce, and economic outcomes including costs and invasive procedures deferred, using diverse population-based samples, and the mechanisms underlying the success of a single application and the potential for SDF to prevent caries found in this study.Trial registration: N/A
Ticks and tick-borne Anaplasma spp. and Rickettsia spp. from hilly area in central China
Authors: Zhang Ke , Li Aijun , Ding Ying , Zhang Jinjuan , Tong Tingting , Chen Yujie , Wang Huijing , Shi Ruixuan , Lu Suxiang , Wu Hongyu , Chen Qiu
Published: August 2020

Background

Ticks are widely distributed in diverse habitats across the globe. Different tick habitats breed different tick varieties and tick-borne diseases. Pingdingshan City, located in central China, is a hilly area where livestock grazing is an everyday activity. Till now, the prevalence of tick-borne Rickettsiales around Pingdingshan City has not yet been explored.
Methods

We used PCR and nest-PCR detected the 16S rRNA gene of ticks, 16S rRNA gene of Anaplasma spp. and 17 KDa gene and gltA gene of Rickettsia spp. in the ticks collected from livestock and vegetation in hilly area of central China, Pingdingshan City.
Results

In this study, we observed a high infection rate of a dominant tick, H. longicorni (98.22%, 166/169), with Anaplasma spp. (48.8%), Rickettsia spp. (30.72%), and co-infection (9.04%, 15/166). It suggests a high public health risk. 16S rRNA sequencing revealed that the A. phagocytophilum, which is present in H. longicorni was more than 99.74% homologous to (MN044900.1) from Zhejiang and (KT276565.1) from Shandong in China, and more than 98.23% homologous to (KR611598.1, KC422267.1) from South Korea. Besides, A. central showed 100% homology to (GU064903.1) from South Korea. Ca. R. jingxinese was detected from 17 kDa gene amplification, and it showed 99.08%-99.77% homology to (MH932039.1) from Xian, China, and 100% homology to Candidatus R. jingxinensis from north-eastern China (KT899089.1).
Conclusions

In the hilly area of central China, a high prevalence of H. longicorni, and high infection rate of Anaplasma spp. and Rickettsia spp., even co-infection, necessitated the current study. Furthermore, an in-depth investigation is required to unravel its pathogenicity. Besides, other tick-borne disease-causing pathogens in H. longicorni, which pose a significant threat to humans and livestock, demand further assessment.
Psychometric validation of the Chinese version of the PaArticular Scales among elderly residents in long-term care facilities with joint contractures
Authors: Chen Yi-chang , Lin Keh-chung , Yeh Shu-Hui , Pan Ay-Woan , Chen Hao-Ling , Chen Chen-Jung
Published: August 2020

Background Joint contractures are common complications among elderly residents in long-term care facilities, causing activity limitations and participation restrictions and affecting quality of life (QOL). The aim of this study is to examine the psychometric properties of the Chinese version of the PaArticular Scales in joint contractures population.Methods A cross-sectional study design. A sample of elderly residents aged over 64 years with joint contractures in one important joint who have lived at a facility for more than 6 months in twelve long-term care facilities in Taiwan (N = 243). The Chinese version of the PaArticular Scales of joint contractures was generated through 5 stages: translation, review, back-translation, a panel of specialists, and a pretest. Test-retest reliability, internal consistency reliability, construct validity, and criterion validity were evaluated, and the results were compared with those for the WHOQOL-BREF and WHODAS 2.0–36 items.Results The Activities and Participation subscales had excellent internal consistency (α = .975; SD = 17.34). The correlation coefficients between the PaArticular Scales and the WHODAS 2.0–36 items (r = .770, p < .001) and WHOQOL-BREF were significant and highly correlated (r = − .553, p < .001).Conclusions The underlying theoretical model of the Chinese version of the PaArticular Scales functions well in Taiwan, and the Chinese version has acceptable levels of reliability and validity.Clinical trial registration:
Reduction of pTau and APP Levels in Mammalian Brain
After Low-Dose Radiation
Authors: Iacono Diego , Murphy Erin , Avantsa Soundarya , Perl Daniel , Day Regina
Published: August 2020

