The Bone Markers Sclerostin, Osteoprotegerin, and Bone-Specific Alkaline Phosphatase Are Related to Insulin Resistance in Children and Adolescents, Independent of Their Association with Growth and Obesity.

Abstract:
BACKGROUND/AIMS
Sclerostin, osteoprotegerin, and bone-specific alkaline phosphatase (B-ALP), which are primarily related to bone metabolism, have been linked with insulin resistance in adults. We aimed to evaluate the association of these markers with growth, obesity, and parameters of insulin resistance in lean and obese children and adolescents.

METHODS
We measured sclerostin, osteoprotegerin, and B-ALP in fasting and oral glucose tolerance test (oGTT) serum samples from 1,325 children and adolescents, and during 24-h profiles and after exercise and glucose exposure in young adults.

RESULTS
In addition to the positive relationship with height standard deviation scores (SDS), sclerostin (r = 0.035, p < 0.001) and B-ALP (r = 0.06, p = 0.028) increased, whereas osteoprotegerin (r = -0.098, p < 0.001) decreased with BMI SDS. Furthermore, B-ALP correlated with fasting- and oGTT-derived markers of glucose and insulin metabolism suggestive of insulin resistance. To evaluate potential confounding diurnal variation of bone markers, we performed 24-h profiles. B-ALP and osteoprotegerin had lower night-time levels. Exercise acutely and transiently increased B-ALP and osteoprotegerin levels, but glucose ingestion had no effect.

CONCLUSIONS
Besides their association with growth, sclerostin and osteoprotegerin levels are altered in childhood obesity. Particularly B-ALP was related to insulin resistance indices. Our findings accent the link between bone, growth, and insulin resistance.

Stanik|Juraj|J| Kratzsch|Jürgen|J| Landgraf|Kathrin|K| Vogel|Mandy|M| Thiery|Joachim|J| Kiess|Wieland|W| Körner|Antje|A|

D048868:Adaptor Proteins, Signal Transducing

Sclerostin
Osteoprotegerin
Bone-specific alkaline phosphatase
Insulin resistance
Children
Growth
Obesity


Fetal aortic valvuloplasty for evolving hypoplastic left heart syndrome: postnatal outcomes of the first 100 patients.

Abstract:
BACKGROUND
Fetal aortic valvuloplasty can be performed for severe midgestation aortic stenosis in an attempt to prevent progression to hypoplastic left heart syndrome (HLHS). A subset of patients has achieved a biventricular (BV) circulation after fetal aortic valvuloplasty. The postnatal outcomes and survival of the BV patients, in comparison with those managed as HLHS, have not been reported.

METHODS AND RESULTS
We included 100 patients who underwent fetal aortic valvuloplasty for severe midgestation aortic stenosis with evolving HLHS from March 2000 to January 2013. Patients were categorized based on postnatal management as BV or HLHS. Clinical records were reviewed. Eighty-eight fetuses were live-born, and 38 had a BV circulation (31 from birth, 7 converted after initial univentricular palliation). Left-sided structures, namely aortic and mitral valve sizes and left ventricular volume, were significantly larger in the BV group at the time of birth (P<0.01). After a median follow-up of 5.4 years, freedom from cardiac death among all BV patients was 96±4% at 5 years and 84±12% at 10 years, which was better than HLHS patients (log-rank P=0.04). There was no cardiac mortality in patients with a BV circulation from birth. All but 1 of the BV patients required postnatal intervention; 42% underwent aortic or mitral valve replacement. On the most recent echocardiogram, the median left ventricular end-diastolic volume z score was +1.7 (range, -1.3 to +8.2), and 80% had normal ejection fraction.

CONCLUSIONS
Short- and intermediate-term survival among patients who underwent fetal aortic valvuloplasty and achieved a BV circulation postnatally is encouraging. However, morbidity still exists, and ongoing assessment is warranted.

Freud|Lindsay R|LR|
McElhinney|Doff B|DB|
Marshall|Audrey C|AC|
Marx|Gerald R|GR|
Friedman|Kevin G|KG|
del Nido|Pedro J|PJ|
Emani|Sitaram M|SM|
Lafranchi|Terra|T|
Silva|Virginia|V|
Wilkins-Haug|Louise E|LE|
Benson|Carol B|CB|
Lock|James E|JE|
Tworetzky|Wayne|W|

D001024:Aortic Valve Stenosis
D063126:Balloon Valvuloplasty
D003326:Coronary Circulation
D018450:Disease Progression
D005260:Female
D005315:Fetal Diseases
D005500:Follow-Up Studies
D005865:Gestational Age
D006801:Humans
D018636:Hypoplastic Left Heart Syndrome
D007231:Infant, Newborn
D053208:Kaplan-Meier Estimate
D011247:Pregnancy
D011256:Pregnancy Outcome
D016216:Ultrasonography, Prenatal

hypoplastic left heart syndrome
aortic valve stenosis
balloon valvuloplasty
fetal heart
heart defects, congenital
pediatrics
treatment outcome


Cellular Phone Use and Risk of Tumors: Systematic Review and Meta-Analysis.

Abstract: We investigated whether cellular phone use was associated with increased risk of tumors using a meta-analysis of case-control studies. PubMed and EMBASE were searched from inception to July 2018. The primary outcome was the risk of tumors by cellular phone use, which was measured by pooling each odds ratio (OR) and its 95% confidence interval (CI). In a meta-analysis of 46 case-control studies, compared with never or rarely having used a cellular phone, regular use was not associated with tumor risk in the random-effects meta-analysis. However, in the subgroup meta-analysis by research group, there was a statistically significant positive association (harmful effect) in the Hardell et al. studies (OR, 1.15-95% CI, 1.00 to 1.33- n = 10), a statistically significant negative association (beneficial effect) in the INTERPHONE-related studies (case-control studies from 13 countries coordinated by the International Agency for Research on Cancer (IARC); (OR, 0.81-95% CI, 0.75 to 0.89-n = 9), and no statistically significant association in other research groups' studies. Further, cellular phone use with cumulative call time more than 1000 h statistically significantly increased the risk of tumors. This comprehensive meta-analysis of case-control studies found evidence that linked cellular phone use to increased tumor risk.

Choi|Yoon-Jung|YJ|
Moskowitz|Joel M|JM|
Myung|Seung-Kwon|SK|
Lee|Yi-Ryoung|YR|
Hong|Yun-Chul|YC|

cellular phone
tumor
meta-analysis
case-control study
electromagnetic field


Cost-effectiveness analysis in the Spanish setting of the PEAK trial of panitumumab plus mFOLFOX6 compared with bevacizumab plus mFOLFOX6 for first-line treatment of patients with wild-type RAS metastatic colorectal cancer.

Abstract:
OBJECTIVE
To assess the cost-effectiveness of panitumumab in combination with mFOLFOX6 (oxaliplatin, 5-fluorouracil, and leucovorin) vs bevacizumab in combination with mFOLFOX6 as first-line treatment of patients with wild-type RAS metastatic colorectal cancer (mCRC) in Spain.

METHODS
A semi-Markov model was developed including the following health states: Progression free; Progressive disease: Treat with best supportive care; Progressive disease: Treat with subsequent active therapy; Attempted resection of metastases; Disease free after metastases resection; Progressive disease: after resection and relapse; and Death. Parametric survival analyses of patient-level progression free survival and overall survival data from the PEAK Phase II clinical trial were used to estimate health state transitions. Additional data from the PEAK trial were considered for the dose and duration of therapy, the use of subsequent therapy, the occurrence of adverse events, and the incidence and probability of time to metastasis resection. Utility weightings were calculated from patient-level data from panitumumab trials evaluating first-, second-, and third-line treatments. The study was performed from the Spanish National Health System (NHS) perspective including only direct costs. A life-time horizon was applied. Probabilistic sensitivity analyses and scenario sensitivity analyses were performed to assess the robustness of the model.

RESULTS
Based on the PEAK trial, which demonstrated greater efficacy of panitumumab vs bevacizumab, both in combination with mFOLFOX6 first-line in wild-type RAS mCRC patients, the estimated incremental cost per life-year gained was €16,567 and the estimated incremental cost per quality-adjusted life year gained was €22,794. The sensitivity analyses showed the model was robust to alternative parameters and assumptions.

LIMITATIONS
The analysis was based on a simulation model and, therefore, the results should be interpreted cautiously.

CONCLUSIONS
Based on the PEAK Phase II clinical trial and taking into account Spanish costs, the results of the analysis showed that first-line treatment of mCRC with panitumumab + mFOLFOX6 could be considered a cost-effective option compared with bevacizumab + mFOLFOX6 for the Spanish NHS.

Rivera|Fernando|F| Valladares|Manuel|M| Gea|Salvador|S| López-Martínez|Noemí|N|

D000971:Antineoplastic Combined Chemotherapy Protocols

cost-effectiveness analysis
Panitumumab
wild-type RAS
metastatic colorectal cancer


Millisecond time resolution correlative light and electron microscopy for dynamic cellular processes.

Abstract: Molecular motors propel cellular components at velocities up to microns per second with nanometer precision. Imaging techniques combining high temporal and spatial resolution are therefore indispensable to understand the cellular mechanics at the molecular level. For example, intraflagellar transport (IFT) trains constantly shuttle ciliary components between the base and tip of the eukaryotic cilium. 3-D electron microscopy has revealed IFT train morphology and position, but was unable to correlate these features with the direction of train movement. Here, we present the methodology required to combine live-cell imaging at millisecond frame rates with electron tomography. Using this approach, we were able to correlate the direction of movement of every IFT train in a flagellum with its morphology and microtubule track. The method is ready to be further adapted for other experimental systems, including studies of single molecule dynamics.

Time-resolved correlative light and electron microscopy


Computerized implementation of higher-order electron-correlation methods and their linear-scaling divide-and-conquer extensions.

Abstract: We have implemented a linear-scaling divide-and-conquer (DC)-based higher-order coupled-cluster (CC) and Møller-Plesset perturbation theories (MPPT) as well as their combinations automatically by means of the tensor contraction engine, which is a computerized symbolic algebra system. The DC-based energy expressions of the standard CC and MPPT methods and the CC methods augmented with a perturbation correction were proposed for up to high excitation orders [e.g., CCSDTQ, MP4, and CCSD(2)TQ ]. The numerical assessment for hydrogen halide chains, polyene chains, and first coordination sphere (C1) model of photoactive yellow protein has revealed that the DC-based correlation methods provide reliable correlation energies with significantly less computational cost than that of the conventional implementations. © 2017 Wiley Periodicals, Inc.

Nakano|Masahiko|M| Yoshikawa|Takeshi|T| Hirata|So|S| Seino|Junji|J| Nakai|Hiromi|H|0000-0001-5646-2931

linear-scaling
tensor contraction engine
divide-and-conquer method
electron-correlation theory


Endoscopic Ultrasound-Guided Direct Intervention for Solid Pancreatic Tumors.

Abstract: Development and use of linear-array echoendoscope and endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) have made endoscopic ultrasound (EUS) more of an interventional procedure than a purely diagnostic procedure. This is a literature review of previously published clinical studies on EUS-guided direct intervention for solid pancreatic tumors, including EUS-guided fine needle injection (EUS-FNI) of antitumor agents, EUS-guided fiducial marker placement, EUS-guided brachytherapy and EUS-guided tumor ablation.

Fine needle injection
Endosonography
Pancreatic neoplasms
Pancreatic neuroendocrine tumor


Short- and long-term reproducibility of BOLD signal change induced by breath-holding at 1.5 and 3 T.