Brain radiation can occur from treatment of brain tumors or accidental exposure. Brain radiation has been rarely considered, though, as a possible tool to alter proteins involved in neurodegenerative disorders. We analyzed molecular and neuropathology changes of phosphorylated-Tau (pTau), all-Tau forms, β-tubulin, amyloid precursor protein (APP), glial fibrillary acidic protein (GFAP), ionized calcium binding adaptor molecule 1 (IBA-1), myelin basic protein (MBP), and GAP43 in Frontal Cortex (FC), Hippocampus (H) and Cerebellum (CRB) of swine brains 4 weeks following total-body radiation (1.79 Gy). Radiated-animals showed lower levels of pTau in FC and H, APP in H and CRB, GAP43 in CRB, and higher level of GFAP in H vs. sham-animals. These changes were not accompanied by obvious neurohistological changes, except for astrogliosis in the H. These findings are novel, and might open new perspectives on brain radiation as a therapeutic tool for interfering with the pathogenesis of various neurodegenerative disorders.
Single-atom Pd-Ru pair on Pt surface for promoting hydrogen oxidation in alkaline media
Authors: Cao Longsheng , Soto Fernando , Li Dan , Deng Tao , Hu Enyuan , Eidson Nico , Yang Xiao-Qing , Balbuena Perla B , Wang Chunsheng
Published: August 2020

The hydrogen oxidation reaction (HOR) in alkaline media is critical for the alkaline fuel cell and electrochemical ammonia compressor. The sluggishness of HOR in the alkaline electrolyte requires platinum nano-catalysts, which are scarce and expensive. Decorating Pt catalysts with transition metals can boost the area specific activity (SA) of Pt nano-catalysts, but it often reduces the electrochemical active surface area (ECSA), resulting in a limited enhancement in Pt mass activity (MA). Single-atom surface modification of Pt catalysts can significantly enhance the reaction kinetics of single molecule, but it is less effective for HOR process that involve multiple molecules, i.e. H2 and OH-. Here we use a single-atom Pd-Ru pair to boost the activity of Pt nano-catalysts without loss of surface-active sites. Using a mildly catalytic thermal pyrolysis approach, single-Pd and single-Ru atom pair are precisely decorated on Pt nanoparticle surfaces, which is confirmed by Extended X-Ray Absorption Fine Structure (EXAFS) analysis. Density functional theory (DFT) calculations and ab-initio molecular dynamics (AIMD) simulations show the preferred adsorption of single-atom Pd and Ru dopants over Pd and Ru clustering on Pt surfaces. The single-atom Pd-Ru pair decorated Pt (Pd-Ru@Pt) catalyst features tri-active sites including: hydrophilic Pd promoting activation of adsorbed hydrogen atoms (Hads) via the hydrogen spill-over effect, oxyphilic Ru facilitating the adsorption of hydroxide molecules (OHads), and highly-catalytic Pt facilitating water formation with increased availability of Hads and OHads. In addition, the dopant decoration also reduces the hydrogen binding energy due to the shift of the (d) band center relative to the Fermi Level. The tri-active Pd-Ru@Pt catalyst shows 15.9 times higher area specific activity (SA) and 17.5 times larger mass activity (MA) than the state-of-the-art nano-Pt catalyst for HOR, and 2 times higher MA than nano-Pt for the hydrogen evolution reaction (HER). The mass exchange current density of single-atom Pd-Ru@Pt/C for the HOR/HER was 6.0 times that of the Pt/C, corresponding to 9.7 times that of Pd@Pt/C and 6.5 times that of Ru@Pt/C. The superior HOR/HER performance of the tri-active site catalyst is also demonstrated in ammonia and hydrogen pumps for practical application.
Immunohistochemical Expression of β-catenin, Ki67, CD3 and CD18 in Canine Colorectal Adenomas and Adenocarcinomas
Authors: Herstad Kristin Marie Valand , Gunnes Gjermund , Rørtveit Runa , Kolbjørnsen Øyvor , Tran Linh , Skancke Ellen
Published: August 2020

Background Inflammation is believed to influence the human colorectal carcinogenesis and may have impact upon prognosis and survival. High presence of tumour-infiltrating CD3+ T-cells, is associated with a better outcome in humans with colorectal cancer. The mucosal immunophenotype in dogs with colorectal cancer is poorly described. The aim of this study was to investigate whether the density, distribution and grade of tumour-infiltrating immune cells (TIIs) in canine colorectal tumours is associated with histologic indicators of malignancy and can be considered a prognostic factor in dogs. This retrospective case-control study was performed on formalin-fixed, paraffin-embedded tissue samples from dogs with histologically confirmed colorectal adenoma (n=18) and adenocarcinoma (n=5) collected from archived samples. The samples had been collected by colonoscopy, surgery or during postmortem examination. Healthy colonic tissue obtained post mortem from dogs euthanized of reasons not involving the gastrointestinal tract, served as control tissue (n=9). Results: The tumour samples had significantly lower numbers of CD3+ T- cells in the epithelium compartment (Wilcoxon test, p=0,0006), as well as significantly lower number of CD18+ cells in the lamina propria, compared to control samples (Wilcoxon test, p=0,001). The Ki67 positive cells showed a strong signal in adenomas and adenocarcinomas. There was no clear distinction with regards to expression levels of the markers for tumour progression (β-catenin, and Ki67) between adenomas and adenocarcinomas. Colonic samples from control dogs had uniform staining of β-catenin along the cell membrane of epithelial cells. When compared to normal colonic cells, the expression levels of cytoplasmic β-catenin were significantly higher in adenomas and adenocarcinomas (Wilcoxon test, p=0,0002). None of the control samples showed positive staining of β-catenin in the nucleus of colonic cells. In contrast, adenocarcinoma and adenoma showed moderate to strong staining of the cell nucleus. Conclusions: β-catenin and Ki67 were not useful markers in distinguishing adenomas from adenocarcinomas. The lower presence of CD18- and CD3+ cells in tumours compared to controls, indicates a reduced presence of histiocytes and T-cells which may have implications for the defense against cancer progression.
Growth Differentiation Factor-15 is a Biomarker for All-cause Mortality but Less Evident for Cardiovascular Outcomes: A Prospective Study
Authors: Bao Xue , Borné Yan , XU BIAO , Orho-Melander Marju , Nilsson Jan , Melander Olle , Engström Gunnar
Published: August 2020