Abstract: Cerebrovascular reactivity (CVR) can give insight into the cerebrovascular function. CVR can be estimated by measuring a blood-oxygen-level-dependent (BOLD) response combined with breath-holding (BH). The reproducibility of this technique has been addressed and existing studies have focused on short-term reproducibility using a 3 T magnetic resonance imaging (MRI) system. However, little is known about the long-term reproducibility of this procedure and the corresponding reproducibility using a 1.5 T MRI system. Here, we systematically examined the short- and long-term reproducibility of BOLD responses to BH across field strengths. Nine subjects participated in three MRI sessions separated by 30 minutes (sessions 1 and 2: short term) and 68-92 days (sessions 1 and 3, long term) at both 1.5 and 3 T MRI. Our findings revealed that significant differences between field strengths were detected in the activated gray matter volume and BOLD signal change (both P < 0.001), with smaller magnitudes at 1.5 T. However, activation patterns were reproducible, independent of the time interval, brain region or field strength. All interscan coefficient of variation values were below the 33% fiducial limit, and the intraclass correlation coefficient values were above 0.4, which is usually considered the acceptability limit in functional studies. These findings suggest that the response of BOLD signal to BH for assessing CVR is reproducible over time at 1.5 and 3 T. This technique can be considered a tool for monitoring longitudinal changes in patients with cerebrovascular diseases, and its use should be encouraged for clinical 1.5 T MRI systems.

Peng|Shin-Lei|SL|0000-0001-9241-1808 Yang|Hui-Chieh|HC| Chen|Chun-Ming|CM| Shih|Cheng-Ting|CT|

cerebrovascular reactivity
field strength
CO2
functional magnetic resonance imaging
hypercapnia


Environmental Cleaning in Resource-Limited Settings.

Abstract:
Purpose of review
Environmental surfaces in healthcare facilities, particularly in a patient room, are a critical pathway for healthcare-associated pathogen transmission. Despite well-established guides and recommendations regarding environmental surface cleaning and disinfection, there are several challenges in resource-limited settings. This viewpoint article will discuss the practice of environmental cleaning in resource-limited settings including challenges and relationship between environment and healthcare-associated infections in this setting and outlines pre-requisites to overcome these challenges.

Recent findings
Despite several barriers and challenges, environmental cleaning is a crucial component to help reduce transmission of healthcare-associated infections and multi-drug-resistant pathogens as well as emerging infectious disease-associated pathogens in resource-limited settings. However, there is a need to develop a multi-modal strategy together with a mechanism for monitor and feedback to improve the practices of environmental cleaning in resource-limited settings.

Summary
Additional researches on the barriers and implementation gaps and the role of collaborative network as well as how to apply technology would provide significant insights on the practices of environmental cleaning in resource-limited settings.

Cleaning
Resource-limited settings
Review
Environment
Healthcare-associated infections
Nosocomial infections


Development and Initial Validation of a Client-Rated MET-CBT Adherence Measure.

Abstract: Traditional mechanisms for rating adherence or fidelity are labor-intensive. We developed and validated a tool to rate adherence to Motivational Enhancement Therapy-Cognitive Behavioral Treatment (MET-CBT) through anonymous client surveys. The instrument was used to survey clients in 3 methadone programs over 2 waves. Explanatory and Confirmatory Factor Analyses were used to establish construct validity for both MET and CBT. Internal consistency based on Cronbach's alpha was within adequate range (α > 0.70) for all but 2 of the subscales in one of the samples. Consensus between clients' ratings (r(wg(j)) scores) were in the range of 0.6 and higher, indicating a moderate to strong degree of agreement among clients' ratings of the same counselor. These results suggest that client surveys could be used to measure adherence to MET-CBT for quality monitoring that is more objective than counselor self-report and less resource-intensive than supervisor review of taped sessions. However, additional work is needed to develop this scale.

Ulaszek|Wendy R|WR|
Lin|Hsiu-Ju|HJ|
Frisman|Linda K|LK|
Sampl|Susan|S|
Godley|Susan Harrington|SH|
Steinberg-Gallucci|Karen L|KL|
Kamon|Jody L|JL|
O'Hagan-Lynch|Margaret|M|

MET-CBT
fidelity
client ratings
implementation


Downregulation of long noncoding RNA DLEU1 attenuates hypersensitivity in chronic constriction injury-induced neuropathic pain in rats by targeting miR-133a-3p/SRPK1 axis.

Abstract:
BACKGROUND
Neuropathic pain belongs to chronic pain and is caused by the primary dysfunction of the somatosensory nervous system. Long noncoding RNAs (lncRNAs) have been reported to regulate neuronal functions and play significant roles in neuropathic pain. DLEU1 has been indicated to have close relationship with neuropathic pain. Therefore, our study focused on the significant role of DLEU1 in neuropathic pain rat models.

METHODS
We first constructed a chronic constrictive injury (CCI) rat model. Paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) were employed to evaluate hypersensitivity in neuropathic pain. RT-qPCR was performed to analyze the expression of target genes. Enzyme-linked immunosorbent assay (ELISA) was conducted to detect the concentrations of interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and IL-1β. The underlying mechanisms of DLEU1 were investigated using western blot and luciferase reporter assays.

RESULTS
Our findings showed that DLEU1 was upregulated in CCI rats. DLEU1 knockdown reduced the concentrations of IL-6, IL-1β and TNF-α in CCI rats, suggesting that neuroinflammation was inhibited by DLEU1 knockdown. Besides, knockdown of DLEU1 inhibited neuropathic pain behaviors. Moreover, it was confirmed that DLEU1 bound with miR-133a-3p and negatively regulated its expression. SRPK1 was the downstream target of miR-133a-3p. DLEU1 competitively bound with miR-133a-3p to upregulate SRPK1. Finally, rescue assays revealed that SRPK1 overexpression rescued the suppressive effects of silenced DLEU1 on hypersensitivity in neuropathic pain and inflammation of spinal cord in CCI rats.

CONCLUSION
DLEU1 regulated inflammation of the spinal cord and mediated hypersensitivity in neuropathic pain in CCI rats by binding with miR-133a-3p to upregulate SRPK1 expression.

Li|Zhen|Z| Li|Aiyuan|A| Yan|Liping|L| Yang|Tian|T| Xu|Wei|W| Fan|Pengju|P|0000-0001-6593-8663


An Essential Role for Coagulase in Staphylococcus aureus Biofilm Development Reveals New Therapeutic Possibilities for Device-Related Infections.

Abstract: High-level resistance to antimicrobial drugs is a major factor in the pathogenesis of chronic Staphylococcus aureus biofilm-associated, medical device-related infections. Antimicrobial susceptibility analysis revealed that biofilms grown for ≤ 24 hours on biomaterials conditioned with human plasma under venous shear in iron-free cell culture medium were significantly more susceptible to antistaphylococcal antibiotics. Biofilms formed under these physiologically relevant conditions were regulated by SaeRS and dependent on coagulase-catalyzed conversion of fibrinogen into fibrin. In contrast, SarA-regulated biofilms formed on uncoated polystyrene in nutrient-rich bacteriological medium were mediated by the previously characterized biofilm factors poly-N-acetyl glucosamine, fibronectin-binding proteins, or autolytic activity and were antibiotic resistant. Coagulase-mediated biofilms exhibited increased antimicrobial resistance over time (>48 hours) but were always susceptible to dispersal by the fibrinolytic enzymes plasmin or nattokinase. Biofilms recovered from infected central venous catheters in a rat model of device-related infection were dispersed by nattokinase, supporting the important role of the biofilm phenotype and identifying a potentially new therapeutic approach with antimicrobials and fibrinolytic drugs, particularly during the early stages of device-related infection.

Zapotoczna|Marta|M|
McCarthy|Hannah|H|
Rudkin|Justine K|JK|
O'Gara|James P|JP|
O'Neill|Eoghan|E|

coagulase Staphylococcus biofilm infection antimicrobial susceptibility


Congenital Hemolytic Anemias: Is There a Role for the Immune System?

Abstract: Congenital hemolytic anemias (CHAs) are a heterogeneous group of rare hereditary conditions including defects of erythrocyte membrane proteins, red cell enzymes, and disorders due to defective erythropoiesis. They are characterized by variable degree of anemia, chronic extravascular hemolysis, reduced erythrocyte life span, splenomegaly, jaundice, biliary lithiasis, and iron overload. Although few data are reported on the role of the immune system in CHAs, several immune-mediated mechanisms may be involved in the pathogenesis of these rare diseases. We reported in ~60% of patients with hereditary spherocytosis (HS), the presence of naturally-occurring autoantibodies (NAbs) directed against different membrane proteins (α- and β-spectrin, band 3, and dematin). Positive HS subjects showed a more hemolytic pattern and NAbs were more evident in aged erythrocytes. The latter is in line with the function of NAbs in the opsonization of damaged/senescent erythrocytes and their consequent removal in the spleen. Splenectomy, usually performed to reduce erythrocyte catheresis and improve Hb levels, has different efficacy in various CHAs. Median Hb increase is 3 g/dL in HS, 1.6-1.8 g/dL in pyruvate kinase deficiency (PKD), and 1 g/dL in congenital dyserythropoietic anemias (CDA) type II. Consistently with clinical severity, splenectomy is performed in 20% of HS, 45% of CDAII, and in 60% of PKD patients. Importantly, sepsis and thrombotic events have been registered, particularly in PKD with a frequency of ~7% for both. Furthermore, we analyzed the role of pro-inflammatory cytokines and found that interleukin 10 and interferon γ, and to a lesser extent interleukin 6, were increased in all CHAs compared with controls. Moreover, CDAII and enzymatic defects showed increased tumor necrosis factor-α and reduced interleukin 17. Finally, we reported that iron overload occurred in 31% of patients with membrane defects, in ~60% of CDAII cases, and in up to 82% of PKD patients (defined by MRI liver iron concentration >4 mg Fe/gdw). Hepcidin was slightly increased in CHAs compared with controls and positively correlated with ferritin and with the inflammatory cytokines interleukin 6 and interferon γ. Overall the results suggest the existence of a vicious circle between chronic hemolysis, inflammatory response, bone marrow dyserythropoiesis, and iron overload.

Zaninoni|Anna|A|
Fermo|Elisa|E|
Vercellati|Cristina|C|
Marcello|Anna Paola|AP|
Barcellini|Wilma|W|
Bianchi|Paola|P|

congenital hemolytic anemias
iron overload
splenectomy
cytokines
inflammation
naturally occurring antibodies


What works in implementation of integrated care programs for older adults with complex needs? A realist review.

Abstract:
Purpose
A realist review of the evaluative evidence was conducted on integrated care (IC) programs for older adults to identify key processes that lead to the success or failure of these programs in achieving outcomes such as reduced healthcare utilization, improved patient health, and improved patient and caregiver experience.

Data sources
International academic literature was searched in 12 indexed, electronic databases and gray literature through internet searches, to identify evaluative studies.

Study selection
Inclusion criteria included evaluative literature on integrated, long-stay health and social care programs, published between January 1980 and July 2015, in English.

Data extraction
Data were extracted on the study purpose, period, setting, design, population, sample size, outcomes, and study results, as well as explanations of mechanisms and contextual factors influencing outcomes.

Results of data synthesis
A total of 65 articles, representing 28 IC programs, were included in the review. Two context-mechanism-outcome configurations (CMOcs) were identified: (i) trusting multidisciplinary team relationships and (ii) provider commitment to and understanding of the model. Contextual factors such as strong leadership that sets clear goals and establishes an organizational culture in support of the program, along with joint governance structures, supported team collaboration and subsequent successful implementation. Furthermore, time to build an infrastructure to implement and flexibility in implementation, emerged as key processes instrumental to success of these programs.

Conclusions
This review included a wide range of international evidence, and identified key processes for successful implementation of IC programs that should be considered by program planners, leaders and evaluators.

Kirst|Maritt|M|
Im|Jennifer|J|
Burns|Tim|T|
Baker|G Ross|GR|
Goldhar|Jodeme|J|
O'Campo|Patricia|P|
Wojtak|Anne|A|
Wodchis|Walter P|WP|

D019033:Delivery of Health Care, Integrated

integrated care
older adults
care coordination
health and social care services


Early treatment of COVID-19 patients with hydroxychloroquine and azithromycin: A retrospective analysis of 1061 cases in Marseille, France.

Abstract:
BACKGROUND
In France, the combination hydroxychloroquine (HCQ) and azithromycin (AZ) is used in the treatment of COVID-19.

METHODS
We retrospectively report on 1061 SARS-CoV-2 positive tested patients treated for at least three days with the following regimen: HCQ (200 mg three times daily for ten days) + AZ (500 mg on day 1 followed by 250 mg daily for the next four days). Outcomes were death, clinical worsening (transfer to ICU, and >10 day hospitalization) and viral shedding persistence (>10 days).

RESULTS
A total of 1061 patients were included in this analysis (46.4% male, mean age 43.6 years - range 14-95 years). Good clinical outcome and virological cure were obtained in 973 patients within 10 days (91.7%). Prolonged viral carriage was observed in 47 patients (4.4%) and was associated to a higher viral load at diagnosis (p < .001) but viral culture was negative at day 10. All but one, were PCR-cleared at day 15. A poor clinical outcome (PClinO) was observed for 46 patients (4.3%) and 8 died (0.75%) (74-95 years old). All deaths resulted from respiratory failure and not from cardiac toxicity. Five patients are still hospitalized (98.7% of patients cured so far). PClinO was associated with older age (OR 1.11), severity of illness at admission (OR 10.05) and low HCQ serum concentration. PClinO was independently associated with the use of selective beta-blocking agents and angiotensin II receptor blockers (p < .05). A total of 2.3% of patients reported mild adverse events (gastrointestinal or skin symptoms, headache, insomnia and transient blurred vision).

CONCLUSION
Administration of the HCQ+AZ combination before COVID-19 complications occur is safe and associated with a very low fatality rate in patients.

Million|Matthieu|M|
Lagier|Jean-Christophe|JC|
Gautret|Philippe|P|
Colson|Philippe|P|
Fournier|Pierre-Edouard|PE|
Amrane|Sophie|S|
Hocquart|Marie|M|
Mailhe|Morgane|M|
Esteves-Vieira|Vera|V|
Doudier|Barbara|B|
Aubry|Camille|C|
Correard|Florian|F|
Giraud-Gatineau|Audrey|A|
Roussel|Yanis|Y|
Berenger|Cyril|C|
Cassir|Nadim|N|
Seng|Piseth|P|
Zandotti|Christine|C|
Dhiver|Catherine|C|
Ravaux|Isabelle|I|
Tomei|Christelle|C|
Eldin|Carole|C|
Tissot-Dupont|Hervé|H|
Honoré|Stéphane|S|
Stein|Andreas|A|
Jacquier|Alexis|A|
Deharo|Jean-Claude|JC|
Chabrière|Eric|E|
Levasseur|Anthony|A|
Fenollar|Florence|F|
Rolain|Jean-Marc|JM|
Obadia|Yolande|Y|
Brouqui|Philippe|P|
Drancourt|Michel|M|
La Scola|Bernard|B|
Parola|Philippe|P|
Raoult|Didier|D|


Co-transport of U(VI), humic acid and colloidal gibbsite in water-saturated porous media.

Abstract: The release of uranyl from uranium tailing sites is a widely concerned environmental issue, with limited investigations on the effect of coexistence of various colloids. Gibbsite colloids extensively exist, together with ubiquitous humic substances, in uranium polluted waters at tailing sites, due to high concentration of dissolved Al in acid mine drainage. In this context, we investigated the co-transport of U(VI), gibbsite colloids and humic acid (HA) as a function of pH and ionic strength at a U(VI) concentration (5.0 × 10-5 M) relevant within mine tailings and related waste. It was found that, owing to electrostatic attraction, gibbsite colloids and HA associated with each other and transported simultaneously regardless of U(VI) presence. Besides the impact of pH and ionic strength, whether gibbsite colloids facilitated U(VI) transport depended on HA concentration. Gibbsite colloids impeded U(VI) transport at relatively low HA concentration (≤5 mg L-1), because associated colloids loaded with U(VI) were positively charged which favored colloid retention on negatively charged quartz sand in the column. U(VI) together with gibbsite colloids and low concentration HA was completely blocked at natural pH and/or high ionic strength. At relatively high HA concentration (20 mg L-1), however, the associated colloids showed negative zeta potential which facilitated U(VI) transport because of repulsion between negatively charged colloids and quartz sand. Meanwhile, high concentration of HA dramatically accelerated the transport of gibbsite colloids. These results implied that gibbsite colloids might imped U(VI) migration at uranium tailing sites unless the aquifers are enriched with abundant humic substances.

Yang|Junwei|J| Ge|Mengtuan|M| Jin|Qiang|Q| Chen|Zongyuan|Z| Guo|Zhijun|Z|

U(VI)
Humic acid
Gibbsite colloids
Transport


Adult Basic Life Support: 2020 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations.

Abstract: This 2020 International Consensus on Cardiopulmonary Resuscitation (CPR) and Emergency Cardiovascular Care Science With Treatment Recommendations on basic life support summarizes evidence evaluations performed for 22 topics that were prioritized by the Basic Life Support Task Force of the International Liaison Committee on Resuscitation. The evidence reviews include 16 systematic reviews, 5 scoping reviews, and 1 evidence update. Per agreement within the International Liaison Committee on Resuscitation, new or revised treatment recommendations were only made after a systematic review. Systematic reviews were performed for the following topics: dispatch diagnosis of cardiac arrest, use of a firm surface for CPR, sequence for starting CPR (compressions-airway-breaths versus airway-breaths-compressions), CPR before calling for help, duration of CPR cycles, hand position during compressions, rhythm check timing, feedback for CPR quality, alternative techniques, public access automated external defibrillator programs, analysis of rhythm during chest compressions, CPR before defibrillation, removal of foreign-body airway obstruction, resuscitation care for suspected opioid-associated emergencies, drowning, and harm from CPR to victims not in cardiac arrest. The topics that resulted in the most extensive task force discussions included CPR during transport, CPR before calling for help, resuscitation care for suspected opioid-associated emergencies, feedback for CPR quality, and analysis of rhythm during chest compressions. After discussion of the scoping reviews and the evidence update, the task force prioritized several topics for new systematic reviews.

Olasveengen|Theresa M|TM|
Mancini|Mary E|ME|
Perkins|Gavin D|GD|
Avis|Suzanne|S|
Brooks|Steven|S|
Castrén|Maaret|M|
Chung|Sung Phil|SP|
Considine|Julie|J|
Couper|Keith|K|
Escalante|Raffo|R|
Hatanaka|Tetsuo|T|
Hung|Kevin K C|KKC|
Kudenchuk|Peter|P|
Lim|Swee Han|SH|
Nishiyama|Chika|C|
Ristagno|Giuseppe|G|
Semeraro|Federico|F|
Smith|Christopher M|CM|
Smyth|Michael A|MA|
Vaillancourt|Christian|C|
Nolan|Jerry P|JP|
Hazinski|Mary Fran|MF|
Morley|Peter T|PT|
|||

emergency medical services communication systems


Chromatin Immunoprecipitation (ChIP) Assay in Candida albicans.

Abstract: Chromatin immunoprecipitation (ChIP) is a widely used technique which can determine the in vivo association of a specific protein on a particular DNA locus in the genome. In this method cross-linked chromatin is sheared and immunoprecipitated with antibodies raised against a target protein of interest. The end result of this process is the enrichment of DNA fragments associated with the desired protein. Thus, interactions between proteins and genomic loci in cellular context can be determined by this technique. Here, we are describing a ChIP protocol that is optimized for Candida albicans. The protocol requires 4-5 days for completion of the assay and has been used to produce robust ChIP results for diverse proteins in this organism and its related species including Candida dubliniensis and Candida tropicalis.

Mitra|Sreyoshi|S|
Rai|Laxmi Shanker|LS|
Chatterjee|Gautam|G|
Sanyal|Kaustuv|K|

D002176:Candida albicans
D047369:Chromatin Immunoprecipitation

Antibody
Candida dubliniensis
Candida tropicalis
Affinity purification
Microarray
Next-generation sequencing
Polymerase chain reaction (PCR)
Protein–DNA interaction


MR-guided vacuum-assisted breast biopsy of MRI-only lesions: a single center experience.

Abstract:
PURPOSE
The purpose of this study was to compare three different biopsy devices on false-negative and underestimation rates in MR-guided, vacuum-assisted breast biopsy (VABB) of MRI-only lesions.

METHODS
This retrospective, single-center study was IRB-approved. Informed consent was waived. 467 consecutive patients underwent 487 MR-guided VABB using three different 8-10-gauge-VABB devices (Atec-9-gauge,A; Mammotome-8-gauge,M; Vacora-10-gauge,V). VABB data (lesion-type, size, biopsy device, histopathology) were compared to final diagnosis (surgery, n = 210 and follow-up, n = 277). Chi-square, and Kruskal-Wallis tests were applied. P values < 0.05 were considered significant.

RESULTS
Final diagnosis was malignant in 104 (21.4 %), high risk in 64 (13.1 %) and benign in 319 (65.5 %) cases. Eleven of 328 (3.4 %) benign-rated lesions were false-negative (1/95, 1.1 %, A; 2/73, 2.7 %, M; 8/160 5.0 % V; P = 0.095). Eleven high-risk (11/77, 14.3 %) lesions proved to be malignant (3/26, 11.5 % A; 4/12, 33.3 % M; 4/39, 10.3 % V; P = 0.228). Five of 34 (14.7 %) DCIS were upgraded to invasive cancer (2/15, 13.3 %, A; 1/6, 16.6 % M; 2/13, 15.3 %, V; P = 0.977). Lesion size (P = 0.05) and type (mass vs. non-mass, P = 0.107) did not differ significantly.

CONCLUSION
MR-guided VABB is an accurate method for diagnosis of MRI-only lesions. No significant differences on false-negative and underestimation rates were observed between three different biopsy devices.

KEY POINTS
• MR-guided VABB is an accurate procedure for the diagnosis of MRI-only lesions. • Similar false-negative and underestimation rates allow all three different MR-guided VABB devices for clinical application. • High-risk lesions should undergo surgery due to a substantial underestimation rate. • Agreement between MR-guided VABB and final diagnosis (benign/malignant) was 95.5% (465/487).

Spick|Claudio|C|
Schernthaner|Melanie|M|
Pinker|Katja|K|
Kapetas|Panagiotis|P|
Bernathova|Maria|M|
Polanec|Stephan H|SH|
Bickel|Hubert|H|
Wengert|Georg J|GJ|
Rudas|Margaretha|M|
Helbich|Thomas H|TH|
Baltzer|Pascal A|PA|

MRI-only lesions
Breast cancer
MR imaging
MR-guided biopsy
Vacuum assisted breast biopsy


Daily Well-Being Benefits of Physical Activity in Older Adults: Does Time or Type Matter?

Abstract:
Purpose of the Study
There is little debate that maintaining some level of physical activity in later life conveys positive benefits both physically and psychologically. What is less understood is the extent to which the type of activity or the length of time spent doing it matters when it comes to these benefits on the daily level. Here, we investigated (a) whether the presence of daily purposeful exercise (Exercise) or non-exercise physical activity (Activity) is sufficient for experiencing day-level benefits, or if time spent matters, and (b) whether there are differential well-being benefits of Exercise and Activity on the daily level.

Design and Methods
Older adults (N = 127; aged 60-95, Mage = 79.4) filled out surveys for 14 days, reporting daily Exercise and Activity behaviors as well as Positive and Negative Affect (PA/NA), Perceived Stress (PS), Perceived Health (PH), and Sleep Quality (SQ).