Background
Previous studies have proposed growth differentiation factor-15 (GDF-15) as a predictor of adverse cardiovascular outcomes and mortality. The present study aimed to determine if such associations remain after accounting for markers of inflammation and cardiac dysfunction as well as death as a competing risk.
Methods
Plasma GDF-15 levels and cardiovascular risk factors were measured in individuals without cardiovascular diseases (n = 4,518, aged 57.4 ± 5.96 years, 39.2% men), who participated in Malmö Diet and Cancer-Cardiovascular Cohort during 1991–1994 and were followed up for more than 20 years. Incidence of coronary events, ischemic stroke, cardiovascular mortality and all-cause mortality was studied in relation to GDF-15 using Cox proportional hazards regression, with adjustment for potential confounders including high sensitive C-reactive protein (hsCRP) and N-terminal prohormone of brain natriuretic peptide (NT-proBNP). Confounding from death as competing risk was carefully checked using the Fine and Gray subdistribution hazard model.
Results
During follow-up, 473 coronary events, 366 ischemic stroke, 405 cardiovascular deaths, and 1,445 all-cause deaths occurred. The associations of GDF-15 with coronary events, ischemic stroke, or cardiovascular mortality were attenuated and non-significant after adjusting for NT-proBNP or controlling for death from other causes as a competing risk. All-cause mortality remained significantly related to GDF-15. After multivariate adjustment, the hazard ratio (95% confidence interval) for all-cause mortality was 1.60 (1.34, 1.91), in the top compared with the bottom quartile of GDF-15.
Conclusions
GDF-15 concentration is a robust biomarker for all-cause mortality but less reliable for coronary event, ischemic stroke or cardiovascular mortality.
Left Hemispheric Deficit in the Sustained Neuromagnetic Response to Periodic Click Trains in Children with ASD.
Authors: Stroganova Tatiana A , Komarov Kirill S , Goiaeva Dzerasa E , Obukhova Tatiana S , Ovsiannikova Tatiana M , Prokofiev Andrey O , Orekhova Elena V
Published: August 2020

Background: Deficits in perception and production of vocal pitch are often observed in people with autism spectrum disorders (ASD), but the neural basis of these abnormalities is unknown. In magnetoencephalogram (MEG), spectrally complex periodic sounds trigger two continuous neural responses – the Auditory Steady State Response (ASSR) and the Sustained Field (SF). It has been shown that the SF in neuro-typical individuals is associated with low-level analysis of pitch in the ‘pitch processing center’ of the Heschl’s gyrus. Therefore, this auditory response may reflect vocal pitch processing abnormalities in ASD. The SF, however, has never been studied in people with these disorders. Methods: We used MEG and individual brain models to investigate the ASSR and SF evoked by monaural 40 Hz click trains in 7-13-year-old boys with ASD (N=35) and neuro-typical (NT) boys (N=35). Results: In agreement with the previous research in adults, the cortical sources of the SF in children were located in the left and right Heschl’s gyri, anterolateral to those of the ASSR. In both groups, the SF and ASSR dominated in the right hemisphere and were higher contralaterally to the stimulated ear. The ASSR increased with age in both NT and ASD children and did not differ between the groups. The SF did not change between 7 and 13 years. It was moderately decreased in both hemispheres and was markedly delayed and displaced in the left hemisphere in boys with ASD. The SF delay in participants with ASD was present irrespective of their intelligence level and severity of autism symptoms. Limitations: We have not tested language abilities of our participants. Therefore, the link between SF and processing of vocal pitch in children with ASD remains speculative. Conclusion: The selective left-hemispheric SF abnormalities found in children with ASD are consistent with a deficit at a low level of pitch processing, which in turn may contribute to their difficulties in perception and production of linguistic prosody.