Results
Multilevel regression models showed that for purposeful exercise, more time spent was beneficial for PA, NA, and PH, but for PS, only the presence of exercise was important (time did not matter). For non-exercise activity, time did not have as great an influence as presence-doing any form of activity was beneficial for both PA and SQ. Exercise and Activity had largely independent (additive) effects.

Implications
Results reveal that both purposeful exercise and non-exercise activity convey independent daily well-being benefits, and that for some aspects of daily well-being, duration does matter. Findings can be applied in the development of physical activity education or engagement programs for older adults.

Whitehead|Brenda R|BR|
Blaxton|Jessica M|JM|

Exercise
Affect
Stress
Perceived health
Sleep


Association of hepatitis B infection with high-risk complications in total joint arthroplasty.

Abstract:
BACKGROUND
An increasing number of patients with hepatitis B virus (HBV) infection are undergoing total joint arthroplasty (TJA) surgery in China. Less attention is provided to the special populations and the purpose of this study is to assess the effect of HBV infection on the prognosis TJAs.

METHODS
We retrospectively reviewed patients who underwent elective primary hip and knee arthroplasties in Shanghai Huashan Hospital from 2013 to 2016. Non-hepatitis B cohort was built to match the case cohort to identify whether HBV infection was a risk factor associated with postoperative complications. A total number of 196 patients who underwent primary TJAs were involved in the study, including 49 patients with hepatitis B and 147 non-hepatitis B subjects.

RESULTS
Among all the patients with TJAs, 5.5% of patients were infected with HBV for the first time. The incidence rate of complications in patients after arthroplasty with hepatitis B infection was significantly higher than that in patients without hepatitis B (10.2% compared to 4.7%, P < 0.01). Surgical related complications (6.1% compared to 3.4%) and general medical complications (4.1% compared to 1.3%) were higher than those in non-B hepatitis group. Compared with non-B hepatitis group, the overall risk of hepatitis B infection increased by 25% (95% CI, 1.04-1.46; p < 0.01). Similar results were obtained for medical and surgical complications. HBV infection presented a 31% increased risk (95% CI, 1.02-1.62; p < 0.01) for medical complication and an 18% increased risk (95% CI, 1.10-1.26; p < 0.01) for surgical complication. No statistical difference was found between the surgical methods and sex. However, a significant difference of C-reactive protein (CRP) level was found between HBV infection group and the matched non-infected group (P < 0.01).

CONCLUSION
This is the first study to investigate the risk of perioperative complications of hepatitis B in Chinese TJAs patients. In consideration of the large population of HBV infection in China, more attention and medical care should be provided to patients with HBV infection who need to undergo TJA operation.

Wang|Jin|J| Zhao|Guanglei|G| Chen|Jie|J| Xia|Jun|J| Wang|Siqun|S| Huang|Gangyong|G| Chen|Feiyan|F| Shi|Jingsheng|J| Yang|Yuanqing|Y| Wei|Yibing|Y|

Hepatitis B infection
Complication
Total joint arthroplasty
Risk factor


Highly efficient catalysis of chalcopyrite with surface bonded ferrous species for activation of peroxymonosulfate toward degradation of bisphenol A: A mechanism study.

Abstract: Chalcopyrite nanoparticles (CuFeS2 NPs) with abundant surface bonded ferrous were successfully prepared, characterized and used as a catalyst for peroxymonosulfate (PMS) activation and BPA degradation. The effect of reaction parameters such as initial pH, catalyst load, PMS concentration, initial BPA concentration and reaction temperature on BPA degradation in CuFeS2-PMS system was systematically investigated. As a bimetallic sulfide, CuFeS2 exhibits ultra-high activity for PMS activation compared with Cu2S, FeS2, CuFeO2 and Co3O4. It was found that by co-use of 0.1 g L-1 CuFeS2 and 0.3 mmol L-1 PMS, 20 mg L-1 of BPA was almost completely degraded (99.7%) and reached a mineralization rate of 75% within 20 min. The highly catalytic activity of CuFeS2 is closely related to two aspects: one is that S2- in the catalysts promotes the cycling of Fe3+/Fe2+ and Cu2+/Cu+ cycles on the surface, and the other is the synergistic effect of Fe3+/Fe2+ and Cu2+/Cu+ cycles in the PMS activation. These interesting findings shed some new insight on the development of metal sulfides for the oxidative treatment of organic contaminants.

Nie|Wenshan|W| Mao|Qihang|Q| Ding|Yaobin|Y| Hu|Yue|Y| Tang|Heqing|H|

Chalcopyrite
Peroxymonosulfate
Bisphenol A
Catalytic degradation
Sulfur


Persistent Legionnaire's disease in an adult with hairy cell leukemia successfully treated with prolonged levofloxacin therapy.

Abstract: Legionnaire's disease (LD) manifests most commonly as an atypical community acquired pneumonia (CAP) with systemic extrapulmonary manifestations. Disorders associated with impaired cell mediated immunity (CMI) are particularly predisposed to LD. Hairy cell leukemia (HCL) is a rare B-cell lymphoproliferative leukemia associated with decreased CMI. LD has only rarely been reported in HCL. We present a most interesting case of persistent LD in a elderly male with HCL who required prolonged antibiotic therapy.

Cunha|Burke A|BA|
Munoz-Gomez|Sigridh|S|
Gran|Arthur|A|
Raza|Muhammad|M|
Irshad|Nadia|N|

Clinical diagnosis of Legionnaire's disease

Legionnaire's disease atypical pneumonia

Legionnaire's disease in compromised hosts


Small scale migration along the interoceanic highway in Madre de Dios, Peru: an exploration of community perceptions and dynamics due to migration.

Abstract:
BACKGROUND
Madre de Dios, a southern state in the Peruvian Amazon basin, has experienced rapid development as well as an influx of migrants since the construction of the Interoceanic Highway (IOH) connecting Brazil, Bolivia, and the Peruvian coast. We explored perceptions of migration and development in up to eight communities along the IOH in Madre de Dios following construction of the highway.

METHODS
We conducted a multiple methods study involving focus group (FG) discussions and interviews with key informants (KIs) in eight communities in Madre de Dios. The data was used to develop and apply a survey on demographics, financial, personal, social, human, and physical capital in four communities between February 2014 and March 2015.

RESULTS
We conducted 12 FGs and 34 KI interviews. A total of 522 people participated in the survey. Comparing migrants (those who had moved to the area after construction of the IOH) and non-migrants, we found no difference in food security or access to health services. The majority (67.6%) of respondents from both groups reported that illness was their primary threat to well-being. Non-migrants owned more land than migrants (p < 0.001), were more likely to have piped water directly in their home (p = 0.046), and were more likely to participate in community groups (p = 0.012). Looking at perceptions about migrants, KIs and FGs discussed both positive perceptions of migrants (increased cultural exchange and new technology) and negative perceptions (increased drugs and alcohol in their communities and a lack of investment in the community). Both migrants and non-migrants reported trusting the local government more than the national government.

CONCLUSIONS
Although we hypothesized that migrants would have decreased access to food, water, health services, and land relative to non-migrants, our results show that the only significant differences were in land ownership and water access. Efforts to improve community infrastructure should be carried out at the local level and focus on improving issues reported by both groups, such as potable water, sewage, and increased access to health services. Furthermore, an emphasis on community cohesion, ensuring land rights, and increasing long-term job opportunities should help ease tensions between migrants and non-migrants.

Jensen|Kelly E|KE|0000-0002-3756-8615
Naik|Nehal N|NN|
O'Neal|Christina|C|
Salmón-Mulanovich|Gabriela|G|
Riley-Powell|Amy R|AR|
Lee|Gwenyth O|GO|
Hartinger|Stella M|SM|
Bausch|Daniel G|DG|
Paz-Soldan|Valerie A|VA|

Community perceptions
Economic growth and development
Rural migration


Development of long-acting ciliary neurotrophic factor by site-specific conjugation with different-sized polyethylene glycols and transferrin.

Abstract: To overcome the deficiency of rapid elimination from blood, the truncated human recombinant ciliary neurotrophic factor was formulated by site-specific attachment of different-sized PEG-maleimide or by cross-linking with human transferrin through a hetero-bi-functional PEG linker (NHS-PEG5k-MAL). The PEGylated CNTF was purified by a two-step chromatography procedure and the transferrin coupling CNTF conjugate was separated through an elegant protocol. The conjugation site on CNTF was identified by peptide mapping analysis and validated that the linkage of the conjugates was specifically happened to Cys17 residue. Although both PEGylated and transferrin coupling CNTF demonstrated decreased cell based residual activity, markedly enhanced pharmacokinetic behaviors in normal male Sprague-Dawley rats were observed, especially for the PEG40k-CNTF with approximately 58-times improvement compared with the unmodified counterpart. The evaluation of the in vivo potency of body weight-losing was performed with normal male C57BL6 mice and the results revealed that both PEGylation and transferrin coupling could achieve improved therapeutic benefits relative to that of CNTF. Besides, PEG20k/40k-CNTF demonstrated more effective than transferrin coupling CNTF (Tf-PEG5k-CNTF) despite that the later showed preferable pharmacokinetic profile and cell based residual activity compared with PEG20k-CNTF. Weekly subcutaneous administration of PEG40k-CNTF with 0.5mg/kg and 1.0mg/kg dose resulted in approximately 35% and 50% decrease in food intake during one interval period of injection, indicating that PEG40k-CNTF is the most potential anti-obese agent for therapeutics.

Zhang|Chun|C| Yu|Rong|R| Li|Zenglan|Z| Feng|Cui|C| Wang|Qi|Q| Liu|Yongdong|Y| Su|Zhiguo|Z|

Long-acting
Ciliary neurotrophic factor
PEGylation
Transferrin coupling
Anti-obese


Chromatographic behavior and characterization of polydisperse surfactants using Ultra-High-Performance Liquid Chromatography hyphenated to High-Resolution Mass Spectrometry.

Abstract: Surfactants are widely used in various petrochemical applications. Thus, it is essential to have highly efficient analytical tools to monitor the different classes of surfactants commonly used. Three among the four known classes of surfactants were studied in the present work: anionic (i.e. alkylbenzene sulfonate, alkyl ether carboxylic acid), nonionic (i.e. alkylcyclohexyl alcohol ethoxylated, alkyl alcohol ethoxylated) and cationic (i.e. alkyl trimethylammonium). Thanks to high-resolution mass spectrometry (HRMS), a useful mass list was created including 119 m/z values (error in mass around 5 ppm). This list was the foundation of a HRMS database, which, for the sake of simplicity, will be further denoted only "database". To avoid ion competition and streamline attribution of structural formulas for isobar molecules, a suitable chromatographic method was used before MS. The retention behavior of six surfactants (trimethyloctadecylammonium bromide, myristyltrimethylammonium bromide, Brij®C10, Triton X-100 reduced, glycolic acid ethoxylate lauryl ether, 4-dodecylbenzenesulfonic acid) was evaluated under three separation modes: reversed-phase liquid chromatography (RPLC), hydrophilic interaction chromatography (HILIC) and mixed-mode chromatography (combination of anion-exchange and reversed-phase mechanisms). In RPLC mode, six columns were tested including C4, C18, C30, polar-embedded C18, PFP and phenyl chemistries. Two HILIC columns were also tested including bare silica and urea chemistries. An anion-exchange combined with RPLC mechanism was investigated as mixed-mode mechanism. Using ammonium formate at 10 mM as buffer provided the best signal in HRMS. In liquid chromatography, acid conditions (pH 3.5) were preferred, to avoid peak tailing due to residual silanols. The mixed-mode separation mode clearly appears as the best compromise for the characterization of the three surfactants classes. Nevertheless, the orthogonality observed for the separations obtained in HILIC and RPLC modes offers some possibilities for further multidimensional separations.

Dufour|Alizée|A| Thiébaut|Didier|D| Ligiero|Leticia|L| Loriau|Matthieu|M| Vial|Jérôme|J|

D002851:Chromatography, High Pressure Liquid

D057927:Hydrophobic and Hydrophilic Interactions

Surfactants
HILIC
Mixed-mode chromatography
High Resolution Mass Spectrometry
Petroleum industry
UHPLC


Highly sensitive colorimetric aptasensor for ochratoxin A detection based on enzyme-encapsulated liposome.

Abstract: A simple, low-cost, and sensitive liposome-based colorimetric aptasensor has been developed to detect ochratoxin A (OTA). Specifically, a dumbbell-shaped probe was designed, including magnetic beads (MBs), double-stranded DNA (dsDNA), and enzyme-encapsulated liposome. The dsDNA formed by the hybridization between OTA aptamer and its complementary probe. And the dsDNA was used to contact the MBs and the enzyme-encapsulated liposome. In the presence of OTA, the aptamer preferred to combine with OTA to form G-quadruplex, resulting in the release of the detection probe and the enzyme-encapsulated liposome. Each liposome contained a large amount of HRP. Thus, when the liposome was lysed by adding the mixed solution of 3,3',5,5'-tetramethylbenzidine (TMB) and H2O2, a large number of HRP were released. HRP could catalyze the H2O2-mediated oxidation of TMB and hence resulted in the color change from colorless to blue with the OTA concentration varying, and this variation can be observed by naked eyes easily. The result showed that the absorption intensity at 652 nm enhanced with the increase of OTA concentration ranging from 0.05 to 2.0 ng mL-1, and the limit of detection was calculated to be 0.023 ng mL-1 (S/N = 3). The developed colorimetric aptasensor has been applied to detect OTA concentration in corn samples with satisfied results.

Lin|Cuiying|C| Zheng|Huixia|H| Sun|Mi|M| Guo|Yajuan|Y| Luo|Fang|F| Guo|Longhua|L| Qiu|Bin|B| Lin|Zhenyu|Z| Chen|Guonan|G|

Colorimetric
Ochratoxin A
Liposomes
Aptamer


To vape or not to vape? Effects of exposure to conflicting news headlines on beliefs about harms and benefits of electronic cigarette use: Results from a randomized controlled experiment.

Abstract: News coverage of novel tobacco products including e-cigarettes has framed the use of these products with both positive and negative slants. Conflicting information may shape public knowledge, perceptions of e-cigarettes, and their harms. The objective of this study is to assess effects of exposure to conflicting news coverage on US adults' beliefs about harms and benefits of e-cigarette use. We conducted a one-way between-subjects randomized controlled experiment in 2016 to compare the effects of viewing either 1) positive, 2) negative, 3) both positive and negative (conflicting) news headlines about the safety of using e-cigarettes, or 4) no-message. Participants were 2056 adults aged 18 and older from an online survey panel. Outcomes were beliefs about harms (3-item scale, α=0.76) and benefits (3-item scale, α=0.82) of using e-cigarettes. Participants who viewed negative headlines reported increased beliefs about harms (B=0.164, p=0.039) and lower beliefs about benefits of e-cigarette use (B=-0.216, p=0.009), compared with those in the positive headlines condition. These differences were replicated in subgroup analyses among never e-cigarette users. In addition, never e-cigarette users who viewed conflicting headlines reported lower beliefs about benefits of e-cigarette use (B=-0.221, p=0.030) than the positive headlines condition. Valence of news coverage about e-cigarettes (positive, negative, or conflicting) could influence people's beliefs about harms and benefits of e-cigarette use.

Tan|Andy S L|ASL|
Lee|Chul-Joo|CJ|
Nagler|Rebekah H|RH|
Bigman|Cabral A|CA|

D066300:Electronic Nicotine Delivery Systems

D007722:Health Knowledge, Attitudes, Practice

Beliefs
Electronic cigarette
News coverage
Conflicting information


Investigation of chimeric reads using the MinION.

Abstract: Following a nanopore sequencing run of PCR products of three amplicons less than 1kb, an abundance of reads failed quality control due to template/complement mismatch. A BLAST search demonstrated that some of the failed reads mapped to two different genes -- an unexpected observation, given that PCR was carried out separately for each amplicon. A further investigation was carried out specifically to search for chimeric reads, using separate barcodes for each amplicon and trying two different ligation methods prior to sample loading. Despite the separation of ligation products, chimeric reads formed from different amplicons were still observed in the base-called sequence. The long-read nature of nanopore sequencing presents an effective tool for the discovery and filtering of chimeric reads. We have found that at least 1.7% of reads prepared using the Nanopore LSK002 2D Ligation Kit include post-amplification chimeric elements. This finding has potential implications for other amplicon sequencing technologies, as the process is unlikely to be specific to the sample preparation used for nanopore sequencing.

chimerism MinION nanopore amplicon R9.4 interferon signal


Sterile working in ultrasonography: the use of dedicated ultrasound covers and sterile ultrasound gel.

Abstract: Ultrasound is currently an important tool for diagnostic and interventional procedures. Ultrasound imaging provides significant advantages as compared to other imaging methods. The widespread use of ultrasound also carries the risk of drawbacks such as cross-infections. A large body of literature reports this possibly life-threatening side effect and specific patient populations are particularly at risk (e.g., neonates). Various methods of ultrasound probe disinfection are described; however, none of the mechanical or chemical probe disinfection procedures is optimal and, in particular, disinfection with high concentration of alcohol might be associated with ultrasound probe damage. The preparation of ultrasound probes with dedicated probe covers is a useful alternative for sterile working conditions. One ultrasound probe cover discussed in this paper is directly glued on to the ultrasound probe without the use of ultrasound coupling gel. By the use of sterile ultrasound coupling gel at the outer surface, additional effects on aseptic working conditions can be obtained.

sterility
ultrasound cover
cross-infection
diagnostic ultrasound
interventional ultrasound
ultrasound transmission gel


Hierarchically Porous Organic Cages.

Abstract: Imparting mesopores to organic cages of an intrinsic microporous nature to build up hierarchically porous cage soft materials is a grand challenge and will reshape the property and application scope of traditional organic cage molecules. Herein, we discovered how to engineer mesopores into microporous organic cages via their host-guest interactions with long chain ionic surfactants. Equally important, the ionic head of surfactants equips the supramolecularly assembled porous structures with charge-selective uptake and release function in solution. Interestingly, such hierarchically porous organic cage can serve as a nanoreactor once trapping enzymes within the cavity, which show 5-fold enhanced activity of enzymatic catalysis when compared with the free enzymes.

Hua|Mingming|M| Wang|Shuping|S| Gong|Yanjun|Y| Wei|Jingjing|J| Yang|Zhijie|Z| Sun|Jian-Ke|JK|0000-0001-6219-5761

porous organic cages
catalysis
hierarchical pores
selective adsorption
self-assembly


Impact of the SYNTAX scores I and II in patients with diabetes and multivessel coronary disease: a pooled analysis of patient level data from the SYNTAX, PRECOMBAT, and BEST trials.

Abstract:
Aims
To assess the impact of the SYNTAX scores I and II in outcomes after percutaneous coronary intervention (PCI) and coronary artery bypass graft (CABG) for patients with diabetes and multivessel disease (MVD).

Methods and results
We performed a patient-level pooled analysis of three large randomized trials of patients with MVD. The impact of coronary anatomic complexity as measured by the SYNTAX score in the differences in outcomes following PCI and CABG was assessed at a median follow-up of 5 years. We also assessed the performance of the SYNTAX II score model in patients with and without diabetes. From the 3280 patients enrolled in the three trials, a total of 1068 (32.6%) had diabetes. The rate of the composite of death, myocardial infarction (MI), or stroke was similar in the PCI and CABG arms in patients with low-intermediate (≤32) SYNTAX scores (15.1% vs. 14.9%, respectively; P = 0.93) while it was significantly higher in the PCI arm in patients with high (≥33) SYNTAX scores (24.5% vs. 13.2%, respectively; P = 0.018). The SYNTAX score II showed good calibration and moderate discrimination ability in patients with diabetes (c-index = 0.68) as well as in those without (c-index = 0.67).

Conclusions
Differences in 5 years outcomes following PCI and CABG for patients with MVD and diabetes were influenced by anatomic complexity as measured by the SYNTAX score. The SYNTAX score II mortality prediction model showed similar performance regardless of the diabetes status.

Cavalcante|Rafael|R|
Sotomi|Yohei|Y|
Mancone|Massimo|M|
Whan Lee|Cheol|C|
Ahn|Jung-Min|JM|
Onuma|Yoshinobu|Y|
Lemos|Pedro A|PA|
van Geuns|Robert-Jan|RJ|
Park|Seung-Jung|SJ|
Serruys|Patrick W|PW|

D029424:Pulmonary Disease, Chronic Obstructive

Coronary disease
Trials
Diabetes mellitus
Stents
Surgery


The development of a classification system for maternity models of care.

Abstract:
BACKGROUND
A lack of standard terminology or means to identify and define models of maternity care in Australia has prevented accurate evaluations of outcomes for mothers and babies in different models of maternity care.

OBJECTIVE
As part of the Commonwealth-funded National Maternity Data Development Project, a classification system was developed utilising a data set specification that defines characteristics of models of maternity care.

METHOD
The Maternity Care Classification System or MaCCS was developed using a participatory action research design that built upon the published and grey literature.

RESULTS
The study identified the characteristics that differentiate models of care and classifies models into eleven different Major Model Categories.

CONCLUSION
The MaCCS will enable individual health services, local health districts (networks), jurisdictional and national health authorities to make better informed decisions for planning, policy development and delivery of maternity services in Australia.

Donnolley|Natasha|N| Butler-Henderson|Kerryn|K| Chapman|Michael|M| Sullivan|Elizabeth|E|

D001315:Australia
D016389:Maternal-Child Nursing
D064872:Patient Care Bundles
D018743:Perinatal Care
D010865:Pilot Projects
D016730:Program Development
D009626:Terminology as Topic

classification
data collection
health care evaluation mechanisms
health information systems
patient care bundles
perinatal care


Implication of the SH3TC2 gene in Charcot-Marie-Tooth disease associated with deafness and/or scoliosis: Illustration with four new pathogenic variants.

Abstract: The autosomal recessive demyelinating form of Charcot-Marie-Tooth can be due to SH3TC2 gene pathogenic variants (CMT4C, AR-CMTde-SH3TC2). We report on a series of 13 patients with AR-CMTde-SH3TC2 among a French cohort of 350 patients suffering from all type of inheritance peripheral neuropathy. The SH3TC2 gene appeared to be the most frequently mutated gene for demyelinating neuropathy in this series by NGS. Four new pathogenic variants have been identified: two nonsense variants (p.(Tyr970*), p.(Trp1199*)) and two missense variants (p.(Leu1126Pro), p.(Ala1206Asp)). The recurrent variant p.Arg954* was present in 62%, and seems to be a founder mutation. The phenotype is fairly homogeneous, as all these patients, except the youngest ones, presented scoliosis and/or hearing loss.

Lerat|J|J|
Magdelaine|C|C|
Lunati|A|A|
Dzugan|H|H|
Dejoie|C|C|
Rego|M|M|
Beze Beyrie|P|P|
Bieth|E|E|
Calvas|P|P|
Cintas|P|P|
Delaubrier|A|A|
Demurger|F|F|
Gilbert-Dussardier|B|B|
Goizet|C|C|
Journel|H|H|
Laffargue|F|F|
Magy|L|L|
Taithe|F|F|
Toutain|A|A|
Urtizberea|J A|JA|
Sturtz|F|F|
Lia|A S|AS|

D047908:Intracellular Signaling Peptides and Proteins

SH3TC2
Charcot-Marie-Tooth
Scoliosis
Neuropathy
NGS
Hearing loss


Is nontraumatic intracerebral hemorrhage different between young and elderly patients?

Abstract: Only a few studies have reported nontraumatic intracerebral hemorrhage in young patients notwithstanding its fatal and devastating characteristics. This study investigated the clinical characteristics and outcome of nontraumatic intracerebral hemorrhage in young patients in comparison to those of the elderly. A retrospective review of consecutive patients admitted at the department of neurosurgery of two tertiary care medical centers presenting with first-ever nontraumatic intracerebral hemorrhage was performed. We identified and compared the demographics, etiologies, risk factors, and laboratory, radiological, and clinical findings between elderly and young patients. Additionally, logistic regression analyses of independent prognostic factors associated with 1-month mortality and favorable functional outcome were performed. Altogether, 247 patients including 69 young patients and 178 elderly patients were enrolled. On multivariate analysis, young patients exhibited significantly more often an infratentorial hematoma location, excessive alcohol consumption, and high body mass index (BMI), but less frequent systemic hypertension. There was no statistical difference between the two groups in 1-month mortality (17.46% and 18.01% for young and elderly patients, respectively), but the favorable functional outcome based on modified Rankin scale score of 0 or 1 was significantly different between the two groups (favorable outcome in 51.79% and 29.93% of patients, respectively). Predictors of 1-month mortality was the presence of herniation in the young group, and lower Glasgow Coma Scale score, renal or heart disease, and leukocytosis (WBC > 10,000) in the elderly group. Lower National Institutes Health Stroke Scale score was associated with favorable functional outcome in both groups. Nontraumatic intracerebral hemorrhage in younger patients appears to be associated with excessive alcohol consumption and high BMI. Younger patients had similar short-term mortality but more favorable functional outcome than the elderly.

Intracerebral hemorrhage
Young patients
Outcome
Risk factor
Mortality
Predictor


Emotional Accessibility Is More Important Than Sexual Accessibility in Evaluating Romantic Relationships - Especially for Women: A Conjoint Analysis.

Abstract: Prior research examining mate expulsion indicates that women are more likely to expel a mate due to deficits in emotional access while men are more likely to expel a mate due to deficits in sexual access. Prior research highlights the importance of accounting for measurement limitations (e.g., the use of incremental vs. forced-choice measures) when assessing attitudes toward sexual and emotional infidelity, Sagarin et al., 2012, Wade and Brown, 2012). The present research uses conjoint analysis, a novel methodology for controlling several limitations of using continuous self-report measures in mate expulsion research. Participants (N = 181, 128 women) recruited from Bucknell University and several psychology recruitment listservs in the United States rated nine profiles that varied in three potential levels of emotional and sexual accessibility. Men were more likely to want to break up with a partner due to sexual accessibility deficits, whereas women were more likely to want to break up due to emotional accessibility deficits. However, regardless of sex, emotional inaccessibility was more likely to produce mate expulsion. These findings are consistent with prior theory and highlight the need to disentangle emotional accessibility into its constituent in-pair benefits. This research also illustrates the utility of conjoint analysis as a statistical tool for studying how humans resolve trade-offs among competing outcomes during romantic decision-making.

accessibility
conjoint analysis
mate expulsion
sex
psychological methods


Effect of solvents on the accuracy of the Mini Root ZX apex locator.

Abstract:
AIM
To evaluate ex vivo, the effects of three solvents on the accuracy of a contemporary electronic root canal length measurement device (ERCLMD), the Mini Root ZX.

METHODOLOGY
The actual working length (AWL) of 56 extracted maxillary incisor teeth were measured with an ERCLMD. All root canals were prepared with the ProTaper system to AWL. Of them, 20 were filled with gutta-percha and a resin-based sealer (Group A), 20 with gutta-percha and a zinc oxide/eugenol-based sealer (Group B), and 16 roots were used as the control group (Group C). Removal of the root filling and repreparation processes were performed using the ProTaper system. Guttasolv and Resosolv were used as the solvents in Group A and Guttasolv and Endosolv E in Group B. After the removal of the root fillings had been achieved, the same ERCLMD was used to measure the working length (WL). Differences between AWL and WL measurements were analysed by paired t-test, and the accuracy of ERCLMD was assessed using chi-squared tests.

RESULTS
There were significant differences between AWL and WL measurements in subgroups A2 (Resosolv group) and B2 (Endosolv E group). In these subgroups, WL was shorter than AWL (P < 0.05). Also, the accuracy of the Resosolv group was significantly lower than the others (P < 0.05) at a ±0.5 mm margin of error.

CONCLUSIONS
Removing root fillings may require use of a solvent. In these cases, ERCLMDs may exhibit a lower accuracy, thus operators must exercise additional care when measuring the working length using ERCLMDs.

Er|O|O|
Uzun|O|O|
Ustun|Y|Y|
Canakcı|B C|BC|
Yalpı|F|F|

working length
dissolving solutions
gutta-percha solvents
retreatment


Use of mixed culture bacteria for photofermentive hydrogen of dark fermentation effluent.

Abstract: Hydrogen production (HP) from dark fermentation effluent of starch wastewater via vertical tubular photo-bioreactor was investigated. The reactor was inoculated with mixed culture of bacteria and operated at light intensity of 190 W/m(2). Hydraulic retention time (HRT) and organic loading rate (OLR) was varied between 0.9 to 4.0 h and 3.2 to 16 g COD/l.d., respectively. Increasing the HRT from 0.9 to 2.5 h, significantly (P<0.05) increased HP from 1±0.04 to 3.05±0.19 l/d, respectively. However, minimal increase in HP occurred when increasing the HRT up to 4.0 h. The HP remained unaffected when increasing the OLR from 3.2 to 6.4 g COD/l.d. Further increase in the OLR up to 8.2 and 16 g COD/l.d., resulted in a drop in HP i.e. 0.96 and 0.19 l/d, respectively. Microbial community analysis of the reactor samples showed the presence and dominance of hydrogen producing purple non-sulfur phototrophic (PNS) bacterium, Rhodopseudomonas palustris in the reactor.

Tawfik|Ahmed|A| El-Bery|Haitham|H| Kumari|Sheena|S| Bux|Faizal|F|

D057919:Biological Oxygen Demand Analysis

D058645:Denaturing Gradient Gel Electrophoresis

Vertical tubular photo-bioreactor
HRT
Bio-hydrogen
Microbial analysis
Photo-fermentation


Inoperable Left Renal Vein Leiomyosarcoma Refractory to Chemotherapy Invades Inferior Vena Cava and Right Atrium: A Case Report.

Abstract: Mesenchymal stem cells differentiate into a plethora of cell types. These differentiated cell types include osteoblasts, chondrocytes, myocytes, and adipocytes. Sarcomas occur secondary to malignant transformation of these mesenchymal, pluripotent stem cells. Involuntary smooth muscle is responsible for the make up of hollow organs and vasculature in our body and is regulated by our autonomic nervous system, hormones, as well as chemical and local mediators. Cancer involving smooth muscle cells is designated as leiomyosarcoma (LMS). LMS can arise from any location in the body where smooth muscle is present and is frequently reported in the abdomen and pelvis, as well as the trunk, extremities, and throughout the retroperitoneum.

Lindblad|Geoffrey|G|
Prater|Stephanie|S|
Chaniotakis|Sotiris E|SE|
Banks|James|J|

ct abdomen
mri abdomen
primary leiomyosarcoma
radiation oncology
radiology
surgical oncology


Emergency department impact following the introduction of an electric scooter sharing service.

Abstract:
OBJECTIVE
We aimed to describe the impact on the single ED serving Dunedin, New Zealand, following the introduction of an electric-scooter (e-scooter) sharing service.

METHODS
A retrospective cohort study comparing the number of vehicle related injuries during identical 6-week periods in 2018 and 2019 was performed. A descriptive analysis of the subset of e-scooter related presentations was undertaken.

RESULTS
A total of 172 and 228 vehicle related injury presentations were identified in samples from 2018 and 2019, respectively. During the 2018 study period zero e-scooter related ED presentations were identified. In 2019 there were 56 e-scooter related ED presentations (P-value <0.001) representing 54 events. There were 52 car, 21 motorbike and 62 bicycle related presentations during the same 2019 time period. Further descriptive analysis showed the majority of e-scooter presentations were for minor injury. Fractures or dislocations were found in 17 (32%) patients and 14 (26%) patients sustained a head injury, one of which was severe. Isolated minor musculoskeletal injuries were seen in 25 (46%) patients. On average one ED bed was occupied by an e-scooter patient for 2 h and 44 min each day during the 6-week study period in 2019.

CONCLUSION
The introduction of an e-scooter sharing service resulted in a new injury hazard. Our study presents the number of e-scooter related ED presentations relative to other vehicles related injury visits and describes the injury patterns associated with e-scooter use which may inform future public policy.

Beck|Sierra|S|0000-0002-1614-5058 Barker|Luke|L| Chan|Annie|A| Stanbridge|Signe|S|

D006259:Craniocerebral Trauma
D004636:Emergency Service, Hospital
D050723:Fractures, Bone
D006801:Humans
D009049:Motorcycles
D012189:Retrospective Studies

electric scooter injury
emergency medicine
wound and injury


A novel recessive mutation affecting DNAJB6a causes myofibrillar myopathy.

Abstract: Mutations in the DNAJB6 gene have been identified as rare causes of myofibrillar myopathies. However, the underlying pathophysiologica mechanisms remain elusive. DNAJB6 has two known isoforms, including the nuclear isoform DNAJB6a and the cytoplasmic isoform DNAJB6b, which was thought to be the pathogenic isoform. Here, we report a novel recessive mutation c.695_699del (p. Val 232 Gly fs*7) in the DNAJB6 gene, associated with an apparently recessively inherited late onset distal myofibrillar myopathy in a Chinese family. Notably, the novel mutation localizes to exon 9 and uniquely encodes DNAJB6a. We further identified that this mutation decreases the mRNA and protein levels of DNAJB6a and results in an age-dependent recessive toxic effect on skeletal muscle in knock-in mice. Moreover, the mutant DNAJB6a showed a dose-dependent anti-aggregation effect on polyglutamine-containing proteins in vitro. Taking together, these findings reveal the pathogenic role of DNAJB6a insufficiency in myofibrillar myopathies and expand upon the molecular spectrum of DNAJB6 mutations.

Qian|Fang-Yuan|FY|
Guo|Yu-Dong|YD|
Zu|Juan|J|
Zhang|Jin-Hua|JH|
Zheng|Yi-Ming|YM|
Abdoulaye|Idriss Ali|IA|
Pan|Zhao-Hui|ZH|
Xie|Chun-Ming|CM|
Gao|Han-Chao|HC|
Zhang|Zhi-Jun|ZJ|

Novel
DNAJB6a
Myofibrillar myopathy
Mice
Homozygous mutation
Human


Assessment of tick-borne pathogens presence in Dermacentor reticulatus ticks in north-eastern Poland.

Abstract:
PURPOSE
Dermacentor reticulatus is the second most common tick species in Poland after Ixodes ricinus. The aim of the study was to analyze the presence of pathogen DNA in D. reticulatus.

MATERIALS AND METHODS
Ticks were collected in The Protected Landscape Area of the Bug and Nurzec Valley (52°40' N and 22°28' E) between 2016 and 2017. End-point PCR for Borrelia burgdorferi sensu lato, Anaplasma phagocytophilum, Babesia spp., Rickettsia spp., Bartonella spp. and Coxiella burnetii detection was performed.

RESULTS
Tick-borne pathogens' DNA was detected in 11.3% of 301 ticks: B. burgdorferi s.l. in 3.6%, Babesia spp. in 6.3%, A. phagocytophilum in 0.7% and B. burgdorferi s.l.-Babesia spp. co-infection in 0.7%. In all 21 Babesia spp. positive samples, sequence analysis confirmed the presence of Babesia canis with an 80.3%-98.3% homology with the B. canis sequences in GenBank. C. burnetii, Bartonella spp., and Rickettsia spp. DNA were not detected.

CONCLUSIONS
Dermacentor reticulatus from north-eastern Poland were found to carry three of the most common tick-borne pathogens (B. burgdorferi s.l., Babesia canis, A. phagocytophilum) which lead to single and mixed infections. Babesia canis was the most prevalent pathogen identified in D. reticulatus.

Dunaj|Justyna|J| Trzeszczkowski|Adam|A| Moniuszko-Malinowska|Anna|A| Rutkowski|Krzysztof|K| Pancewicz|Sławomir|S|

Dermacentor reticulatus
Anaplasma phagocytophilum
Babesia canis
Borrelia burgdorferi s.l.


Altered Repolarization Reserve in Failing Rabbit Ventricular Myocytes: Calcium and β-Adrenergic Effects on Delayed- and Inward-Rectifier Potassium Currents.

Abstract:
BACKGROUND
Electrophysiological remodeling and increased susceptibility for cardiac arrhythmias are hallmarks of heart failure (HF). Ventricular action potential duration (APD) is typically prolonged in HF, with reduced repolarization reserve. However, underlying K+ current changes are often measured in nonphysiological conditions (voltage clamp, low pacing rates, cytosolic Ca2+ buffers).

METHODS AND RESULTS
We measured the major K+ currents (IKr, IKs, and IK1) and their Ca2+- and β-adrenergic dependence in rabbit ventricular myocytes in chronic pressure/volume overload-induced HF (versus age-matched controls). APD was significantly prolonged only at lower pacing rates (0.2-1 Hz) in HF under physiological ionic conditions and temperature. However, when cytosolic Ca2+ was buffered, APD prolongation in HF was also significant at higher pacing rates. Beat-to-beat variability of APD was also significantly increased in HF. Both IKr and IKs were significantly upregulated in HF under action potential clamp, but only when cytosolic Ca2+ was not buffered. CaMKII (Ca2+/calmodulin-dependent protein kinase II) inhibition abolished IKs upregulation in HF, but it did not affect IKr. IKs response to β-adrenergic stimulation was also significantly diminished in HF. IK1 was also decreased in HF regardless of Ca2+ buffering, CaMKII inhibition, or β-adrenergic stimulation.

CONCLUSIONS
At baseline Ca2+-dependent upregulation of IKr and IKs in HF counterbalances the reduced IK1, maintaining repolarization reserve (especially at higher heart rates) in physiological conditions, unlike conditions of strong cytosolic Ca2+ buffering. However, under β-adrenergic stimulation, reduced IKs responsiveness severely limits integrated repolarizing K+ current and repolarization reserve in HF. This would increase arrhythmia propensity in HF, especially during adrenergic stress.

Hegyi|Bence|B|
Bossuyt|Julie|J|
Ginsburg|Kenneth S|KS|
Mendoza|Lynette M|LM|
Talken|Linda|L|
Ferrier|William T|WT|
Pogwizd|Steven M|SM|
Izu|Leighton T|LT|
Chen-Izu|Ye|Y|
Bers|Donald M|DM|

calcium/calmodulin-dependent protein kinase II


Inhibition of infectious bursal disease virus by vector delivered SiRNA in cell culture.

Abstract: Infectious Bursal Disease (IBD) is major threat to poultry industry. It causes severe immunosuppression and mortality in chicken generally at 3 to 6 weeks of age. RNA intereference (RNAi) emerges as a potent gene regulatory tool in last few years. The present study was conducted to evaluate the efficiency of RNAi to inhibit the IBD virus (IDBV) replication in-vitro. VP2 gene of virus encodes protein involved in capsid formation, cell entry and induction of protective immune responses against it. Thus, VP2 gene of IBDV is the candidate target for the molecular techniques applied for IBDV detection and inhibition assay. In this study, IBDV was isolated from field cases and confirmed by RT-PCR. The virus was then adapted on chicken embryo fibroblast cells (CEF) in which it showed severe cytopathic effects (CPE). The short hairpin RNA (shRNAs) constructs homologous to the VP2 gene were designed and one, having maximum score and fulfilling maximum Reynolds criteria, was selected for evaluation of effective inhibition. Selected shRNA construct (i.e., VP2-shRNA) was observed to be the most effective for inhibiting VP2 gene expression. Real time PCR analysis was performed to measure the relative expression of VP2 gene in different experimental groups. The VP2 gene was less expressed in virus infected cells co-transfected with VP2-shRNA as compared to mock transfected cells and IBDV+ cells (control) at dose 1.6 µ g. The result showed ∼95% efficient down regulation of VP2 gene mRNA in VP2-shRNA treated cells. These findings suggested that designed shRNA construct achieved high level of inhibition of VP2 gene expression in-vitro.

Sahare|Amol Ashok|AA|
Bedekar|Megha Kadam|MK|
Jain|Sudhir Kumar|SK|
Singh|Azad|A|
Singh|Sanjeev|S|
Sarkhel|Bikas Chandra|BC|

D060888:Real-Time Polymerase Chain Reaction

RNAi
iBD virus
VP2 gene
Cytopathic effects
Gene knockdown
Interleukin response


Maximum shear strain-based algorithm can predict proteoglycan loss in damaged articular cartilage.

Abstract: Post-traumatic osteoarthritis (PTOA) is a common disease, where the mechanical integrity of articular cartilage is compromised. PTOA can be a result of chondral defects formed due to injurious loading. One of the first changes around defects is proteoglycan depletion. Since there are no methods to restore injured cartilage fully back to its healthy state, preventing the onset and progression of the disease is advisable. However, this is problematic if the disease progression cannot be predicted. Thus, we developed an algorithm to predict proteoglycan loss of injured cartilage by decreasing the fixed charge density (FCD) concentration. We tested several mechanisms based on the local strains or stresses in the tissue for the FCD loss. By choosing the degeneration threshold suggested for inducing chondrocyte apoptosis and cartilage matrix damage, the algorithm driven by the maximum shear strain showed the most substantial FCD losses around the lesion. This is consistent with experimental findings in the literature. We also observed that by using coordinate system-independent strain measures and selecting the degeneration threshold in an ad hoc manner, all the resulting FCD distributions would appear qualitatively similar, i.e., the greatest FCD losses are found at the tissue adjacent to the lesion. The proposed strain-based FCD degeneration algorithm shows a great potential for predicting the progression of PTOA via biomechanical stimuli. This could allow identification of high-risk defects with an increased risk of PTOA progression.

Eskelinen|Atte S A|ASA|
Mononen|Mika E|ME|
Venäläinen|Mikko S|MS|
Korhonen|Rami K|RK|
Tanska|Petri|P|

Proteoglycan
Cartilage
Osteoarthritis
Strain
Finite element analysis
Modeling


Allostatic load and mental health: a latent class analysis of physiological dysregulation.

Abstract: This study explored the associations between specific profiles of biological dysregulation and mental health outcomes in a national, community sample of healthy adults in the United States. A latent class analysis of data from the Midlife Development in the United States study (n = 1,757) was conducted to determine classes of biological dysregulation. Multinomial logistic regressions of class membership were employed to determine associations with measures related to depression, including whether or not individuals had sought treatment, Center for Epidemiological Studies Depression Scale, and both the generalized distress and anhedonia subscales of the Mood and Anxiety Symptoms Questionnaire. Four classes of dysregulation emerged: baseline/low dysregulation, metabolic and inflammatory dysregulation, parasympathetic dysregulation, and SAM pathway dysregulation. Individuals who met the criteria for depression measures were more likely to be in the metabolic and immune dysregulation and parasympathetic dysregulation groups as compared to the baseline group. The results suggest that mental health outcomes, such as depression, are differentially associated with specific profiles of biological dysregulation. A more nuanced approach to profiles of dysregulation could better inform treatment decisions.Lay summaryHigher levels of allostatic load, which represents the cumulative wear and tear of exposure to stress, are associated with increased rates of depression and anhedonia. Specifically, parasympathetic dysregulation and immunometabolic dysregulation are associated with negative mental health outcomes.

depression anhedonia parasympathetic Stress immunometabolic allostasis


Performance fatigability during gait in adults with Charcot-Marie-Tooth disease.

Abstract:
BACKGROUND
Fatigue is common in people with Charcot-Marie-Tooth (pwCMT) disease. However, no studies have characterized performance fatigability during gait in this population. Characterizing performance fatigability during gait, and assessing its relation to life satisfaction could improve understanding and treatment of mobility challenges in pwCMT.

RESEARCH QUESTIONS
How do gait outcomes change with fatigue in pwCMT? Do these changes relate to life satisfaction?

METHODS
31 pwCMT completed a 6-minute, fast-as-possible walk while gait outcomes were captured via inertial sensors. Gait outcomes were separated into six sequential bins of equal size. The mean value, variability, and asymmetry (step time only) of outcomes were calculated for each bin. Perceived fatigue and general life satisfaction were assessed via questionnaire.

RESULTS
Of the five mean gait outcomes measured, four showed statistically significant changes over the 6-minute fast-as-possible walk: velocity (reduced; p = 0.008); cadence (reduced; p < 0.001), step time (increased; p < 0.001), and trunk ROM (increased; p = 0.032). Of the four variability and one asymmetry outcomes, only stride length variability changed during the walking task (p = 0.015), decreasing from bins 1-2, and remaining stable for bins 2-6. Changes in velocity, cadence, step time were related to general life satisfaction (0.038 < ps<0.04), but not perceived fatigue (ps>0.343).

SIGNIFICANCE
pwCMT exhibit statistically significant changes in mean gait outcomes, but not variability outcomes, across a 6-minute, fast-as-possible walking bout. Changes correlated to life satisfaction, suggesting performance fatigability during gait could be a target for rehabilitation for pwCMT. Perceived fatigue did not correlate to gait fatigue, underscoring the differentiation between perceived fatigue and performance fatigability.

Peterson|Daniel S|DS|
Moore|Allison|A|
Ofori|Edward|E|

Gait
Charcot-Marie-Tooth disease
Fatigue
Variability
Kinematics


Reduction of Ischemia Reperfusion-Related Brain Hemorrhage by Stachybotrys Microspora Triprenyl Phenol-7 in Mice With Antioxidant Effects.

Abstract:
BACKGROUND
Stachybotrys microspora triprenyl phenol-7 (SMTP-7) has both thrombolytic and anti-inflammatory effects, but its neuroprotective effects on cerebral ischemia are still unclear. The present study assessed the antioxidative and neurovascular unit (NVU) protective effects of SMTP-7 using transient middle cerebral artery occlusion (tMCAO) mice.

METHODS
After 60 minutes tMCAO, 0.9% NaCl, tissue-type plasminogen activator (tPA), SMTP-7 or tPA + SMTP-7 was intravenously administrated through subclavian vein just before the reperfusion, and these mice were examined at 24 hours after reperfusion. We histologically assessed the hemorrhage and expressive changes of antioxidative markers in brains.

RESULTS
SMTP-7 treatment showed a similar antithrombotic effect to tPA, but significantly decreased the hemorrhage volumes and the number of 4-HNE, 3-NT and 8-OHdG positive cells, meanwhile, ameliorated the decrease of collagen IV in the ischemic brains. However, tPA + SMTP-7 treatment did not decrease hemorrhage volumes nor showed NVU protective effect.

CONCLUSIONS
The present study suggested that SMTP-7 provided therapeutic benefits for ischemic stroke through antioxidative and NVU protective effects unlike tPA alone or tPA + SMTP-7.

Huang|Yong|Y| Ohta|Yasuyuki|Y| Shang|Jingwei|J| Li|Xianghong|X| Liu|Xia|X| Shi|Xiaowen|X| Feng|Tian|T| Yamashita|Toru|T| Sato|Kota|K| Takemoto|Mami|M| Hishikawa|Nozomi|N| Suzuki|Eriko|E| Hasumi|Keiji|K| Abe|Koji|K|

D020244:Infarction, Middle Cerebral Artery

Antioxidative
SMTP-7
neurovascular unit
Tpa
ischemic stroke


Thiadiazolo[3,4-c]pyridine as an Acceptor toward Fast-Switching Green Donor-Acceptor-Type Electrochromic Polymer with Low Bandgap.

Abstract: Thiadiazolo[3,4-c]pyridine (PT), an important analog of benzothiadiazole (BT), has most recently been explored as a novel electron acceptor. It exhibits more electron-accepting ability and other unique properties and potential advantages over BT, thus inspiring us to investigate PT-based donor-acceptor-type (D-A) conjugated polymer in electrochromics. Herein, PT was employed for the rational design of novel donor-acceptor-type systems to yield a neutral green electrochromic polymer poly(4,7-di(2,3-dihydrothieno[3,4-b][1,4]dioxin-5-yl)-[1,2,5] thiadiazolo[3,4-c]pyridine) (PEPTE). PEPTE revealed a lower bandgap (Eg,ele=0.85 eV, Eg,opt=1.12 eV) than its BT analog and also favorable redox activity and stability. Furthermore, electrochromic kinetic studies demonstrated that PEPTE displayed higher coloration efficiency than BT analog, good optical memory, and very fast switching time (0.3 s at all three wavelengths), indicating that PT would probably be a promising choice for developing novel neutral green electrochromic polymers by matching with various donor units.

Ming|Shouli|S| Zhen|Shijie|S| Lin|Kaiwen|K| Zhao|Li|L| Xu|Jingkun|J| Lu|Baoyang|B|

thiadiazolo[3,4-c]pyridine
low bandgap
green electrochromics
PEDOT
donor−acceptor-type conjugated polymers


Oxidative Injury and Iron Redistribution Are Pathological Hallmarks of Marmoset Experimental Autoimmune Encephalomyelitis.

Abstract: Oxidative damage and iron redistribution are associated with the pathogenesis and progression of multiple sclerosis (MS), but these aspects are not entirely replicated in rodent experimental autoimmune encephalomyelitis (EAE) models. Here, we report that oxidative burst and injury as well as redistribution of iron are hallmarks of the MS-like pathology in the EAE model in the common marmoset. Active lesions in the marmoset EAE brain display increased expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (p22phox, p47phox, and gp91phox) and inducible nitric oxide synthase immunoreactivity within lesions with active inflammation and demyelination, coinciding with enhanced expression of mitochondrial heat-shock protein 70 and superoxide dismutase 1 and 2. The EAE lesion-associated liberation of iron (due to loss of iron-containing myelin) was associated with altered expression of the iron metabolic markers FtH1, lactoferrin, hephaestin, and ceruloplasmin. The enhanced expression of oxidative damage markers in inflammatory lesions indicates that the enhanced antioxidant enzyme expression could not counteract reactive oxygen and nitrogen species-induced cellular damage, as is also observed in MS brains. This study demonstrates that oxidative injury and aberrant iron distribution are prominent pathological hallmarks of marmoset EAE thus making this model suitable for therapeutic intervention studies aimed at reducing oxidative stress and associated iron dysmetabolism.

Dunham|Jordon|J|
Bauer|Jan|J|
Campbell|Graham R|GR|
Mahad|Don J|DJ|
van Driel|Nikki|N|
van der Pol|Susanne M A|SMA|
't Hart|Bert A|BA|
Lassmann|Hans|H|
Laman|Jon D|JD|
van Horssen|Jack|J|
Kap|Yolanda S|YS|

Experimental autoimmune encephalomyelitis (EAE)


Small and large number discrimination in goldfish (Carassius auratus) with extensive training.

Abstract: Previous studies on relative quantity discrimination in birds and mammals with training procedures have employed hundreds or thousands of trials whereas studies with fish typically use dozens of trials. The goal of this study was to examine whether more extensive training improves the performance of fish tested on stimuli in the small (<4) and large (>4) number range. Goldfish were trained with dot array stimuli using the ratio 0.5 (2 vs. 4, 6 vs. 12) across two blocks of training sessions with a total of approximately 1200 trials. They were tested after each block of training sessions with the ratios 0.33 (1 vs. 3, 5 vs. 15), 0.5 (2 vs. 4, 6 vs. 12), and 0.67 (2 vs. 3, 10 vs. 15). Performance exceeded 90% correct on both test blocks. Accuracy was not affected by manipulating the surface area, density, or space of stimuli. Performance was best on the ratio 0.5 in test block 1, but ratio-independent in test block 2. There was no difference in performance in the small vs. large number range across the study. These results suggest that fish given extensive training can achieve accuracy on a numerical task comparable to well-trained birds, humans, or non-human primates.

DeLong|Caroline M|CM|
Barbato|Stephanie|S|
O'Leary|Taylor|T|
Wilcox|K Tyler|KT|

Goldfish
Quantity discrimination
Training procedure
Numerical cognition


Cardiopulmonary Resuscitation Outcomes of Patients with COVID-19; a One-Year Survey.

Abstract:
Introduction
Assessing cardiopulmonary resuscitation (CPR) outcomes of patients with COVID-19 and employing effective strategies for their improvement are essential. This study is designed in this regard.

Methods
This cross-sectional study was conducted between January 20, 2020 and January 20, 2021 in the emergency departments of two hospitals in Hamadan and Kermanshah, Iran. Participants were 487 patients with confirmed COVID-19 and cardiac arrest (CA) who had undergone CPR during the study period. Data were collected using the available CPR documentation forms developed based on the Utstein Style and analyses were performed using Chi-square, Fisher's exact, and Mann-Whitney U tests and the logistic regression analysis.

Results
Participants' mean age was 69.31±14.73 years and most of them were male (61.8%) and suffered from at least one underlying disease (58.1%). The rate of total and in-hospital CA was 9.67% and 9.39%, respectively. The most prevalent first documented rhythm was asystole (67.9%) and the highest responsivity to CPR was for shockable rhythms. The rate of the return of spontaneous circulation (ROSC) was 9% and the rate of survival to hospital discharge was 2%. The significant predictors of CPR success were age (p = 0.035), epinephrine administration time interval (p = 0.00), CPR duration (p = 0.00), and First documented rhythm (p = 0.009).

Conclusion
The rate of in-hospital CA among studied COVID-19 cases was 9.39% with 9% ROSC and 2% survival to hospital discharge rates after CPR. Primary CPR success among patients with COVID-19 was poor, particularly among those with asystole and bradycardia. It seems that old age and improper doses of epinephrine can reduce CPR success.

Goodarzi|Afshin|A| Khodaveisi|Masoud|M| Abdi|Alireza|A| Salimi|Rasoul|R| Oshvandi|Khodayar|K|

Cardiopulmonary resuscitation
COVID-19
Epinephrine
Heart Arrest


Crystal structure and Hirshfeld surface analysis of the ortho-rhom-bic polymorph of a ZnII complex with 3,5-di-nitro-benzoic acid and ethyl-enedi-amine.

Abstract: During systematic investigations of the biological action enhancement of well known compounds, a new metal complex, namely, bis-(3,5-di-nitro-benzoato)(ethane-1,2-di-amine)zinc(II), [Zn(C7H3N2O6)2(C2H8N2)], was synthesized and the structure of its ortho-rhom-bic form has determined. The synthesis and crystal structure of the monoclinic polymorph has previously been reported [Ibragimov et al. (2020 ▸). Rep. Uzb. Acad. Sci. 1, 45-50]. The zinc ion has a distorted tetra--hedral environment formed by two monodentate 3,5-di-nitro-benzoato anions and chelating ethyl-enedi-amine mol-ecule. In the crystal, the complex mol-ecules are linked by N-H⋯O and C-H⋯O hydrogen bonds into a two-dimensional network parallel to the ac plane. The Hirshfeld surface analysis indicates that the most important contributions to the crystal packing are from H⋯O/O⋯H (43.4%) and O⋯C/C⋯O (17.7%) inter-actions.

Ibragimov|Avazbek|A| Ashurov|Jamshid|J| Dusmatov|Aziz|A| Ibragimov|Aziz|A|

crystal structure
Hirshfeld surface analysis
hydrogen bonding
3,5-dinitrobenzoic acid
ethylenediamine


Aortic valve replacement within an unexpected porcelain aorta: the sutureless valve option.

Abstract: Four patients referred for surgical treatment of aortic stenosis presented an unexpected extremely calcified (porcelain) ascending aorta at the intraoperative epiaortic ultrasonography scanning. In each patient, replacement of the aortic valve was successfully performed using a sutureless implantable bioprosthesis during a short period of hypothermic circulatory arrest. In the era of transcatheter aortic valve implantation procedures, the sutureless valve may be a valuable option for surgical units that do not dispose of transcatheter technology or a hybrid operative theatre.

Gatti|Giuseppe|G| Benussi|Bernardo|B| Camerini|Fulvio|F| Pappalardo|Aniello|A|

D019918:Heart Valve Prosthesis Implantation

Aortic valve
Replacement
Bioprosthesis
Aortic calcification
Cerebral protection
Heart valve


The role of the glucocorticoid receptor gene (NR3C1) for the processing of aversive stimuli.

Abstract: The glucocorticoid receptor (GR) is a crucial component of the hypothalamus-pituitary-adrenal (HPA) axis and as such a part of the stress response system. An impairment of the GR not only alters the level of glucocorticoids, but also modulates cognitive functions and the processing of emotional stimuli. We tested the effects of functional polymorphisms of the GR-encoding gene (NR3C1) on the processing of emotional stimuli on a basal level. In a sample of n=182 participants, we found a haplotype (NR3C1-CTGGACA) to modulate the performance in an emotional reaction time task. Compared to non-carriers, participants who carried the haplotype were quicker to react after aversive stimuli had been presented. In contrast, the presence of the haplotype had no effect on the processing of neutral stimuli. We conclude that properties of the glucocorticoid receptor contribute to the processing of emotional stimuli and influence the intensity of their processing even in the absence of acute stressors.

Schneider|Katja Kerstin|KK|
Frings|Christian|C|
Meyer|Jobst|J|
Schote|Andrea B|AB|

Glucocorticoid receptor
Emotional processing
NR3C1 gene


Controlling Antibiotic Release from Polymethylmethacrylate Bone Cement.

Abstract: Bone cement is used as a mortar for securing bone implants, as bone void fillers or as spacers in orthopaedic surgery. Antibiotic-loaded bone cements (ALBCs) have been used to prevent and treat prosthetic joint infections by providing a high antibiotic concentration around the implanted prosthesis. High antibiotic concentrations are, on the other hand, often associated with tissue toxicity. Controlling antibiotic release from ALBCS is key to achieving effective infection control and promoting prosthesis integration with the surrounding bone tissue. However, current ALBCs still need significant improvement in regulating antibiotic release. In this review, we first provide a brief introduction to prosthetic joint infections, and the background concepts of therapeutic efficacy and toxicity in antibiotics. We then review the current state of ALBCs and their release characteristics before focusing on the research and development in controlling the antibiotic release and osteo-conductivity/inductivity. We then conclude by a discussion on the need for better in vitro experiment designs such that the release results can be extrapolated to predict better the local antibiotic concentrations in vivo.

antibiotics
release
cement
bone implant
PMMA
bacterial infection
delivery